Background A potential role of IL-17 in the pathogenesis and ongoing inflammation of psoriatic disease, with similar pathways impacting skin and joint disease, suggests that cytokine-targeting strategies aimed at blocking signaling through the IL-17 receptor may be beneficial in treatment of psoriatic arthritis (PsA).
Objectives To determine efficacy and safety of brodalumab, a human anti-interleukin-17 receptor A monoclonal antibody, in patients with PsA.
Methods Adults (age 18 to 75 years) with PsA (Classification Criteria for Psoriatic Arthritis [CASPAR] and ≥3 tender and ≥3 swollen joints) for ≥6 months were randomized to receive brodalumab (140 or 280 mg Q2W) or placebo (pbo), stratified by body weight (≤100 kg, >100 kg) and by prior biologic use. Primary endpoint was proportion of subjects achieving an American College of Rheumatology 20% response (ACR20) at week 12. Secondary endpoints included ACR50, ACR70, changes in DAS 28 and ACR components. Safety was assessed by monitoring adverse events (AEs). Analyses were based on intent to treat using non-responder imputation (binary endpoints) or last observation carried forward imputation (continuous endpoints).
Results 168 subjects were randomized; 113 to brodalumab and 55 to pbo. 159 subjects (95%) completed the study (defined as 12 weeks of study evaluations). The majority of subjects were female (64%), white (94%), and rheumatoid factor negative (92%). Mean (SD) age, weight, and duration of PsA were 52.2 (11.6) years, 90.6 (21.1) kg, 8.7 (7.6) years, respectively. Median C-reactive protein (CRP) was 5.0 mg/L. Biologics were previously used by 51% (86/168) of subjects.
ACR20 was achieved at week 12 by 37% and 39% of subjects in the 140- and 280-mg brodalumab groups, respectively, compared with 18% of subjects in the pbo group (p < .05). The ACR20 response rates in biologic-naïve subjects were 36% (140 mg), 37% (280 mg), and 20% (pbo); comparable with the respective rates of 37%, 42%, and 16%, in subjects with prior biologic exposure. At week 12, the ACR50 responses were 4% (pbo), 14 (140 mg; p=.051), and 14% (280 mg; p=.047). There were consistent improvements in other secondary endpoints such as DAS 28 and components of the ACR including CRP.
AEs were generally balanced among treatment groups and pbo. The most common AEs were upper respiratory tract infection (7% pbo; 12% brodalumab), headache (7%; 6%), nasopharyngitis (6%; 0%), psoriatic arthropathy (6%; 4%), injection site erythema (6%; 3%), injection site pain (6%; 2%), fatigue (4%, 7%), diarrhea (4%; 6%), nausea (4%; 5%), dizziness (4%; 5%) and arthralgia (2%; 4%). A total of 4 subjects reported SAEs during the study: cellulitis (pbo), abdominal pain (140 mg), cellulitis and cholecystitis (280 mg). No clinically significant neutropenia (≥Grade 2) was reported in this study. No deaths and no mycobacterial or fungal/opportunistic infections were reported.
Conclusions Brodalumab treatment was associated with significant clinical response and acceptable safety profile in subjects with PsA. These results support continued evaluation of brodalumab for treatment of PsA.
Acknowledgements This study was funded by Amgen Inc. Jon Nilsen, PhD (Amgen Inc.) provided medical writing support.
Disclosure of Interest P. Mease Grant/research support from: Abbvie, Amgen, BiogenIdec, Bristol Myers, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Consultant for: Abbvie, Amgen, BiogenIdec, Bristol Myers, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BiogenIdec, Bristol Myers, Janssen, Lilly, Pfizer, UCB, M. Genovese Grant/research support from: Amgen Inc, Consultant for: Amgen Inc, M. Greenwald Grant/research support from: Amgen Inc, C. Ritchlin Grant/research support from: Amgen Inc, Consultant for: Amgen Inc, Abbott Laboratories, Centocor Inc, Ortho Biotech Inc, Genentech, and Wyeth, A. Beaulieu 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