SAT0491 PSORIASIS ASSOCIATED WITH MONOCLONAL-ANTIBODY-TNF-Α INHIBITORS VS. FUSION PROTEIN ETANERCEPT IN JUVENILE IDIOPATHIC ARTHRITIS PATIENTS - ANALYSIS OF THE BIKER REGISTRY

Abstract

Background:Although efficacy of Tumor necrosis factor inhibitors (TNFi) for treatment of psoriasis is well established, patients may develop psoriasis for the first time while on TNFi as a paradoxical effect. Few data are available in patients with juvenile idiopathic arthritis (JIA).Objectives:To analyze the incidence of psoriasis in TNFi – treated JIA patients and to identify associated factors.Methods:Safety data from patients registered in the German Biologics registry (BIKeR) were analyzed. Cohorts of patients were grouped by treatment: any or multiple TNFi, single TNFi, biologics other than TNFi and no biologics (control group on methotrexate (MTX) only). TNFi-associated psoriasis was defined as incident diagnosis of psoriasis after starting a TNFi. Patients with personal history of psoriasis prior to TNFi therapy were excluded. Rates and events per 100 patient-years (PY) of exposure were calculated using AEs reported after first dose under therapy and under the age of 18 years. Rates were compared by X2-test, event rates by Wald test.Results:A total of 4149 treatment episodes with TNFi (Etanercept, Adalimumab, Golimumab, Infliximab), with a total exposure time of 8437 PY, were identified. There were 676 treatments with a non-TNFi- biologic (Tocilizumab, Abatacept, Anakinra, Canakinumab) with a total exposure time of 1112 PY. MTX monotherapy was conducted in 1692 patients with a total exposure time of 3971 PY. In total, 31 patients were diagnosed with incident psoriasis on JIA-treatment (Table 1). The mean duration of therapy until incident psoriasis was 2.2 (± 1.8) years. Multiple psoriatic skin manifestations were observed.Psoriasis events were significantly more frequent in any or multiple TNFi compared to MTX-monotherapy, and specifically in the subgroup of TNF-antibody treatment (all) or Adalimumab compared to MTX or Etanercept (Table 2). Interestingly, psoriasis events were also observed with non-TNFi at high frequency. At occurrence of the event, patients exposed to biologics received MTX or steroids less frequently compared to the total patient cohort and had a higher JADAS10.Table 1.N/PYTotalCohort*4792/13519All TNFi4149/8437ADA1105/1859ETA2824/6307GOL144/145INF76/126Non-TNFi676/1112MTX only1692/3971Psoriasis events/rate(%)31/0.623/0.613/1.27/0.22/1.41/1.37/0.61/0.1Pso**/100 PY (95%CI)0.2(0.2-0.3)0.3(0.2-0.4)0.7(0.4-1.2)0.1(0.1-0.2)1.4(0.3-5.5)0.8(0.1-5.6)1.0(0.5-2.1)0.03(0.004-0.2)Age at eventMean ± SD13.9(±3.1)13.9(± 3.2)14.0(±3.0)13.0(±4.0)15.1(±3.4)16.413.4(±3.1)17.3Female24(77%)18(78%)10(77%)5(71%)2(100%)1(100%)5(71%)1(100%)ANA positive22(71%)16(70%)10(77%)4(57%)1(50%)1(100%)5(71)1(100%)Treatment duration until event (years) Mean ±SD2.2±1.82.4±2.32.2±1.42.8±2.20.6±0.53.81.4±2.05.6ConcomitantMTX11(36%)6(26%)3(23%)2(29%)1(50%)04(57%)1(100%)ConcomitantSteroids4(13%)2(9%)01(14%)01(100%)2(29%)0JADAS10 Median [IQR]***2.5(0.6-8.8)4.2(1.0-11.0)2.0(0.6-10.1)5.8(1.5-11.4)18.06.61.3(0.8-3.4)1.7*individual therapy numbers add to a sum > the total cohort number, because some patients switched between multiple drugs; ** Pso= Psoriasis event; *** at time of eventTable 2.ReferencePsoriasis eventn/100 PYComparatorPsoriasis eventn/100 PYRisk ratioP-valueNon-TNFi0.63TNFi0.270.4 (0.2 -1.0)0.052MTX0.03TNFi0.2710.8 (1.5-80.1)0.019MTX0.03ETA0.114.4 (0.5-35.8)0.165MTX0.03TNF-antibodies0.7542.9 (5.8-317)0.0002ETA0.11TNF-antibodies0.756.8 (2.8-16.5)0.00002MTX0.03ADA0.6927.4 (3.6-2209)0.001Non-TNFi0.63ADA0.691.1 (0.4-2.7)0.847Non-TNFi0.63ETA0.110.2(0.1-0.5)0.0012ETA0.11ADA0.696.2 (0.5-15.6)0.0001Conclusion:Our findings demonstrate a higher incidence of psoriasis in monoclonal-antibody-TNFi-treated JIA-patients, whereas in Etanercept-treated JIA patients no significant increase was detected. On average, psoriasis-manifestation occurred more than two years after treatment-initiation. Teenage females with ANA-positivity were most often affected.Disclosure of Interests:Angela Zimmer: None declared, Ariane Klein Consultant of: Celgene, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche