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Abstract
Background The interleukin-17 (IL-17) cytokine family plays a key role in the pathogenesis of psoriatic diseases of skin and joint. Brodalumab is a fully human anti–IL-17 receptor monoclonal antibody that blocks the activity of IL-17A, IL-17F, and IL-17A/F.
Objectives To evaluate the long-term safety and efficacy of brodalumab in patients with psoriatic arthritis (PsA) in an open-label extension (OLE) of a phase 2 study.
Methods In a phase 2 study (NCT01516957), adults (18–75 years) with active PsA were randomized to brodalumab (140 or 280 mg) or placebo at weeks 0, 1, 2, 4, 6, 8, and 10. At week 12, patients could enter an OLE and receive brodalumab 280 mg every 2 weeks (Q2W); a protocol amendment in November 2013 resulted in dosage reduction to 210 mg Q2W for all patients. Outcome measures based on observed data through week 108 included percentages of patients with 20% and 50% improvement in American College of Rheumatology criteria (ACR20 and ACR50) and changes in ACR components and Psoriasis Symptom Inventory (PSI) score. Safety was assessed by adverse events (AEs).
Results At baseline, patients were 64% female, 94% white, with mean age and weight of 52 years and 91 kg, respectively. Mean PsA duration was 9 years, 92% were rheumatoid factor negative, and mean PSI score was 12.7. Of 168 patients randomized at baseline, 156 (52 placebo, 53 brodalumab 140 mg, and 51 brodalumab 280 mg) entered the OLE and 109 (70%) remained at week 108.
Through week 108, 149 (96%) patients reported an AE and 23 (15%) reported a serious AE (SAE). The most frequent SAEs (n=2 each) were coronary artery disease, cholelithiasis, and cellulitis; the most frequent AEs (≥10% of all patients) were nasopharyngitis, upper respiratory tract infection, psoriatic arthropathy, urinary tract infection, arthralgia, diarrhea, sinusitis, and bronchitis. Exposure-adjusted AE rate (per 100 patient-years) for all patients was 526; exposure-adjusted SAE rate was 14. There were no deaths, 1 laboratory report of neutropenia, 1 case of suicidal ideation, and 11 cases of oral candidiasis.
At week 12 of the study (double-blind phase), percentages of patients with ACR20 and ACR50 (non-responder imputation [NRI] analysis) were significantly greater in each brodalumab group than placebo: ACR20 37% (140 mg) and 39% (280 mg) vs 18% (placebo); ACR50 14% and 14% vs 4%. Through week 108 of the OLE, we continued to observe meaningful clinical benefit in ACR20 and ACR50 (Figure 1, as observed). Continued clinical benefit was also demonstrated by NRI analysis. Responses for other outcome measures were also sustained from week 12 to 108 in patients remaining in the OLE.
Conclusions Treatment with brodalumab resulted in an acceptable safety profile and meaningful clinical benefit that was maintained through week 108 in patients with PsA in this ongoing OLE.
Acknowledgements Jessica Ma (Amgen Inc) provided medical writing support.
Disclosure of Interest P. Mease Grant/research support from: AbbVie, Amgen Inc, Biogen Idec, BMS, Celgene, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Novartis, Pfizer, UCB, and Vertex, Consultant for: AbbVie, Amgen Inc, Biogen Idec, BMS, Celgene, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Novartis, Pfizer, UCB, and Vertex, Speakers bureau: AbbVie, Amgen Inc, Biogen Idec, BMS, Celgene, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Novartis, Pfizer, UCB, and Vertex, M. Genovese Grant/research support from: Amgen Inc, M. Greenwald Grant/research support from: Amgen Inc, C. Ritchlin Grant/research support from: Amgen Inc, A. Beaulieu Grant/research support from: Amgen Inc, A. Deodhar Grant/research support from: Amgen Inc, R. Newmark Shareholder of: Amgen Inc, Employee of: Amgen Inc, J. Feng Shareholder of: Amgen Inc, Employee of: Amgen Inc, N. Erondu Shareholder of: Amgen Inc, Employee of: Amgen Inc, A. Nirula Shareholder of: Amgen Inc, Employee of: Amgen Inc