Health-related Quality of Life in Patients With Recurrent Pericarditis: Results From a Phase 2 Study of Rilonacept

Health-related Quality of Life in Patients With Recurrent Pericarditis: Results From a Phase 2 Study of Rilonacept | 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 Health-related Quality of Life in Patients With Recurrent Pericarditis: Results From a Phase 2 Study of Rilonacept David Lin, Allan Klein, David Cella, Anna Beutler, Fang Fang, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-258868/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Apr, 2021 Read the published version in BMC Cardiovascular Disorders → Version 1 posted 14 You are reading this latest preprint version Abstract Background: Impact of recurrent pericarditis (RP) on patient health-related quality of life (HRQoL) was evaluated through qualitative patient interviews and as an exploratory endpoint in a Phase 2 trial evaluating the efficacy and safety of rilonacept (IL-1α/IL-1β blocker) to treat RP. Methods: Qualitative interviews were conducted with ten adults with RP to understand symptoms and HRQoL impacts, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS Global) v1.2 was evaluated to determine questionnaire coverage of patient experience. The Phase 2 trial enrolled participants with active symptomatic RP (A-RP, n=16) and corticosteroid-dependent participants with no active recurrence at baseline (CSD-RP, n=9). All participants received rilonacept weekly for 6 weeks during a base treatment period (TP) plus an optional 18-week extension period (EP). Concomitant medications, including corticosteroids (CS), were tapered, if possible, during EP. HRQoL was assessed using the PROMIS Global, and patient-reported pain and blood levels of c-reactive protein (CRP) were also collected at Baseline and follow-up periods. Results: Information from qualitative interviews demonstrated that PROMIS GH concepts are relevant to adults with RP. From the Phase 2 trial, both participant groups showed impacted HRQoL at Baseline [mean PROMIS Global Physical Health (GPH) and Global Mental Health (GMH), were lower than population norm average]. In A-RP, GPH/MPH improved by end of base TP and were sustained through EP (similar trends were observed for pain and CRP). Similarly, in CSD-RP, GPH/MPH improved by end of TP and further improved at EP, during CS tapering or discontinuation, without disease recurrence (low pain scores and CRP levels continued during the TP and EP). Conclusion: This is the first study demonstrating impaired HRQoL in RP. Rilonacept treatment was associated with HRQoL improvements using PROMIS GH scores. Maintained/improved HRQoL during tapering/withdrawal of CS without recurrence suggests that rilonacept may provide an alternative to corticosteroids. Trial Registration: ClinicalTrials.Gov; NCT03980522; 5 June 2019, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03980522 Cardiac & Cardiovascular Systems Pericarditis interleukin-1 receptor blocker health-related quality of life recurrent pericarditis Figures Figure 1 Figure 2 Figure 3 Introduction Pericarditis, or inflammation of the pericardium, has a variety of etiologies but is most commonly referred to as idiopathic. The primary symptom of pericarditis is debilitating chest pain. Pericarditis is considered recurrent if symptoms and inflammation recur at least 4 weeks after an initial acute episode. Recurrent pericarditis (RP) affects approximately 15–30% of patients who have an acute episode of pericarditis, and up to 50% of patients who experience one recurrence will experience two or more. There are currently no FDA-approved therapies for pericarditis or RP; however, exploratory therapy with nonsteroidal anti-inflammatory drugs [NSAIDs] and colchicine is a standard often used successfully to treat the first pericarditis episode or initial recurrence. Treatment options are limited and there is a high unment medical need for patients who have inadequate response (i.e., continued recurrence or incomplete symptom resolution) to or who cannot tolerate standard therapy. While the impact of RP on patients’ health-related quality of life (HRQoL) has been reported in the literature [ 1 – 4 ] and is thought to be due to the primary symptom of the condition (e.g., chest pain) and the resulting uncertainty and anxiety of new recurrences, impact to HRQoL has not been explicitly evaluated in previous clinical research. In addition, corticosteroids are widely used to treat RP [ 5 ], putting patients at risk for steroid-dependence [ 6 ]; comorbidities associated with chronic corticosteroid use may also lead to adverse impacts on HRQoL [ 7 , 8 ]. Both qualitative and quantitative research approaches were used to explore the HRQoL impacts experienced by adults with RP and how those impacts may change in response to treatment. Qualitative interviews were conducted with ten adults with RP to document the patient experience of RP symptoms and HRQoL impacts (known as concept elicitation interviews). Results from these interviews were used to develop a conceptual model of RP. In addition, a Phase 2 clinical trial of rilonacept (an IL-1α/IL-1β blocker) for the treatment of RP included a HRQoL patient-reported outcome (PRO) questionnaire as an exploratory endpoint. Therefore, the objective of these two streams of research is to evaluate HRQoL in patients with RP; specifically, to confirm whether the concepts assessed with the HRQoL PRO questionnaire used in the Phase 2 clinical trial are relevant to patients with RP (based on patient reports during the qualitative interviews) and to evaluate the effect of rilonacept treatment on physical and mental aspects of HRQoL. Methods The sections below describe the methodology used for both the qualitative interviews with patients and the clinical trial study design relevant to the current research objective. Methods for qualitative patient interviews to develop a patient-centric conceptual model To understand the patient experience of RP, one-on-one telephone interviews were conducted with adults with a confirmed diagnosis of RP. Participants for qualitative interviews The qualitative interview study was approved by a centralized independent review board (IRB) and following approval, potentially eligible participants were identified from clinical sites through review of medical records. Key inclusion criteria for the qualitative study included: age 18 years or older and a clinical diagnosis of RP (either idiopathic or due to post-pericardiotomy syndrome, adult onset Still’s Disease, or Dressler’s Syndrome), defined as the first episode of acute pericarditis (as defined by the 2015 European Society of Cardiology [ESC] Guidelines for the Diagnosis and Management of Pericardial Diseases) [ 9 ] followed by at least one pericarditis recurrence after a symptom-free interval of at least 4–6 weeks. Key exclusion criteria for the study included: individual was currently enrolled in another clinical interventional study for RP; individual had a diagnosis of RP that was secondary to specific prohibited etiologies, including tuberculosis, neoplastic, purulent, or radiation, post-thoracic blunt trauma, myocarditis, or systemic autoimmune diseases (with the exception of adult onset Still’s Disease). Potentially eligible participants were presented with study information by a recruiting clinician (or his/her representative), and once participants provided a signed informed consent form, the clinical site completed a screening document to determine participants’ eligibility. Participant interviews were scheduled once eligibility was confirmed. Interview conduct One-on-one, 60-minute telephone interviews with ten adults aged 18 to 75 years with RP were conducted. Interviewers used a semi-structured interview guide to facilitate the conversation and included open-ended questions to understand the patient experience of RP and its treatments, specifically, what signs, symptoms, and HRQoL impacts are experienced in relation to RP from the patient perspective. Interview guide questions included: “Could you please start by telling me about the first signs or symptoms of [participant’s term for RP] you noticed? “Does the [patient-reported sign/symptom] have any impact on your daily life? If so, how?” “Have there been any changes to your daily life because of [participant’s term for RP]? If so, can you please describe?” Data handing and analysis Interviews were audio-recorded after obtaining participant consent, transcribed and anonymized. These transcripts were coded and qualitatively analyzed using the ATLAS.ti software program. The goals of transcript coding were to organize and catalog participants’ descriptions of the characteristics of RP, in order to develop a patient-centric conceptual model of RP signs, symptoms, and impact concepts. A conceptual model is a heuristic classification scheme that links a specified disease state or condition to its proximal and increasingly distal health outcomes [ 10 ], acts as a framework for understanding a disease and/or its treatment, specifies the potentially relevant outcomes for a program of research, and informs the selection of measurement concepts to foster the development of questionnaires, outcomes, and endpoints. Specifically, to characterize the specific applicability of the Patient Reported Outcome Measurement Information System Global Health (PROMIS GH v1.2) [ 10 ] questionnaire (described below) for capturing the HRQoL impacts experienced by patients with RP, conceptual mapping was conducted to compare the concepts within the conceptual model against PROMIS GH v1.2 individual items. Methods for the Phase 2 study KPL-914-C001 The methodology of the Phase 2 clinical trial of rilonacept for the treatment of RP (clinicaltrial.gov: NCT03980522) is provided in detail in Klein and colleagues (in press). To summarize, this was a multicenter, open-label, single-active-arm Phase 2 study which enrolled adults with RP who either were having an active recurrence at baseline or who were not having an active recurrence but were dependent on corticosteroids. All participants received weekly subcutaneous (SC) injections of rilonacept for 6 weeks during the treatment period (TP) and were invited to continue weekly SC injections for up to 18 weeks in the extension period (EP). Participants Adults (18–75 years of age) with RP (idiopathic or post-pericardiotomy syndrome etiology) were enrolled and stratified into one of two participant groups: (1) those with an active recurrence at baseline (with at least two additional prior recurrences; A-RP), or (2) those without an active recurrence who were dependent on corticosteroids (and had had at least three prior recurrences; CSD-RP). Participants in the A-RP group had either evidence of elevated c-reactive protein (CRP) at baseline or did not have elevated CRP potentially due to concomitant medications (such as corticosteroids) but had evidence of pericardial inflammation by cardiac Magnetic Resonance Imaging. Participants in the CSD-RP group had corticosteroid-dependent disease (based on information from the investigator regarding prior recurrences when taking medication) and did not have active pericarditis symptomatology or elevated CRP at baseline. Assessments Weekly in TP, and then monthly blood levels of CRP, were evaluated to measure inflammation from baseline to the end of the EP for all participants. In addition, two PRO questionnaires were completed by all participants during the clinical trial. They included: A single-item 11-point numeric rating scale (NRS) for average pericarditis pain intensity with a 24-hour recall window (with 0 = no pain to 10 = pain as bad as it could be) [ 11 – 13 ] was completed weekly in TP and monthly in EP from baseline to the end of the EP. The 10-item PROMIS GH v1.2 questionnaire was also completed by participants at up to five time points during the clinical trial to assess HRQoL [ 14 ]. The analyses presented here focused on the following three most critical timepoints: baseline (Day 0), end of TP (Week 6), Final Visit (end of EP). Items 1–7 ask participants to think about their general health and are rated on a five-point response scale (with higher number associated with better quality of life). Items 8–10 ask participants to report on the emotional problems, fatigue, and pain over last seven days, with Items 8 and 9 rated on a five-point response scale (with higher scores associated with better quality of life), and Item 10 rated on a 0–10 NRS (with higher scores associated with more pain). Two domain scores are created from the 10-item scale, the global physical health (GPH), and the global mental health (GMH). The GPH is scored by by averaging together the global03 (physical health), global06 (physical function), global07 (pain) and global08 (fatigue) items. The GMH is scored by averaging together the global02 (quality of life), global04 (mental health), global05 (satisfaction with discretionary social activities), and global10 (emotional problems) [ 14 ]. The published US-generalized normative scores for both of these domains are a mean score of 50, and a standard deviation of 10 [ 14 ]. Procedure and Analyses All participants received rilonacept SC injections weekly for 6 weeks until the end of TP and were invited to continue weekly SC injections (at the same dose) during an optional 18-week EP. For those on other concomitant medications for RP at baseline (participants in both the A-RP and CSD-RP groups), including corticosteroids, the option to taper was offered during the EP. Participants completed the PRO questionnaires (PROMIS and Pain NRS) at study visits, including telephone and site visits. Blood levels for CRP were also assessed during clinical site visits or via visiting nurse or local contract laboratory; CRP was analysed via a central laboratory. The analyses presented in the results are descriptive, given the small sample size of the clinical trial and the single-active arm design. Specifically, results are reported as Means and Standard Deviations, with ranges of values for each participant group. While participants were asked to complete the HRQoL questionnaire at multiple time points in the clinical trial, the analyses focus on the baseline, (Day 0), end of base TP (Week 6), and Final Visit at end of EP timepoints. In addition, the descriptive analyses also include the weekly pericardial pain NRS scores and CRP blood levels that were collected at study visits. Results Qualitative patient interviews: Qualitative interviews were conducted via telephone with ten adults diagnosed with RP to understand the patient experience of the condition, including the signs, symptoms, and health-related quality of life impacts. Participants were recruited from three clinical sites in the US. The mean age of the participants was 58.5 years (SD = 11.5), and six participants (60.0%) were female. Clinicians reported that participants exhibited the following RP types: idiopathic (n = 4, 40.0%), post-pericardiotomy syndrome (n = 4, 40.0%), adult-onset Still’s Disease (n = 1, 10.0%), or Dressler’s syndrome (n = 1, 10.0%). The majority of participants reported taking over-the-counter or prescription anti-inflammatory medications (n = 7, 70.0%), and half reported that they had previously taken corticosteroids (n = 5, 50.0%) for their RP. A total of 13 symptoms and 34 impacts across 11 domains were reported by participants during these qualitative interviews and were organized into a conceptual model (Fig. 1 ). All participants reported experiencing chest pain (n = 10, 100.0%), with seven (n = 7, 70.0%) stating it is the most bothersome symptom, and five (n = 5, 50.0%) reporting it is the most important symptom to improve. After chest pain, the next most frequently reported signs or symptoms reported by at least half of participants, were tiredness (n = 8, 80.0%), shortness of breath (n = 7, 70.0%), fever (n = 6, 60.0%), and heart palpitations (n = 5, 50.0%). The most frequently reported impacts (reported by at least half of the participants) were inability to exercise (n = 8, 80.0%), disrupted sleep (n = 7, 70.0%), fear (n = 6, 60.0%), inability to go to social events (n-6, 60.0%), interruption of daily activities (n = 6, 60.0%), absenteeism (n = 5, 50.0%), and impaired ability to do housework (n = 5, 50.0%). In order to confirm that the assessment of HRQoL completed by participants in the Phase 2 clinical trial captured concepts relevant to adults with RP, concepts reported during the qualitative interviews were mapped to the ten items of the PROMIS Global Health v1.2 questionnaire. Table 1 shows the results of this exercise, with representative patient quotes from the qualitative interviews for each of the items of the PROMIS GH questionnaire. In particular, adults reported symptoms and HRQoL impacts during the interviews, that are included in the PROMIS GH questionnaire, such as pain, social and emotional impacts, and physical functioning. Due to technical limitations, table 1 is only available as a download in the Supplemental Files section. Phase 2 study rilonacept Twenty-five participants were enrolled in a multicenter, open-label, single-active-arm Phase 2 clinical trial of rilonacept, with an average age of 42.8 ± 10.5 years (± indicates standard deviation; range 26–62); most were female (n = 15, 60.0%) and white (n = 22, 88.0%). Participants had a mean number of prior recurrences of 2.6 (range 1–8), and average duration of disease of 2.2 ± 1.9 years (range 0.2 to 7.9 years), and average number of pericarditis episodes per year of 3.9 ± 3.7 (range 0.54-15). Based on their baseline symptoms and signs of pericardial inflammation, there were two groups of participants: those experiencing an active recurrence (A-RP; n = 16), and those who were corticosteroid-dependent but not acutely symptomatic at baseline (CSD-RP; n = 9). See Table 2 for the demographics and health characteristics of these two participant groups. Table 2 Demographics and health characteristics of Phase 2 clinical trial sample Characteristic Active recurrence (A-RP) N = 16 Not symptomatic, Corticosteroid-dependent (CSD-RP) N = 9 Age (years) (Mean ± standard deviation [SD] [range]) 39.8 ± 10.52 (26–58) 48.2 ± 8.56 (36–62) Gender (% female) 75.0% (n = 12) 33.3% (n = 3) Race (% white) 81.3% (n = 13) 100% (n = 9) BMI (kg/m2) (Mean ± SD [range]) 31.99 ± 7.51 (23.4–52.7) 28.97 ± 4.68 (22.5–34.3) Duration of disease (years) (Mean ± SD [range]) 2.6 ± 2.13 (0.2–7.9) 1.4 ± 0.97 (0.6–3.4) Number of prior recurrences (median, [range]) 2 (1–8) 3 (2–5) Baseline NRS (Pain Rating 0–10; Mean ± SD [range]) 4.6 ± 1.82 (2–8) 1.4 ± 1.51 (0–5) Baseline CRP values (mg/dL) (Mean ± SD [range]) 3.8 ± 5.30 (0.09–19.84) 0.19 ± 0.11 (0.05–0.36) Concomitant medications at baseline Aspirin (n [%]) 0 (0%) 2 (22.2%) NSAID (n [%]) 7 (43.8%) 5 (55.6%) Colchicine (n [%]) 12 (75.0%) 8 (88.9%) Corticosteroids (CS) (n [%]) 6 (37.5%) * 9 (100.0%) † * 4/6 (66.7%) discontinued CS and 1/6 (16.7%) tapered CS by end of EP; 1/6 (16.7%) did not enter EP. † 7/9 (77.8%) discontinued CS and 1/9 (11.1%) tapered CS by end of EP; 1/9 (11.1%) did not enter EP. Scores from the PROMIS GH questionnaire items and domains were evaluated for each of the participant groups over time (baseline, end of TP, and end of EP). Figure 2 shows the baseline scores for the two domains of the PROMIS GH health questionnaire. For both the A-RP and CSD-RP groups, average scores for these domains are below the US normative average score of 50. Additionally, Table 3 shows a trend for improvement in some item and domain scores for both the A-RP and CSD-RP groups. Table 3 PROMIS Global Health item and domain scores over time (mean ± standard deviation), by participant group PROMIS GH item/ domain* A-RP CSD-RP Baseline (n = 16) End of TP visit (n = 15) End of EP visit (n = 15) Baseline (n = 7) End of TP visit (n = 9) End of EP visit (n = 8) Global Physical Health (GPH) 39.94 ± 8.94 51.35 ± 7.96 51.32 ± 6.56 43.30 ± 5.31 45.09 ± 4.06 46.81 ± 9.27 Item 3: physical health 2.6 ± 0.96 3.2 ± 1.01 3.5 ± 0.83 2.8 ± 0.46 3.1 ± 0.33 3.0 ± 0.93 Item 7: physical activities 3.3 ± 1.39 4.4 ± 1.06 4.1 ± 1.03 3.4 ± 0.74 3.3 ± 0.87 3.8 ± 1.04 Item 9: fatigue 3.1 ± 0.96 3.7 ± 0.49 3.7 ± 0.82 3.1 ± 0.69 3.2 ± 0.44 3.4 ± 1.06 Item 10: pain 4.8 ± 1.88 0.6 ± 1.18 0.5 ± 1.13 1.7 ± 1.60 1.0 ± 1.32 1.4 ± 2.50 Global Mental Health (GMH) 44.50 ± 10.48 50.13 ± 11.33 50.54 ± 11.00 46.49 ± 7.77 47.91 ± 5.51 50.66 ± 6.30 Item 2: quality of life 3.0 ± 1.03 3.6 ± 1.06 4.0 ± 1.00 3.3 ± 1.04 3.6 ± 0.73 3.4 ± 0.74 Item 4: mental health 3.3 ± 1.13 3.7 ± 1.23 3.6 ± 1.12 3.4 ± 0.74 3.6 ± 0.73 3.9 ± 0.83 Item 5: social activities and relation-ships 3.1 ± 1.34 3.7 ± 1.18 3.6 ± 1.12 3.1 ± 0.83 3.3 ± 0.50 3.6 ± 0.92 Item 8: emotional problems 3.1 ± 1.41 3.5 ± 1.36 3.4 ± 1.12 3.4 ± 0.98 3.3 ± 0.71 4.0 ± 0.53 Items that are not included in above domains Item 1: general health 2.9 ± 0.72 3.5 ± 0.83 3.6 ± 0.91 2.9 ± 0.64) 3.1 ± 0.33 3.1 ± 0.64 Item 6: social activities and roles 3.1 ± 1.09 3.5 ± 1.25 3.5 ± 1.13 2.9 ± 0.99 3.1 ± 0.93 3.5 ± 0.93 *For Items 1–9, higher scores indicate improvement, and for Item 10, lower scores indicate improvement. Scoring for Item 10 is adjusted when calculating the GPH. For participants in the A-RP group, increases in the average scores for items of the PROMIS GH questionnaire that assess general health, quality of life, and physical health indicate improvement over the study period. In addition, for the A-RP group, the average score of the PROMIS GH pain item shows the largest decrease over the study period, with a mean score of nearly 5 on the 0–10 NRS at baseline, and less than 1 at end of EP. At baseline, both the physical and mental domain scores (GPH/MPH) were lower than the normative average of 50, but by end of TP mean scores for the GPH were above the US norm (and remained above at end of EP), and mean scores for the GMH were at the US norm (and remained at the normative average at end of EP). For participants in the CSD-RP group, there were some increases (improvements) on the PROMIS GH items assessing mental health, social activities and relationships, social activities and roles, and emotional problems, but the average scores for the other items did not change. Similar to the A-RP group, average scores for the CSD-RP group were also below the US norm for both the GPH and GMH domains at baseline. For the GMH domain, average scores were at the normative average at the end of EP. Figure 3 also shows the change in the GPH and GMH domain scores over the study period, and the relationship between these HRQoL scores and patient-reported pericardial pain and serum marker of inflammation (CRP). For the A-RP group, pain scores and CRP levels decrease over the study period, while HRQoL scores increase. For the CSD-RP group, pericardial pain and CRP (low at baseline, as expected as these participants entered the trial while not in active flare) remain low over the course of the study even while tapering and discontinuing corticosteroids, while HRQoL scores increase over time. Please note that participants who completed the EP and were taking corticosteroids at Baseline (all participants in the CSD-RP [n = 8], and 83.3% [n = 5/6] of participants in the A-RP), were able to taper and/or discontinue using corticosteroids by the end of the EP (i.e., the end of the study) without recurrence or pericarditis symptomatology (e.g., patient-reported pericardial pain) or inflammation (e.g., elevated CRP level). Discussion While a substantial negative impact of RP on patients’ HRQoL has traditionally been assumed, to our knowledge this is the first analysis using qualitative and quantitative methods to explore the ways that symptoms of pericarditis recurrence impact patients’ quality of life. The results from the baseline timepoint of the Phase 2 clinical trial align with the assumption of patients’ decreased HRQoL, showing that scores on the GMH and GPH of the PROMIS GH questionnaire were on average lower than normative scores for both the A-RP and CSD-RP groups. In addition, the improvement in HRQoL scores over the course of the study tracks with improvements in patient-reported pericardial pain and CRP levels for the A-RP group, and with the tapering and discontinuing corticosteroids for the CSD-RP group while pericardial pain and CRP remained stable and low while on rilonacept treatment. Therefore, these results show that RP negatively impacts patients’ quality of life physically and emotionally, and that improvements in quality of life may be associated with improvement in disease symptomatology and a decrease in pericardial inflammation, in particular, while patients receive targeted treatment. Furthermore, results from qualitative interviews, where adults with RP spoke about the unpredictable nature of the condition, supported that pericarditis recurrences impact patient physical and mental health.. Specifically, using the qualitative data, a conceptual model of RP was developed, and HRQoL concepts included in the concept model (e.g., ability to carry out daily activities, impacts on mood, and limitation on social activities), were mapped against the ten items of the PROMIS GH v1.2 questionnaire (included in the Phase 2 clinical trial of rilonacept), which demonstrate that this questionnaire is assessing concepts that are relevant to adults with RP. Limitations include the small sample sizes for both the qualitative interviews and the clinical trial, the single-active-arm design of the clinical trial, and the relatively short duration (24 weeks) of the clinical trial compared to the overall duration of this chronic disease. In addition, while the inclusion criteria for the qualitative interview study were intended to be similar to those of the clinical trial, they were less restrictive (i.e., adults interviewed did not experience as many recurrences as the participants in the clinical trial). Nevertheless, these results provide preliminary support for the importance of including a multidimensional assessment of HRQoL for future clinical research of RP. It is also important to consider that some HRQoL impacts may be dependent on age and gender, therefore given the age range of the participants who completed the qualitative interviews and the Phase 2 clinical trial, the resulting conceptual model should be considered representative of adult RP. Strengths include leveraging qualitative results to support the importance of the item- and domain-level scores of the PROMIS GH v1.2 questionnaire to adults with RP. The representative patient quotes help contextualize how participants may be interpreting each item of the PROMIS GH questionnaire. In addition, the means for the GH domain scores at baseline in the rilonacept clinical trial provides evidence of the impact RP has on patients’ HRQoL, as they are lower compared to population norm scores. These findings are consistent with other clinical studies reporting lower PROMIS GH questionnaire scores and associated impacts in physical, mental, and social domains in cardiac and vascular populations [ 15 – 17 ]. The increase in both the physical and mental component scores over the course of the study for both the A-RP and CSD-RP, in conjunction with improvements and/or stable pericardial pain scores and CRP levels, shows that HRQoL scores may also be responsive to treatment as the patient’s condition improves. Conclusions Given the exercise restrictions that patients are expected to adhere to following a diagnosis of RP and the anxiety associated with the unpredictability of recurrences, it is important to evaluate both physical and emotional impacts of the condition. As more clinical trials move to incorporate patient-centric outcomes to evaluate treatments not only in terms of resolution of a physiological indicator of disease but also to ensure that patients feel and function better, future clinical trials of adults with RP should include HRQoL PRO questionnaires. In addition, future studies should explicitly examine the effect of concomitant medications, including corticosteroids, and their independent impact on patient HRQoL. The results of this pilot study demonstrate an early signal of a positive impact of rilonacept on clinical outcome measures and improvements in patient HRQoL over the study time period which tracked with improvements in pericardial pain and inflammation. For those participants in the CSD-RP group, who were weaning off corticosteroids while taking rilonacept, patient-reported pericardial pain and CRP levels were stable, while HRQoL scores improved over the course of the study, without recurrences. Abbreviation A-RP active recurrence of pericarditis at baseline CRP c-reactive protein CSD-RP active recrurecne of pericarditis at baseline dependent on corticosteroids EP extension period ESC European Society of Cardiology GMH global mental health GPH global physical health HRQoL health-related quality of life IRB independent review board NRS numeric rating scale NSAIDs nonsteroidal anti-inflammatory drugs PRO patient-reported outcome PROMIS GH Patient Reported Outcome Measurement Information System Global Health RP recurrent pericarditis SC subcutaneous TP treatment period Declarations Ethics approval and consent to participate Ethics approval for the qualitative interviews was granted by Sterling IRB under IRB ID# 6406. Ethics approval for the Phase 2 study was granted by the central IRB Aspire under IRB ID# KPL-914-C001 as well as by site-specific local IRBs as applicable. Consent for publication N/A Availability of data and materials Data will be made available upon reasonable request. Competing interests David Lin: None Allan Klein: Research grant, scientific advisory board Kiniksa Pharmaceuticals, Ltd., advisory board Swedish Orphan Biovitrum AB, advisory board Pfizer, Inc., modest. David Cella: Consultant for Kiniksa Pharmaceuticals, Ltd., modest. Anna Beutler: Kiniksa Pharmaceuticals, Ltd. consultant. Fang Fang: Kiniksa Pharmaceuticals, Corp. employee. Matt Magestro: Kiniksa Pharmaceuticals, Corp. employee. Paul Cremer: Advisory board Swedish Orphan Biovitrum AB, advisory board Kiniksa Pharmaceuticals, Ltd., modest. Martin M. LeWinter: One seminar for Kiniksa Pharmaceuticals, Ltd., modest. Sushil Allen Luis: Advisory board member for Kiniksa Pharmaceuticals, Ltd., modest. Consultant and advisory board member for Swedish Orphan Biovitrum AB, significant. Antonio Abbate: Research grants from Kiniksa Pharmaceuticals, Ltd., Swedish Orphan Biovitrum AB, Olatec Therapeutics LLC, Serpin Pharma, LLC; consultant fees: Kiniksa Pharmaceuticals, Ltd., Olatec Therapeutics LLC, Serpin Pharma, LLC, Merck & Co., Inc., modest. Andrew Ertel: None Leighann Litcher-Kelly: Employed by Adelphi Values, which received funding from Kiniksa Pharmaceuticals, Ltd. for PRO work in pericarditis Brittany Klooster: Employed by Adelphi Values, which received funding from Kiniksa Pharmaceuticals, Ltd. for PRO work in pericarditis John F. Paolini: Kiniksa Pharmaceuticals, Corp. employee Funding This study was funded by Kiniksa Pharmaceuticals, Ltd Authors’ contributions Study design: JFP, AB, AK, PC, LLK (qualitative interview study), BK (qualitative interview study) Study investigator: AK, MLW, DL, PC, SAL, AA, AE, SN Enrolled patients: AK, MLV, DL, PC, SAL, AA, AE, SN. Collection and assembly of data: AB, FF, AK, PC, SAL, LLK (qualitative interview study), BK (qualitative interview study) Data analysis: JFP, AB, FF, AK, PC, LLK (qualitative interview study), BK (qualitative interview study) Data interpretation: All authors Manuscript preparation: JFP, MM, LLK, BK Manuscript review and revisions: All authors Final approval of manuscript: All authors Independent data access and analysis: throughout the writing of this paper, all authors had the ability to query any aspect of the data either directly or through independent analysis and retain this ability until publication. Anna Beutler, John Paolini, and Fang Fang had full access to all the data in the study and take responsibility for its integrity and the data analysis. Acknowledgments All MRI findings were analyzed by the Imaging Core Laboratory C5Research (Cleveland Clinic). Sharon Crugnale and Larisa Collins were employed by Kiniksa Pharmaceuticals Corp. as clinical operations managers at the time the study was conducted; Kasia Warchol, Steven Chang, Cory Burke, Heather Cong, Randy Perrin and Jeannie Celiberti, all employees of Kiniksa Pharmaceuticals Corp., contributed to data collection and/or analysis. Kristi Wort, project manager at TCTM, contributed to the design of the study and its data collection. Scott Mellis, Regeneron Pharmaceuticals, Inc. employee, offered greatly valuable insights to the program. Eugene Luau and Bruce Green, from Model Answers performed the pharmacokinetic analyses and interpretation. Monica Brova and Sylvia Su contributed to the design of the qualitative study and its data collection and analysis. We want to thank all the patients and their caregivers, the study coordinators, the investigators and all the investigative site personnel who participated in this study; medical writing assistance was provided by Emmanuelle Hugentobler, a Kiniksa Pharmaceuticals Corp. employee, and in part by Peloton Advantage, an OPEN Health company, funded by Kiniksa Pharmaceuticals Ltd. References Imazio M, Gribaudo E, Gaita F. Recurrent Pericarditis. Progress in cardiovascular diseases. 2017;59(4):360-8. Lotan D, Wasserstrum Y, Fardman A, Kogan M, Adler Y. Usefulness of Novel Immunotherapeutic Strategies for Idiopathic Recurrent Pericarditis. Am J Cardiol. 2016;117(5):861-6. Soler-Soler J, Sagristà-Sauleda J, Permanyer-Miralda G. Relapsing pericarditis. Heart. 2004;90(11):1364. Raatikka M, Pelkonen PM, Karjalainen J, Jokinen EV. Recurrent pericarditis in children and adolescents: report of 15 cases. J Am Coll Cardiol. 2003;42(4):759-64. Imazio M, Brucato A, Cumetti D, Brambilla G, Demichelis B, Ferro S, et al. Corticosteroids for Recurrent Pericarditis. Circulation. 2008;118(6):667-71. Assolari A, Maestroni S, Cumetti D, Valenti A, Parisi F, Brucato A. Clinical management and therapy of idiopathic recurrent pericarditis. Clinical Management Issues. 2018;12. Judson MA, Chaudhry H, Louis A, Lee K, Yucel R. The effect of corticosteroids on quality of life in a sarcoidosis clinic: the results of a propensity analysis. Respir Med. 2015;109(4):526-31. McDonald CM, Henricson EK, Abresch RT, Duong T, Joyce NC, Hu F, et al. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study. Lancet. 2018;391(10119):451-61. Adler Y, Charron P, Imazio M, Badano L, Barón-Esquivias G, Bogaert J, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases. The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC). Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). European Heart Journal. 2015;36(42):2921-64. Wilson IB, Cleary PD. Linking clinical variables with health-related quality of life. A conceptual model of patient outcomes. JAMA. 1995;273(1):59-65. Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005;113(1-2):9-19. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res (Hoboken). 2011;63 Suppl 11:S240-52. Mannion AF, Balague F, Pellise F, Cedraschi C. Pain measurement in patients with low back pain. NatClin PractRheumatol. 2007;3(11):610-8. Hays RD, Bjorner JB, Revicki DA, Spritzer KL, Cella D. Development of physical and mental health summary scores from the patient-reported outcomes measurement information system (PROMIS) global items. QualLife Res. 2009;18(7):873-80. Charles E, Mehaffey J, Hawkins R, Burks S, McMurry T, Yarboro L, et al. Meaningful Patient-centered Outcomes 1 Year Following Cardiac Surgery. Annals of Surgery. 2019:1. Lam KH, Kwa VIH. Validity of the PROMIS-10 Global Health assessed by telephone and on paper in minor stroke and transient ischaemic attack in the Netherlands. BMJ open. 2018;8(7):e019919-e. Ahmad FS, Kallen MA, Schifferdecker KE, Carluzzo KL, Yount SE, Gelow JM, et al. Development and Initial Validation of the PROMIS®-Plus-HF Profile Measure. Circ Heart Fail. 2019;12(6):e005751. Supplementary Files Table1.docx Cite Share Download PDF Status: Published Journal Publication published 21 Apr, 2021 Read the published version in BMC Cardiovascular Disorders → Version 1 posted Review # 1 received at journal 08 Mar, 2021 Editorial decision: Major revision 08 Mar, 2021 Review # 2 received at journal 07 Mar, 2021 Review # 4 received at journal 28 Feb, 2021 Review # 3 received at journal 28 Feb, 2021 Reviewer # 4 agreed at journal 25 Feb, 2021 Reviewer # 3 agreed at journal 22 Feb, 2021 Reviewer # 2 agreed at journal 21 Feb, 2021 Reviewers invited by journal 19 Feb, 2021 Reviewer # 1 agreed at journal 19 Feb, 2021 Editor assigned by journal 18 Feb, 2021 Submission checks completed at journal 18 Feb, 2021 Editor invited by journal 18 Feb, 2021 First submitted to journal 03 Feb, 2021 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. 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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-258868","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":12789917,"identity":"78ee7b71-1523-4c5e-85e4-5e1755f71975","order_by":0,"name":"David Lin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIiWNgGAWjYBACeyA+wANC7A2MBx4YEKHFsAGmhecAw4EEYrQYHAASQC0MDBIJQC3EOMzg+BnDA28YDsiYSz5+cCCh4I48A/vhoxvwajmTY3BwDtBhlrPTDIAOe2bYwJOWdgO/w9ISDoP8YnA7AaTlMGODBI8Zfi3nn0G13Dz+AaTFnrCWG8kHIFpu8IBtSSSoxXDG4wMH5xgAtZzJKQBpSW4j5Bd7/sTmD28q/tkbHD++8cGHP4dt+9kPH8OrBeo8JDYbYeWjYBSMglEwCggBALOUVv4TFmcYAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-5076-8737","institution":"Minneapolis Heart Institute, Minneapolis, Minnesota, USA","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Lin","suffix":""},{"id":12789918,"identity":"89573c3c-18e1-456c-ab38-66b5849cfb74","order_by":1,"name":"Allan Klein","email":"","orcid":"","institution":"Cleveland Clinic","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Allan","middleName":"","lastName":"Klein","suffix":""},{"id":12789919,"identity":"5448deb7-d297-41bb-b0d2-e99259845d9e","order_by":2,"name":"David Cella","email":"","orcid":"","institution":"Northwestern University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Cella","suffix":""},{"id":12789920,"identity":"7f04e5ef-0640-4c45-964a-afded6f7d273","order_by":3,"name":"Anna Beutler","email":"","orcid":"","institution":"Kiniksa Pharmaceuticals Ltd","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Beutler","suffix":""},{"id":12789921,"identity":"f02bc3de-2b8f-443c-8212-bc3c44ab1328","order_by":4,"name":"Fang Fang","email":"","orcid":"","institution":"Kiniksa Pharmaceuticals Corp","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fang","middleName":"","lastName":"Fang","suffix":""},{"id":12789922,"identity":"c3b1a1cc-c1e9-4b6c-90c0-87e4815215fd","order_by":5,"name":"Matt Magestro","email":"","orcid":"","institution":"Kiniksa Pharmaceutical Corp","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Matt","middleName":"","lastName":"Magestro","suffix":""},{"id":12789923,"identity":"00e7d969-9238-4a03-bb93-d1b13418af9e","order_by":6,"name":"Paul Cremer","email":"","orcid":"","institution":"Cleveland Clinic","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Paul","middleName":"","lastName":"Cremer","suffix":""},{"id":12789924,"identity":"5bdf3f1d-2a66-4496-a8e2-0838762cd19a","order_by":7,"name":"Martin M. LeWinter","email":"","orcid":"","institution":"University of Vermont Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Martin","middleName":"M.","lastName":"LeWinter","suffix":""},{"id":12789925,"identity":"93660233-f6f0-46c5-b409-f803a60b339e","order_by":8,"name":"Sushil Allen Luis","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sushil","middleName":"Allen","lastName":"Luis","suffix":""},{"id":12789926,"identity":"9b332b1f-84ac-4912-a799-a84919633452","order_by":9,"name":"Antonio Abbate","email":"","orcid":"","institution":"Virginia Commonwealth University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Antonio","middleName":"","lastName":"Abbate","suffix":""},{"id":12789927,"identity":"e38a37d1-9d09-43e3-83a6-b2f22c73fcb5","order_by":10,"name":"Andrew Ertel","email":"","orcid":"","institution":"Medstar Heart and Vascular Institute","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Andrew","middleName":"","lastName":"Ertel","suffix":""},{"id":12789928,"identity":"155853bc-2ac2-4de7-9f07-d5e69d33fd21","order_by":11,"name":"Leighann Litcher-Kelly","email":"","orcid":"","institution":"Adelphi Values","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Leighann","middleName":"","lastName":"Litcher-Kelly","suffix":""},{"id":12789929,"identity":"15939908-aa5a-4f7d-b824-00bd867602cb","order_by":12,"name":"Brittany Klooster","email":"","orcid":"https://orcid.org/0000-0002-2018-8982","institution":"Adelphi Values","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Brittany","middleName":"","lastName":"Klooster","suffix":""},{"id":12789930,"identity":"72d479fb-acd5-4518-a093-c4c6dc575be8","order_by":13,"name":"John F. Paolini","email":"","orcid":"","institution":"Kiniksa Pharmaceuticals Corp.","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"John","middleName":"F.","lastName":"Paolini","suffix":""}],"badges":[],"createdAt":"2021-02-20 12:12:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-258868/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-258868/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12872-021-02008-3","type":"published","date":"2021-04-21T19:07:10+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":6471610,"identity":"afd70abd-39c3-4150-b252-d2f003206108","added_by":"auto","created_at":"2021-03-01 15:30:06","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":84083,"visible":true,"origin":"","legend":"Patient-centric conceptual model for recurrent pericarditis\n*Khandaker MH, Espinosa RE. Nishimura RA, et al. Pericanlial disease diagnosis management. Mayo Clin Proc. 2010;85(6):572-593\n","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-258868/v1/1b7713d898a7bb7846163890.jpg"},{"id":6471267,"identity":"fb7c3317-1eb3-4845-87c0-1ab78be6a1a1","added_by":"auto","created_at":"2021-03-01 15:27:06","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":37905,"visible":true,"origin":"","legend":"Mean PROMIS GPH/MPH at Baseline for A-RP and CSD-RP\nA-RP, active symptomatic recurrent pericarditis; CSD-RP, corticosteroid-dependent recurrent pericarditis with no active recurrence; GPH, Global Physical Health; GMH, Global Mental Health; PROMIS GH, Patient-Reported Outcomes Measurement Information System Global Physical Health.\n","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-258868/v1/8c10b4bfd1b1694ceb4af184.jpg"},{"id":6471614,"identity":"18dc31fb-5429-497f-8cf6-6fb2abe8eb4a","added_by":"auto","created_at":"2021-03-01 15:30:06","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":94944,"visible":true,"origin":"","legend":"PROMIS GH domain scores, pericardial pain, and c-reactive protein levels over time by participant group\nBL, baseline; CRP, c-reactive protein; D, day; EoEP, end of extension period; NRS, numeric rating scale; W, week.\n","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-258868/v1/60a509ad7cce3e3c6f31eb7f.jpg"},{"id":13673287,"identity":"2c4d0bc1-d587-46d0-afd6-31dba406685c","added_by":"auto","created_at":"2021-09-17 11:16:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":639952,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-258868/v1/8b49ea24-1cf0-46e9-a47f-32b22f4a194b.pdf"},{"id":6471269,"identity":"59fd0440-67b2-43c4-81d9-72b8061e2b7a","added_by":"auto","created_at":"2021-03-01 15:27:06","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":14152,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-258868/v1/7b0feb70a8de2b697fad7b21.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eHealth-related Quality of Life in Patients With Recurrent Pericarditis: Results From a Phase 2 Study of Rilonacept\u003c/p\u003e","fulltext":[{"header":"Introduction","content":" \u003cp\u003ePericarditis, or inflammation of the pericardium, has a variety of etiologies but is most commonly referred to as idiopathic. The primary symptom of pericarditis is debilitating chest pain. Pericarditis is considered recurrent if symptoms and inflammation recur at least 4 weeks after an initial acute episode. Recurrent pericarditis (RP) affects approximately 15\u0026ndash;30% of patients who have an acute episode of pericarditis, and up to 50% of patients who experience one recurrence will experience two or more. There are currently no FDA-approved therapies for pericarditis or RP; however, exploratory therapy with nonsteroidal anti-inflammatory drugs [NSAIDs] and colchicine is a standard often used successfully to treat the first pericarditis episode or initial recurrence. Treatment options are limited and there is a high unment medical need for patients who have inadequate response (i.e., continued recurrence or incomplete symptom resolution) to or who cannot tolerate standard therapy.\u003c/p\u003e \u003cp\u003eWhile the impact of RP on patients\u0026rsquo; health-related quality of life (HRQoL) has been reported in the literature [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and is thought to be due to the primary symptom of the condition (e.g., chest pain) and the resulting uncertainty and anxiety of new recurrences, impact to HRQoL has not been explicitly evaluated in previous clinical research. In addition, corticosteroids are widely used to treat RP [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], putting patients at risk for steroid-dependence [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]; comorbidities associated with chronic corticosteroid use may also lead to adverse impacts on HRQoL [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBoth qualitative and quantitative research approaches were used to explore the HRQoL impacts experienced by adults with RP and how those impacts may change in response to treatment. Qualitative interviews were conducted with ten adults with RP to document the patient experience of RP symptoms and HRQoL impacts (known as concept elicitation interviews). Results from these interviews were used to develop a conceptual model of RP. In addition, a Phase 2 clinical trial of rilonacept (an IL-1α/IL-1β blocker) for the treatment of RP included a HRQoL patient-reported outcome (PRO) questionnaire as an exploratory endpoint. Therefore, the objective of these two streams of research is to evaluate HRQoL in patients with RP; specifically, to confirm whether the concepts assessed with the HRQoL PRO questionnaire used in the Phase 2 clinical trial are relevant to patients with RP (based on patient reports during the qualitative interviews) and to evaluate the effect of rilonacept treatment on physical and mental aspects of HRQoL.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eThe sections below describe the methodology used for both the qualitative interviews with patients and the clinical trial study design relevant to the current research objective.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eMethods for qualitative patient interviews to develop a patient-centric conceptual model\u003c/h2\u003e\u003cp\u003eTo understand the patient experience of RP, one-on-one telephone interviews were conducted with adults with a confirmed diagnosis of RP.\u003c/p\u003e\u003cdiv id=\"Sec4\" class=\"Section3\"\u003e\u003ch2\u003eParticipants for qualitative interviews\u003c/h2\u003e\u003cp\u003eThe qualitative interview study was approved by a centralized independent review board (IRB) and following approval, potentially eligible participants were identified from clinical sites through review of medical records. Key inclusion criteria for the qualitative study included: age 18 years or older and a clinical diagnosis of RP (either idiopathic or due to post-pericardiotomy syndrome, adult onset Still\u0026rsquo;s Disease, or Dressler\u0026rsquo;s Syndrome), defined as the first episode of acute pericarditis (as defined by the 2015 European Society of Cardiology [ESC] Guidelines for the Diagnosis and Management of Pericardial Diseases) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] followed by at least one pericarditis recurrence after a symptom-free interval of at least 4\u0026ndash;6 weeks. Key exclusion criteria for the study included: individual was currently enrolled in another clinical interventional study for RP; individual had a diagnosis of RP that was secondary to specific prohibited etiologies, including tuberculosis, neoplastic, purulent, or radiation, post-thoracic blunt trauma, myocarditis, or systemic autoimmune diseases (with the exception of adult onset Still\u0026rsquo;s Disease).\u003c/p\u003e\u003cp\u003e Potentially eligible participants were presented with study information by a recruiting clinician (or his/her representative), and once participants provided a signed informed consent form, the clinical site completed a screening document to determine participants\u0026rsquo; eligibility. Participant interviews were scheduled once eligibility was confirmed.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section3\"\u003e\u003ch2\u003eInterview conduct\u003c/h2\u003e\u003cp\u003eOne-on-one, 60-minute telephone interviews with ten adults aged 18 to 75 years with RP were conducted. Interviewers used a semi-structured interview guide to facilitate the conversation and included open-ended questions to understand the patient experience of RP and its treatments, specifically, what signs, symptoms, and HRQoL impacts are experienced in relation to RP from the patient perspective.\u003c/p\u003e\u003cp\u003eInterview guide questions included:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e\u0026ldquo;Could you please start by telling me about the first signs or symptoms of [participant\u0026rsquo;s term for RP] you noticed?\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u0026ldquo;Does the [patient-reported sign/symptom] have any impact on your daily life? If so, how?\u0026rdquo;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u0026ldquo;Have there been any changes to your daily life because of [participant\u0026rsquo;s term for RP]? If so, can you please describe?\u0026rdquo;\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section3\"\u003e\u003ch2\u003eData handing and analysis\u003c/h2\u003e\u003cp\u003eInterviews were audio-recorded after obtaining participant consent, transcribed and anonymized. These transcripts were coded and qualitatively analyzed using the ATLAS.ti software program. The goals of transcript coding were to organize and catalog participants\u0026rsquo; descriptions of the characteristics of RP, in order to develop a patient-centric conceptual model of RP signs, symptoms, and impact concepts. A conceptual model is a heuristic classification scheme that links a specified disease state or condition to its proximal and increasingly distal health outcomes [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], acts as a framework for understanding a disease and/or its treatment, specifies the potentially relevant outcomes for a program of research, and informs the selection of measurement concepts to foster the development of questionnaires, outcomes, and endpoints. Specifically, to characterize the specific applicability of the Patient Reported Outcome Measurement Information System Global Health (PROMIS GH v1.2) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] questionnaire (described below) for capturing the HRQoL impacts experienced by patients with RP, conceptual mapping was conducted to compare the concepts within the conceptual model against PROMIS GH v1.2 individual items.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eMethods for the Phase 2 study KPL-914-C001\u003c/h2\u003e\u003cp\u003e The methodology of the Phase 2 clinical trial of rilonacept for the treatment of RP (clinicaltrial.gov: NCT03980522) is provided in detail in Klein and colleagues (in press). To summarize, this was a multicenter, open-label, single-active-arm Phase 2 study which enrolled adults with RP who either were having an active recurrence at baseline or who were not having an active recurrence but were dependent on corticosteroids. All participants received weekly subcutaneous (SC) injections of rilonacept for 6 weeks during the treatment period (TP) and were invited to continue weekly SC injections for up to 18 weeks in the extension period (EP).\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section3\"\u003e\u003ch2\u003eParticipants\u003c/h2\u003e\u003cp\u003eAdults (18\u0026ndash;75 years of age) with RP (idiopathic or post-pericardiotomy syndrome etiology) were enrolled and stratified into one of two participant groups: (1) those with an active recurrence at baseline (with at least two additional prior recurrences; A-RP), or (2) those without an active recurrence who were dependent on corticosteroids (and had had at least three prior recurrences; CSD-RP). Participants in the A-RP group had either evidence of elevated c-reactive protein (CRP) at baseline or did not have elevated CRP potentially due to concomitant medications (such as corticosteroids) but had evidence of pericardial inflammation by cardiac Magnetic Resonance Imaging. Participants in the CSD-RP group had corticosteroid-dependent disease (based on information from the investigator regarding prior recurrences when taking medication) and did not have active pericarditis symptomatology or elevated CRP at baseline.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section3\"\u003e\u003ch2\u003eAssessments\u003c/h2\u003e\u003cp\u003eWeekly in TP, and then monthly blood levels of CRP, were evaluated to measure inflammation from baseline to the end of the EP for all participants. In addition, two PRO questionnaires were completed by all participants during the clinical trial. They included:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eA single-item 11-point numeric rating scale (NRS) for average pericarditis pain intensity with a 24-hour recall window (with 0\u0026thinsp;=\u0026thinsp;no pain to 10\u0026thinsp;=\u0026thinsp;pain as bad as it could be) [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] was completed weekly in TP and monthly in EP from baseline to the end of the EP.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe 10-item PROMIS GH v1.2 questionnaire was also completed by participants at up to five time points during the clinical trial to assess HRQoL [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The analyses presented here focused on the following three most critical timepoints: baseline (Day 0), end of TP (Week 6), Final Visit (end of EP). Items 1\u0026ndash;7 ask participants to think about their general health and are rated on a five-point response scale (with higher number associated with better quality of life). Items 8\u0026ndash;10 ask participants to report on the emotional problems, fatigue, and pain over last seven days, with Items 8 and 9 rated on a five-point response scale (with higher scores associated with better quality of life), and Item 10 rated on a 0\u0026ndash;10 NRS (with higher scores associated with more pain). Two domain scores are created from the 10-item scale, the global physical health (GPH), and the global mental health (GMH). The GPH is scored by by averaging together the global03 (physical health), global06 (physical function), global07 (pain) and global08 (fatigue) items. The GMH is scored by averaging together the global02 (quality of life), global04 (mental health), global05 (satisfaction with discretionary social activities), and global10 (emotional problems) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The published US-generalized normative scores for both of these domains are a mean score of 50, and a standard deviation of 10 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section3\"\u003e\u003ch2\u003eProcedure and Analyses\u003c/h2\u003e\u003cp\u003e All participants received rilonacept SC injections weekly for 6 weeks until the end of TP and were invited to continue weekly SC injections (at the same dose) during an optional 18-week EP. For those on other concomitant medications for RP at baseline (participants in both the A-RP and CSD-RP groups), including corticosteroids, the option to taper was offered during the EP. Participants completed the PRO questionnaires (PROMIS and Pain NRS) at study visits, including telephone and site visits. Blood levels for CRP were also assessed during clinical site visits or via visiting nurse or local contract laboratory; CRP was analysed via a central laboratory.\u003c/p\u003e\u003cp\u003eThe analyses presented in the results are descriptive, given the small sample size of the clinical trial and the single-active arm design. Specifically, results are reported as Means and Standard Deviations, with ranges of values for each participant group. While participants were asked to complete the HRQoL questionnaire at multiple time points in the clinical trial, the analyses focus on the baseline, (Day 0), end of base TP (Week 6), and Final Visit at end of EP timepoints. In addition, the descriptive analyses also include the weekly pericardial pain NRS scores and CRP blood levels that were collected at study visits.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eQualitative patient interviews:\u003c/h2\u003e\u003cp\u003eQualitative interviews were conducted via telephone with ten adults diagnosed with RP to understand the patient experience of the condition, including the signs, symptoms, and health-related quality of life impacts. Participants were recruited from three clinical sites in the US. The mean age of the participants was 58.5 years (SD\u0026thinsp;=\u0026thinsp;11.5), and six participants (60.0%) were female. Clinicians reported that participants exhibited the following RP types: idiopathic (n\u0026thinsp;=\u0026thinsp;4, 40.0%), post-pericardiotomy syndrome (n\u0026thinsp;=\u0026thinsp;4, 40.0%), adult-onset Still\u0026rsquo;s Disease (n\u0026thinsp;=\u0026thinsp;1, 10.0%), or Dressler\u0026rsquo;s syndrome (n\u0026thinsp;=\u0026thinsp;1, 10.0%). The majority of participants reported taking over-the-counter or prescription anti-inflammatory medications (n\u0026thinsp;=\u0026thinsp;7, 70.0%), and half reported that they had previously taken corticosteroids (n\u0026thinsp;=\u0026thinsp;5, 50.0%) for their RP.\u003c/p\u003e\u003cp\u003eA total of 13 symptoms and 34 impacts across 11 domains were reported by participants during these qualitative interviews and were organized into a conceptual model (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). All participants reported experiencing chest pain (n\u0026thinsp;=\u0026thinsp;10, 100.0%), with seven (n\u0026thinsp;=\u0026thinsp;7, 70.0%) stating it is the most bothersome symptom, and five (n\u0026thinsp;=\u0026thinsp;5, 50.0%) reporting it is the most important symptom to improve. After chest pain, the next most frequently reported signs or symptoms reported by at least half of participants, were tiredness (n\u0026thinsp;=\u0026thinsp;8, 80.0%), shortness of breath (n\u0026thinsp;=\u0026thinsp;7, 70.0%), fever (n\u0026thinsp;=\u0026thinsp;6, 60.0%), and heart palpitations (n\u0026thinsp;=\u0026thinsp;5, 50.0%). The most frequently reported impacts (reported by at least half of the participants) were inability to exercise (n\u0026thinsp;=\u0026thinsp;8, 80.0%), disrupted sleep (n\u0026thinsp;=\u0026thinsp;7, 70.0%), fear (n\u0026thinsp;=\u0026thinsp;6, 60.0%), inability to go to social events (n-6, 60.0%), interruption of daily activities (n\u0026thinsp;=\u0026thinsp;6, 60.0%), absenteeism (n\u0026thinsp;=\u0026thinsp;5, 50.0%), and impaired ability to do housework (n\u0026thinsp;=\u0026thinsp;5, 50.0%).\u003c/p\u003e\u003cp\u003eIn order to confirm that the assessment of HRQoL completed by participants in the Phase 2 clinical trial captured concepts relevant to adults with RP, concepts reported during the qualitative interviews were mapped to the ten items of the PROMIS Global Health v1.2 questionnaire. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the results of this exercise, with representative patient quotes from the qualitative interviews for each of the items of the PROMIS GH questionnaire. In particular, adults reported symptoms and HRQoL impacts during the interviews, that are included in the PROMIS GH questionnaire, such as pain, social and emotional impacts, and physical functioning.\u003c/p\u003e\n\n\u003cp\u003eDue to technical limitations, table 1 is only available as a download in the Supplemental Files section.\u003c/p\u003e\n\n\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003ePhase 2 study rilonacept\u003c/h2\u003e\u003cp\u003e Twenty-five participants were enrolled in a multicenter, open-label, single-active-arm Phase 2 clinical trial of rilonacept, with an average age of 42.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5 years (\u0026plusmn;\u0026thinsp;indicates standard deviation; range 26\u0026ndash;62); most were female (n\u0026thinsp;=\u0026thinsp;15, 60.0%) and white (n\u0026thinsp;=\u0026thinsp;22, 88.0%). Participants had a mean number of prior recurrences of 2.6 (range 1\u0026ndash;8), and average duration of disease of 2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9 years (range 0.2 to 7.9 years), and average number of pericarditis episodes per year of 3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7 (range 0.54-15). Based on their baseline symptoms and signs of pericardial inflammation, there were two groups of participants: those experiencing an active recurrence (A-RP; n\u0026thinsp;=\u0026thinsp;16), and those who were corticosteroid-dependent but not acutely symptomatic at baseline (CSD-RP; n\u0026thinsp;=\u0026thinsp;9). See Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e for the demographics and health characteristics of these two participant groups.\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\u003eDemographics and health characteristics of Phase 2 clinical trial sample\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eActive recurrence (A-RP)\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;16\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNot symptomatic, Corticosteroid-dependent (CSD-RP)\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;9\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\u003eAge (years)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation [SD] [range])\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.52 (26\u0026ndash;58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.56 (36\u0026ndash;62)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGender (% female)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e75.0% (n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33.3% (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRace (% white)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e81.3% (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100% (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI (kg/m2)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD [range])\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31.99\u0026thinsp;\u0026plusmn;\u0026thinsp;7.51 (23.4\u0026ndash;52.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.97\u0026thinsp;\u0026plusmn;\u0026thinsp;4.68 (22.5\u0026ndash;34.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDuration of disease (years)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD [range])\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.13 (0.2\u0026ndash;7.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97 (0.6\u0026ndash;3.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber of prior recurrences (median, [range])\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (1\u0026ndash;8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (2\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBaseline NRS (Pain Rating 0\u0026ndash;10;\u003c/b\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD [range])\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.82 (2\u0026ndash;8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.51 (0\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBaseline CRP values (mg/dL)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD [range])\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.30 (0.09\u0026ndash;19.84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11 (0.05\u0026ndash;0.36)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eConcomitant medications at baseline\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAspirin (n [%])\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (22.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNSAID (n [%])\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (43.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (55.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eColchicine (n [%])\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (75.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (88.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCorticosteroids (CS) (n [%])\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (37.5%)\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (100.0%)\u003csup\u003e\u0026dagger;\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\"\u003e\u003csup\u003e*\u003c/sup\u003e4/6 (66.7%) discontinued CS and 1/6 (16.7%) tapered CS by end of EP; 1/6 (16.7%) did not enter EP.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e 7/9 (77.8%) discontinued CS and 1/9 (11.1%) tapered CS by end of EP; 1/9 (11.1%) did not enter EP.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eScores from the PROMIS GH questionnaire items and domains were evaluated for each of the participant groups over time (baseline, end of TP, and end of EP). Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the baseline scores for the two domains of the PROMIS GH health questionnaire. For both the A-RP and CSD-RP groups, average scores for these domains are below the US normative average score of 50. Additionally, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows a trend for improvement in some item and domain scores for both the A-RP and CSD-RP groups.\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\u003ePROMIS Global Health item and domain scores over time (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation), by participant group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePROMIS GH item/ domain*\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eA-RP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003eCSD-RP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eBaseline (n\u0026thinsp;=\u0026thinsp;16)\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eEnd of TP visit\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;15)\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eEnd of EP visit\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;15)\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eBaseline\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;7)\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eEnd of TP visit\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;9)\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003eEnd of EP visit\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;8)\u003c/b\u003e\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\u003eGlobal Physical Health (GPH)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39.94\u0026thinsp;\u0026plusmn;\u0026thinsp;8.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51.35\u0026thinsp;\u0026plusmn;\u0026thinsp;7.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e51.32\u0026thinsp;\u0026plusmn;\u0026thinsp;6.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e43.30\u0026thinsp;\u0026plusmn;\u0026thinsp;5.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e45.09\u0026thinsp;\u0026plusmn;\u0026thinsp;4.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e46.81\u0026thinsp;\u0026plusmn;\u0026thinsp;9.27\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eItem 3: physical health\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eItem 7: physical activities\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eItem 9: fatigue\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eItem 10: pain\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.50\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGlobal Mental Health (GMH)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44.50\u0026thinsp;\u0026plusmn;\u0026thinsp;10.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50.13\u0026thinsp;\u0026plusmn;\u0026thinsp;11.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e50.54\u0026thinsp;\u0026plusmn;\u0026thinsp;11.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e46.49\u0026thinsp;\u0026plusmn;\u0026thinsp;7.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e47.91\u0026thinsp;\u0026plusmn;\u0026thinsp;5.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e50.66\u0026thinsp;\u0026plusmn;\u0026thinsp;6.30\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eItem 2: quality of life\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eItem 4: mental health\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eItem 5: social activities and relation-ships\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.92\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eItem 8: emotional problems\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eItems that are not included in above domains\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eItem 1: general health\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eItem 6: social activities and roles\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e*For Items 1\u0026ndash;9, higher scores indicate improvement, and for Item 10, lower scores indicate improvement. Scoring for Item 10 is adjusted when calculating the GPH.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eFor participants in the A-RP group, increases in the average scores for items of the PROMIS GH questionnaire that assess general health, quality of life, and physical health indicate improvement over the study period. In addition, for the A-RP group, the average score of the PROMIS GH pain item shows the largest decrease over the study period, with a mean score of nearly 5 on the 0\u0026ndash;10 NRS at baseline, and less than 1 at end of EP. At baseline, both the physical and mental domain scores (GPH/MPH) were lower than the normative average of 50, but by end of TP mean scores for the GPH were above the US norm (and remained above at end of EP), and mean scores for the GMH were at the US norm (and remained at the normative average at end of EP).\u003c/p\u003e\u003cp\u003eFor participants in the CSD-RP group, there were some increases (improvements) on the PROMIS GH items assessing mental health, social activities and relationships, social activities and roles, and emotional problems, but the average scores for the other items did not change. Similar to the A-RP group, average scores for the CSD-RP group were also below the US norm for both the GPH and GMH domains at baseline. For the GMH domain, average scores were at the normative average at the end of EP.\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e also shows the change in the GPH and GMH domain scores over the study period, and the relationship between these HRQoL scores and patient-reported pericardial pain and serum marker of inflammation (CRP). For the A-RP group, pain scores and CRP levels decrease over the study period, while HRQoL scores increase. For the CSD-RP group, pericardial pain and CRP (low at baseline, as expected as these participants entered the trial while not in active flare) remain low over the course of the study even while tapering and discontinuing corticosteroids, while HRQoL scores increase over time.\u003c/p\u003e\u003cp\u003ePlease note that participants who completed the EP and were taking corticosteroids at Baseline (all participants in the CSD-RP [n\u0026thinsp;=\u0026thinsp;8], and 83.3% [n\u0026thinsp;=\u0026thinsp;5/6] of participants in the A-RP), were able to taper and/or discontinue using corticosteroids by the end of the EP (i.e., the end of the study) without recurrence or pericarditis symptomatology (e.g., patient-reported pericardial pain) or inflammation (e.g., elevated CRP level).\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":" \u003cp\u003eWhile a substantial negative impact of RP on patients\u0026rsquo; HRQoL has traditionally been assumed, to our knowledge this is the first analysis using qualitative and quantitative methods to explore the ways that symptoms of pericarditis recurrence impact patients\u0026rsquo; quality of life. The results from the baseline timepoint of the Phase 2 clinical trial align with the assumption of patients\u0026rsquo; decreased HRQoL, showing that scores on the GMH and GPH of the PROMIS GH questionnaire were on average lower than normative scores for both the A-RP and CSD-RP groups. In addition, the improvement in HRQoL scores over the course of the study tracks with improvements in patient-reported pericardial pain and CRP levels for the A-RP group, and with the tapering and discontinuing corticosteroids for the CSD-RP group while pericardial pain and CRP remained stable and low while on rilonacept treatment. Therefore, these results show that RP negatively impacts patients\u0026rsquo; quality of life physically and emotionally, and that improvements in quality of life may be associated with improvement in disease symptomatology and a decrease in pericardial inflammation, in particular, while patients receive targeted treatment.\u003c/p\u003e \u003cp\u003eFurthermore, results from qualitative interviews, where adults with RP spoke about the unpredictable nature of the condition, supported that pericarditis recurrences impact patient physical and mental health.. Specifically, using the qualitative data, a conceptual model of RP was developed, and HRQoL concepts included in the concept model (e.g., ability to carry out daily activities, impacts on mood, and limitation on social activities), were mapped against the ten items of the PROMIS GH v1.2 questionnaire (included in the Phase 2 clinical trial of rilonacept), which demonstrate that this questionnaire is assessing concepts that are relevant to adults with RP.\u003c/p\u003e \u003cp\u003eLimitations include the small sample sizes for both the qualitative interviews and the clinical trial, the single-active-arm design of the clinical trial, and the relatively short duration (24 weeks) of the clinical trial compared to the overall duration of this chronic disease. In addition, while the inclusion criteria for the qualitative interview study were intended to be similar to those of the clinical trial, they were less restrictive (i.e., adults interviewed did not experience as many recurrences as the participants in the clinical trial). Nevertheless, these results provide preliminary support for the importance of including a multidimensional assessment of HRQoL for future clinical research of RP. It is also important to consider that some HRQoL impacts may be dependent on age and gender, therefore given the age range of the participants who completed the qualitative interviews and the Phase 2 clinical trial, the resulting conceptual model should be considered representative of adult RP.\u003c/p\u003e \u003cp\u003eStrengths include leveraging qualitative results to support the importance of the item- and domain-level scores of the PROMIS GH v1.2 questionnaire to adults with RP. The representative patient quotes help contextualize how participants may be interpreting each item of the PROMIS GH questionnaire. In addition, the means for the GH domain scores at baseline in the rilonacept clinical trial provides evidence of the impact RP has on patients\u0026rsquo; HRQoL, as they are lower compared to population norm scores. These findings are consistent with other clinical studies reporting lower PROMIS GH questionnaire scores and associated impacts in physical, mental, and social domains in cardiac and vascular populations [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The increase in both the physical and mental component scores over the course of the study for both the A-RP and CSD-RP, in conjunction with improvements and/or stable pericardial pain scores and CRP levels, shows that HRQoL scores may also be responsive to treatment as the patient\u0026rsquo;s condition improves.\u003c/p\u003e "},{"header":"Conclusions","content":" \u003cp\u003eGiven the exercise restrictions that patients are expected to adhere to following a diagnosis of RP and the anxiety associated with the unpredictability of recurrences, it is important to evaluate both physical and emotional impacts of the condition. As more clinical trials move to incorporate patient-centric outcomes to evaluate treatments not only in terms of resolution of a physiological indicator of disease but also to ensure that patients feel and function better, future clinical trials of adults with RP should include HRQoL PRO questionnaires. In addition, future studies should explicitly examine the effect of concomitant medications, including corticosteroids, and their independent impact on patient HRQoL.\u003c/p\u003e \u003cp\u003eThe results of this pilot study demonstrate an early signal of a positive impact of rilonacept on clinical outcome measures and improvements in patient HRQoL over the study time period which tracked with improvements in pericardial pain and inflammation. For those participants in the CSD-RP group, who were weaning off corticosteroids while taking rilonacept, patient-reported pericardial pain and CRP levels were stable, while HRQoL scores improved over the course of the study, without recurrences.\u003c/p\u003e "},{"header":"Abbreviation ","content":"\u003cp\u003eA-RP active recurrence of pericarditis at baseline\u003c/p\u003e\n\u003cp\u003eCRP c-reactive protein\u003c/p\u003e\n\u003cp\u003eCSD-RP active recrurecne of pericarditis at baseline dependent on corticosteroids\u003c/p\u003e\n\u003cp\u003eEP extension period\u003c/p\u003e\n\u003cp\u003eESC European Society of Cardiology\u003c/p\u003e\n\u003cp\u003eGMH global mental health\u003c/p\u003e\n\u003cp\u003eGPH global physical health\u003c/p\u003e\n\u003cp\u003eHRQoL health-related quality of life\u003c/p\u003e\n\u003cp\u003eIRB independent review board\u003c/p\u003e\n\u003cp\u003eNRS numeric rating scale\u003c/p\u003e\n\u003cp\u003eNSAIDs nonsteroidal anti-inflammatory drugs\u003c/p\u003e\n\u003cp\u003ePRO patient-reported outcome\u003c/p\u003e\n\u003cp\u003ePROMIS GH Patient Reported Outcome Measurement Information System Global Health\u003c/p\u003e\n\u003cp\u003eRP recurrent pericarditis\u003c/p\u003e\n\u003cp\u003eSC subcutaneous\u003c/p\u003e\n\u003cp\u003eTP treatment period\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eEthics approval for the qualitative interviews was granted by Sterling IRB under IRB ID# 6406.\u003c/p\u003e\n\u003cp\u003eEthics approval for the Phase 2 study was granted by the central IRB Aspire under IRB ID# KPL-914-C001 as well as by site-specific local IRBs as applicable.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eData will be made available upon reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eDavid Lin: None\u003c/p\u003e\n\u003cp\u003eAllan Klein: Research grant, scientific advisory board Kiniksa Pharmaceuticals, Ltd., advisory board Swedish Orphan Biovitrum AB, advisory board Pfizer, Inc., modest.\u003c/p\u003e\n\u003cp\u003eDavid Cella: Consultant for Kiniksa Pharmaceuticals, Ltd., modest.\u003c/p\u003e\n\u003cp\u003eAnna Beutler: Kiniksa Pharmaceuticals, Ltd. consultant.\u003c/p\u003e\n\u003cp\u003eFang Fang: Kiniksa Pharmaceuticals, Corp. employee.\u003c/p\u003e\n\u003cp\u003eMatt Magestro: Kiniksa Pharmaceuticals, Corp. employee.\u003c/p\u003e\n\u003cp\u003ePaul Cremer: Advisory board Swedish Orphan Biovitrum AB, advisory board Kiniksa Pharmaceuticals, Ltd., modest.\u003c/p\u003e\n\u003cp\u003eMartin M. LeWinter: One seminar for Kiniksa Pharmaceuticals, Ltd., modest.\u003c/p\u003e\n\u003cp\u003eSushil Allen Luis: Advisory board member for Kiniksa Pharmaceuticals, Ltd., modest. Consultant and advisory board member for Swedish Orphan Biovitrum AB, significant.\u003c/p\u003e\n\u003cp\u003eAntonio Abbate: Research grants from Kiniksa Pharmaceuticals, Ltd., Swedish Orphan Biovitrum AB, Olatec Therapeutics LLC, Serpin Pharma, LLC; consultant fees: Kiniksa Pharmaceuticals, Ltd., Olatec Therapeutics LLC, Serpin Pharma, LLC, Merck \u0026amp; Co., Inc., modest.\u003c/p\u003e\n\u003cp\u003eAndrew Ertel: None\u003c/p\u003e\n\u003cp\u003eLeighann Litcher-Kelly: Employed by Adelphi Values, which received funding from Kiniksa Pharmaceuticals, Ltd. for PRO work in pericarditis\u003c/p\u003e\n\u003cp\u003eBrittany Klooster: Employed by Adelphi Values, which received funding from Kiniksa Pharmaceuticals, Ltd. for PRO work in pericarditis\u003c/p\u003e\n\u003cp\u003eJohn F. Paolini: Kiniksa Pharmaceuticals, Corp. employee\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis study was funded by Kiniksa Pharmaceuticals, Ltd\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003eStudy design: JFP, AB, AK, PC, LLK (qualitative interview study), BK (qualitative interview study)\u003c/p\u003e\n\u003cp\u003eStudy investigator: AK, MLW, DL, PC, SAL, AA, AE, SN\u003c/p\u003e\n\u003cp\u003eEnrolled patients: AK, MLV, DL, PC, SAL, AA, AE, SN.\u003c/p\u003e\n\u003cp\u003eCollection and assembly of data: AB, FF, AK, PC, SAL, LLK (qualitative interview study), BK (qualitative interview study)\u003c/p\u003e\n\u003cp\u003eData analysis: JFP, AB, FF, AK, PC, LLK (qualitative interview study), BK (qualitative interview study)\u003c/p\u003e\n\u003cp\u003eData interpretation: All authors\u003c/p\u003e\n\u003cp\u003eManuscript preparation: JFP, MM, LLK, BK\u003c/p\u003e\n\u003cp\u003eManuscript review and revisions: All authors\u003c/p\u003e\n\u003cp\u003eFinal approval of manuscript: All authors\u003c/p\u003e\n\u003cp\u003eIndependent data access and analysis: throughout the writing of this paper, all authors had the ability to query any aspect of the data either directly or through independent analysis and retain this ability until publication. Anna Beutler, John Paolini, and Fang Fang had full access to all the data in the study and take responsibility for its integrity and the data analysis.\u003c/p\u003e\n\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eAll MRI findings were analyzed by the Imaging Core Laboratory C5Research (Cleveland Clinic). Sharon Crugnale and Larisa Collins were employed by Kiniksa Pharmaceuticals Corp. as clinical operations managers at the time the study was conducted; Kasia Warchol, Steven Chang, Cory Burke, Heather Cong, Randy Perrin and Jeannie Celiberti, all employees of Kiniksa Pharmaceuticals Corp., contributed to data collection and/or analysis. Kristi Wort, project manager at TCTM, contributed to the design of the study and its data collection. Scott Mellis, Regeneron Pharmaceuticals, Inc. employee, offered greatly valuable insights to the program. Eugene Luau and Bruce Green, from Model Answers performed the pharmacokinetic analyses and interpretation. Monica Brova and Sylvia Su contributed to the design of the qualitative study and its data collection and analysis. We want to thank all the patients and their caregivers, the study coordinators, the investigators and all the investigative site personnel who participated in this study; medical writing assistance was provided by Emmanuelle Hugentobler, a Kiniksa Pharmaceuticals Corp. employee, and in part by Peloton Advantage, an OPEN Health company, funded by Kiniksa Pharmaceuticals Ltd.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eImazio M, Gribaudo E, Gaita F. Recurrent Pericarditis. Progress in cardiovascular diseases. 2017;59(4):360-8.\u003c/li\u003e\n\u003cli\u003eLotan D, Wasserstrum Y, Fardman A, Kogan M, Adler Y. Usefulness of Novel Immunotherapeutic Strategies for Idiopathic Recurrent Pericarditis. Am J Cardiol. 2016;117(5):861-6.\u003c/li\u003e\n\u003cli\u003eSoler-Soler J, Sagrist\u0026agrave;-Sauleda J, Permanyer-Miralda G. Relapsing pericarditis. Heart. 2004;90(11):1364.\u003c/li\u003e\n\u003cli\u003eRaatikka M, Pelkonen PM, Karjalainen J, Jokinen EV. Recurrent pericarditis in children and adolescents: report of 15 cases. J Am Coll Cardiol. 2003;42(4):759-64.\u003c/li\u003e\n\u003cli\u003eImazio M, Brucato A, Cumetti D, Brambilla G, Demichelis B, Ferro S, et al. Corticosteroids for Recurrent Pericarditis. Circulation. 2008;118(6):667-71.\u003c/li\u003e\n\u003cli\u003eAssolari A, Maestroni S, Cumetti D, Valenti A, Parisi F, Brucato A. Clinical management and therapy of idiopathic recurrent pericarditis. Clinical Management Issues. 2018;12.\u003c/li\u003e\n\u003cli\u003eJudson MA, Chaudhry H, Louis A, Lee K, Yucel R. The effect of corticosteroids on quality of life in a sarcoidosis clinic: the results of a propensity analysis. Respir Med. 2015;109(4):526-31.\u003c/li\u003e\n\u003cli\u003eMcDonald CM, Henricson EK, Abresch RT, Duong T, Joyce NC, Hu F, et al. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study. Lancet. 2018;391(10119):451-61.\u003c/li\u003e\n\u003cli\u003eAdler Y, Charron P, Imazio M, Badano L, Bar\u0026oacute;n-Esquivias G, Bogaert J, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases. The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC). Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). European Heart Journal. 2015;36(42):2921-64.\u003c/li\u003e\n\u003cli\u003eWilson IB, Cleary PD. Linking clinical variables with health-related quality of life. A conceptual model of patient outcomes. JAMA. 1995;273(1):59-65.\u003c/li\u003e\n\u003cli\u003eDworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005;113(1-2):9-19.\u003c/li\u003e\n\u003cli\u003eHawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res (Hoboken). 2011;63 Suppl 11:S240-52.\u003c/li\u003e\n\u003cli\u003eMannion AF, Balague F, Pellise F, Cedraschi C. Pain measurement in patients with low back pain. NatClin PractRheumatol. 2007;3(11):610-8.\u003c/li\u003e\n\u003cli\u003eHays RD, Bjorner JB, Revicki DA, Spritzer KL, Cella D. Development of physical and mental health summary scores from the patient-reported outcomes measurement information system (PROMIS) global items. QualLife Res. 2009;18(7):873-80.\u003c/li\u003e\n\u003cli\u003eCharles E, Mehaffey J, Hawkins R, Burks S, McMurry T, Yarboro L, et al. Meaningful Patient-centered Outcomes 1 Year Following Cardiac Surgery. Annals of Surgery. 2019:1.\u003c/li\u003e\n\u003cli\u003eLam KH, Kwa VIH. Validity of the PROMIS-10 Global Health assessed by telephone and on paper in minor stroke and transient ischaemic attack in the Netherlands. BMJ open. 2018;8(7):e019919-e.\u003c/li\u003e\n\u003cli\u003eAhmad FS, Kallen MA, Schifferdecker KE, Carluzzo KL, Yount SE, Gelow JM, et al. Development and Initial Validation of the PROMIS\u0026reg;-Plus-HF Profile Measure. Circ Heart Fail. 2019;12(6):e005751.\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":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pericarditis, interleukin-1 receptor blocker, health-related quality of life, recurrent pericarditis","lastPublishedDoi":"10.21203/rs.3.rs-258868/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-258868/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eImpact of recurrent pericarditis (RP) on patient health-related quality of life (HRQoL) was evaluated through qualitative patient interviews and as an exploratory endpoint in a Phase 2 trial evaluating the efficacy and safety of rilonacept (IL-1α/IL-1β blocker) to treat RP.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eQualitative interviews were conducted with ten adults with RP to understand symptoms and HRQoL impacts, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS Global) v1.2 was evaluated to determine questionnaire coverage of patient experience. The Phase 2 trial enrolled participants with active symptomatic RP (A-RP, n=16) and corticosteroid-dependent participants with no active recurrence at baseline (CSD-RP, n=9). All participants received rilonacept weekly for 6 weeks during a base treatment period (TP) plus an optional 18-week extension period (EP). Concomitant medications, including corticosteroids (CS), were tapered, if possible, during EP. HRQoL was assessed using the PROMIS Global, and patient-reported pain and blood levels of c-reactive protein (CRP) were also collected at Baseline and follow-up periods. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e \u0026nbsp;Information from qualitative interviews demonstrated that PROMIS GH concepts are relevant to adults with RP. From the Phase 2 trial, both participant groups showed impacted HRQoL at Baseline [mean PROMIS Global Physical Health (GPH) and Global Mental Health (GMH), were lower than population norm average]. In A-RP, GPH/MPH improved by end of base TP and were sustained through EP (similar trends were observed for pain and CRP). Similarly, in CSD-RP, GPH/MPH improved by end of TP and further improved at EP, during CS tapering or discontinuation,\u0026nbsp;without disease recurrence (low pain scores and CRP levels continued during the TP and EP). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This is the first study demonstrating impaired HRQoL in RP. Rilonacept treatment was associated with HRQoL improvements using PROMIS GH scores. Maintained/improved HRQoL during tapering/withdrawal of CS without recurrence suggests that rilonacept may provide an alternative to corticosteroids. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTrial Registration: \u003c/strong\u003eClinicalTrials.Gov; NCT03980522; 5 June 2019, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03980522\u003c/p\u003e","manuscriptTitle":"Health-related Quality of Life in Patients With Recurrent Pericarditis: Results From a Phase 2 Study of Rilonacept","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-03-01 15:27:04","doi":"10.21203/rs.3.rs-258868/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2021-03-09T00:00:00+00:00","index":1,"fulltext":"Recommendation: Accept without revision\nForm responses:\n---\n\nComments to Author:\n---\nThe manuscript is appropriate for publication now* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons after the final decision on the manuscript has been made. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **no**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"decision","content":"Major revision","date":"2021-03-09T00:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-03-08T00:00:00+00:00","index":2,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nThis paper is an important publication for the pericarditis field describing the quality of life effects for patients with pericarditis and how those factors improve with symptom improvement. Below are comments for improvement of the publication.\n\nIntroduction: Additional information is needed in the introduction for rilonacept. There is currently no description or information such as other trials, other uses and mechanisms/predicted outcomes\nMethods: If the publication describing the trail is not published and not able to be referenced then the full trail information must be described\nMethods: Further describe why the two groups are distinct (A-RP and CSD-RP)\nTable 1: The actual questions asked leading to the qualitative example answers should be documents with each example answer in addition to what question on PROMIS the answers correlate to\nTable 1: Questions described in methods should be included with examples in the table\nTables: Abbreviations used in each table should be included in the legend for the table (example: CRP or NSAID)\nTable 3: Include the information on the scale range for each of the items in the table legend\nFigure legends: Explanation of the figure legends are needed. Currently the figure legends are just a title of the figure. Additional description of the figure and methods is needed to fully comprehend the figures.\nFigure 2: Improve the figure's appearance by removing the box around the figure\nFigure 2: Standard deviations need to be added to the figure\nFigure 2: Comparison to the population normal score needs to be displayed including with standard deviations to allow statical comparison between population normal score, A-RP and CSD-RP.\nData: Qualitative results that are discussed in results should also be in tables. This includes what symptoms these patients had and what percent of the patients had each symptom\nData: All data needs to be compared to the US standard (average and sd is provided in text but no statistical analysis is preformed to compare the results from these patient populations to the normal standard.\nData: There are no statistical measures in the data. Results of improvement are discussed but this improvement is not measured statistically. Comparisons are needed between baseline and follow up measures to show improvement.\nData: Comparisons statistically are also needed between the two populations of patients\nData: Correlation analysis is needed between CRP and scores as well as pain measure and scores is needed. Currently the results are discussed in the paper but no statistical comparisons are made and the data is not graphed\nReferences: Additional references are needed from 2020 and 2021. The last reference is from 2019\nReferences: Additional references are needed in introduction especially the first paragraph\n\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons after the final decision on the manuscript has been made. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **No**\n* Are the methods sufficiently described to allow the study to be repeated?: **No**\n* Is the use of statistics and treatment of uncertainties appropriate?: **No**\n* Is the presentation of the work clear?: **No**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorInvitedReview","content":"","date":"2021-03-01T00:00:00+00:00","index":4,"fulltext":"Recommendation: Reviewer's comments unavailable pending editorial decision\n"},{"type":"editorInvitedReview","content":"","date":"2021-03-01T00:00:00+00:00","index":3,"fulltext":"Recommendation: Accept after discretionary revisions\nForm responses:\n---\n\nComments to Author:\n---\nThis was a study to evaluate the impact of a rilanocept treatment on the HRQoL assessment of patients with recurrent pericarditis in a Phase 2 trial. The study design was appropriate - a descriptive cohort study.\nIt is a novel study in this field.\n\nIt consists of a qualitative and quantitative arm of assessment of impact. The qualitative arm was to evaluate the treatment outcomes relevant to the patients with a view to determine if the HRQoL assessment tool would measure the right outcomes. The HRQoL assessment tool was the PROMIS GH which was used to assess QoL in two major domains : physical health domain and mental health.\n\nThe aims and objective were met.\nMinor Comments\nWere there any real differences between the A - RP group and CSD-RP group in terms of the impact of therapy on the HRQoL. I think it would be important to see these differences (or lack there of) given the clinical presentation* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). 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For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **declare that I have no competing interests.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2021-02-26T00:00:00+00:00","index":4,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-02-23T00:00:00+00:00","index":3,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-02-22T00:00:00+00:00","index":2,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-02-20T00:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-02-20T00:00:00+00:00","index":1,"fulltext":""},{"type":"editorAssigned","content":"","date":"2021-02-19T00:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-02-18T23:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-02-18T23:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2021-02-04T00:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3741a32e-f438-4e49-9fa0-2da5c052bb3c","owner":[],"postedDate":"March 1st, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":2662567,"name":"Cardiac \u0026 Cardiovascular Systems"}],"tags":[],"updatedAt":"2021-08-18T19:47:08+00:00","versionOfRecord":{"articleIdentity":"rs-258868","link":"https://doi.org/10.1186/s12872-021-02008-3","journal":{"identity":"bmc-cardiovascular-disorders","isVorOnly":false,"title":"BMC Cardiovascular Disorders"},"publishedOn":"2021-04-21 19:07:10","publishedOnDateReadable":"April 21st, 2021"},"versionCreatedAt":"2021-03-01 15:27:04","video":"","vorDoi":"10.1186/s12872-021-02008-3","vorDoiUrl":"https://doi.org/10.1186/s12872-021-02008-3","workflowStages":[]},"version":"v1","identity":"rs-258868","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-258868","identity":"rs-258868","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}