Drug survival and reasons for discontinuation of the first course of biological therapy in 363 juvenile idiopathic arthritis patients

Background: The introduction of TNF-blocking agents since 2000 has tremendously changed the treatment of JIA. From randomized controlled trials (RCTs) there is evidence that TNF-blocking agents are efficacious and safe, but data on their long-term expected and unexpected effects remain relatively scarce. Objectives: To determine long-term effectiveness and safety of 1st biological treatment (BT) in a cohort of 363 Juvenile Idiopathic Arthritis (JIA) pts, non-responders to DMARDs, in terms of drug survival (continuation rate on therapy) and to identify the baseline predictors of treatment discontinuation. Methods: Each JIA pt enrolled in BT is prospectively assessed at the start of treatment and then every 2 months for the evaluation of safety and efficacy according to ACR-Pedi core set criteria. All clinical charts of pts who started a BT between Nov'99 and Jul'10 have been reviewed. Survival analysis methods suitable for competing risks were used to study time to drug discontinuation due to disease control (defined according to Wallace criteria) or failure (adverse event [AE], lack of efficacy [LaE] or loss of efficacy [LoE]. Results: In total 750 different courses of BTs were administered to our 363 pts. In 287/363 pts a BT treatment is still ongoing, 147 pts maintain the 1st BT, 140 pts switched one or more times. 298 pts were included in the analysis for drug discontinuation. A median follow-up on treatment, before discontinuation due to every causes, was 53.7 months (range 0.45-124.45). One hundred and sixty-five pts discontinued BT: 27 due to disease control, 135 because of failure (78 AEs, 12 LaE and 45 LoE), 3 pts temporarily stopped for pregnancy. Among 135 pts who discontinued for failure, 117 switched to a 2nd BT. Among 27 pts who discontinued due to disease control, 13 pts restarted on BT for relapse of disease activity (10 pts restarted with the same BT, 3 switched to a different one). Predictors of discontinuation due to AE were female gender (p=0.1) and longer disease duration (p=0.02). Predictors of discontinuation due to LaE or LoE were systemic onset and polyarthritis FR positive (vs other JIA subtypes) (p<0.05) and use of mAb-anti-TNF (vs sTNFR) (p=0.02). Predictors of discontinuation due to inactive disease were male gender and shorter disease duration (p<0.05). Conclusions: Although only few pts discontinued BT due to a complete and persistent disease control, the majority of them remained on BT for a long time, suggesting that in our cohort of JIA pts, affected by a severe long lasting refractory disease, BT was globally well tolerate and efficacious in controlling the disease. References: 1. Gerloni V, Pontikaki I, Gattinara M, Fantini F. Focus on adverse events of tumour necrosis factor α blockade in juvenile idiopathic arthritis in an open monocentric long-term prospective study of 163 patients. Ann Rheum Dis 2008; 67: 1145-52. 2. Tynjälä P, Vähäsalo P, Honkanen V, Lahdenne P. Drug survival of the first and second course of anti-TNF agents in juvenile idiopathic arthritis. Ann Rheum Dis 2009; 68: 552-7.