Background/Purpose: Psoriasis-associated skin and joint disorders are characterized by ongoing inflammation mediated by similar molecular pathways. IL-17 plays a potential role in the pathogenesis and ongoing inflammation of psoriatic disease. We sought to assess the efficacy and safety of brodalumab, a human anti-IL-17 receptor A monoclonal antibody, in patients with psoriatic arthritis (PsA).

Methods: Adults (age 18 to 75 years) with active PsA (Classification Criteria for Psoriatic Arthritis and ≥3 tender and ≥3 swollen joints) for ≥6 months were randomized to brodalumab (140 or 280 mg Q2W) or placebo. At week 12 subjects could enroll in an open-label extension (OLE) in which all subjects received 280 mg brodalumab. Outcomes based on available data up to week 24 from the ongoing study included American College of Rheumatology 20% response (ACR20), ACR50, and ACR70, changes in DAS 28 and ACR response components, and adverse events (AEs).

Results: At baseline, the majority of enrolled subjects (113 brodalumab and 55 placebo) were female (64%), white (94%), and rheumatoid factor negative (92%). Mean (SD) age, weight, and duration of PsA at baseline were 52 (12) years, 91 (21) kg, and 9 (8) years, respectively. 156 subjects entered in the OLE (52 prior placebo, 53 prior 140 mg, 51 prior 280 mg).

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 placebo subjects (p < .05) (Fig. 1). The percent of ACR20 responders (observed) increased at week 24 (44%, 51%, 64%, in prior placebo, prior 140 mg, and prior 280 mg groups, respectively) (Fig. 1). The percent of ACR50 responders (observed) across all groups increased from week 12 to week 24 (Fig. 1). There were improvements in other secondary endpoints such as DAS 28, CDAI, and several components of the ACR from baseline to week 12 that continued through week 24 in all treatment groups.

AEs were balanced among treatment groups and placebo, with 85% of subjects reporting an AE during the OLE. The most commonly reported adverse events were nasopharyngitis, arthralgia, psoriatic arthropathy, upper respiratory tract infection, and oropharyngeal pain. SAEs were reported in 11 subjects during the full study through data cutoff (double-blind phase and OLE). No deaths, clinically significant neutropenia (≥ Grade 2), or  mycobacterial/fungal/opportunistic infections were reported in this study.

Conclusion: Brodalumab treatment was associated with significant clinical response with continued improvement from week 12 to 24. The benefit:risk profile supports continued evaluation of brodalumab for treatment of PsA.