SAT0491 PSORIASIS ASSOCIATED WITH MONOCLONAL-ANTIBODY-TNF-Α INHIBITORS VS. FUSION PROTEIN ETANERCEPT IN JUVENILE IDIOPATHIC ARTHRITIS PATIENTS - ANALYSIS OF THE BIKER REGISTRY
Authors: A. Zimmer, A. Klein, G. Horneff
Journal: Annals of the Rheumatic Diseases (2020)

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/PY TotalCohort* 4792/13519 All TNFi 4149/8437 ADA 1105/1859 ETA 2824/6307 GOL 144/145 INF 76/126 Non-TNFi 676/1112 MTX only 1692/3971 Psoriasis events/rate(%) 31/0.6 23/0.6 13/1.2 7/0.2 2/1.4 1/1.3 7/0.6 1/0.1 Pso**/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 event Mean ± SD 13.9 (±3.1) 13.9 (± 3.2) 14.0 (±3.0) 13.0 (±4.0) 15.1 (±3.4) 16.4 13.4 (±3.1) 17.3 Female 24 (77%) 18 (78%) 10 (77%) 5 (71%) 2 (100%) 1 (100%) 5 (71%) 1 (100%) ANA positive 22 (71%) 16 (70%) 10 (77%) 4 (57%) 1 (50%) 1 (100%) 5 (71) 1 (100%) Treatment duration until event (years) Mean ±SD 2.2 ±1.8 2.4 ±2.3 2.2 ±1.4 2.8 ±2.2 0.6 ±0.5 3.8 1.4 ±2.0 5.6 Concomitant MTX 11 (36%) 6 (26%) 3 (23%) 2 (29%) 1 (50%) 0 4 (57%) 1 (100%) Concomitant Steroids 4 (13%) 2 (9%) 0 1 (14%) 0 1 (100%) 2 (29%) 0 JADAS10 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) 18.0 6.6 1.3 (0.8-3.4) 1.7 *individual therapy numbers add to a sum &gt; the total cohort number, because some patients switched between multiple drugs; ** Pso= Psoriasis event; *** at time of event Table 2. Reference Psoriasis event n/100 PY Comparator Psoriasis event n/100 PY Risk ratio P-value Non-TNFi 0.63 TNFi 0.27 0.4 (0.2 -1.0) 0.052 MTX 0.03 TNFi 0.27 10.8 (1.5-80.1) 0.019 MTX 0.03 ETA 0.11 4.4 (0.5-35.8) 0.165 MTX 0.03 TNF-antibodies 0.75 42.9 (5.8-317) 0.0002 ETA 0.11 TNF-antibodies 0.75 6.8 (2.8-16.5) 0.00002 MTX 0.03 ADA 0.69 27.4 (3.6-2209) 0.001 Non-TNFi 0.63 ADA 0.69 1.1 (0.4-2.7) 0.847 Non-TNFi 0.63 ETA 0.11 0.2(0.1-0.5) 0.0012 ETA 0.11 ADA 0.69 6.2 (0.5-15.6) 0.0001 Conclusion: 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 &amp; Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche