Safety and efficacy of anakinra as first-line or second-line therapy for systemic onset juvenile idiopathic arthritis - data from the German BIKER registry

ABSTRACT

Background: The IL-1 receptor-antagonist anakinra is recommended for the treatment of systemic juvenile idiopathic arthritis (sJIA) and was recently approved for first-line treatment. Long-term data from clinical practise are scarce.

Methods: SJIA patients from the German biologics in pediatric rheumatology (BIKER) registry starting anakinra were grouped into two cohorts: Patients in the first-line cohort received no prior sJIA treatment except NSAID and a maximum of 3 days of steroids. Second-line cohort patients were pre-treated with steroids; DMARDs or biologics. Patient characteristics, disease-activity parameters, efficacy, and safety-parameters were compared.

Results: Until December 2018, 51 anakinra patients were documented, representing 117.96 patient-years. Mean disease duration was 3.5 (± 3.8) years. At baseline, all anakinra first-line users had active systemic disease compared to 82% in the second-line users. Significant JADAS-10 improvement at last follow-up was observed in both cohorts (p = 0.02, p = 0.0014). Substantial numbers of patients in both groups reached JADAS-MDA/JADAS-remission/inactive disease (66.7%50%50% in first-liners and 60%45%70% in second-liners). Rates of serious adverse events were comparable and consistent with the overall AE profile of anakinra in patients.

Conclusion: This analysis adds to the established safety profile of anakinra and demonstrates that anakinra is effective as first-line or second-line treatment.

KEYWORDS:

• Systemic juvenile idiopathic arthritis
• anakinra
• interleukin-1 inhibition
• safety
• still´s disease

Acknowledgments

The authors would like to thank all the participating paediatric rheumatology departments at the universities and hospitals and the rheumatology practices in Austria and Germany included in the BIKER study group: Dennis Conzelmann, Frank Dressler, Ivan Foeldvari, Gerd Ganser, J-Peter Haas, Sandra Hansmann, Anton Hospach, Boris Hügle, Jasmin Kuemmerle-Deschner, Rolf Küster, Eggert Lilienthal, Kirsten Minden, Christoph Rietschel, Tobias Scharz, Angelika Thon, and Frank Weller-Heinemann and especially all patients and their families for participating in the register. This study would not have been possible without the collaboration of numerous German and Austrian paediatric rheumatologists, patients and their parents.

Ethics approval and consent to participate

The study was conducted in accordance with the protocol, International Conference for Harmonization (ICH), Good Clinical Practice (GCP), FDA regulations governing clinical study conduct, ethical principles that have their origin in the Declaration of Helsinki, 1996 revision and 2000 revision with subsequent clarifications, and all applicable local regulations. Before the study was initiated, the study protocol, the informed consent form, and subject information were submitted for review to the responsible independent ethics committee of the AerztekammerNordrhein, Duesseldorf, Germany, reference number 2/2015/7441. Parents/legal guardians signed the informed consent form before any study-related procedures occurred.

Declaration of interest

G Horneff has received grants and honorary fees from Abbvie, Pfizer, Novartis, Sanofi, GSK and Roche/Chugai. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Abbreviations

ACR: American Colleague of Rheumatology; AE: Adverse event; DMARD: disease-modifying drug; BIKER: Biologics in Pediatric Rheumatology Registry; CHAQ: Childhood Health Assessment Questionnaire; CRP: C-reactive protein; csDMARD: Conventional disease-modifying drug; DMARD: disease-modifying antirheumatic drug; EMA: European Medicines Agency; ESR: Erythrocyte sedimentation rate; ETA: Etanercept; FDA: Food and Drug Administration; IL: Interleukin; IL-1i: Interleukin-1 inhibitor; JADAS: Juvenile Disease Activity Score; JIA: Juvenile idiopathic arthritis; MAS: Macrophage activation syndrome; MDA: Minimal disease activity; MRP: Myeloid-related protein; MTX: Methotrexate; NSAIDs: Nonsteroidal anti-inflammatory drugs; OR: Odds ratio; PedACR: Pediatric ACR criteria; RR: Risk ratio; SAE: Serious adverse event; SD: Standard deviation; sJIA: Systemic juvenile idiopathic arthritis; TNF: Tumor necrosis factor; TOC: Tocilizumab; VAS: Visual analogue scale.

Additional information

Funding

The BIKER registry is supported by unrestricted grants from Abbvie, Chugai, MSD, Novartis, Pfizer and Roche. The data accumulation, analysis and publication is not influenced by the sponsors and lay in the full and only responsibility of the authors.