Efficacy and safety of tofacitinib treatment in Finnish patients with juvenile idiopathic arthritis: A real-life study

Efficacy and safety of tofacitinib treatment in Finnish patients with juvenile idiopathic arthritis: A real-life study | 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 Efficacy and safety of tofacitinib treatment in Finnish patients with juvenile idiopathic arthritis: A real-life study Tiina Levälampi, Katariina Rebane, Katriina Mikola, Hannu Kautiainen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6827548/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Oct, 2025 Read the published version in Arthritis Research & Therapy → Version 1 posted 11 You are reading this latest preprint version Abstract Background Tofacitinib (TOFA), a newly introduced Janus kinase inhibitor, has been approved for the treatment of juvenile idiopathic arthritis (JIA). In this real-life study, we describe the effectiveness of TOFA treatment as well as possible interruptions and the reasons for discontinuations among all consecutive JIA patients who started TOFA treatment. Methods We reported data from 53 JIA patients from the catchment area of the Helsinki University Hospital who consecutively started TOFA treatment between February 2022 and October 2024. Physicians evaluated the patients’ disease activity and treatment efficacy at each visit. Disease activity was assessed using Juvenile Arthritis Disease Activity Score 10 (JADAS10). Results The majority of patients (96%) started TOFA due to active disease following previous treatment failure. Both JADAS10 scores and the patients’ active joint counts decreased significantly during the first 3 months of TOFA treatment. The Kaplan–Meier estimate indicated a 30% discontinuation of TOFA treatment during the 12-month follow-up period. Conclusion In this real-life study involving 53 JIA patients, TOFA treatment was initiated consecutively and demonstrated effectiveness after 3 months, with no serious side effects reported. Juvenile idiopathic arthritis janus kinase inhibitors tofacitinib Figures Figure 1 Figure 2 Figure 3 Background Juvenile idiopathic arthritis (JIA) encompasses a heterogeneous group of chronic inflammatory arthritis with unknown origin in children who present with onset before the age of 16 ( 1 ). This condition is the most common rheumatic disease in childhood, with a global prevalence ranging from 16 to 150 cases per 100,000. Different subtypes are characterised by various clinical features and distributed frequencies ( 2 ). The most common forms of JIA are oligoarthritis and rheumatoid-factor negative polyarthritis (RF-negative polyarthritis), with a lower prevalence of systemic arthritis, rheumatoid factor-positive polyarthritis, enthesitis-related arthritis, psoriatic arthritis and undifferentiated arthritis ( 2 ). Due to the nature of JIA, treatment approaches vary among different clinical phenotypes ( 3 , 4 ). According to the recommendation of the American College of Rheumatology (ACR), conventional synthetic disease-modifying antirheumatic drugs (csDMARD), most commonly methotrexate, are typically the first-line treatment for JIA patients with active disease ( 3 , 4 ). Although methotrexate is effective and generally well tolerated among JIA patients ( 5 ), a significant number do not achieve remission or struggle with tolerance, necessitating the addition of biological disease-modifying antirheumatic drugs (bDMARD), particularly tumor necrosis factor inhibitors, as recommended ( 3 , 4 ). While bDMARDs are effective, a considerable proportion of JIA patients still discontinue treatment due to active disease ( 6 ). Furthermore, adverse events (AE) and, in some cases, injection anxiety lead to discontinuation of the medication and a need to switch to alternative bDMARD treatments ( 7 ). Janus kinase inhibitors (JAKis), which belong to the class of targeted synthetic DMARDs, are small oral synthetic molecules that increase the production of an inflammatory cytokine through direct cytoplasmic effects on the JAK/STAT signalling pathway ( 8 , 9 ). JAKis have been successfully used in treating adult rheumatoid arthritis (RA), either as monotherapy ( 10 ) or in combination with methotrexate or other csDMARDs ( 11 , 12 ). The recently introduced JAKi, tofacitinib (TOFA) (a JAK1/JAK3 inhibitor), was approved by the European Medicines Agency in August 2021 for patients with polyarticular JIA or juvenile psoriatic arthritis ( 13 ). After establishing the pharmacokinetic and safety profile of TOFA in JIA patients ( 14 ), a randomized clinical trial involving 225 patients with TOFA demonstrated its effectiveness and safety in treating JIA ( 15 ). After two years of follow-up, JIA patients treated with TOFA continued to respond to treatment ( 16 ). In the present real-life study, we describe all JIA patients who were compelled to discontinue their previous drug treatments due to poor responses and who subsequently started TOFA treatment. Our focus is on the effectiveness and discontinuation of TOFA treatment and the reasons for discontinuation. Methods Patients and methods In this observational retrospective real-life study, all consecutive patients with the polyarticular type of JIA who had failed their previous medication and were under 16 years of age started treatment with TOFA between February 2022 and October 2024. There were no exclusions. All patients were from the Helsinki University Hospital catchment area. Patients were evaluated by their physicians at the commencement of TOFA and then at three-, six- and 12-month intervals. Disease activity was evaluated at each visit using the patient/parent global assessment of well-being (PaGA) and the physician’s global assessment (PhGA) on a 10-cm visual analogue scale (VAS), along with the number of active joints and inflammation markers (erythrocyte sedimentation rate [ESR] and C reactive protein [CRP]). As a result of these parameters, disease activity was calculated using the Juvenile Arthritis Disease Activity Score (JADAS10) or clinical JADAS10 (cJADAS10), where cJADAS10 is a modified and validated version of JADAS10, excluding ESR ( 17 ). The cut-off values of JADAS10 in a polyarticular disease were as follows: a JADAS10 score of 0–0.7 indicated inactive disease, 0.8–3.9 indicated low disease activity (LDA) and ≥ 4.0 indicated moderate disease activity (MDA) ( 18 ). All patients started TOFA twice daily according to the pharmaceutical company’s instructions, with a weight-based dose: patients weighing 10–20 kg received 6.3 mg per day, patients weighing 20–40 kg received 8 mg per day and patients weighing over 40 kg received 10 mg per day ( 19 ). Concomitant drug treatments, including oral and intra-articular glucocorticoids and DMARDs, were documented as were the reasons for discontinuation (inefficiency, AE, and poor compliance). Ethics This register-based study was conducted by collecting clinical data from patient records. Therefore, according to Finnish legislation, no ethical committee approval or informed consent was required. The Helsinki University Hospital granted permission to collect patient data. Statistics The descriptive statistics were presented as means with standard deviation (SD), and range, or as counts with percentages. Repeated measures were analyzed using generalizing estimating equations (GEE) models with the appropriate distribution and link function and with the unstructured correlation structure. Kaplan-Meier method was used to estimate the cumulative mort Discontinuation of TOFA treatment. In the case of violation of the assumptions (e.g. non-normality) for continuous variables, a bootstrap-type method or Monte Carlo p-values (small number of observations) for categorical variables were used. The normality of variables was evaluated graphically (diagnostic plots) and using the Shapiro–Wilk test. Stata 18.0 (StataCorp LP; College Station, Texas, USA) statistical package was used for the analysis. Results The data of the 53 patients with JIA who started TOFA treatment, of whom 41 (77%) were female and 12 (23%) were male, were analysed at the 12-month follow-up. At the start of TOFA treatment, the mean age of the JIA patients was 11 years (range 3–16 years) and the mean disease duration was 7 years (range 1–15 years). Of these 53 JIA patients, 26 patients (49%) had rheumatoid factor-negative polyarthritis, 17 patients (32%) had extended oligoarthritis, five patients (9%) had psoriatic arthritis, three patients (6%) had undifferentiated arthritis, one patient (2%) had enthesitis-related arthritis, and one patient (2%) had rheumatoid factor-positive polyarthritis. The mean TOFA dose was 0.25 [0.12–0.45] mg/kg. At the start of TOFA treatment, two of the 53 patients had active uveitis and were using dexamethasone sodium phosphate eye drops. One patient successfully discontinued the eye drops, while the other was allowed to reduce the dosage during TOFA treatment. A significant portion of the patients, 51 (96%), started TOFA due to active disease resulting from previous treatment failures. Two patients (4%) initiated treatment due to MTX -induced nausea. Almost half of the patients, 25 (47%), had previously received bDMARD medication. Etanercept was the most commonly used bDMARD prior to TOFA (12 patients), followed by infliximab, adalimumab, golimumab and tocilizumab. Seven patients had been treated with several bDMARDs before starting TOFA. Most patients continued concomitant medications during TOFA treatment: 24 patients (45%) used MTX, 14 patients (26%) used prednisolone, five patients (9%) used leflunomide and one patient (2%) used mycophenolate. Nineteen patients (30%) used TOFA as monotherapy without any concomitant medication. At the start of TOFA treatment, the mean active joint count (AJC) was 3.5 (range 0–16), the mean patient global assessment of well-being (PaGA) was 26 (range 0–99), the mean physician global assessment of disease activity (PhGA) was 21 (range 0–76), the mean ESR was 16 mm/h (range 2–97), the mean CRP was 9 mg/l (range 1–126), the mean juvenile JADAS10 was 8.4 (range 0–24.2), and the mean cJADAS10 was 7.8 (range 0–20.3). Data at the start of TOFA treatment are shown in Table 1 . Table 1 Clinicodemographic characteristics of 53 patients at the beginning of TOFA treatment. Variable Measures Female, n (%) 41 (77) Age, years, mean (SD) [Range] 11.2 (3.3) [3–16] Disease duration, years, mean (SD) [Range] 7.4 (4.0) [1–15] Height, cm, mean (SD) [Range] 145 ( 20 ) [97–180] Weight, kg, mean (SD) [Range] 41 ( 17 ) [14–81] Diagnose, n (%) Psoriatic arthritis 5 ( 9 ) Undifferentiated arthritis 3 ( 6 ) Enthesitis related arthritis 1 ( 2 ) Polyarthritis, RF-positive 1 ( 2 ) Polyarthritis, RF-negative 26 (49) Oligoarthritis, extended 17 (32) Reason to start TOFA, n (%) Active disease (JADAS10 > 0.7) 51 (96) Other reason 2 ( 4 ) Previous bDMARD, n (%) 25 (47) Concomitant medication, n (%) None 19 (36) Prednisolone 14 (25) Methotrexate 24 (45) Leflunomide 5 ( 9 ) Mycophenolate 1 ( 2 ) AJC, mean (SD) [Range] 3.5 (3.5) [0–16] PaGA, mean (SD) [Range] 26 (26) [0–99] PhGA, mean (SD) [Range] 21 ( 15 ) [0 − 76] ESR (mm/h), mean (SD) [Range] 16 ( 20 ) [2–97] CRP (mg/l), mean (SD) [Range] 9 ( 22 ) [1–126] JADAS10 8.4 (5.9) [0–24.2] cJADAS10 7.8 (5.2) [0–20.3] TOFA: tofacitinib, RF: rheumatoid factor, JADAS10: Juvenile Arthritis Disease Activity Score 10, bDMARD: biological disease-modifying antirheumatic drug, AJC: active joint count, PaGA: patient global assessment of well-being, PhGA: physician global assessment of disease activity, ESR: erythrocyte sedimentation rate, CRP: C-reactive protein, cJADAS10: clinical Juvenile Arthritis Disease Activity Score 10 Disease activity as assessed by JADAS10 decreased most significantly at the three-month follow-up with a change of -4.4 (95% CI: -6.0–2.8) and continued to decrease at the 12-month follow-up with a change of -6.4 (95% CI: -8.1 – -4.7) (Fig. 1 A). After three months of TOFA treatment, 27% (95% CI: 15–40) of JIA patients had inactive disease (Fig. 1 B). Patients’ AJC decreased most significantly during the first 3 months by -1.8 (2.8 – -0.8) and continued to decrease until the 12-month visit with an overall change of -2.6 (-3.4 – -1.8) (Fig. 2 A). PhGA decreased steadily during the one-year follow-up -17 (-23 – -10), with the most impressive reduction occurring during the first 3 months with a change of 13 (-17 – -9) (Fig. 2 B). During the 12-month follow-up, the Kaplan–Meier estimate for discontinuation of TOFA treatment was 30% (Fig. 3 ). In total, 12 patients (23%) discontinued treatment during the one-year follow-up period (Fig. 3 ). Of these, six patients (11%) had an insufficient clinical response, and two patients (4%) had poor compliance with TOFA (Fig. 3 ). Four patients (7%) experienced AEs: one patient discontinued treatment due to recurrent migraines and another due to facial eczema (Fig. 3 ). Both AEs resolved after the discontinuation of TOFA treatment. In addition, two patients developed uveitis for the first time during TOFA treatment. In both patients, a 9-year-old girl and a 13-year-old boy, newly diagnosed uveitis occurred after 4 months of treatment with TOFA. After the diagnosis of uveitis, both patients were treated concomitantly with dexamethasone sodium phosphate eye drops without adequate response, and TOFA treatment had to be discontinued. Discussion To our knowledge, the present study is unique, as it represents real-life data of JIA patients treated with TOFA. The study included all paediatric JIA patients treated with TOFA from the Helsinki University Hospital catchment area. The decision to start TOFA treatment was made at the discretion of an experienced paediatric rheumatologist rather than as a randomised enrolment in a clinical trial, thereby providing data on the outcomes of TOFA treatment in everyday practice. Response to TOFA treatment is usually evident after 2 weeks of treatment, when over 50% of JIA patients have been reported to achieve at least a JIA/ACR30 response ( 15 ). A rapid response was also seen in adult patients with RA after 2 weeks of TOFA treatment with significant improvement in physical function, and after 3 months of treatment, 20% of patients had significant improvement in arthritis and met the ACR70 criteria ( 10 ). Our results show a similar trend and are even more promising for achieving remission. In the present study, the most pronounced effect of TOFA was seen after 3 months of treatment, with more than 50% improvement in JADAS10 at 3 months and continuing. According to the Finnish National Consensus and the Social Insurance Institution of Finland (KELA) ( 20 ), the criteria for starting treatment with TOFA as monotherapy or in combination with csDMARDs are that the patient has severe and refractory disease despite active drug treatment. In the present study, the majority of paediatric JIA patients were started TOFA due to active disease despite ongoing drug treatment and almost half of the patients were on a bDMARD prior to TOFA, whereas Ruperto et al reported that 38% of patients starting TOFA had prior bDMARD exposure. The concurrent use of MTX during TOFA treatment is notable; in Ruperto et al’s study ( 15 ), 65% of patients used concomitant MTX, compared to 45% in the present study. In an adult real-life study involving RA patients, 50% were treated with concomitant MTX ( 21 ). Previous studies have shown that oral glucocorticoids are commonly used, especially at the beginning of TOFA treatment. In the studies by Ruperto et al ( 15 ) and Brunner et al. ( 16 ), 32% and 45% of patients used oral glucocorticoids, respectively. In our study, 25% of the patients used oral glucocorticoids at the start of TOFA. It remains unclear whether the higher proportion of patients on concomitant MTX in study by Ruperto et al. ( 15 ) accounts for the lower use of oral glucocorticoids compared to our findings. It is possible that the patients in our study had milder disease or that intra-articular injections were preferred over oral glucocorticoids. In our study, patients who achieved low disease activity continued TOFA treatment after a 12-month follow-up. Ruperto et al. ( 15 ) reported that 26% of patients with JIA reached inactive disease and 4% attained clinical remission after 44 weeks of TOFA treatment. In a study of adult patients with JIA, three of the nine patients received TOFA and reached remission after 3 months ( 22 ). In a real-life study of RA patients treated with JAKis, 26 of 54 patients continued treatment with a median duration of 23.5 months ( 21 ). Safety data from Brunner et al ( 16 ) indicated that 13% of JIA patients permanently discontinued TOFA treatment and 37% temporarily discontinued or reduced their dose. In the present study, AEs leading to discontinuation occurred in 7.5% of patients during the one-year follow-up, with no patients discontinuing treatment due to infections. Although varicella-zoster infections have been reported during TOFA treatment in both paediatric and adult patients ( 16 , 23 ), our study found no cases of varicella-zoster infections. In Finland, the varicella vaccine is included in the national vaccination programme for children. Uveitis is the most common and potentially serious extra-articular manifestation in JIA and presents a treatment challenge. Brunner et al ( 16 ) reported two patients who developed uveitis during TOFA treatment; both resolved and continued TOFA with no change in dose. In the present study, we also diagnosed two new cases of uveitis during TOFA treatment, but both patients had to discontinue TOFA due to persistent uveitis activity. We also started TOFA in two JIA patients with active uveitis at the start of the treatment, and they successfully continued TOFA treatment with favourable effects on both arthritis and uveitis. In a study of adult JIA patients, uveitis was diagnosed prior to TOFA treatment in five patients, two of whom had active uveitis. All patients survived 3 months of follow-up without relapse, and patients with active uveitis were able to discontinue topical corticosteroid therapy ( 22 ). A case report of patients treated with TOFA for JIA-associated uveitis has been published ( 24 ), but more comprehensive data are lacking and further studies are needed. The strength of our study is that it represents all consecutive patients who were assigned to TOFA as soon as possible in terms of official reimbursement for paediatric patients with JIA in Finland. Although our cohort of 53 JIA patients is smaller than the 225 patients from multicentre studies, they were sourced from the defined catchment area of Helsinki University Hospital. There are limitations to consider; this study was register-based, clinical data were collected retrospectively from patients’ records and the number of patients was limited. However, this type of data provides valuable real-life insights for clinicians. Conclusions In conclusion, this real-life study of JIA patients indicates that TOFA treatment appears effective after 3 months, with no serious side effects reported. Abbreviations JIA Juvenile idiopathic arthritis RF rheumatoid factor ACR American College of Rheumatology csDMARD conventional synthetic disease modifying antirheumatic drugs MTX methotrexate bDMARD biological disease modifying antirheumatic drugs AE adverse event JAKi Janus kinase inhibitor TOFA tofacitinib tDMARDs targeted synthetic VAS visual analogue scale ESR erythrocyte sedimentation rate CRP C reactive protein JADAS10 Juvenile Arthritis Disease Activity Score or clinical JADAS10 cJADAS10 clinical JADAS10 LDA low disease activity MDA moderate disease activity PaGA Patient Global Assessment PhGA Physician Global Assessment IDA Inactive Disease Activity Declarations Ethics approval and consent to participate This retrospective study is based on clinical data of JIA patients collected from patient records and from Finnish Rheumatology Quality Register. Therefore, according to Finnish legislation, there was no need of approval by an ethical committee. Consent for publication Not applicable. Availability of data and materials All data generated or analyzed during this study are included in this published article. Competing interests The authors have no competing of interest to declare. Funding Part time Government Research Funding was received by Tiina Levälampi, Katariina Rebane, Katriina Mikola, and Kristiina Aalto Open Access funding provided by the University of Helsinki (including Helsinki University Central Hospital) Author contributions All the authors (Tiina Levälampi, Katariina Rebane, Katriina Mikola, Hannu Kautiainen and Kristiina Aalto) participated in designing the study and participated in statistical analysis and interpretation of data, and in drafting and revising the final version. Tiina Levälampi has written the first draft of the manuscript. Tiina Levälampi, Katariina Rebane, Katriina Mikola and Kristiina Aalto participated in collecting the data. Hannu Kautiainen participated in designing the research and analyzing the data. The final manuscript has been read and approved by all the authors, and they all have given necessary attention to ensure the integrity of the work. Acknowledgements Heini Pohjankoski, Department of Pediatrics, Päijät-Häme Central Hospital, Lahti, Finland Author information Tiina Levälampi, New Children’s Hospital, University of Helsinki, Helsinki University Hospital, Stenbäckinkatu 9, 00290 Helsinki, Finland. Corresponding author. E-mail: [email protected] Katariina Rebane, New Children’s Hospital, University of Helsinki, Helsinki University Hospital, Stenbäckinkatu 9, 00290 Helsinki, Finland. E-mail: [email protected] Katriina Mikola, New Children’s Hospital, University of Helsinki, Helsinki University Hospital, Stenbäckinkatu 9, 00290 Helsinki, Finland. E-mail: [email protected] . Hannu Kautiainen: Primary Health Care Unit, Kuopio University Hospital, Kuopio, Finland; Folkhälsan Research Center, Helsinki, Finland. E-mail: [email protected] Kristiina Aalto, New Children’s Hospital, University of Helsinki, Helsinki University Hospital, Stenbäckinkatu 9, 00290 Helsinki, Finland. E-mail: [email protected] . References Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–2. Ravelli A, Martini A. Juvenile idiopathic arthritis. The Lancet. 2007;369(9563):767–78. Ringold S, Angeles-Han ST, Beukelman T, Lovell D, Cuello CA, Becker ML, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Rheumatol. 2019;71(6):846–63. 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Cite Share Download PDF Status: Published Journal Publication published 31 Oct, 2025 Read the published version in Arthritis Research & Therapy → Version 1 posted Editorial decision: Revision requested 16 Jul, 2025 Reviews received at journal 16 Jul, 2025 Reviews received at journal 14 Jul, 2025 Reviews received at journal 11 Jul, 2025 Reviewers agreed at journal 26 Jun, 2025 Reviewers agreed at journal 25 Jun, 2025 Reviewers agreed at journal 24 Jun, 2025 Reviewers invited by journal 23 Jun, 2025 Editor assigned by journal 10 Jun, 2025 Submission checks completed at journal 10 Jun, 2025 First submitted to journal 05 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-6827548","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":475844080,"identity":"771bfc4b-0237-417e-9476-61a1b3605bf9","order_by":0,"name":"Tiina Levälampi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYDACZsYGIGkBYoEYEnIGINEKA9w6eCBaJIAYwjAGKz6DTwuEgmthSNwA1oLHXfbszG0PfoDcc/xg46ebOyzSt0ukP2A4UIDXYe2GPSD3nElsls49I5G7c0aOAcMB/H5pk+BhkEic2ZDYIJ3bJpG74UYOA/MHAlok/zBI1M/sf9j8G6gl3eAGyGEEtEgDbUngl0hsA9mSYHAjgYDDDgO1yBhIGPZLPGyzBvrFcMOZNwYH8Glh7z/+TPJNhY08G3/y4du5O+rkDY6nP3xw4A9uLRAAMxMSNQwMBwhpQACYllEwCkbBKBgFyAAA+/hMnmM3Ja4AAAAASUVORK5CYII=","orcid":"","institution":"New Children’s Hospital, University of Helsinki, Helsinki University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Tiina","middleName":"","lastName":"Levälampi","suffix":""},{"id":475844081,"identity":"4b2e722d-805c-4abd-9f51-822b426ad00a","order_by":1,"name":"Katariina Rebane","email":"","orcid":"","institution":"New Children’s Hospital, University of Helsinki, Helsinki University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Katariina","middleName":"","lastName":"Rebane","suffix":""},{"id":475844082,"identity":"256fe025-4287-4314-94a8-ccfad6b0c3a5","order_by":2,"name":"Katriina Mikola","email":"","orcid":"","institution":"New Children’s Hospital, University of Helsinki, Helsinki University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Katriina","middleName":"","lastName":"Mikola","suffix":""},{"id":475844083,"identity":"00e25b8c-fa3c-413f-a2c2-e828766bd0b3","order_by":3,"name":"Hannu Kautiainen","email":"","orcid":"","institution":"Kuopio University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hannu","middleName":"","lastName":"Kautiainen","suffix":""},{"id":475844084,"identity":"67bedc90-34f9-414c-a476-0b9cbe2aaead","order_by":4,"name":"Kristiina Aalto","email":"","orcid":"","institution":"New Children’s Hospital, University of Helsinki, Helsinki University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kristiina","middleName":"","lastName":"Aalto","suffix":""}],"badges":[],"createdAt":"2025-06-05 09:23:41","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6827548/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6827548/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13075-025-03669-7","type":"published","date":"2025-10-31T15:57:05+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":85617074,"identity":"69825b5c-0edc-41cc-bc74-fb938a932405","added_by":"auto","created_at":"2025-06-29 14:43:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":15182,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA)\u003c/strong\u003e Disease activity During TOFA treatment was assessed by JADAS10 (Juvenile Arthritis Disease Activity Score 10). Dashed lines demonstrates the score thresholds for JADAS disease activity: area above upper dashed line represent moderate disease activity (MDA), area between upper and lower dashed line represent low disease activity (LDA) and area below lower dashed line represent inactive disease activity (IDA) (18). \u003cstrong\u003eB)\u003c/strong\u003e Proportion of the JIA patients with inactive disease increased most evidently during first three months.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6827548/v1/e97fbac948ee06a5c9de6614.png"},{"id":85617081,"identity":"b3297462-8a5e-4ee4-92b1-6f130ca39425","added_by":"auto","created_at":"2025-06-29 14:43:58","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":11778,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA)\u003c/strong\u003eActive joint count (AJC) diminished during 12 months. \u003cstrong\u003eB)\u003c/strong\u003e Physician Global Assessment (PhGA) measured by 10 cm visual analogue scale (VAS) improved during 12 months.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6827548/v1/f930600a8b30f58e688b3e17.png"},{"id":85617075,"identity":"44c6223b-638f-4e89-bc7f-d59daec2e1ad","added_by":"auto","created_at":"2025-06-29 14:43:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":21335,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier estimate for discontinuation of TOFA treatment was 30% (95%CI: 17,7 to 47,6).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6827548/v1/04318f7774ca4d7268a360d4.png"},{"id":95039858,"identity":"ee798619-1895-40c4-8cbd-1cba8a227242","added_by":"auto","created_at":"2025-11-03 16:04:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":554566,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6827548/v1/c762259d-7dfc-4c7d-8b35-abf81c37c84c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy and safety of tofacitinib treatment in Finnish patients with juvenile idiopathic arthritis: A real-life study","fulltext":[{"header":"Background","content":"\u003cp\u003eJuvenile idiopathic arthritis (JIA) encompasses a heterogeneous group of chronic inflammatory arthritis with unknown origin in children who present with onset before the age of 16 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). This condition is the most common rheumatic disease in childhood, with a global prevalence ranging from 16 to 150 cases per 100,000. Different subtypes are characterised by various clinical features and distributed frequencies (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The most common forms of JIA are oligoarthritis and rheumatoid-factor negative polyarthritis (RF-negative polyarthritis), with a lower prevalence of systemic arthritis, rheumatoid factor-positive polyarthritis, enthesitis-related arthritis, psoriatic arthritis and undifferentiated arthritis (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDue to the nature of JIA, treatment approaches vary among different clinical phenotypes (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). According to the recommendation of the American College of Rheumatology (ACR), conventional synthetic disease-modifying antirheumatic drugs (csDMARD), most commonly methotrexate, are typically the first-line treatment for JIA patients with active disease (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Although methotrexate is effective and generally well tolerated among JIA patients (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), a significant number do not achieve remission or struggle with tolerance, necessitating the addition of biological disease-modifying antirheumatic drugs (bDMARD), particularly tumor necrosis factor inhibitors, as recommended (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). While bDMARDs are effective, a considerable proportion of JIA patients still discontinue treatment due to active disease (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Furthermore, adverse events (AE) and, in some cases, injection anxiety lead to discontinuation of the medication and a need to switch to alternative bDMARD treatments (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eJanus kinase inhibitors (JAKis), which belong to the class of targeted synthetic DMARDs, are small oral synthetic molecules that increase the production of an inflammatory cytokine through direct cytoplasmic effects on the JAK/STAT signalling pathway (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). JAKis have been successfully used in treating adult rheumatoid arthritis (RA), either as monotherapy (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) or in combination with methotrexate or other csDMARDs (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe recently introduced JAKi, tofacitinib (TOFA) (a JAK1/JAK3 inhibitor), was approved by the European Medicines Agency in August 2021 for patients with polyarticular JIA or juvenile psoriatic arthritis (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). After establishing the pharmacokinetic and safety profile of TOFA in JIA patients (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), a randomized clinical trial involving 225 patients with TOFA demonstrated its effectiveness and safety in treating JIA (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). After two years of follow-up, JIA patients treated with TOFA continued to respond to treatment (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn the present real-life study, we describe all JIA patients who were compelled to discontinue their previous drug treatments due to poor responses and who subsequently started TOFA treatment. Our focus is on the effectiveness and discontinuation of TOFA treatment and the reasons for discontinuation.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003ePatients and methods\u003c/p\u003e \u003cp\u003eIn this observational retrospective real-life study, all consecutive patients with the polyarticular type of JIA who had failed their previous medication and were under 16 years of age started treatment with TOFA between February 2022 and October 2024. There were no exclusions. All patients were from the Helsinki University Hospital catchment area. Patients were evaluated by their physicians at the commencement of TOFA and then at three-, six- and 12-month intervals. Disease activity was evaluated at each visit using the patient/parent global assessment of well-being (PaGA) and the physician\u0026rsquo;s global assessment (PhGA) on a 10-cm visual analogue scale (VAS), along with the number of active joints and inflammation markers (erythrocyte sedimentation rate [ESR] and C reactive protein [CRP]). As a result of these parameters, disease activity was calculated using the Juvenile Arthritis Disease Activity Score (JADAS10) or clinical JADAS10 (cJADAS10), where cJADAS10 is a modified and validated version of JADAS10, excluding ESR (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The cut-off values of JADAS10 in a polyarticular disease were as follows: a JADAS10 score of 0\u0026ndash;0.7 indicated inactive disease, 0.8\u0026ndash;3.9 indicated low disease activity (LDA) and \u0026ge;\u0026thinsp;4.0 indicated moderate disease activity (MDA) (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAll patients started TOFA twice daily according to the pharmaceutical company\u0026rsquo;s instructions, with a weight-based dose: patients weighing 10\u0026ndash;20 kg received 6.3 mg per day, patients weighing 20\u0026ndash;40 kg received 8 mg per day and patients weighing over 40 kg received 10 mg per day (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Concomitant drug treatments, including oral and intra-articular glucocorticoids and DMARDs, were documented as were the reasons for discontinuation (inefficiency, AE, and poor compliance).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEthics\u003c/h2\u003e \u003cp\u003eThis register-based study was conducted by collecting clinical data from patient records. Therefore, according to Finnish legislation, no ethical committee approval or informed consent was required. The Helsinki University Hospital granted permission to collect patient data.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStatistics\u003c/h3\u003e\n\u003cp\u003eThe descriptive statistics were presented as means with standard deviation (SD), and range, or as counts with percentages. Repeated measures were analyzed using generalizing estimating equations (GEE) models with the appropriate distribution and link function and with the unstructured correlation structure. Kaplan-Meier method was used to estimate the cumulative mort Discontinuation of TOFA treatment. In the case of violation of the assumptions (e.g. non-normality) for continuous variables, a bootstrap-type method or Monte Carlo p-values (small number of observations) for categorical variables were used. The normality of variables was evaluated graphically (diagnostic plots) and using the Shapiro\u0026ndash;Wilk test. Stata 18.0 (StataCorp LP; College Station, Texas, USA) statistical package was used for the analysis.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe data of the 53 patients with JIA who started TOFA treatment, of whom 41 (77%) were female and 12 (23%) were male, were analysed at the 12-month follow-up. At the start of TOFA treatment, the mean age of the JIA patients was 11 years (range 3\u0026ndash;16 years) and the mean disease duration was 7 years (range 1\u0026ndash;15 years). Of these 53 JIA patients, 26 patients (49%) had rheumatoid factor-negative polyarthritis, 17 patients (32%) had extended oligoarthritis, five patients (9%) had psoriatic arthritis, three patients (6%) had undifferentiated arthritis, one patient (2%) had enthesitis-related arthritis, and one patient (2%) had rheumatoid factor-positive polyarthritis. The mean TOFA dose was 0.25 [0.12\u0026ndash;0.45] mg/kg. At the start of TOFA treatment, two of the 53 patients had active uveitis and were using dexamethasone sodium phosphate eye drops. One patient successfully discontinued the eye drops, while the other was allowed to reduce the dosage during TOFA treatment.\u003c/p\u003e \u003cp\u003eA significant portion of the patients, 51 (96%), started TOFA due to active disease resulting from previous treatment failures. Two patients (4%) initiated treatment due to MTX -induced nausea. Almost half of the patients, 25 (47%), had previously received bDMARD medication. Etanercept was the most commonly used bDMARD prior to TOFA (12 patients), followed by infliximab, adalimumab, golimumab and tocilizumab. Seven patients had been treated with several bDMARDs before starting TOFA. Most patients continued concomitant medications during TOFA treatment: 24 patients (45%) used MTX, 14 patients (26%) used prednisolone, five patients (9%) used leflunomide and one patient (2%) used mycophenolate. Nineteen patients (30%) used TOFA as monotherapy without any concomitant medication.\u003c/p\u003e \u003cp\u003eAt the start of TOFA treatment, the mean active joint count (AJC) was 3.5 (range 0\u0026ndash;16), the mean patient global assessment of well-being (PaGA) was 26 (range 0\u0026ndash;99), the mean physician global assessment of disease activity (PhGA) was 21 (range 0\u0026ndash;76), the mean ESR was 16 mm/h (range 2\u0026ndash;97), the mean CRP was 9 mg/l (range 1\u0026ndash;126), the mean juvenile JADAS10 was 8.4 (range 0\u0026ndash;24.2), and the mean cJADAS10 was 7.8 (range 0\u0026ndash;20.3). Data at the start of TOFA treatment are shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinicodemographic characteristics of 53 patients at the beginning of TOFA treatment.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeasures\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (77)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years, mean (SD) [Range]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.2 (3.3) [3\u0026ndash;16]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease duration, years, mean (SD) [Range]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.4 (4.0) [1\u0026ndash;15]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight, cm, mean (SD) [Range]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145 (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) [97\u0026ndash;180]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight, kg, mean (SD) [Range]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) [14\u0026ndash;81]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnose, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsoriatic arthritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUndifferentiated arthritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnthesitis related arthritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyarthritis, RF-positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyarthritis, RF-negative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOligoarthritis, extended\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReason to start TOFA, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eActive disease (JADAS10\u0026thinsp;\u0026gt;\u0026thinsp;0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther reason\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious bDMARD, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConcomitant medication, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (36)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrednisolone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethotrexate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeflunomide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycophenolate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAJC, mean (SD) [Range]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.5 (3.5) [0\u0026ndash;16]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaGA, mean (SD) [Range]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (26) [0\u0026ndash;99]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhGA, mean (SD) [Range]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) [0 \u0026minus;\u0026thinsp;76]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESR (mm/h), mean (SD) [Range]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) [2\u0026ndash;97]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/l), mean (SD) [Range]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) [1\u0026ndash;126]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJADAS10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.4 (5.9) [0\u0026ndash;24.2]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecJADAS10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.8 (5.2) [0\u0026ndash;20.3]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTOFA: tofacitinib, RF: rheumatoid factor, JADAS10: Juvenile Arthritis Disease Activity Score 10, bDMARD: biological disease-modifying antirheumatic drug, AJC: active joint count, PaGA: patient global assessment of well-being, PhGA: physician global assessment of disease activity, ESR: erythrocyte sedimentation rate, CRP: C-reactive protein, cJADAS10: clinical Juvenile Arthritis Disease Activity Score 10\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eDisease activity as assessed by JADAS10 decreased most significantly at the three-month follow-up with a change of -4.4 (95% CI: -6.0\u0026ndash;2.8) and continued to decrease at the 12-month follow-up with a change of -6.4 (95% CI: -8.1 \u0026ndash; -4.7) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). After three months of TOFA treatment, 27% (95% CI: 15\u0026ndash;40) of JIA patients had inactive disease (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatients\u0026rsquo; AJC decreased most significantly during the first 3 months by -1.8 (2.8 \u0026ndash; -0.8) and continued to decrease until the 12-month visit with an overall change of -2.6 (-3.4 \u0026ndash; -1.8) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). PhGA decreased steadily during the one-year follow-up -17 (-23 \u0026ndash; -10), with the most impressive reduction occurring during the first 3 months with a change of 13 (-17 \u0026ndash; -9) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eDuring the 12-month follow-up, the Kaplan\u0026ndash;Meier estimate for discontinuation of TOFA treatment was 30% (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In total, 12 patients (23%) discontinued treatment during the one-year follow-up period (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Of these, six patients (11%) had an insufficient clinical response, and two patients (4%) had poor compliance with TOFA (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Four patients (7%) experienced AEs: one patient discontinued treatment due to recurrent migraines and another due to facial eczema (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Both AEs resolved after the discontinuation of TOFA treatment. In addition, two patients developed uveitis for the first time during TOFA treatment. In both patients, a 9-year-old girl and a 13-year-old boy, newly diagnosed uveitis occurred after 4 months of treatment with TOFA. After the diagnosis of uveitis, both patients were treated concomitantly with dexamethasone sodium phosphate eye drops without adequate response, and TOFA treatment had to be discontinued.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, the present study is unique, as it represents real-life data of JIA patients treated with TOFA. The study included all paediatric JIA patients treated with TOFA from the Helsinki University Hospital catchment area. The decision to start TOFA treatment was made at the discretion of an experienced paediatric rheumatologist rather than as a randomised enrolment in a clinical trial, thereby providing data on the outcomes of TOFA treatment in everyday practice.\u003c/p\u003e \u003cp\u003eResponse to TOFA treatment is usually evident after 2 weeks of treatment, when over 50% of JIA patients have been reported to achieve at least a JIA/ACR30 response (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). A rapid response was also seen in adult patients with RA after 2 weeks of TOFA treatment with significant improvement in physical function, and after 3 months of treatment, 20% of patients had significant improvement in arthritis and met the ACR70 criteria (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Our results show a similar trend and are even more promising for achieving remission. In the present study, the most pronounced effect of TOFA was seen after 3 months of treatment, with more than 50% improvement in JADAS10 at 3 months and continuing.\u003c/p\u003e \u003cp\u003eAccording to the Finnish National Consensus and the Social Insurance Institution of Finland (KELA) (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), the criteria for starting treatment with TOFA as monotherapy or in combination with csDMARDs are that the patient has severe and refractory disease despite active drug treatment. In the present study, the majority of paediatric JIA patients were started TOFA due to active disease despite ongoing drug treatment and almost half of the patients were on a bDMARD prior to TOFA, whereas Ruperto et al reported that 38% of patients starting TOFA had prior bDMARD exposure. The concurrent use of MTX during TOFA treatment is notable; in Ruperto et al\u0026rsquo;s study (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), 65% of patients used concomitant MTX, compared to 45% in the present study.\u003c/p\u003e \u003cp\u003eIn an adult real-life study involving RA patients, 50% were treated with concomitant MTX (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Previous studies have shown that oral glucocorticoids are commonly used, especially at the beginning of TOFA treatment. In the studies by Ruperto et al (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) and Brunner et al. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), 32% and 45% of patients used oral glucocorticoids, respectively. In our study, 25% of the patients used oral glucocorticoids at the start of TOFA. It remains unclear whether the higher proportion of patients on concomitant MTX in study by Ruperto et al. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) accounts for the lower use of oral glucocorticoids compared to our findings. It is possible that the patients in our study had milder disease or that intra-articular injections were preferred over oral glucocorticoids.\u003c/p\u003e \u003cp\u003eIn our study, patients who achieved low disease activity continued TOFA treatment after a 12-month follow-up. Ruperto et al. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) reported that 26% of patients with JIA reached inactive disease and 4% attained clinical remission after 44 weeks of TOFA treatment. In a study of adult patients with JIA, three of the nine patients received TOFA and reached remission after 3 months (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). In a real-life study of RA patients treated with JAKis, 26 of 54 patients continued treatment with a median duration of 23.5 months (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSafety data from Brunner et al (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) indicated that 13% of JIA patients permanently discontinued TOFA treatment and 37% temporarily discontinued or reduced their dose. In the present study, AEs leading to discontinuation occurred in 7.5% of patients during the one-year follow-up, with no patients discontinuing treatment due to infections. Although varicella-zoster infections have been reported during TOFA treatment in both paediatric and adult patients (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), our study found no cases of varicella-zoster infections. In Finland, the varicella vaccine is included in the national vaccination programme for children.\u003c/p\u003e \u003cp\u003eUveitis is the most common and potentially serious extra-articular manifestation in JIA and presents a treatment challenge. Brunner et al (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) reported two patients who developed uveitis during TOFA treatment; both resolved and continued TOFA with no change in dose. In the present study, we also diagnosed two new cases of uveitis during TOFA treatment, but both patients had to discontinue TOFA due to persistent uveitis activity. We also started TOFA in two JIA patients with active uveitis at the start of the treatment, and they successfully continued TOFA treatment with favourable effects on both arthritis and uveitis. In a study of adult JIA patients, uveitis was diagnosed prior to TOFA treatment in five patients, two of whom had active uveitis. All patients survived 3 months of follow-up without relapse, and patients with active uveitis were able to discontinue topical corticosteroid therapy (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). A case report of patients treated with TOFA for JIA-associated uveitis has been published (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e), but more comprehensive data are lacking and further studies are needed.\u003c/p\u003e \u003cp\u003eThe strength of our study is that it represents all consecutive patients who were assigned to TOFA as soon as possible in terms of official reimbursement for paediatric patients with JIA in Finland. Although our cohort of 53 JIA patients is smaller than the 225 patients from multicentre studies, they were sourced from the defined catchment area of Helsinki University Hospital. There are limitations to consider; this study was register-based, clinical data were collected retrospectively from patients\u0026rsquo; records and the number of patients was limited. However, this type of data provides valuable real-life insights for clinicians.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, this real-life study of JIA patients indicates that TOFA treatment appears effective after 3 months, with no serious side effects reported.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eJIA Juvenile idiopathic arthritis\u003c/p\u003e\n\u003cp\u003eRF rheumatoid factor\u003c/p\u003e\n\u003cp\u003eACR American College of Rheumatology\u003c/p\u003e\n\u003cp\u003ecsDMARD conventional synthetic disease modifying antirheumatic drugs\u003c/p\u003e\n\u003cp\u003eMTX methotrexate\u003c/p\u003e\n\u003cp\u003ebDMARD biological disease modifying antirheumatic drugs \u003c/p\u003e\n\u003cp\u003eAE adverse event\u003c/p\u003e\n\u003cp\u003eJAKi Janus kinase inhibitor\u003c/p\u003e\n\u003cp\u003eTOFA tofacitinib\u003c/p\u003e\n\u003cp\u003etDMARDs targeted synthetic\u003c/p\u003e\n\u003cp\u003eVAS visual analogue scale \u003c/p\u003e\n\u003cp\u003eESR erythrocyte sedimentation rate \u003c/p\u003e\n\u003cp\u003eCRP C reactive protein\u003c/p\u003e\n\u003cp\u003eJADAS10 Juvenile Arthritis Disease Activity Score or clinical JADAS10\u003c/p\u003e\n\u003cp\u003ecJADAS10 clinical JADAS10\u003c/p\u003e\n\u003cp\u003eLDA low disease activity\u003c/p\u003e\n\u003cp\u003eMDA moderate disease activity\u003c/p\u003e\n\u003cp\u003ePaGA Patient Global Assessment\u003c/p\u003e\n\u003cp\u003ePhGA Physician Global Assessment\u003c/p\u003e\n\u003cp\u003eIDA Inactive Disease Activity\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study is based on clinical data of JIA patients collected from patient records and from Finnish Rheumatology Quality Register. Therefore, according to Finnish legislation, there was no need of approval by an ethical committee.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no competing of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePart time Government Research Funding was received by Tiina Lev\u0026auml;lampi, Katariina Rebane, Katriina Mikola, and Kristiina Aalto\u003c/p\u003e\n\u003cp\u003eOpen Access funding provided by the University of Helsinki (including Helsinki University Central Hospital)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors (Tiina Lev\u0026auml;lampi, Katariina Rebane, Katriina Mikola, Hannu Kautiainen and Kristiina Aalto) participated in designing the study and participated in statistical analysis and interpretation of data, and in drafting and revising the final version.\u003c/p\u003e\n\u003cp\u003eTiina Lev\u0026auml;lampi has written the first draft of the manuscript.\u003c/p\u003e\n\u003cp\u003eTiina Lev\u0026auml;lampi, Katariina Rebane, Katriina Mikola and Kristiina Aalto participated in collecting the data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHannu Kautiainen participated in designing the research and analyzing the data.\u003c/p\u003e\n\u003cp\u003eThe final manuscript has been read and approved by all the authors, and they all have given necessary attention to ensure the integrity of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHeini Pohjankoski, Department of Pediatrics, P\u0026auml;ij\u0026auml;t-H\u0026auml;me Central Hospital, Lahti, Finland\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTiina Lev\u0026auml;lampi, New Children\u0026rsquo;s Hospital, University of Helsinki, Helsinki University Hospital, Stenb\u0026auml;ckinkatu 9, 00290 Helsinki, Finland. \u0026nbsp;\u003cstrong\u003eCorresponding author. E-mail:\u003c/strong\u003e [email protected]\u003c/p\u003e\n\u003cp\u003eKatariina Rebane, New Children\u0026rsquo;s Hospital, University of Helsinki, Helsinki University Hospital, Stenb\u0026auml;ckinkatu 9, 00290 Helsinki, Finland. \u0026nbsp;E-mail: [email protected]\u003c/p\u003e\n\u003cp\u003eKatriina Mikola, New Children\u0026rsquo;s Hospital, University of Helsinki, Helsinki University Hospital, Stenb\u0026auml;ckinkatu 9, 00290 Helsinki, Finland. \u0026nbsp;E-mail: [email protected].\u003c/p\u003e\n\u003cp\u003eHannu Kautiainen:\u003csup\u003e\u0026nbsp;\u003c/sup\u003ePrimary Health Care Unit, Kuopio University Hospital, Kuopio, Finland; \u0026nbsp;Folkh\u0026auml;lsan Research Center, Helsinki, Finland. E-mail: [email protected]\u003c/p\u003e\n\u003cp\u003eKristiina Aalto, New Children\u0026rsquo;s Hospital, University of Helsinki, Helsinki University Hospital, Stenb\u0026auml;ckinkatu 9, 00290 Helsinki, Finland. \u0026nbsp;E-mail: [email protected].\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePetty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390\u0026ndash;2. \u003c/li\u003e\n\u003cli\u003eRavelli A, Martini A. Juvenile idiopathic arthritis. The Lancet. 2007;369(9563):767\u0026ndash;78. \u003c/li\u003e\n\u003cli\u003eRingold S, Angeles-Han ST, Beukelman T, Lovell D, Cuello CA, Becker ML, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Rheumatol. 2019;71(6):846\u0026ndash;63. \u003c/li\u003e\n\u003cli\u003eOnel KB, Horton DB, Lovell DJ, Shenoi S, Cuello CA, Angeles‐Han ST, et al. 2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis. Arthritis Care Res. 2022;74(4):521\u0026ndash;37. \u003c/li\u003e\n\u003cli\u003eKearsley-Fleet L, Vicente Gonz\u0026aacute;lez L, Steinke D, Davies R, De Cock D, Baildam E, et al. Methotrexate persistence and adverse drug reactions in patients with juvenile idiopathic arthritis. Rheumatology. 2019;58(8):1453\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eMannion ML, Xie F, Horton DB, Ringold S, Correll CK, Dennos A, et al. Biologic Switching Among Nonsystemic Juvenile Idiopathic Arthritis Patients: A Cohort Study in the Childhood Arthritis and Rheumatology Research Alliance Registry. J Rheumatol. 2021;48(8):1322\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eTynj\u0026auml;l\u0026auml; P, V\u0026auml;h\u0026auml;salo P, Honkanen V, Lahdenne P. Drug survival of the first and second course of anti-tumour necrosis factor agents in juvenile idiopathic arthritis. Ann Rheum Dis. 2009;68(4):552\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eMelki I, Fr\u0026eacute;mond ML. JAK Inhibition in Juvenile Idiopathic Arthritis (JIA): Better Understanding of a Promising Therapy for Refractory Cases. J Clin Med. 2023;12(14):4695. \u003c/li\u003e\n\u003cli\u003eHodge JA, Kawabata TT, Krishnaswami S, Clark JD, Telliez JB, Dowty ME, et al. The mechanism of action of tofacitinib - an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2016;34(2):318\u0026ndash;28. \u003c/li\u003e\n\u003cli\u003eFleischmann R, Kremer J, Cush J, Schulze-Koops H, Connell CA, Bradley JD, et al. Placebo-Controlled Trial of Tofacitinib Monotherapy in Rheumatoid Arthritis. N Engl J Med. 2012;367(6):495\u0026ndash;507. \u003c/li\u003e\n\u003cli\u003eVan Der Heijde D, Tanaka Y, Fleischmann R, Keystone E, Kremer J, Zerbini C, et al. Tofacitinib (CP‐690,550) in patients with rheumatoid arthritis receiving methotrexate: Twelve‐month data from a twenty‐four\u0026ndash;month phase III randomized radiographic study. Arthritis Rheum. 2013;65(3):559\u0026ndash;70. \u003c/li\u003e\n\u003cli\u003eKremer J, Li ZG, Hall S, Fleischmann R, Genovese M, Martin-Mola E, et al. Tofacitinib in Combination With Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis: A Randomized Trial. Ann Intern Med. 2013;159(4):253\u0026ndash;61.\u003c/li\u003e\n\u003cli\u003eEuropean Medicines Agency. Xeljanz. https://www.ema.europa.eu/en/documents/product-information/xeljanz-epar-product-information_en.pdf\u003c/li\u003e\n\u003cli\u003efor the Pediatric Rheumatology International Trials Organization (PRINTO), the Pediatric Rheumatology Collaborative Study Group (PRCSG), Ruperto N, Brunner HI, Zuber Z, Tzaribachev N, et al. Pharmacokinetic and safety profile of tofacitinib in children with polyarticular course juvenile idiopathic arthritis: results of a phase 1, open-label, multicenter study. Pediatr Rheumatol. 2017;15(1):86. \u003c/li\u003e\n\u003cli\u003eRuperto N, Brunner HI, Synoverska O, Ting TV, Mendoza CA, Spindler A, et al. Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial. The Lancet. 2021;398(10315):1984\u0026ndash;96. \u003c/li\u003e\n\u003cli\u003eBrunner HI, Akikusa JD, Al-Abadi E, Bohnsack JF, Boteanu AL, Chedeville G, et al. Safety and efficacy of tofacitinib for the treatment of patients with juvenile idiopathic arthritis: preliminary results of an open-label, long-term extension study. Ann Rheum Dis. 2024;83(11):1561\u0026ndash;1571. \u003c/li\u003e\n\u003cli\u003eMcerlane F, Beresford MW, Baildam EM, Chieng SEA, Davidson JE, Foster HE, et al. Validity of a three-variable Juvenile Arthritis Disease Activity Score in children with new-onset juvenile idiopathic arthritis. Ann Rheum Dis. 2013;72(12):1983\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eBackstr\u0026ouml;m M, Tynj\u0026auml;l\u0026auml; P, Ylijoki H, Aalto K, K\u0026auml;rki J, Pohjankoski H, et al. Finding specific 10-joint Juvenile Arthritis Disease Activity Score (JADAS10) and clinical JADAS10 cut-off values for disease activity levels in non-systemic juvenile idiopathic arthritis: a Finnish multicentre study. Rheumatology. 2016;55(4):615\u0026ndash;23. \u003c/li\u003e\n\u003cli\u003eXeljanz - tofacitinib tablets. Prescribing information. https://labeling.pfizer.com/ShowLabeling.aspx?id=959\u003c/li\u003e\n\u003cli\u003eFinnish National Consensus and the Social Insurance Institution of Finland: tofacitinib. https://www.kela.fi/laake291\u003c/li\u003e\n\u003cli\u003eFitton J, Melville AR, Emery P, Nam JL, Buch MH. Real-world single centre use of JAK inhibitors across the rheumatoid arthritis pathway. Rheumatology. 2021;60(9):4048\u0026ndash;54. \u003c/li\u003e\n\u003cli\u003eChighizola CB, Pellico MR, Pandolfi M, Marelli L, Cornalba M, Pontikaki I, et al. JAK inhibitors in the treatment of adult patients with juvenile idiopathic arthritis: a retrospective monocentric experience. Clin Exp Rheumatol. 2024;42(5):974-982\u003c/li\u003e\n\u003cli\u003eWollenhaupt J, Lee EB, Curtis JR, Silverfield J, Terry K, Soma K, et al. Safety and efficacy of tofacitinib for up to 9.5 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study. Arthritis Res Ther. 2019;21(1):89. \u003c/li\u003e\n\u003cli\u003eDutta Majumder P, Abraham S, Sudharshan S, Janarthanan M, Ramanan AV. Tofacitinib for Refractory Uveitis and Scleritis in Children: A Case Series. Ocul Immunol Inflamm. 2024;32(9):2092\u0026ndash;5. \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":"arthritis-research-and-therapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arrt","sideBox":"Learn more about [Arthritis Research \u0026 Therapy](http://arthritis-research.biomedcentral.com/)","snPcode":"13075","submissionUrl":"https://submission.nature.com/new-submission/13075/3","title":"Arthritis Research \u0026 Therapy","twitterHandle":"@ArthritisRes","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Juvenile idiopathic arthritis, janus kinase inhibitors, tofacitinib","lastPublishedDoi":"10.21203/rs.3.rs-6827548/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6827548/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003e Tofacitinib (TOFA), a newly introduced Janus kinase inhibitor, has been approved for the treatment of juvenile idiopathic arthritis (JIA). In this real-life study, we describe the effectiveness of TOFA treatment as well as possible interruptions and the reasons for discontinuations among all consecutive JIA patients who started TOFA treatment.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe reported data from 53 JIA patients from the catchment area of the Helsinki University Hospital who consecutively started TOFA treatment between February 2022 and October 2024. Physicians evaluated the patients\u0026rsquo; disease activity and treatment efficacy at each visit. Disease activity was assessed using Juvenile Arthritis Disease Activity Score 10 (JADAS10).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe majority of patients (96%) started TOFA due to active disease following previous treatment failure. Both JADAS10 scores and the patients\u0026rsquo; active joint counts decreased significantly during the first 3 months of TOFA treatment. The Kaplan\u0026ndash;Meier estimate indicated a 30% discontinuation of TOFA treatment during the 12-month follow-up period.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn this real-life study involving 53 JIA patients, TOFA treatment was initiated consecutively and demonstrated effectiveness after 3 months, with no serious side effects reported.\u003c/p\u003e","manuscriptTitle":"Efficacy and safety of tofacitinib treatment in Finnish patients with juvenile idiopathic arthritis: A real-life study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-29 14:43:53","doi":"10.21203/rs.3.rs-6827548/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-16T21:27:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-16T21:22:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-14T08:18:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-11T08:44:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"313244047440071778913512308062024652715","date":"2025-06-26T14:06:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"5384136409150710988833287483194207116","date":"2025-06-25T18:40:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"209697882568521290390051543935835523805","date":"2025-06-24T14:54:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-23T17:49:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-11T02:44:13+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-11T01:25:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"Arthritis Research \u0026 Therapy","date":"2025-06-05T09:13:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"arthritis-research-and-therapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arrt","sideBox":"Learn more about [Arthritis Research \u0026 Therapy](http://arthritis-research.biomedcentral.com/)","snPcode":"13075","submissionUrl":"https://submission.nature.com/new-submission/13075/3","title":"Arthritis Research \u0026 Therapy","twitterHandle":"@ArthritisRes","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9db422ab-4ff5-43da-acbf-046013be2a62","owner":[],"postedDate":"June 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T15:59:50+00:00","versionOfRecord":{"articleIdentity":"rs-6827548","link":"https://doi.org/10.1186/s13075-025-03669-7","journal":{"identity":"arthritis-research-and-therapy","isVorOnly":false,"title":"Arthritis Research \u0026 Therapy"},"publishedOn":"2025-10-31 15:57:05","publishedOnDateReadable":"October 31st, 2025"},"versionCreatedAt":"2025-06-29 14:43:53","video":"","vorDoi":"10.1186/s13075-025-03669-7","vorDoiUrl":"https://doi.org/10.1186/s13075-025-03669-7","workflowStages":[]},"version":"v1","identity":"rs-6827548","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6827548","identity":"rs-6827548","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}