Background Biological agents (BA) are high efficacy options for current therapy for patients (pts) with juvenile idiopathic arthritis (JIA). They are successfully used not only for the arthritis but also for uveitis, psoriasis and inflammatory bowel disease (IBD). However, paradoxical induction of these conditions in pts treated with BA is a well-established phenomenon.
Objectives To evaluate the frequency of new onset of uveitis, psoriasis or IBD occurring under BA therapy in JIA pts, to establish clinical features, which may be associated with development of such effects.
Methods Retrospective cohort study involved all JIA pts (740) who were treated with BA in our clinic from 2004 to 2016. All cases of new onset (no)-uveitis/psoriasis/IBD collected; clinical features of disease onset and course, activity level, JIA category, exposure to Methotrexate (MTX) and BA, presence of ANA, HLA B27 were studied.
Results We identified 20 (2.7%) pts (11 female/9 male) with no-uveitis under BA, mostly during etanercept (ETA) therapy (18 cases from 285 ETA courses, 6.3%), 1/112 - in abatacept (ABA) and 1/233 - in adalimumab (ADA); 2.46 events/100 patient-year (PY) vs 0.31 in ABA, and 0.15 in ADA), ETA exposure was 14.9±9.9 months (mo). JIA subtypes were as follows: RF-neg polyarthritis 5 (25%), persistent oligoarthritis 3 (15%), extended oligoarthritis 10 (50%) ERA - 2 (10%). JIA started in this group at the age of 4.5±3.9 yrs.18/20 patients had high laboratory activity (CRP 55±25 mg/l) and severe arthritis before BA initiation. Most of pts (16/20) achieved 90–100% ACRpedi-response by the uveitis development. 1 pt was treated by ADA for the 71 mo and switched to ABA. in 1 pt no-uveitis was obseved under ABA. 12/20 pts were ANA-positive, 10/20 pts had HLAB27, 1 pt did not have ANA or HLAB27. Uveitis was occurred earlier in ANA plus B27 positive pts (mean exposure - 10.7 mo vs 27.4 in ANA+ and 21.6 in B27+ pts). 17/20 (85%) of pts received MTX. In all cases of no-uveitis BA was switched. 5 pts from 740 (0.7%) developed no-psoriasis under BA: INF - 2 cases (0.62/100PY), ADA - 2 (0.15/100PY), ABA -1 (0.31/100PY). JIA subtypes were presented by RF-negative polyarthritis (1), extended oligoarthritis – 3. All received MTX. 1/5 pts was ANA+, 2/5 - HLAB27+. Average age of disease onset was 9.8±7.8 years; BA exposure before psoriasis was 25±11.5 mo. Therapy was continued in 3/5 pts; switched from INF to ADA in 2. Only 1 case of no-IBD was occurred in female patient fulfilled to systemic-onset JIA criteria years. She was treated by INF for the 62 months and switched to ADA due to secondary inefficiency presented by active polyarthritis and sacroiliitis (HLAB27neg), but 2 months later severe gastrointestinal symptoms appeared and diagnosis of Crohn's disease was established by endoscopy.
Conclusions Our study suggested that new onset of uveitis, psoriasis and IBD is rare adverse event during BA therapy in JiA. It seemes to be as delayed implication of disease natura. but not therapy complication. Uveitis observed mostly in pts receiving ETA, unlike the psoriasis mainly developed during TNF-monoclonal antibodies using. High activity aggressive manifestations at disease onset and good initial response to BA are typical features for all pts, who developed paradoxical effects under BA therapy.
Disclosure of Interest None declared