Adalimumab versus adalimumab and methotrexate for the treatment of juvenile idiopathic arthritis: long-term data from the German BIKER registry

Abstract

Objective: Adalimumab (ADA) has become a valuable treatment option for juvenile idiopathic arthritis (JIA). The importance of combination with methotrexate (MTX) is unclear.

Method: Data from the German Biologics in Paediatric Rheumatology (BIKER) registry are reported. Response to treatment was analysed using JIA American College of Rheumatology (ACR) scores, 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), and improvement of functional status and ACR inactive disease criteria. Compa-risons between rates of adverse events (AEs) and serious adverse events (SAEs) provided data for the safety assessment.

Results: Overall, 584 patients with non-systemic JIA started ADA therapy, 61% of whom received concomitant MTX treatment at baseline. The latter patients were younger (p < 0.001), with shorter disease duration (p = 0.001), more frequently had antinuclear antibodies (p = 0.04), and had higher baseline JADAS10 scores (p = 0.03). In patients with ADA monotherapy, enthesitis-related arthritis (p = 0.004) and presence of human leucocyte antigen-B27 (p = 0.008) were documented more often. Mean treatment duration in both cohorts was 15 months. Comparable last follow-up rates for JIA ACR 30/50/70/90% response, JADAS minimal disease activity, JADAS remission, and ACR inactive disease were, respectively, 75/72/64/49%, 66%, 46%, and 58% for ADA monotherapy, and 77/72/61/45%, 64%, 48%, and 55%, for ADA + MTX. During 1082 patient-years (PY) of ADA exposure, 725 AEs (67/100 PY), including 57 SAEs (5.3/100 PY), were reported. Serious infections were reported in 10 patients (0.9/100 PY) and 11 (1.0/100 PY) had varicella infections/zoster reactivation. Rates of AEs, SAEs, infectious events, and serious infections did not differ between the cohorts. Elevated transaminases (p = 0.005) and gastrointestinal events (p < 0.0001) were reported more often in the combination cohort. Two pregnancies and no deaths were reported.

Conclusion: ADA demonstrated an acceptable risk profile and high percentages of patients in both cohorts showed sufficient treatment response. No differences in treatment response or adherence to treatment were found.

Acknowledgements

This study would not have been possible without the collaboration of numerous German and Austrian paediatric rheumatologists, the patients and their parents.

Collaborators: T Berger, G Böschow, M Borte, I Feddersen, D Föll, G Ganser, T Geikowski, HJ Girschick, MH Haller, C Hedrich, G Heubner, I Hospach, MA Hufnagel, B Keck, H Kössel, J Kümmerle-Deschner, M Küster, E Lilienthal, J Maier, S Mrusek, T Müller, P Oommen, M Prelog, J Quietzsch, C Rietschel, B Rogalski, M Rühlmann, P Rühner, M Sailer-Höck, R Schatz, T Schmalbach, W Seibert, A Thon, R Trauzeddel, A Urban, F Weller-Heinemann, and D Windschall.

The German Registry is supported by an unrestricted grant from Pfizer, Germany, Abbvie, Germany, MSD, Germany, and Roche, Germany. Abbvie, Pfizer, MSD, and Roche had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. Publication of this article was not contingent upon approval by the study sponsors.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supporting information

Additional Supporting Information may be found in the online version of this article.

Supplementary table S1. Response rates of patients receiving exclusively either ADA monotherapy or ADA + MTX combination.

Supplementary figure S1. Response rates of patients receiving exclusively either ADA monotherapy or ADA + MTX combination after 12 and 24 months and at last follow-up (LFU) in the respective cohort.

Please note that the editors are not responsible for the content or functionality of any supplementary material supplied by the authors. Any queries should be directed to the corresponding author.

Additional information

Funding

0