Abstract

Background:Juvenile idiopathic arthritis (JIA) associated uveitis is an extra-articular manifestation of the JIA disease that may cause vision-threatening complications and an uncontrolled uveitis may even lead to blindness. Uveitis occurs in up to 20% of patients with JIA, depending on the JIA category. The majority of patients develop uveitis within the first two years after JIA symptom onset, but uveitis can continue into adulthood.Objectives:The main objective of this study was to analyze the risk for uveitis events after discontinuing disease-modifying antirheumatic drugs (DMARD) in patients with extended oligoarthritis and rheumatoid factor (RF)-negative polyarthritis.Methods:Data of the two ongoing multicenter biologic registers: German Biologics in Pediatric Rheumatology (BiKeR) and the Juvenile arthritis Methotrexate/Biologics long-term Observation (JuMBO) were used to analyze the adverse-event (AE) and events of special interest (ESI) reports about uveitis events during treatment and after discontinuation of DMARDs. Biker started recruitment of children and adolescent patients with JIA exposed to biological (b) or conventional (cs) DMARD’s in 2001. The patients were further followed in JuMBO after reaching the age of 18 or transitioning to an adult rheumatologist. Disease characteristics, treatment data, AE’s and ESI’s were reported by the pediatric or adults rheumatologist, respectively.Results:A total of 2,041 patients with RF-negative polyarthritis (n=1,280) or extended oligoarthritis (n=761) were included into the analyses. The mean follow-up of this study was 7.6 years (SD 5.3). About half of the patients were enrolled in BiKeR with start of etanercept (1,137, 55.7%), followed by 635 (31.1%) patients with start of methotrexate (MTX) monotherapy or adalimumab (ADA, n=198, 9.7%). A history of uveitis was reported for 238 (11.7%) patients at enrolment in BiKeR. More patients with a history of uveitis treated with ADA were included in BiKeR initiating ADA (n=98 of 238, 41.2%). Patients with uveitis had a lower age at JIA onset in comparison to patients without uveitis (mean 3.6 (SD 3.0) versus 7.0 (SD 4.5) years). A total of 142 recurrent (84% of 169) uveitis events were reported in 93 patients and for 27 patients (1.3% of 2,041) was an incident uveitis reported during follow-up. More than one uveitis event was reported for 32 patients with a maximum number of 4 uveitis flares in 3 patients. Nineteen uveitis flares (11.2% of 169) were reported for patients after the age of 18. The longer the time since DMARD discontinuation the fewer uveitis events occurred. Uveitis events were significantly more often reported in the first 24 months after MTX discontinuation (<6 months: OR=3.19, 95%CI: 1.70 to 5.96; 6 to <12 months: OR=2.06, 95%CI: 1.01 to 4.66; 12 to <24 months: OR=2.20, 95%CI: 1.14 to 4.25) and in the first three months after biological DMARD discontinuation (OR=5.4, 95%CI: 1.56 to 18.33). Patients with a MTX dose of ≤ 10 mg/m2 at last MTX intake had a higher likelihood for uveitis events (OR=1.40, 95%CI: 1.02 to 1.92).Conclusion:This is the first study that analyzed the risk of uveitis after DMARD withdrawal. Uveitis relapses are common. Patients who discontinued DMARD therapy were at high risk for uveitis within the first 3 to 24 months after discontinuation. Rheumatologists and ophthalmologists should be aware about this risk which should lead to a regular uveitis screening after DMARD withdrawal.Disclosure of Interests:Jens Klotsche: None declared, Ariane Klein: None declared, Martina Niewerth: None declared, Tilmann Kallinich: None declared, Daniel Windschall: None declared, Johannes-Peter Haas: None declared, Frank Weller-Heinemann Speakers bureau: Pfizer, Abbvie, SOBI, Roche, Novartis, Toni Hospach: None declared, Frank Dressler: None declared, Kirsten Minden: None declared, Gerd Horneff: None declared

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