POS1301 DRUG SURVIVAL OF BIOLOGICS WITH RESPECT TO COMBINATION WITH METHOTREXATE IN TREATMENT OF POLYARTICULAR JIA
Authors: G. Horneff, D. Windschall, K. Minden, T. Hospach, F. Dressler, F. Weller-Heinemann, B. Huegle, I. Foeldvari, A. Klein
Journal: Annals of the Rheumatic Diseases (2021)

Background: In polyarticular juvenile idiopathic arthritis (pJIA) biologic therapies are often combined with methotrexate (MTX). This combination was shown to increase efficacy in adult rheumatoid arthritis patients. MTX may also have a protective effect on the formation of anti-drug antibodies and thus may prolong drug survival. In pJIA, there are few and sometimes controversial data available. Objectives: To compare the effect of combination treatment with MTX on discontinuation due to inefficacy and on drug survival discontinuation of biologics approved for first line treatment of pJIA. Methods: Patients from the German BIKER registry with their first treatment course with Adalimumab, Etanercept, Golimumab or Tocilizumab were selected. Rates of ineffectiveness-related withdrawal were analysed and compared using χ2-test, Wald-test and Kaplan-Meier analysis of patients receiving biologic monotherapy or concomitant methotrexate. Cases were censored if MTX was discontinued before the biologic. Results: 2173 pJIA patients were identified who for the first time received a biologic. Etanercept (ETA) was by far the most frequently used biologic for first line biologic treatment in pJIA (77%) followed by Adalimumab (ADA, 16%). Patients on Golimumab (GOL) received most frequently a combination with MTX (86.5%), while patients on Tocilizumab (TOC) had the lowest rate of combination treatment (53%). ETA/ADA/GOL/TOC was given as monotherapy in 500(30%)/89(26%)/5(13.5%)/46(47%) and combined with MTX in 1179 (70%)/259(74%)/32(86.5%)/51(53%) cases. More patients with rheumatoid-factor negative (54 vs 50%; p=0.04) and rheumatoid-factor positive pJIA (13 vs 10%, p=0.04) received combination with MTX, while more patients in the monotherapy cohort had extended oligoarthritis (40 vs 32%, p&lt;0.001). Patients with MTX had a shorter disease duration (4 vs 5.5years, p&lt;0.001) and received concomitant steroid more often (34 vs 24%), p&lt;0.001). There was no statistical difference regarding disease activity parameters (active joint count, patient assessment and physician assessment of disease activity, ESR, CRP, CHAQ-DI, JADAS10). Discontinuation due to ineffectiveness was reported for ETA/ADA/GOL/TOC in 20%/18%/14%/28% of patients, respectively in 3.7/4.9/6/10.5 patients/100 treatment years. Thus discontinuation due to inefficacy was reported less frequently with ETA compared to ADA (p=0.046) and TOC (p&lt;0.001) and with ADA compared to TOC (p&lt;0.001). Patients on ETA and ADA had a slightly, but not statistically significant lower rate of withdrawal for ineffectiveness if on methotrexate (Figure 1). There was no difference regarding baseline disease activity parameters in patients with ETA/ADA monotherapy compared with combination with MTX, apart from patients with ETA+MTX receiving more often systemic steroids at baseline (36vs 24%,p&lt;0-001). For both GOL and TOC treatment, no baseline differences in disease activity between cohorts with monotherapy and MTX combination could be shown. The combination with MTX led to significantly lower rates of discontinuation due to inefficacy (p&lt;0.05) with GOL and TOC (Figure 1). Conclusion: Patients with pJIA mostly were treated with a combination of the biologic and MTX rather than with biologic monotherapy. Treatment was discontinued due to lack of efficacy in 14% to 28%. No statistically significant effect of combination treatment with MTX versus monotherapy could be observed regarding the rate of treatment failures in patients treated with ETA or ADA. However, combination treatment with MTX significantly prolonged the survival of GOL and TOC in patients with polyarticular JIA. The results are limited by low patient numbers in the GOL cohort and possible bias by JIA category. Figure 1. Kaplan Meier plot of drug survival in patients with monotherapy or with combination with MTX of the indicated biologic Disclosure of Interests: Gerd Horneff Speakers bureau: MSD, Grant/research support from: Pfizer, Roche, Chugai, MSD, Daniel Windschall: None declared, Kirsten Minden Speakers bureau: Pfizer, Abbvie, Grant/research support from: Pfizer, Toni Hospach: None declared, Frank Dressler: None declared, Frank Weller-Heinemann: None declared, Boris Huegle: None declared, Ivan Foeldvari Speakers bureau: Pfizer, Ariane Klein: None declared