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Efficacy and Safety of Anti–Interleukin‐20 Monoclonal Antibody in Patients With Rheumatoid Arthritis: A Randomized Phase IIa Trial
Author(s) -
Šenolt Ladislav,
Leszczynski Piotr,
Dokoupilová Eva,
Göthberg Marie,
Valencia Xavier,
Hansen Brian Bekker,
Cañete Juan D.
Publication year - 2015
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39083
Subject(s) - medicine , rheumatoid arthritis , tolerability , rheumatology , placebo , adverse effect , clinical endpoint , methotrexate , randomized controlled trial , gastroenterology , surgery , pathology , alternative medicine
Objective Interleukin‐20 (IL‐20) is implicated in the pathogenesis of rheumatoid arthritis (RA). The efficacy, safety, and tolerability of NNC0109‐0012, a selective anti–IL‐20 recombinant human monoclonal antibody (mAb), were assessed in patients with active RA who had an inadequate response to methotrexate therapy. Methods Sixty‐seven patients with RA were enrolled and randomized (2:1) to receive NNC0109‐0012 (3 mg/kg per week, subcutaneously) or placebo in a phase IIa, double‐blind, 12‐week trial with a 13‐week followup. The primary end point was change in the Disease Activity Score in 28 joints based on C‐reactive protein level (DAS28‐CRP) from baseline to week 12. Results In patients treated with NNC0109‐0012, the primary end point, improvement in the DAS28‐CRP at week 12, was achieved (estimated difference −0.88; P = 0.02), with significant improvement starting at week 1. A greater response was observed in seropositive patients (estimated difference −1.66; P < 0.001), which was sustained through 13 weeks of followup, whereas no improvement was noted in patients with seronegative RA. A significant proportion of patients with seropositive RA receiving NNC0109‐0012, compared to those receiving placebo, achieved treatment responses according to the American College of Rheumatology 20% (ACR20) (59% versus 21%), ACR50 (48% versus 14%), and ACR70 (35% versus 0%) levels of improvement, and showed greater improvements in the Health Assessment Questionnaire disability index ( P = 0.047). The most frequent adverse events reported with NNC0109‐0012 were injection site reactions and infections (e.g., herpes, nasopharyngitis, respiratory, and urinary). No serious infections or discontinuations associated with NNC0109‐0012 were observed. Conclusion In this phase IIa trial, treatment with NNC0109‐0012 (anti–IL‐20 mAb) was effective in patients with seropositive RA as early as week 1, with further improvements to week 12. No safety or tolerability concerns were identified with weekly NNC0109‐0012 administration.