Background Cytokine-targeting strategies aimed at blocking IL-17 receptor signaling may be beneficial in treatment of psoriatic arthritis (PsA).
Objectives To assess long-term efficacy and safety of brodalumab, a human anti-interleukin-17 receptor A monoclonal antibody, in patients with PsA in an open-label extension (OLE) of a Phase 2 study (NCT01516957).
Methods Adult patients (age 18 to 75 years) with active 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). At week 12, subjects could enter the open-label extension (OLE). All subjects in the OLE received 280 mg brodalumab (Q2W). Outcomes, including American College of Rheumatology 20% response (ACR20), ACR50, changes in Disease Activity Score for 28-joint count (DAS28) and ACR response components, were assessed based on available data up to week 52 from the ongoing study. Safety was assessed by monitoring adverse events (AEs).
Results 168 subjects were randomized; 113 to brodalumab and 55 to pbo. 159 subjects (95%) completed 12 weeks of study evaluations, 156 subjects entered in the OLE (52 prior pbo, 53 prior 140 mg, 51 prior 280 mg), and 22 subjects discontinued by week 52 (9 prior pbo, 7 prior 140 mg, 6 prior 280 mg). At baseline of the parent study, mean (SD) age, body mass index, and duration of PsA were 52.2 (11.6) years, 32.3.6 (7.1) kg/m2, 8.7 (7.6) years. Median C-reactive protein (CRP) was 5.0 mg/L. Biologics were previously used by 51% (86/168) of subjects.
The percent of ACR20 and ACR50 responders (observed) at week 12 was higher in the brodalumab arms than in pbo (Table 1). ACR20 and 50 response rates continued to improve during the OLE and were sustained through week 52 across all treatment groups (Table 1). DAS 28, Clinical Disease Activity Index (CDAI), dactylitis, enthesitis, Psoriasis Symptom Inventory score, and several components of the ACR improved from baseline to week 12 and continued to improve through week 52 in all treatment groups.
Adverse events most commonly reported (≥5 subjects in any treatment group) during the OLE phase (through week 52) were nasopharyngitis, arthralgia, psoriatic arthropathy, upper respiratory tract infection, bronchitis, nausea, sinusitis, and oropharyngeal pain. During the OLE through week 52, a total of 10 subjects reported SAEs: including 1 case each of acute myocardial infarction, invasive ductal breast carcinoma, metastatic lung cancer, melanoma, pyelonephritis, and streptococcal septic arthritis. There were no AEs of neutropenia but there were 8 cases ≤ grade 2 based on lab reports. No deaths or mycobacterial/fungal/opportunistic infections were reported.
Conclusions Brodalumab treatment was associated with improvements in musculoskeletal and skin symptoms in subjects with PsA. Clinical responses were sustained through week 52. These results support continued evaluation of brodalumab for treatment of PsA.
Disclosure of Interest P. Mease Grant/research support: Amgen Inc., AbbVie, Biogen Idec, Bristol Myers Squibb,Celgene, Crescendo, Genentech, Janssen, Lilly, Merk, Novartis, Pfizer, UCB, Vertex, Consultant for: Amgen Inc., AbbVie, Biogen Idec, Bristol Myers Squibb,Celgene, Crescendo, Genentech, Janssen, Lilly, Merk, Novartis, Pfizer, UCB, Vertex, M. Genovese Grant/research support: Amgen Inc., Consultant for: Amgen Inc., M. Greenwald Grant/research support: Amgen Inc., C. Ritchlin Grant/research support: Amgen Inc., UCB, Janssen, Consultant for: Amgen Inc., Abbvie, Janssen, UCB, Regeneron, A. Beaulieu Grant/research support: Amgen Inc., A. Deodhar Grant/research support: Amgen Inc., Abbvie, UCB, Pfizer, Novartis, Consultant for: AbbVie, UCB, Novartis, Pfizer, MSD, 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.