Abstract

Background:Biological agents (BA), especially TNF inhibitors, 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 JIA-associated uveitis, however, development of uveitis de novo in pts treated with BA is a well-established paradoxical phenomenon.Objectives:to evaluate the frequency of new onset (no-) uveitis, 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 (1136) who were treated with BA in our clinic from 2004 to 2020. All cases of no-uveitis were collected for the describing of their clinical features in disease onset and course, activity level, JIA category, exposure to Methotrexate (MTX) and BA, presence of ANA, HLA B27.Results:among of 1136 pts treated with different BA we identified 36 (3.3%) pts (19 female/17 male) with no-uveitis under BA. Mostly during etanercept (ETA) therapy (34 cases from 488 ETA courses, 7%), 1/166 - in abatacept (ABA) and 1/372 - in adalimumab (ADA). 30 pts (83%) with no-uveitis developed it on the 1st line of BA treatment (29 ETA vs 1 ADA). 4pts (11%) developed no-uveitis on 2 nd line (3 ETA vs 1 ABA). 2 pts (6%) on third line (all ETA, both pts had also psoriasis). There are no cases of no-uveitis under other BA. Frequency of no-uveitis was much higher in ETA group. ETA exposure was 26.8 ± 28.8 months (mo). It means there are no “safe” period of therapy from paradoxical phenomenon of no-uveitis. JIA subtypes were as follows: RF-neg polyarthritis 9 (25%), persistent oligoarthritis 3 (8%), extended oligoarthritis 21 (59%), enthesitis-related arthritis (ERA) - 3 (8%). Average age at JIA onset was 4.6 ± 3.9 yrs. 20/36 patients had high laboratory activity (CRP 54 ± 23 mg/l; ESR 41 ± 19 mm/h) and severe arthritis before BA initiation. However most of pts (25/36) achieved 90-100% ACRpedi-response by the uveitis development. 23/36 pts were ANA-positive, 17/36 pts had HLAB27, including 7 pts who had the both features. Uveitis was occurred earlier in ANA plus HLAB27 positive pts (mean exposure - 15.3 mo) than in only ANA-positive or HLAB27-positive pts (27.7 mo and 27.6 mo accordingly). 29/36 (81%) of pts received methotrexate (MTX) in mean dosage 11.5 mg/m2/week. There are no differences in time of uveitis development depending of MTX. In all cases of no-uveitis BA was switched.Conclusion:Our study suggested that new onset of uveitis is rare adverse event during BA therapy in JIA. Uveitis can develop despite the excellent effect of therapy on joint manifestation. The most typical development of no-uveitis is under ETA therapy, especially in the predisposed cases (certain variants of JIA, ANF positivity, HLAB27 presence) and in patients with very high disease activity at the time of the start of biological therapy.Disclosure of Interests:Irina Nikishina Speakers bureau: Novartis, MSD, Pfizer, Abbvie, Hofman la Roche, Svetlana Arsenyeva: None declared, Maria Kaleda Speakers bureau: Novartis, Roche, MSD, Olga Kostareva: None declared, Anna Shapovalenko: None declared, Ekaterina Denisova: None declared, Anna Panova: None declared

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