Safety evaluation of deucravacitinib: a real-world analysis based on the FDA adverse event reporting system database

Safety evaluation of deucravacitinib: a real-world analysis based on the FDA adverse event reporting system database | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Safety evaluation of deucravacitinib: a real-world analysis based on the FDA adverse event reporting system database Haowen Tan, Xiubi Chen, Xuan Ou, Ying Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6346752/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Deucravacitinib is a novel, highly selective tyrosine kinase 2 allosteric inhibitor recently approved for the treatment of moderate-to-severe psoriasis in adults, though post-marketing safety data remain limited. Objective The purpose of this study was to perform a post-marketing safety evaluation of deucravacitinib base on the Food and Drug Administration Adverse Event Reporting System (FAERS). Mothed Adverse events (AEs) due to deucravacitinib from 2022Q3 to 2024Q4 identified as the primary suspect were screened. Four main methods of the disproportionality analysis, including reporting odds ratio, proportional reporting ratio, bayesian confidence propagation neural network, and multi-item gamma poisson shrinker, were employed for signal detection. The important medical event (IME) terms list was used to identify IMEs of deucravacitinib. Additionally, the Weibull distribution was used to evaluate the time-to-onset (TTO) characteristics. Results 39 preferred terms (PTs) were identified as potential risk signals. The most commonly reported PT were acne, mouth ulceration and folliculitis. 16 PTs with potential risk signals not mentioned on the label were also identified, including urticaria, oral pain, oropharyngeal pain, swelling face, lip swelling, and others. Rhabdomyolysis, Bell’s palsy, facial paralysis, and central nervous system infection were the IMEs of deucravacitinib. The Weibull distribution indicated that the TTO characteristics of deucravacitinib-associated AEs followed an early failure type. Conclusion This study provides preliminary safety data for deucravacitinib in the real world, confirming some known AEs, uncovering some underlying risks and identifying several IMEs. Further post-marketing safety surveillance studies on deucravacitinib remain necessary in the future. adverse event deucravacitinib data mining FAERS psoriasis Figures Figure 1 Figure 2 Figure 3 Impact statements • Acne, mouth ulceration and folliculitis were the most commonly reported events associated with deucravacitinib. • Potential adverse reactions such as urticaria, swelling face, eye swelling, lip swelling, pharyngeal swelling, respiratory tract congestion, swollen tongue, dermatitis allergicetc, which were not listed on the drug label, may indicate deucravacitinib-induced hypersensitivity and should be carefully evaluated. • Clinically important medical events associated with deucravacitinib include rhabdomyolysis, neurological effects (Bell’s palsy, facial paralysis), and central nervous system infections. • Deucravacitinib-associated adverse events followed an early failure type, underscoring the need for vigilant early monitoring. Introduction Psoriasis is a chronic inflammatory, immune-mediated disease that affects at least 100 million individuals worldwide [ 1 ]. This disease affects not only the skin, nails, and joints, but is also associated with comorbidities such as cardiovascular disease, metabolic syndrome, and diabetes mellitus, significantly compromising patients’ health and quality of life [ 2 , 3 ]. Treatment of psoriasis depends on disease severity. Patients with moderate to severe psoriasis may receive treatment including topical therapies, phototherapy, and systemic therapies (such as traditional oral medications and biologics) [ 2 ]. Traditional oral medications, including fumaric acid esters, cyclosporine, and methotrexate, have been associated with numerous side effects, long-term toxicity, and potential drug interactions [ 4 ]. Apremilast, an oral small-molecule inhibitor of phosphodiesterase-4, has limited efficacy in the treatment of psoriasis [ 5 ]. In recent years, biologic agents – including tumor necrosis factor-α inhibitors, interleukin (IL)-12, IL-17, and IL-23 inhibitors – have demonstrated positive therapeutic advances in psoriasis management. However, these biologics are associated with immunogenicity risks, injection-site reactions, and diminishing treatment efficacy over time [ 2 , 4 , 6 ]. Consequently, patients with moderate to severe psoriasis continue to have unmet clinical needs for therapies that are safe, effective, and durable. Previous studies have suggested that tyrosine kinase 2 (TYK2) mediates psoriasis-associated cytokine signaling [ 7 , 8 ], making it a potential therapeutic target. In September 2022, the United States Food and Drug Administration (FDA) approved deucravacitinib, a highly selective TYK2 allosteric inhibitor, for the treatment of moderate-to-severe psoriasis in adults. This marked the approval of a new therapeutic option for this condition. Although clinical trials have shown that deucravacitinib’s adverse effects are predominantly mild and transient [ 9 , 10 , 11 , 12 ], its long-term safety requires further real-world evaluation due to the rigor of the study design of clinical trials. Therefore, enhanced post-marketing surveillance is essential to fully evaluate the safety of deucravacitinib. The FDA Adverse Event Reporting System (FAERS) is a publicly accessible database designed for post-market pharmacovigilance and safety monitoring. Healthcare professionals (e.g., physicians, pharmacists) and non-healthcare individuals (e.g., patients, lawyers) voluntarily submit adverse event (AE) and medication error reports to the FAERS [ 13 ]. As a result, the FAERS database provides a valuable platform for collecting and analyzing AEs associated with deucravacitinib post-marketing, revealing safety signals that clinical trials may not capture due to their inherent limitations. Aim of the study Our study aims to utilize FAERS database to conduct a comprehensive post-marketing safety evaluation of deucravacitinib. Ethics approval This study did not require institutional review board approval because it met the Department of Health and Human Services regulations exemption from the Office for Protection from Research Risks [ 14 ]. Methods Data source and collection The FAERS database is updated quarterly, with all data files accessible for download on the FDA’s official website ( https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html ). Subfiles in the data files include DEMO (demographic characteristics), DRUG (drug information), REAC (information for AEs), OUTC (patients' clinical outcomes), RPSR (reporting source), THER (starting and ending time of drug treatment), and INDI (indications for drug therapy). Using a special identification number (e.g., PRIMARYID), we can find the relevant data for an AE report in seven distinct subfiles. Due to the FDA approval for marketing of deucravacitinib in September 2022, we conducted this study using data from the third quarter of 2022 to the fourth quarter of 2024. Data mining To extract the data and remove duplicate reports, R software ( https://www.r-project.org/ , version 4.4.1) was used. For the purpose of removing duplicate reports, we carried out data cleansing using methods that were advised by the FDA. The preferred term (PT) and system organ classification (SOC) of the Medical Dictionary for Regulatory Activities (MedDRA) (version 27.1) were used to code, classify, and locate AEs in the FAERS database. This was done so that the specific PTs and SOCs involved in AEs could be studied. AE-related drugs can be reported as primary suspect (PS), secondary suspect, concomitant, and interacting. To increase the reliability of our study’s findings, we used the terms “deucravacitinib” (generic name) and “sotyktu” (trade name), with the role of PS, to find the target drug in our study. Statistical analysis The disproportionality analysis, which is based on the 2*2 table (Table 1 ), has been used in pharmacovigilance studies to assess potential risk signals between AEs and drugs. In our study, the potential risk signals between deucravacitinib and AEs were evaluated using four main methods of the disproportionality analysis: the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the bayesian confidence propagation neural network (BCPNN), and the empirical bayes geometric mean (EBGM) derived from the multi-item gamma poisson shrinker (MGPS) [ 15 , 16 , 17 , 18 ]. Higher signal values indicate a stronger risk of AE with deucravacitinib. Table 2 displays the formula and criteria for the four main methods of disproportionality analysis. Using several algorithms in tandem reduces false positives by acting as cross-validation, resulting in more reliable findings. Therefore, a potential risk signal was considered significant when it matched all of the criteria of ROR, PRR, BCPNN and MGPS. Among AEs with significant signals, those not mentioned on the drug’s label were considered as unexpected AEs. Additionally, we utilized the MedDRA important medical event (IME) list (version 27.1) [ 19 ], as provided by the european medicine agency, to identify IMEs associated with deucravacitinib. Table 1 Two-by-two contingency table for disproportionality analysis Target AE Non-target AE Total Deucravacitinib a b a + b Other drugs c d c + d Total a + c b + d n = a + b + c + d Footnotes: AE, adverse events; a, the number of cases with deucravacitinib-associated target AE; b, the number of cases with deucravacitinib-associated non-target AE; c, the number of cases with target AE of all other drugs; d, the number of cases with non-target AE of all other drugs. Table 2 The formula and criteria of ROR, PRR, BCPNN and MGPS Algorithms Formula Criteria ROR ROR = ad/bc lower limit of 95% CI > 1, a ≥ 3 95%CI = e ln(ROR)±1.96(1/a+1/b+1/c+1/d)^0.5 PRR PRR = a(c + d)/c/(a + b) PRR ≥ 2, χ 2 ≥ 4, a ≥ 3 χ 2 =[(ad-bc)^2](a + b + c + d)/[(a + b)(c + d)(a + c)(b + d)] BCPNN IC = log 2 a(a + b + c + d)(a + c)(a + b) IC025 > 0 95%CI = E(IC) ± 2V(IC)^0.5 MGPS EBGM = a(a + b + c + d)/(a + c)/(a + b) EBGM05 > 2 95%CI = e ln(EBGM)±1.96(1/a+1/b+1/c+1/d)^0.5 Footnotes: 95%CI, 95% confidence interval; BCPNN, Bayesian confidence propagation neural network; EBGM, empirical Bayesian geometric mean; EBGM05, the lower limit of 95% CI of EBGM; E(IC), the IC expectations; IC, information component; IC025, the lower limit of 95% CI of the IC; MGPS, multi-item Gamma Poisson Shrinker; PRR, proportional reporting ratio; ROR, reporting odds ratio; V(IC), the variance of IC; χ 2 , chi-squared. Time-to-onset (TTO) analysis TTO for deucravacitinib-associated AEs was calculated as the interval between the AE occurrence date (EVENT_DT in the DEMO file) and the drug initiation date (START_DT in the THER file). Cases containing incorrect or missing dates were excluded. TTO characteristics were then evaluated using median values, interquartile ranges (IQR), and the shape parameter β of the Weibull distribution [ 20 , 21 ]. When the shape parameter β was < 1 and its 95% confidence interval (CI) was lower than 1, the hazard was considered to have decreased over time (early failure type); when the shape parameter β was equal to or nearly 1 and its 95% CI included the value 1, the hazard was estimated to constantly occur over time (random failure type); and when the shape parameter β was > 1 and its 95% CI excluded the value 1, the hazard was considered to increase over time (wear-out failure type)[ 22 ]. Additionally, we employed Kaplan-Meier analysis to evaluate differences in TTO across demographic subgroups (age, gender). Results Descriptive results The FAERS database collected a total of 4223456 case reports between the third quarter of 2022 and the fourth quarter of 2024. After duplicates were removed, there were 3690649 case reports left. Among them, the total number of AEs associated with deucravacitinib as the PS drug was 3552, involving 1963 patients. After excluding patients with unknown sex (n = 251), there were more female patients (n = 1105, 56.29%) than male patients (n = 607, 30.92%). Among the reports that included explicit age data, the patients who aged 18 to < 60 years made up the biggest number (n = 682), accounting for 34.75%. Furthermore, the majority of reports collected in this study were from the United States, accounting for 93.68%. Health professionals were the primary source of the reports, with a total of 1159 cases (59.04%). Figure 1 shows additional details of the data mining process, and Table 3 presents the basic information on reports of deucravacitinib-associated AEs in detail. Table 3 Basic information on reports of deucravacitinib-associated AEs in the FAERS database between 2022Q3 and 2024Q4. (n = 1963) Basic information Case reports Case proportion (%) Gender Male 607 30.92 Female 1105 56.29 Unknown 251 12.79 Age <18 years 31 1.58 18 years ≤ and <60 years 682 34.74 ≥ 60 years 663 33.78 Unknown 587 29.90 The top 5 reported country United States 1839 93.68 Japan 81 4.12 Germany 16 0.82 Australia 11 0.56 Canada 5 0.25 Reporter type Health professional 1159 59.04 Non-health professional 781 39.79 Missing 23 1.17 Signals detection associated with deucravacitinib-associated AEs We first ruled out auto-disease-related AEs such as psoriasis, erythema, pruritus, and other accompanying symptoms of psoriasis, as well as medication-independent AEs like off-label use, product dose omission issues and others. After that, using the four methods of ROR, PRR, MGPS, and BCPNN, we identified 39 PTs with significant signals by simultaneously meeting the criteria of four methods. The three most common PTs in this study were acne (n = 201, ROR 73.09, PRR 69.01, EBGM 67.60, IC 6.08), mouth ulceration (n = 62, ROR 51.29, PRR 50.41, EBGM 49.66, IC 5.63), folliculitis (n = 55, ROR47.11, PRR 46.40, EBGM 45.76, IC 5.52). Interestingly, we identified 16 unexpected PTs with significant signals that were not listed on the label, including urticaria, oral pain, oropharyngeal pain, swelling face, lip swelling, eye swelling, cellulitis, ear pain, pharyngeal swelling, Bell’s palsy, mouth swelling, cheilitis, mycobacterium tuberculosis complex test positive, facial paralysis, hepatitis A, and central nervous system (CNS) infection. Additionally, four IMEs were identified: rhabdomyolysis, Bell’s palsy, facial paralysis, and CNS infection. Table 4 provides detailed information on these findings. Table 4 The PTs with significant signal for deucravacitinib ranked by case reports number at the PT level in the FAERS database. Rank PT Case reports ROR PRR EBGM IC (95%CI) (χ 2 ) (EBGM05) (IC025) 1 Acne 201 73.09(63.30-84.39) 69.01(13203.59) 67.60(59.94) 6.08(5.87) 2 Mouth ulceration 62 51.29(39.82–66.06) 50.41(2958.17) 49.66(40.19) 5.63(5.26) 3 Folliculitis 55 47.11(36.03–61.61) 46.40(2409.68) 45.76(36.56) 5.52(5.12) 4 Urticaria * 42 4.82(3.56–6.54) 4.78(125.49) 4.77(3.70) 2.25(1.81) 5 Hypersensitivity 31 3.28(2.30–4.67) 3.26(48.55) 3.25(2.42) 1.70(1.19) 6 Oral pain * 29 26.24(18.18–37.87) 26.03(692.80) 25.84(19.01) 4.69(4.16) 7 Oral herpes 28 19.46(13.40-28.26) 19.31(483.57) 19.21(14.06) 4.26(3.72) 8 Myalgia 27 3.31(2.27–4.83) 3.29(43.15) 3.29(2.40) 1.72(1.17) 9 Oropharyngeal pain * 26 4.35(2.96–6.40) 4.33(66.57) 4.32(3.13) 2.11(1.55) 10 Swelling face * 24 8.17(5.47–12.21) 8.12(149.67) 8.11(5.79) 3.02(2.44) 11 Aphthous ulcer 24 29.61(19.79–44.32) 29.42(653.13) 29.16(20.81) 4.87(4.28) 12 Stomatitis 21 5.62(3.66–8.63) 5.59(79.14) 5.58(3.90) 2.48(1.86) 13 Herpes zoster 20 5.99(3.86–9.30) 5.96(82.56) 5.96(4.12) 2.57(1.94) 14 Upper respiratory tract infection 14 5.06(2.99–8.55) 5.04(45.30) 5.03(3.24) 2.33(1.58) 15 Blood triglycerides increased 14 22.06(13.03–37.35) 21.98(278.50) 21.84(14.06) 4.45(3.70) 16 Dermatitis acneiform 11 31.67(17.47–57.40) 31.57(322.56) 31.28(19.02) 4.97(4.13) 17 Acne cystic 10 88.61(47.24-166.21) 88.36(840.98) 86.06(50.84) 6.43(5.54) 18 Oral mucosal blistering 10 32.83(17.59–61.25) 32.74(304.64) 32.42(19.24) 5.02(4.14) 19 Lip swelling * 10 6.44(3.46–11.98) 6.42(45.70) 6.41(3.81) 2.68(1.81) 20 Eye swelling * 9 4.92(2.56–9.47) 4.91(27.99) 4.90(2.84) 2.29(1.38) 21 Blood creatine phosphokinase increased 9 8.02(4.17–15.44) 8.00(55.05) 7.99(4.62) 3.00(2.08) 22 Cellulitis * 9 3.55(1.84–6.83) 3.54(16.42) 3.54(2.05) 1.82(0.91) 23 Herpes simplex 7 22.14(10.52–46.59) 22.10(140.05) 21.95(11.78) 4.46(3.43) 24 Rosacea 7 26.41(12.54–55.60) 26.36(169.40) 26.15(14.03) 4.71(3.68) 25 Rhabdomyolysis † 7 4(1.91–8.41) 4.00(15.72) 3.99(2.15) 2.00(0.98) 26 Ear pain * 7 6.23(2.96–13.08) 6.22(30.60) 6.21(3.34) 2.63(1.61) 27 Pharyngeal swelling * 5 4.92(2.05–11.84) 4.91(15.57) 4.91(2.36) 2.30(1.12) 28 Bell’s palsy * † 5 19.57(8.12–47.18) 19.55(87.48) 19.44(9.31) 4.28(3.10) 29 Furuncle 4 9.26(3.47–24.72) 9.25(29.35) 9.23(4.06) 3.21(1.91) 30 Tongue ulceration 4 27.37(10.23–73.27) 27.34(100.68) 27.12(11.90) 4.76(3.46) 31 Pharyngitis 4 6.06(2.27–16.17) 6.05(16.85) 6.05(2.66) 2.60(1.30) 32 Herpes virus infection 4 13.13(4.92–35.09) 13.12(44.61) 13.07(5.75) 3.71(2.41) 33 Acne pustular 4 81.1(30.05-218.83) 81.01(308.43) 79.07(34.46) 6.31(4.99) 34 Mouth swelling * 3 8.91(2.87–27.67) 8.90(20.98) 8.88(3.44) 3.15(1.70) 35 Cheilitis * 3 12.49(4.02–38.82) 12.48(31.55) 12.43(4.81) 3.64(2.19) 36 Mycobacterium tuberculosis complex test positive * 3 19.78(6.35–61.56) 19.76(53.12) 19.65(7.60) 4.30(2.85) 37 Facial paralysis * † 3 5.69(1.83–17.67) 5.69(11.57) 5.68(2.20) 2.51(1.06) 38 Hepatitis A * 3 73.06(23.26-229.51) 73.00(208.37) 71.42(27.41) 6.16(4.69) 39 Central nervous system infection * † 3 43.70(13.98–136.60) 43.67(123.42) 43.10(16.61) 5.43(3.97) Footnotes: CI, confidence interval; EBGM, empirical bayesian geometric mean; EBGM05, the lower limit of 95% confidence interval of EBGM; IC, information component; IC025, the lower limit of 95% confidence interval of the IC; PRR, proportional reporting ratio; PT, preferred term; ROR, reporting odds ratio; χ 2 , Chi-squared. * The PT is not listed on the label of deucravacitinib; † The PT is an important medical event for deucravacitinib. 39 PTs with significant signals were categorized using the SOC of MedDRA (version 27.1). Figure 2 shows the distribution of PTs with significant signals at the SOC level. The three most frequently involved SOCs were skin and subcutaneous tissue disorders, gastrointestinal disorders, and infections and infestations. TTO Only 104 cases with complete dates of drug initiation and AE onset were gathered. Overall, the median TTO for deucravacitinib-associated AEs was 20 days (IQR: 6–97). The Weibull distribution shape parameter (β = 0.63, 95% CI: 0.54–0.72) indicates an early failure type for the TTO of deucravacitinib-associated AEs. However, subgroup analyses revealed no significant impact of age (P = 0.27) and gender (P = 0.98) on the TTO. Figure 3 provides more details on the TTO of deucravacitinib-associated AEs Discussion Deucravacitinib, a novel therapeutic agent with demonstrated efficacy and favorable safety profile, has recently been introduced for the treatment of moderate-to-severe psoriasis. Given the widespread use of deucravacitinib in clinical practice, continued pharmacovigilance studies are necessary. Based on the real-world data from the FAERS database, this study provided additional data to refine the safety profile of deucravacitinib. According to pooled data [ 23 ] from the placebo-controlled periods of POETYK PSO-1 [ 10 ] and POETYK PSO-2 [ 11 ], the most commonly reported adverse reactions in patients with psoriasis receiving deucravacitinib were upper respiratory tract infections (19.2%), blood creatine phosphokinase increased (2.7%), herpes simplex (2.0%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). This shares some similarities, but also some differences with the most common AEs which we discovered in the current study. In clinical trials, the most common adverse reactions were upper respiratory tract infections, including nasopharyngitis, pharyngitis, sinusitis, rhinitis, rhinotracheitis, tracheitis, laryngitis, and tonsillitis. The current study identified a relatively small number of AE cases (n = 14) coded to the PT ‘upper respiratory tract infection’. This result may be attributable to the classification of upper respiratory tract infection in the FAERS database, where distinct preferred terms (PTs) such as sinusitis, pharyngitis, and bronchitis were reported separately.In contrast, the most common AE in the current study were acne. The skin microbiome and altered immune-mediated responses due to deucravacitinib’s inhibition of TYK2-dependent signaling pathways may play a role in the pathogenesis of this skin event, even though the exact mechanism is yet unknown [ 24 ]. In patients with acne, topical therapies (benzoyl peroxide cream, clindamycin solution, or chlorhexidine ointment for acne) were often helpful, resulting in minimal withdrawal from deucravacitinib treatment [ 25 ]. In this study, we identified some unexpected AEs such as urticaria, swelling face, eye swelling, lip swelling, pharyngeal swelling, respiratory tract congestion, swollen tongue, dermatitis allergicetc, etc. There was a possibility that these AEs may signal the onset of deucravacitinib-induced allergic reactions, since anaphylactic reactions could lead to urticaria, angioedema, dyspnea, among other symptoms [ 26 , 27 ]. Therefore, we should be wary of allergic reactions caused by deucravacitinib and provide prompt symptomatic treatment or discontinue the drug if necessary. We identified four IMEs associated with deucravacitinib therapy, including Bell’s palsy, facial paralysis, rhabdomyolysis, and CNS infection. In MedDRA, ‘facial nerve disorders’ is the higher-level term for Bell’s palsy and facial paralysis. Notably, herpes virus infection is explicitly listed as a known adverse reaction on the label of deucravacitinib. Herpes virus can infiltrate the facial nerve, constituting a principal etiological factor in peripheral facial paralysis and Bell’s palsy [ 28 ]. Evidence suggests that combining antivirals with corticosteroids improves patient outcomes [ 29 ]. Additionally, patients receiving deucravacitinib may experience elevated blood creatine phosphokinase levels, which are associated with rhabdomyolysis. As a result, comprehensive medication education should be provided to patients, instructing them to immediately report any unexplained muscle pain, tenderness, or weakness – particularly when accompanied by fever – during treatment. If rhabdomyolysis is confirmed, deucravacitinib should be discontinued immediately and targeted therapeutic measures initiated without delay. During subsequent management, the potential benefits and risks of reinitiating deucravacitinib therapy should be comprehensively reassessed based on the patient's recovery status. Based on findings from POETYK PSO-1 and POETYK PSO-2 trials, pneumonia and COVID-19 emerged as the most serious infection types among in deucravacitinib-treated patients [ 10 , 11 ]. It is worth noting that the current study has identified potential CNS infection risks (ROR 43.70, PRR 43.67, EBGM 43.10, IC 5.43) associated with deucravacitinib therapy. Given the severe consequences of CNS infections, prompt anti-infection treatment is warranted upon diagnosis to mitigate neurological sequelae. TYK2 constitutes a core member of the Janus kinase (JAK) family along with JAK1, JAK2, and JAK3. In recent years, regulation agencies have been focusing on serious safety concerns (e.g., venous thromboembolic events, major adverse cardiac events, cancer) regarding JAK inhibitors [ 30 , 31 ]. The mechanism underlying these risks was not fully elucidated but might be related to JAK inhibitors’ inhibitory effects on JAK homology 1 domain [ 30 , 32 ]. Nowadays, it is unclear whether TYK2 inhibition shares the serious safety concerns of traditional JAK inhibitions. Therefore, deucravacitinib’s prescribing information does not include a boxed warning for these risks. In the current study, our disproportionality analysis did not reveal significant signals for deucravacitinib-related serious safety concerns. This finding may be attributable to the following factors. On the one hand, deucravacitinib’s unique allosteric inhibition mechanism targeting TYK2 may confer distinct safety profiles. Previous studies have suggested that deucravacitinib binds to the JAK homology 2 regulatory domain via a highly specific allosteric mechanism rather than the JAK homology 1 domain, as do other JAK inhibitors [ 33 , 34 ]. This makes deucravacitinib more selective for TYK2 than for JAK 1, 2, and 3, reducing the likelihood of off-target effects. On the other hand, the short monitoring period (< 3 years) and limited patient exposure (< 2000) in the current study may have prevented complete characterization of deucravacitinib’s serious AE profile. Therefore, whether deucravacitinib shares similar serious safety concerns with other JAK inhibitors remains to be established through post-marketing safety studies with expanded cohort sizes and prolonged surveillance periods. The Weibull distribution analysis revealed that deucravacitinib-associated AEs exhibited an early failure type (β = 0.63, 95% CI: 0.54–0.72), indicating higher AE risk during early treatment period. Based on this finding, close attention should be paid to patients’ discomfort symptoms during the initial medication period, with particular vigilance against AEs such as allergic reactions. However, there is substantial missing data on the TTO in this study, potentially leading to biased results. Therefore, future studies are still needed to evaluate the TTO of deucravacitinib-associated AEs. Studies based on the FAERS database have limitations as well. Firstly, the FAERS database only contains reports of AEs, but the overall number of people using deucravacitinib is unknown. It is impossible to calculate the frequency of deucravacitinib-associated AEs. Secondly, the spontaneous reporting system can only passively collect information on AE reports; underreporting or misreporting could potentially impact the study’s results. Thirdly, potential risk signals were identified through disproportionality analysis, reflecting only pharmacovigilance statistical associations. The exact causal relationship between AEs and deucravacitinib requires further investigation due to potential confounding by concomitant medications, individual variability, and underlying disease states. Fourthly, the current study only gathered AE reports nearly two years after the launch of deucravacitinib; this short safety monitoring period may have left some potential AEs unidentified. Conclusion Analysis of postmarketing surveillance data from the FAERS identified acne, mouth ulceration, and folliculitis as the most frequently reported AEs associated with deucravacitinib. Additionally, unexpected AEs not mentioned on the label were also identified, including urticaria, oral pain, oropharyngeal pain, swelling face, lip swelling, eye swelling, and others. Rhabdomyolysis, Bell’s palsy, facial paralysis, and central nervous system infection were the IMEs of deucravacitinib. These findings have somewhat supplemented the safety data for deucravacitinib. However, given the FAERS’ limitations, further real-world prospective cohort studies are needed to optimize deucravacitinib post-market safety assessment. Declarations Conflict of interest Authors declare no conflict of interests for this article. Funding This study was supported by the Self-funded Research Project in Western Medicine, Health Commission of Guangxi, China [grant number Z-D20231663]. Author Contribution H. T. wrote the original manuscript. X. C. and X. O. collected the data. Y. C. designed the study and review the manuscript. All authors contributed to the manuscript’s revision and read and approved the submitted version. Acknowledgments The FAERS database, which was made available by the FDA, was used to conduct this study. The FDA does not have any opinion about the data, findings, or interpretation of the current study. Data Availability https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html References World Health Organization. Global Report on Psoriasis:World Health Organization, 2016. https://iris.who.int/handle/10665/204417. Accessed March 14, 2025. Armstrong AW, Read C. 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SOTYKTU™ (deucravacitinib) tablets, for oral use: US prescribing information. 2022. Accessed March 14, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214958s000lbl.pdf Lebwohl M, Warren RB, Sofen H, Imafuku S, Paul C, Szepietowski JC, et al. Deucravacitinib in plaque psoriasis: 2-year safety and efficacy results from the phase III POETYK trials. Br J Dermatol. 2024 Apr 17;190(5):668-679. doi: 10.1093/bjd/ljae014. Catlett IM, Aras U, Hansen L, Liu Y, Bei D, Girgis IG, et al. First-in-human study of deucravacitinib: A selective, potent, allosteric small-molecule inhibitor of tyrosine kinase 2. Clin Transl Sci. 2023 Jan;16(1):151-164. doi: 10.1111/cts.13435. Hanschmann T, Francuzik W, Dölle-Bierke S, Hofmeier KS, Grabenhenrich L, Ruëff F, et al. Different phenotypes of drug-induced anaphylaxis-Data from the European Anaphylaxis Registry. Allergy. 2023 Jun;78(6):1615-1627. doi: 10.1111/all.15612. Cardona V, Ansotegui IJ, Ebisawa M, El-Gamal Y, Fernandez Rivas M, Fineman S, et al. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J. 2020 Oct 30;13(10):100472. doi: 10.1016/j.waojou.2020.100472. Murakami S, Mizobuchi M, Nakashiro Y, Doi T, Hato N, Yanagihara N. Bell palsy and herpes simplex virus: identification of viral DNA in endoneurial fluid and muscle. Ann Intern Med. 1996 Jan 1;124(1 Pt 1):27-30. doi: 10.7326/0003-4819-124-1_part_1-199601010-00005. Gagyor I, Madhok VB, Daly F, Somasundara D, Sullivan M, Gammie F, et al. Antiviral treatment for Bell's palsy (idiopathic facial paralysis). Cochrane Database Syst Rev. 2015 Nov 9;(11):CD001869. doi: 10.1002/14651858.CD001869.pub8. Kragstrup TW, Glintborg B, Svensson AL, McMaster C, Robinson PC, Deleuran B, et al. Waiting for JAK inhibitor safety data. RMD Open. 2022 Feb;8(1):e002236. doi: 10.1136/rmdopen-2022-002236. Singh JA. The Emerging Safety Profile of JAK Inhibitors in Rheumatic Diseases. BioDrugs. 2023 Sep;37(5):625-635. doi: 10.1007/s40259-023-00612-7. Di Martino RMC, Maxwell BD, Pirali T. Deuterium in drug discovery: progress, opportunities and challenges. Nat Rev Drug Discov. 2023 Jul;22(7):562-584. doi: 10.1038/s41573-023-00703-8. Epub 2023 Jun 5. Wrobleski ST, Moslin R, Lin S, Zhang Y, Spergel S, Kempson J, et al. Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165. J Med Chem. 2019 Oct 24;62(20):8973-8995. doi: 10.1021/acs.jmedchem.9b00444. Attwood MM, Fabbro D, Sokolov AV, Knapp S, Schiöth HB. Trends in kinase drug discovery: targets, indications and inhibitor design. Nat Rev Drug Discov. 2021 Nov;20(11):839-861. doi: 10.1038/s41573-021-00252-y. Epub 2021 Aug 5. Erratum in: Nat Rev Drug Discov. 2021 Oct;20(10):798. doi: 10.1038/s41573-021-00303-4. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 29 May, 2025 Reviews received at journal 28 May, 2025 Reviewers agreed at journal 04 May, 2025 Reviews received at journal 17 Apr, 2025 Reviewers agreed at journal 01 Apr, 2025 Reviewers invited by journal 01 Apr, 2025 Editor assigned by journal 01 Apr, 2025 Submission checks completed at journal 01 Apr, 2025 First submitted to journal 31 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6346752","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":445339100,"identity":"e3f45a3a-2c88-47da-9a13-8b9d7cd5d3a4","order_by":0,"name":"Haowen Tan","email":"","orcid":"","institution":"Wuzhou Red Cross Hospital","correspondingAuthor":false,"prefix":"","firstName":"Haowen","middleName":"","lastName":"Tan","suffix":""},{"id":445339101,"identity":"d37c2bb5-c9d9-4046-882f-b15afa2fe306","order_by":1,"name":"Xiubi Chen","email":"","orcid":"","institution":"Center for Adverse Drug Reaction Monitoring of Mianyang","correspondingAuthor":false,"prefix":"","firstName":"Xiubi","middleName":"","lastName":"Chen","suffix":""},{"id":445339102,"identity":"50515885-d6e7-4fb0-92c5-b88dc6bb57f5","order_by":2,"name":"Xuan Ou","email":"","orcid":"","institution":"Wuzhou Red Cross Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xuan","middleName":"","lastName":"Ou","suffix":""},{"id":445339103,"identity":"fd5552f7-b9ab-4876-bc20-06f383952ce2","order_by":3,"name":"Ying Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYDACZiBmbGBgkOdvPvjgg4GNHfFaDGccSzacUZCWTJxNIC0MB3LMpHk+HAKz8QKD47yHX/zcYZPH2HAs2djG4AAzA/vhoxvwajnMl2bZeyatmJ25+eDjHIM7fAw8aWk38GkxO8xjZszYdjixEWRLjsEzZgYJHjNitPxPbAD5xcLgMGMDEVqMHzO2HYBoYSBGiz3QFsbetuTEjaBA7jFIS2Yj5BfJ/jPGH3622SXOB0Xljz82dvzsh4/h1QIEbBKoXALKQYD5AxGKRsEoGAWjYCQDALa6T/QnC2trAAAAAElFTkSuQmCC","orcid":"","institution":"Wuzhou Red Cross Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ying","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-03-31 16:53:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6346752/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6346752/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":81125608,"identity":"17553c95-8881-4418-ad7b-eff04f19fc3e","added_by":"auto","created_at":"2025-04-22 13:50:44","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":121737,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of process for data mining on deucravacitinib\u003c/p\u003e\n\u003cp\u003eFootnotes: DEMO, demographic characteristics; DRUG, drug information; FAERS, food and drug administration adverse event reporting system; PS, primary suspect. REAC, information for adverse events.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6346752/v1/efabe8a4c6374bbee77ed330.jpg"},{"id":81125612,"identity":"64c822b3-72c6-40f2-a5db-fff3ffc94ef7","added_by":"auto","created_at":"2025-04-22 13:50:44","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":144553,"visible":true,"origin":"","legend":"\u003cp\u003eThe Sankey diagram illustrates the relationship between the PTs and the SOCs in the MedDRA\u003c/p\u003e\n\u003cp\u003eFootnotes: PT, preferred term; SOC, system organ classification.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6346752/v1/3faaa649b5bea3616c3738ec.jpg"},{"id":81126648,"identity":"9a951a6a-760c-4da6-8fb7-5e9c030cf3b5","added_by":"auto","created_at":"2025-04-22 13:58:44","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":91342,"visible":true,"origin":"","legend":"\u003cp\u003eTime to onset analysis for deucravacitinib-associated AEs.\u003c/p\u003e\n\u003cp\u003eFootnotes: (a) Histograms, boxplots and weibull distribution depict the onset time distribution of deucravacitinib-associated AEs. (b-c) The cumulative distribution curves show the onset time of deucravacitinib-associated AEs in different subgroups (gender, and age). Statistical tests were conducted using the nonparametric Wilcoxon rank sum test.\u003c/p\u003e\n\u003cp\u003eTTO, time to onset; CI, confidence interval.\u003c/p\u003e\n\u003cp\u003eFootnotes: IQR, interquartile range; TTO, time-to-onset.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6346752/v1/14bafc10cbf9eff5eab38b10.jpg"},{"id":81128199,"identity":"1b4abf78-3b61-4774-9817-59a227860b63","added_by":"auto","created_at":"2025-04-22 14:14:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1258087,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6346752/v1/15f9acb0-53ed-49f1-a4fd-796d2909408d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Safety evaluation of deucravacitinib: a real-world analysis based on the FDA adverse event reporting system database","fulltext":[{"header":"Impact statements","content":"\u003cp\u003e\u0026bull; Acne, mouth ulceration and folliculitis were the most commonly reported events associated with deucravacitinib.\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp; Potential adverse reactions such as urticaria, swelling face, eye swelling, lip swelling, pharyngeal swelling, respiratory tract congestion, swollen tongue, dermatitis allergicetc, which were not listed on the drug label, may indicate deucravacitinib-induced hypersensitivity and should be carefully evaluated.\u003c/p\u003e\n\u003cp\u003e\u0026bull; Clinically important medical events associated with deucravacitinib include rhabdomyolysis, neurological effects (Bell\u0026rsquo;s palsy, facial paralysis), and central nervous system infections.\u003c/p\u003e\n\u003cp\u003e\u0026bull; Deucravacitinib-associated adverse events followed an early failure type, underscoring the need for vigilant early monitoring.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003ePsoriasis is a chronic inflammatory, immune-mediated disease that affects at least 100\u0026nbsp;million individuals worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This disease affects not only the skin, nails, and joints, but is also associated with comorbidities such as cardiovascular disease, metabolic syndrome, and diabetes mellitus, significantly compromising patients\u0026rsquo; health and quality of life [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTreatment of psoriasis depends on disease severity. Patients with moderate to severe psoriasis may receive treatment including topical therapies, phototherapy, and systemic therapies (such as traditional oral medications and biologics) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Traditional oral medications, including fumaric acid esters, cyclosporine, and methotrexate, have been associated with numerous side effects, long-term toxicity, and potential drug interactions [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Apremilast, an oral small-molecule inhibitor of phosphodiesterase-4, has limited efficacy in the treatment of psoriasis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In recent years, biologic agents \u003cb\u003e\u0026ndash;\u003c/b\u003e including tumor necrosis factor-α inhibitors, interleukin (IL)-12, IL-17, and IL-23 inhibitors \u003cb\u003e\u0026ndash;\u003c/b\u003e have demonstrated positive therapeutic advances in psoriasis management. However, these biologics are associated with immunogenicity risks, injection-site reactions, and diminishing treatment efficacy over time [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Consequently, patients with moderate to severe psoriasis continue to have unmet clinical needs for therapies that are safe, effective, and durable.\u003c/p\u003e \u003cp\u003ePrevious studies have suggested that tyrosine kinase 2 (TYK2) mediates psoriasis-associated cytokine signaling [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], making it a potential therapeutic target. In September 2022, the United States Food and Drug Administration (FDA) approved deucravacitinib, a highly selective TYK2 allosteric inhibitor, for the treatment of moderate-to-severe psoriasis in adults. This marked the approval of a new therapeutic option for this condition. Although clinical trials have shown that deucravacitinib\u0026rsquo;s adverse effects are predominantly mild and transient [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], its long-term safety requires further real-world evaluation due to the rigor of the study design of clinical trials. Therefore, enhanced post-marketing surveillance is essential to fully evaluate the safety of deucravacitinib.\u003c/p\u003e \u003cp\u003eThe FDA Adverse Event Reporting System (FAERS) is a publicly accessible database designed for post-market pharmacovigilance and safety monitoring. Healthcare professionals (e.g., physicians, pharmacists) and non-healthcare individuals (e.g., patients, lawyers) voluntarily submit adverse event (AE) and medication error reports to the FAERS [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. As a result, the FAERS database provides a valuable platform for collecting and analyzing AEs associated with deucravacitinib post-marketing, revealing safety signals that clinical trials may not capture due to their inherent limitations.\u003c/p\u003e\n\u003ch3\u003eAim of the study\u003c/h3\u003e\n\u003cp\u003eOur study aims to utilize FAERS database to conduct a comprehensive post-marketing safety evaluation of deucravacitinib.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEthics approval\u003c/h2\u003e \u003cp\u003eThis study did not require institutional review board approval because it met the Department of Health and Human Services regulations exemption from the Office for Protection from Research Risks [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData source and collection\u003c/h2\u003e \u003cp\u003eThe FAERS database is updated quarterly, with all data files accessible for download on the FDA\u0026rsquo;s official website (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html\u003c/span\u003e\u003cspan address=\"https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). Subfiles in the data files include DEMO (demographic characteristics), DRUG (drug information), REAC (information for AEs), OUTC (patients' clinical outcomes), RPSR (reporting source), THER (starting and ending time of drug treatment), and INDI (indications for drug therapy). Using a special identification number (e.g., PRIMARYID), we can find the relevant data for an AE report in seven distinct subfiles. Due to the FDA approval for marketing of deucravacitinib in September 2022, we conducted this study using data from the third quarter of 2022 to the fourth quarter of 2024.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData mining\u003c/h3\u003e\n\u003cp\u003eTo extract the data and remove duplicate reports, R software (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.r-project.org/\u003c/span\u003e\u003cspan address=\"https://www.r-project.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e, version 4.4.1) was used. For the purpose of removing duplicate reports, we carried out data cleansing using methods that were advised by the FDA. The preferred term (PT) and system organ classification (SOC) of the Medical Dictionary for Regulatory Activities (MedDRA) (version 27.1) were used to code, classify, and locate AEs in the FAERS database. This was done so that the specific PTs and SOCs involved in AEs could be studied. AE-related drugs can be reported as primary suspect (PS), secondary suspect, concomitant, and interacting. To increase the reliability of our study\u0026rsquo;s findings, we used the terms \u0026ldquo;deucravacitinib\u0026rdquo; (generic name) and \u0026ldquo;sotyktu\u0026rdquo; (trade name), with the role of PS, to find the target drug in our study.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe disproportionality analysis, which is based on the 2*2 table (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), has been used in pharmacovigilance studies to assess potential risk signals between AEs and drugs. In our study, the potential risk signals between deucravacitinib and AEs were evaluated using four main methods of the disproportionality analysis: the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the bayesian confidence propagation neural network (BCPNN), and the empirical bayes geometric mean (EBGM) derived from the multi-item gamma poisson shrinker (MGPS) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Higher signal values indicate a stronger risk of AE with deucravacitinib. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e displays the formula and criteria for the four main methods of disproportionality analysis. Using several algorithms in tandem reduces false positives by acting as cross-validation, resulting in more reliable findings. Therefore, a potential risk signal was considered significant when it matched all of the criteria of ROR, PRR, BCPNN and MGPS. Among AEs with significant signals, those not mentioned on the drug\u0026rsquo;s label were considered as unexpected AEs. Additionally, we utilized the MedDRA important medical event (IME) list (version 27.1) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], as provided by the european medicine agency, to identify IMEs associated with deucravacitinib.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTwo-by-two contingency table for disproportionality analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTarget AE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-target AE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeucravacitinib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ea\u0026thinsp;+\u0026thinsp;b\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther drugs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ec\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ea\u0026thinsp;+\u0026thinsp;c\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eb\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;a\u0026thinsp;+\u0026thinsp;b\u0026thinsp;+\u0026thinsp;c\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eFootnotes: AE, adverse events; a, the number of cases with deucravacitinib-associated target AE; b, the number of cases with deucravacitinib-associated non-target AE; c, the number of cases with target AE of all other drugs; d, the number of cases with non-target AE of all other drugs.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe formula and criteria of ROR, PRR, BCPNN and MGPS\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlgorithms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFormula\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCriteria\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eROR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eROR\u0026thinsp;=\u0026thinsp;ad/bc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003elower limit of 95% CI\u0026thinsp;\u0026gt;\u0026thinsp;1, a\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95%CI\u0026thinsp;=\u0026thinsp;e\u003csup\u003eln(ROR)\u0026plusmn;1.96(1/a+1/b+1/c+1/d)^0.5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePRR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePRR\u0026thinsp;=\u0026thinsp;a(c\u0026thinsp;+\u0026thinsp;d)/c/(a\u0026thinsp;+\u0026thinsp;b)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePRR\u0026thinsp;\u0026ge;\u0026thinsp;2, χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026ge;\u0026thinsp;4, a\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e=[(ad-bc)^2](a\u0026thinsp;+\u0026thinsp;b\u0026thinsp;+\u0026thinsp;c\u0026thinsp;+\u0026thinsp;d)/[(a\u0026thinsp;+\u0026thinsp;b)(c\u0026thinsp;+\u0026thinsp;d)(a\u0026thinsp;+\u0026thinsp;c)(b\u0026thinsp;+\u0026thinsp;d)]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBCPNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIC\u0026thinsp;=\u0026thinsp;log\u003csub\u003e2\u003c/sub\u003ea(a\u0026thinsp;+\u0026thinsp;b\u0026thinsp;+\u0026thinsp;c\u0026thinsp;+\u0026thinsp;d)(a\u0026thinsp;+\u0026thinsp;c)(a\u0026thinsp;+\u0026thinsp;b)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIC025\u0026thinsp;\u0026gt;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95%CI\u0026thinsp;=\u0026thinsp;E(IC)\u0026thinsp;\u0026plusmn;\u0026thinsp;2V(IC)^0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMGPS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEBGM\u0026thinsp;=\u0026thinsp;a(a\u0026thinsp;+\u0026thinsp;b\u0026thinsp;+\u0026thinsp;c\u0026thinsp;+\u0026thinsp;d)/(a\u0026thinsp;+\u0026thinsp;c)/(a\u0026thinsp;+\u0026thinsp;b)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEBGM05\u0026thinsp;\u0026gt;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95%CI\u0026thinsp;=\u0026thinsp;e\u003csup\u003eln(EBGM)\u0026plusmn;1.96(1/a+1/b+1/c+1/d)^0.5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eFootnotes: 95%CI, 95% confidence interval; BCPNN, Bayesian confidence propagation neural network; EBGM, empirical Bayesian geometric mean; EBGM05, the lower limit of 95% CI of EBGM; E(IC), the IC expectations; IC, information component; IC025, the lower limit of 95% CI of the IC; MGPS, multi-item Gamma Poisson Shrinker; PRR, proportional reporting ratio; ROR, reporting odds ratio; V(IC), the variance of IC; χ\u003csup\u003e2\u003c/sup\u003e, chi-squared.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eTime-to-onset (TTO) analysis\u003c/h2\u003e \u003cp\u003eTTO for deucravacitinib-associated AEs was calculated as the interval between the AE occurrence date (EVENT_DT in the DEMO file) and the drug initiation date (START_DT in the THER file). Cases containing incorrect or missing dates were excluded. TTO characteristics were then evaluated using median values, interquartile ranges (IQR), and the shape parameter β of the Weibull distribution [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. When the shape parameter β was \u0026lt;\u0026thinsp;1 and its 95% confidence interval (CI) was lower than 1, the hazard was considered to have decreased over time (early failure type); when the shape parameter β was equal to or nearly 1 and its 95% CI included the value 1, the hazard was estimated to constantly occur over time (random failure type); and when the shape parameter β was \u0026gt;\u0026thinsp;1 and its 95% CI excluded the value 1, the hazard was considered to increase over time (wear-out failure type)[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Additionally, we employed Kaplan-Meier analysis to evaluate differences in TTO across demographic subgroups (age, gender).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eDescriptive results\u003c/h2\u003e \u003cp\u003eThe FAERS database collected a total of 4223456 case reports between the third quarter of 2022 and the fourth quarter of 2024. After duplicates were removed, there were 3690649 case reports left. Among them, the total number of AEs associated with deucravacitinib as the PS drug was 3552, involving 1963 patients. After excluding patients with unknown sex (n\u0026thinsp;=\u0026thinsp;251), there were more female patients (n\u0026thinsp;=\u0026thinsp;1105, 56.29%) than male patients (n\u0026thinsp;=\u0026thinsp;607, 30.92%). Among the reports that included explicit age data, the patients who aged 18 to \u0026lt;\u0026thinsp;60 years made up the biggest number (n\u0026thinsp;=\u0026thinsp;682), accounting for 34.75%. Furthermore, the majority of reports collected in this study were from the United States, accounting for 93.68%. Health professionals were the primary source of the reports, with a total of 1159 cases (59.04%). Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows additional details of the data mining process, and Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e presents the basic information on reports of deucravacitinib-associated AEs in detail.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBasic information on reports of deucravacitinib-associated AEs in the FAERS database between 2022Q3 and 2024Q4. (n\u0026thinsp;=\u0026thinsp;1963)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasic information\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase reports\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCase proportion (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e607\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30.92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e251\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;18 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18 years\u0026thinsp;\u0026le;\u0026thinsp;and \u0026lt;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e682\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34.74\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e663\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e587\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29.90\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThe top 5 reported country\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited States\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1839\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e93.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGermany\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAustralia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCanada\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReporter type\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHealth professional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1159\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e59.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-health professional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e781\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e39.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSignals detection associated with deucravacitinib-associated AEs\u003c/h2\u003e \u003cp\u003eWe first ruled out auto-disease-related AEs such as psoriasis, erythema, pruritus, and other accompanying symptoms of psoriasis, as well as medication-independent AEs like off-label use, product dose omission issues and others. After that, using the four methods of ROR, PRR, MGPS, and BCPNN, we identified 39 PTs with significant signals by simultaneously meeting the criteria of four methods.\u003c/p\u003e \u003cp\u003eThe three most common PTs in this study were acne (n\u0026thinsp;=\u0026thinsp;201, ROR 73.09, PRR 69.01, EBGM 67.60, IC 6.08), mouth ulceration (n\u0026thinsp;=\u0026thinsp;62, ROR 51.29, PRR 50.41, EBGM 49.66, IC 5.63), folliculitis (n\u0026thinsp;=\u0026thinsp;55, ROR47.11, PRR 46.40, EBGM 45.76, IC 5.52). Interestingly, we identified 16 unexpected PTs with significant signals that were not listed on the label, including urticaria, oral pain, oropharyngeal pain, swelling face, lip swelling, eye swelling, cellulitis, ear pain, pharyngeal swelling, Bell\u0026rsquo;s palsy, mouth swelling, cheilitis, mycobacterium tuberculosis complex test positive, facial paralysis, hepatitis A, and central nervous system (CNS) infection. Additionally, four IMEs were identified: rhabdomyolysis, Bell\u0026rsquo;s palsy, facial paralysis, and CNS infection. Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e provides detailed information on these findings.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe PTs with significant signal for deucravacitinib ranked by case reports number at the PT level in the FAERS database.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRank\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCase reports\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eROR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePRR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEBGM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIC\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(χ\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(EBGM05)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(IC025)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcne\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e201\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73.09(63.30-84.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e69.01(13203.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e67.60(59.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6.08(5.87)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMouth ulceration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51.29(39.82\u0026ndash;66.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e50.41(2958.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e49.66(40.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5.63(5.26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFolliculitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47.11(36.03\u0026ndash;61.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e46.40(2409.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e45.76(36.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5.52(5.12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrticaria\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.82(3.56\u0026ndash;6.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.78(125.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.77(3.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.25(1.81)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypersensitivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.28(2.30\u0026ndash;4.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.26(48.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.25(2.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.70(1.19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOral pain\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.24(18.18\u0026ndash;37.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e26.03(692.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e25.84(19.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.69(4.16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOral herpes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.46(13.40-28.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e19.31(483.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e19.21(14.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.26(3.72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMyalgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.31(2.27\u0026ndash;4.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.29(43.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.29(2.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.72(1.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOropharyngeal pain\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.35(2.96\u0026ndash;6.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.33(66.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.32(3.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.11(1.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSwelling face\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.17(5.47\u0026ndash;12.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8.12(149.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e8.11(5.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.02(2.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAphthous ulcer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.61(19.79\u0026ndash;44.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e29.42(653.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e29.16(20.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.87(4.28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStomatitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.62(3.66\u0026ndash;8.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.59(79.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.58(3.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.48(1.86)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHerpes zoster\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.99(3.86\u0026ndash;9.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.96(82.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.96(4.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.57(1.94)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUpper respiratory tract infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.06(2.99\u0026ndash;8.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.04(45.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.03(3.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.33(1.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBlood triglycerides increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.06(13.03\u0026ndash;37.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e21.98(278.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e21.84(14.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.45(3.70)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDermatitis acneiform\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31.67(17.47\u0026ndash;57.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e31.57(322.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e31.28(19.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.97(4.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcne cystic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88.61(47.24-166.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e88.36(840.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e86.06(50.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6.43(5.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOral mucosal blistering\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.83(17.59\u0026ndash;61.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e32.74(304.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e32.42(19.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5.02(4.14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLip swelling\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.44(3.46\u0026ndash;11.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.42(45.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6.41(3.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.68(1.81)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEye swelling\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.92(2.56\u0026ndash;9.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.91(27.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.90(2.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.29(1.38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBlood creatine phosphokinase increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.02(4.17\u0026ndash;15.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8.00(55.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e7.99(4.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.00(2.08)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCellulitis\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.55(1.84\u0026ndash;6.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.54(16.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.54(2.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.82(0.91)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHerpes simplex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.14(10.52\u0026ndash;46.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e22.10(140.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e21.95(11.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.46(3.43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRosacea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.41(12.54\u0026ndash;55.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e26.36(169.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e26.15(14.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.71(3.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRhabdomyolysis\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(1.91\u0026ndash;8.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.00(15.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.99(2.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.00(0.98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEar pain\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.23(2.96\u0026ndash;13.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.22(30.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6.21(3.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.63(1.61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePharyngeal swelling\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.92(2.05\u0026ndash;11.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.91(15.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.91(2.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.30(1.12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBell\u0026rsquo;s palsy\u003csup\u003e*\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.57(8.12\u0026ndash;47.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e19.55(87.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e19.44(9.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.28(3.10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFuruncle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.26(3.47\u0026ndash;24.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9.25(29.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e9.23(4.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.21(1.91)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTongue ulceration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.37(10.23\u0026ndash;73.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e27.34(100.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e27.12(11.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.76(3.46)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePharyngitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.06(2.27\u0026ndash;16.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.05(16.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6.05(2.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.60(1.30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHerpes virus infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.13(4.92\u0026ndash;35.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13.12(44.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e13.07(5.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.71(2.41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcne pustular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e81.1(30.05-218.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e81.01(308.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e79.07(34.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6.31(4.99)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMouth swelling\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.91(2.87\u0026ndash;27.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8.90(20.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e8.88(3.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.15(1.70)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCheilitis\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.49(4.02\u0026ndash;38.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12.48(31.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e12.43(4.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.64(2.19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMycobacterium tuberculosis complex test positive\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.78(6.35\u0026ndash;61.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e19.76(53.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e19.65(7.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.30(2.85)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFacial paralysis\u003csup\u003e*\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.69(1.83\u0026ndash;17.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.69(11.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.68(2.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.51(1.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHepatitis A\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73.06(23.26-229.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e73.00(208.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e71.42(27.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6.16(4.69)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCentral nervous system infection\u003csup\u003e*\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43.70(13.98\u0026ndash;136.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e43.67(123.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e43.10(16.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5.43(3.97)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eFootnotes: CI, confidence interval; EBGM, empirical bayesian geometric mean; EBGM05, the lower limit of 95% confidence interval of EBGM; IC, information component; IC025, the lower limit of 95% confidence interval of the IC; PRR, proportional reporting ratio; PT, preferred term; ROR, reporting odds ratio; χ\u003csup\u003e2\u003c/sup\u003e, Chi-squared.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cb\u003e*\u003c/b\u003e The PT is not listed on the label of deucravacitinib; \u003cb\u003e\u0026dagger;\u003c/b\u003e The PT is an important medical event for deucravacitinib.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e39 PTs with significant signals were categorized using the SOC of MedDRA (version 27.1). Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the distribution of PTs with significant signals at the SOC level. The three most frequently involved SOCs were skin and subcutaneous tissue disorders, gastrointestinal disorders, and infections and infestations.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eTTO\u003c/h2\u003e \u003cp\u003eOnly 104 cases with complete dates of drug initiation and AE onset were gathered. Overall, the median TTO for deucravacitinib-associated AEs was 20 days (IQR: 6\u0026ndash;97). The Weibull distribution shape parameter (β\u0026thinsp;=\u0026thinsp;0.63, 95% CI: 0.54\u0026ndash;0.72) indicates an early failure type for the TTO of deucravacitinib-associated AEs. However, subgroup analyses revealed no significant impact of age (P\u0026thinsp;=\u0026thinsp;0.27) and gender (P\u0026thinsp;=\u0026thinsp;0.98) on the TTO. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e provides more details on the TTO of deucravacitinib-associated AEs\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eDeucravacitinib, a novel therapeutic agent with demonstrated efficacy and favorable safety profile, has recently been introduced for the treatment of moderate-to-severe psoriasis. Given the widespread use of deucravacitinib in clinical practice, continued pharmacovigilance studies are necessary. Based on the real-world data from the FAERS database, this study provided additional data to refine the safety profile of deucravacitinib.\u003c/p\u003e \u003cp\u003eAccording to pooled data [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] from the placebo-controlled periods of POETYK PSO-1 [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and POETYK PSO-2 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], the most commonly reported adverse reactions in patients with psoriasis receiving deucravacitinib were upper respiratory tract infections (19.2%), blood creatine phosphokinase increased (2.7%), herpes simplex (2.0%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). This shares some similarities, but also some differences with the most common AEs which we discovered in the current study. In clinical trials, the most common adverse reactions were upper respiratory tract infections, including nasopharyngitis, pharyngitis, sinusitis, rhinitis, rhinotracheitis, tracheitis, laryngitis, and tonsillitis. The current study identified a relatively small number of AE cases (n\u0026thinsp;=\u0026thinsp;14) coded to the PT \u0026lsquo;upper respiratory tract infection\u0026rsquo;. This result may be attributable to the classification of upper respiratory tract infection in the FAERS database, where distinct preferred terms (PTs) such as sinusitis, pharyngitis, and bronchitis were reported separately.In contrast, the most common AE in the current study were acne. The skin microbiome and altered immune-mediated responses due to deucravacitinib\u0026rsquo;s inhibition of TYK2-dependent signaling pathways may play a role in the pathogenesis of this skin event, even though the exact mechanism is yet unknown [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In patients with acne, topical therapies (benzoyl peroxide cream, clindamycin solution, or chlorhexidine ointment for acne) were often helpful, resulting in minimal withdrawal from deucravacitinib treatment [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, we identified some unexpected AEs such as urticaria, swelling face, eye swelling, lip swelling, pharyngeal swelling, respiratory tract congestion, swollen tongue, dermatitis allergicetc, etc. There was a possibility that these AEs may signal the onset of deucravacitinib-induced allergic reactions, since anaphylactic reactions could lead to urticaria, angioedema, dyspnea, among other symptoms [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Therefore, we should be wary of allergic reactions caused by deucravacitinib and provide prompt symptomatic treatment or discontinue the drug if necessary.\u003c/p\u003e \u003cp\u003eWe identified four IMEs associated with deucravacitinib therapy, including Bell\u0026rsquo;s palsy, facial paralysis, rhabdomyolysis, and CNS infection. In MedDRA, \u0026lsquo;facial nerve disorders\u0026rsquo; is the higher-level term for Bell\u0026rsquo;s palsy and facial paralysis. Notably, herpes virus infection is explicitly listed as a known adverse reaction on the label of deucravacitinib. Herpes virus can infiltrate the facial nerve, constituting a principal etiological factor in peripheral facial paralysis and Bell\u0026rsquo;s palsy [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Evidence suggests that combining antivirals with corticosteroids improves patient outcomes [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Additionally, patients receiving deucravacitinib may experience elevated blood creatine phosphokinase levels, which are associated with rhabdomyolysis. As a result, comprehensive medication education should be provided to patients, instructing them to immediately report any unexplained muscle pain, tenderness, or weakness \u0026ndash; particularly when accompanied by fever \u0026ndash; during treatment. If rhabdomyolysis is confirmed, deucravacitinib should be discontinued immediately and targeted therapeutic measures initiated without delay. During subsequent management, the potential benefits and risks of reinitiating deucravacitinib therapy should be comprehensively reassessed based on the patient's recovery status. Based on findings from POETYK PSO-1 and POETYK PSO-2 trials, pneumonia and COVID-19 emerged as the most serious infection types among in deucravacitinib-treated patients [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. It is worth noting that the current study has identified potential CNS infection risks (ROR 43.70, PRR 43.67, EBGM 43.10, IC 5.43) associated with deucravacitinib therapy. Given the severe consequences of CNS infections, prompt anti-infection treatment is warranted upon diagnosis to mitigate neurological sequelae.\u003c/p\u003e \u003cp\u003eTYK2 constitutes a core member of the Janus kinase (JAK) family along with JAK1, JAK2, and JAK3. In recent years, regulation agencies have been focusing on serious safety concerns (e.g., venous thromboembolic events, major adverse cardiac events, cancer) regarding JAK inhibitors [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The mechanism underlying these risks was not fully elucidated but might be related to JAK inhibitors\u0026rsquo; inhibitory effects on JAK homology 1 domain [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Nowadays, it is unclear whether TYK2 inhibition shares the serious safety concerns of traditional JAK inhibitions. Therefore, deucravacitinib\u0026rsquo;s prescribing information does not include a boxed warning for these risks. In the current study, our disproportionality analysis did not reveal significant signals for deucravacitinib-related serious safety concerns. This finding may be attributable to the following factors. On the one hand, deucravacitinib\u0026rsquo;s unique allosteric inhibition mechanism targeting TYK2 may confer distinct safety profiles. Previous studies have suggested that deucravacitinib binds to the JAK homology 2 regulatory domain via a highly specific allosteric mechanism rather than the JAK homology 1 domain, as do other JAK inhibitors [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. This makes deucravacitinib more selective for TYK2 than for JAK 1, 2, and 3, reducing the likelihood of off-target effects. On the other hand, the short monitoring period (\u0026lt;\u0026thinsp;3 years) and limited patient exposure (\u0026lt;\u0026thinsp;2000) in the current study may have prevented complete characterization of deucravacitinib\u0026rsquo;s serious AE profile. Therefore, whether deucravacitinib shares similar serious safety concerns with other JAK inhibitors remains to be established through post-marketing safety studies with expanded cohort sizes and prolonged surveillance periods.\u003c/p\u003e \u003cp\u003eThe Weibull distribution analysis revealed that deucravacitinib-associated AEs exhibited an early failure type (β\u0026thinsp;=\u0026thinsp;0.63, 95% CI: 0.54\u0026ndash;0.72), indicating higher AE risk during early treatment period. Based on this finding, close attention should be paid to patients\u0026rsquo; discomfort symptoms during the initial medication period, with particular vigilance against AEs such as allergic reactions. However, there is substantial missing data on the TTO in this study, potentially leading to biased results. Therefore, future studies are still needed to evaluate the TTO of deucravacitinib-associated AEs.\u003c/p\u003e \u003cp\u003eStudies based on the FAERS database have limitations as well. Firstly, the FAERS database only contains reports of AEs, but the overall number of people using deucravacitinib is unknown. It is impossible to calculate the frequency of deucravacitinib-associated AEs. Secondly, the spontaneous reporting system can only passively collect information on AE reports; underreporting or misreporting could potentially impact the study\u0026rsquo;s results. Thirdly, potential risk signals were identified through disproportionality analysis, reflecting only pharmacovigilance statistical associations. The exact causal relationship between AEs and deucravacitinib requires further investigation due to potential confounding by concomitant medications, individual variability, and underlying disease states. Fourthly, the current study only gathered AE reports nearly two years after the launch of deucravacitinib; this short safety monitoring period may have left some potential AEs unidentified.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAnalysis of postmarketing surveillance data from the FAERS identified acne, mouth ulceration, and folliculitis as the most frequently reported AEs associated with deucravacitinib. Additionally, unexpected AEs not mentioned on the label were also identified, including urticaria, oral pain, oropharyngeal pain, swelling face, lip swelling, eye swelling, and others. Rhabdomyolysis, Bell\u0026rsquo;s palsy, facial paralysis, and central nervous system infection were the IMEs of deucravacitinib. These findings have somewhat supplemented the safety data for deucravacitinib. However, given the FAERS\u0026rsquo; limitations, further real-world prospective cohort studies are needed to optimize deucravacitinib post-market safety assessment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interest\u003c/h2\u003e \u003cp\u003eAuthors declare no conflict of interests for this article.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was supported by the Self-funded Research Project in Western Medicine, Health Commission of Guangxi, China [grant number Z-D20231663].\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eH. T. wrote the original manuscript. X. C. and X. O. collected the data. Y. C. designed the study and review the manuscript. All authors contributed to the manuscript\u0026rsquo;s revision and read and approved the submitted version.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eThe FAERS database, which was made available by the FDA, was used to conduct this study. The FDA does not have any opinion about the data, findings, or interpretation of the current study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003ehttps://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Health Organization. Global Report on Psoriasis:World Health Organization, 2016. https://iris.who.int/handle/10665/204417. Accessed March 14, 2025.\u003c/li\u003e\n\u003cli\u003eArmstrong AW, Read C. Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review. JAMA. 2020 May 19;323(19):1945-1960. doi: 10.1001/jama.2020.4006. \u003c/li\u003e\n\u003cli\u003eMichalek IM, Loring B, John SM. 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J Eur Acad Dermatol Venereol. 2024 Aug;38(8):1543-1554. doi: 10.1111/jdv.19925. \u003c/li\u003e\n\u003cli\u003eFAERS database. Accessed March 14, 2025. https://www.fda.gov/drugs/surveillance/questions-and-answers-fdas-adverse-event-reporting-system-faers. \u003c/li\u003e\n\u003cli\u003eCFR \u0026sect; 600.80 - Postmarketing reporting of adverse experiences. https://www.govinfo.gov/app/details/CFR-2018-title21-vol7/CFR2018-title21-vol7-sec600-80. Accessed March 14, 2025.\u003c/li\u003e\n\u003cli\u003eRothman KJ, Lanes S, Sacks ST. The reporting odds ratio and its advantages over the proportional reporting ratio. Pharmacoepidemiol Drug Saf. 2004 Aug;13(8):519-23. doi: 10.1002/pds.1001. \u003c/li\u003e\n\u003cli\u003eEvans SJ, Waller PC, Davis S. Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports. 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A signal detection method to detect adverse drug reactions using a parametric time-to-event model in simulated cohort data. Drug Saf. 2012 Jul 1;35(7):599-610. doi: 10.2165/11599740-000000000-00000. \u003c/li\u003e\n\u003cli\u003eSauzet O, Carvajal A, Escudero A, Molokhia M, Cornelius VR. Illustration of the weibull shape parameter signal detection tool using electronic healthcare record data. Drug Saf. 2013 Oct;36(10):995-1006. doi: 10.1007/s40264-013-0061-7. \u003c/li\u003e\n\u003cli\u003eKinoshita S, Hosomi K, Yokoyama S, Takada M. Time-to-onset analysis of amiodarone-associated thyroid dysfunction. J Clin Pharm Ther. 2020 Feb;45(1):65-71. doi: 10.1111/jcpt.13024. \u003c/li\u003e\n\u003cli\u003eBristol Myers Squibb. SOTYKTU\u0026trade; (deucravacitinib) tablets, for oral use: US prescribing information. 2022. Accessed March 14, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214958s000lbl.pdf\u003c/li\u003e\n\u003cli\u003eLebwohl M, Warren RB, Sofen H, Imafuku S, Paul C, Szepietowski JC, et al. Deucravacitinib in plaque psoriasis: 2-year safety and efficacy results from the phase III POETYK trials. Br J Dermatol. 2024 Apr 17;190(5):668-679. doi: 10.1093/bjd/ljae014. \u003c/li\u003e\n\u003cli\u003eCatlett IM, Aras U, Hansen L, Liu Y, Bei D, Girgis IG, et al. First-in-human study of deucravacitinib: A selective, potent, allosteric small-molecule inhibitor of tyrosine kinase 2. Clin Transl Sci. 2023 Jan;16(1):151-164. doi: 10.1111/cts.13435. \u003c/li\u003e\n\u003cli\u003eHanschmann T, Francuzik W, D\u0026ouml;lle-Bierke S, Hofmeier KS, Grabenhenrich L, Ru\u0026euml;ff F, et al. Different phenotypes of drug-induced anaphylaxis-Data from the European Anaphylaxis Registry. Allergy. 2023 Jun;78(6):1615-1627. doi: 10.1111/all.15612. \u003c/li\u003e\n\u003cli\u003eCardona V, Ansotegui IJ, Ebisawa M, El-Gamal Y, Fernandez Rivas M, Fineman S, et al. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J. 2020 Oct 30;13(10):100472. doi: 10.1016/j.waojou.2020.100472. \u003c/li\u003e\n\u003cli\u003eMurakami S, Mizobuchi M, Nakashiro Y, Doi T, Hato N, Yanagihara N. Bell palsy and herpes simplex virus: identification of viral DNA in endoneurial fluid and muscle. Ann Intern Med. 1996 Jan 1;124(1 Pt 1):27-30. doi: 10.7326/0003-4819-124-1_part_1-199601010-00005. \u003c/li\u003e\n\u003cli\u003eGagyor I, Madhok VB, Daly F, Somasundara D, Sullivan M, Gammie F, et al. Antiviral treatment for Bell\u0026apos;s palsy (idiopathic facial paralysis). Cochrane Database Syst Rev. 2015 Nov 9;(11):CD001869. doi: 10.1002/14651858.CD001869.pub8.\u003c/li\u003e\n\u003cli\u003eKragstrup TW, Glintborg B, Svensson AL, McMaster C, Robinson PC, Deleuran B, et al. Waiting for JAK inhibitor safety data. RMD Open. 2022 Feb;8(1):e002236. doi: 10.1136/rmdopen-2022-002236. \u003c/li\u003e\n\u003cli\u003eSingh JA. The Emerging Safety Profile of JAK Inhibitors in Rheumatic Diseases. BioDrugs. 2023 Sep;37(5):625-635. doi: 10.1007/s40259-023-00612-7. \u003c/li\u003e\n\u003cli\u003eDi Martino RMC, Maxwell BD, Pirali T. Deuterium in drug discovery: progress, opportunities and challenges. Nat Rev Drug Discov. 2023 Jul;22(7):562-584. doi: 10.1038/s41573-023-00703-8. Epub 2023 Jun 5. \u003c/li\u003e\n\u003cli\u003eWrobleski ST, Moslin R, Lin S, Zhang Y, Spergel S, Kempson J, et al. Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165. J Med Chem. 2019 Oct 24;62(20):8973-8995. doi: 10.1021/acs.jmedchem.9b00444. \u003c/li\u003e\n\u003cli\u003eAttwood MM, Fabbro D, Sokolov AV, Knapp S, Schi\u0026ouml;th HB. Trends in kinase drug discovery: targets, indications and inhibitor design. Nat Rev Drug Discov. 2021 Nov;20(11):839-861. doi: 10.1038/s41573-021-00252-y. Epub 2021 Aug 5. Erratum in: Nat Rev Drug Discov. 2021 Oct;20(10):798. doi: 10.1038/s41573-021-00303-4. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-pharmacy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijcp","sideBox":"Learn more about [International Journal of Clinical Pharmacy](https://www.springer.com/journal/11096)","snPcode":"11096","submissionUrl":"https://submission.nature.com/new-submission/11096/3","title":"International Journal of Clinical Pharmacy","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"adverse event, deucravacitinib, data mining, FAERS, psoriasis","lastPublishedDoi":"10.21203/rs.3.rs-6346752/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6346752/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDeucravacitinib is a novel, highly selective tyrosine kinase 2 allosteric inhibitor recently approved for the treatment of moderate-to-severe psoriasis in adults, though post-marketing safety data remain limited.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThe purpose of this study was to perform a post-marketing safety evaluation of deucravacitinib base on the Food and Drug Administration Adverse Event Reporting System (FAERS).\u003c/p\u003e\u003ch2\u003eMothed\u003c/h2\u003e \u003cp\u003eAdverse events (AEs) due to deucravacitinib from 2022Q3 to 2024Q4 identified as the primary suspect were screened. Four main methods of the disproportionality analysis, including reporting odds ratio, proportional reporting ratio, bayesian confidence propagation neural network, and multi-item gamma poisson shrinker, were employed for signal detection. The important medical event (IME) terms list was used to identify IMEs of deucravacitinib. Additionally, the Weibull distribution was used to evaluate the time-to-onset (TTO) characteristics.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e39 preferred terms (PTs) were identified as potential risk signals. The most commonly reported PT were acne, mouth ulceration and folliculitis. 16 PTs with potential risk signals not mentioned on the label were also identified, including urticaria, oral pain, oropharyngeal pain, swelling face, lip swelling, and others. Rhabdomyolysis, Bell\u0026rsquo;s palsy, facial paralysis, and central nervous system infection were the IMEs of deucravacitinib. The Weibull distribution indicated that the TTO characteristics of deucravacitinib-associated AEs followed an early failure type.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis study provides preliminary safety data for deucravacitinib in the real world, confirming some known AEs, uncovering some underlying risks and identifying several IMEs. Further post-marketing safety surveillance studies on deucravacitinib remain necessary in the future.\u003c/p\u003e","manuscriptTitle":"Safety evaluation of deucravacitinib: a real-world analysis based on the FDA adverse event reporting system database","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-22 13:50:39","doi":"10.21203/rs.3.rs-6346752/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-29T06:25:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-29T02:18:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"265018577358338749751158547754136483909","date":"2025-05-04T21:02:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-17T15:12:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"304953980193637123682717817846106550087","date":"2025-04-01T21:17:13+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-01T17:28:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-01T06:34:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-01T06:31:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Clinical Pharmacy","date":"2025-03-31T16:39:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-pharmacy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijcp","sideBox":"Learn more about [International Journal of Clinical Pharmacy](https://www.springer.com/journal/11096)","snPcode":"11096","submissionUrl":"https://submission.nature.com/new-submission/11096/3","title":"International Journal of Clinical Pharmacy","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a7fa622d-023a-4044-9260-f7c207164976","owner":[],"postedDate":"April 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-07-11T16:23:13+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-22 13:50:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6346752","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6346752","identity":"rs-6346752","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}