1. Brodalumab was found to produce a 20% improvement in various clinical domains for patients with active psoriatic arthritis by week 12 of treatment.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Psoriatic arthritis (PsA) affects approximately up to 30% of patients with a history of psoriasis. In addition to skin manifestations, other symptoms that can produce severe disability include inflammation of small joints, enthesitis, bone and axial skeleton involvement. Interleukin-17 (IL-17) is one of several cytokines involved with the pathogenesis of PsA. High levels of IL-17 receptors and IL-17 positive T-cells have been identified in the synovial fluid of these patients. Brodalumab is a novel antibody directed against one of the IL-17 receptors.
This phase 2 study compared brodalumab against placebo in patients with active PsA (both non-exposed and exposed to prior biologic therapy) to a primary endpoint of 20% improvement of American College of Rheumatology (ACR) criteria at week 12. However, beyond the primary endpoint, this study then became an open-label trial up to week 52. Patients previously exposed to another biologic in the past responded similarly (in terms of improvement in ACR criteria) as compared to those who were biologic-naïve in this study.
While clinical benefit was observed in the groups randomized to brodalumab, this study was not adequately powered to determine the optimal dose and regimen required for treatment of PsA. Furthermore, the long-term safety of brodalumab remains to be determined in the phase three study.
Click to read the study, published today in NEJM
Relevant Reading: The Interleukin-17 Pathway in Psoriasis and Psoriatic Arthritis: Disease Pathogenesis and Possibilities of Treatment
In-Depth [randomized controlled trial]: This study enrolled a total of 168 patients randomized 1:1:1 into the following groups: brodalumab 140mg, brodalumab 280mg and placebo. All participants had active psoriatic arthritis as determined by several validated clinical scores (e.g., DAS28, CDI, HAQ-DI). Baseline characteristics among the three groups were well-matched for age, gender, body mass index, duration since diagnosis, prior use of any therapies (DMARDs, biologics, steroids) and clinical scores indicating disease activity. The placebo group did enroll more patients with higher enthesitis and dactylitis scores. Primary outcome of ACR 20 response rate at week 12 were as follows: 37% for brodalumab 140mg (p=0.03), 39% for brodalumab 280mg (p=0.02), and 18% for placebo. Beyond this time point, the study became an open-label trial whereby all participants received 280mg brodalumab each week. In this part of the trial, as expected, brodalumab showed the most benefit in the ACR20 of those previously on placebo. There was not a significant difference in serious adverse events among patients on brodalumab or placebo. However, common adverse events such as upper respiratory tract infections, diarrhea and nausea were noted to be more common in the brodalumab-treated groups.
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