TY - JOUR T1 - Of Mice and Men: Defining the Role of Interleukin 17 in Rheumatoid Arthritis JF - The Journal of Rheumatology JO - J Rheumatol SP - 1069 LP - 1071 DO - 10.3899/jrheum.150554 VL - 42 IS - 7 AU - ERIC M. RUDERMAN Y1 - 2015/07/01 UR - http://www.jrheum.org/content/42/7/1069.abstract N2 - In a recent issue of The Journal, Pavelka and colleagues reported on a negative study of brodalumab, the interleukin 17 (IL-17) inhibitor, in rheumatoid arthritis (RA)1. In addition to the authors’ conclusion that there is no reason to pursue further evaluation of the molecule, an antibody against the IL-17 receptor A (IL-17RA), in this disease, there are a number of other important lessons to be learned from this publication. Combined with previously published data for secukinumab2 and ixekizumab3, 2 anti-IL-17A antibodies, the results of this study strongly suggest that the IL-17 pathway is not an appropriate target in RA. This conclusion comes despite both animal data suggesting potential benefit and clinical evidence that IL-17 inhibition is effective in psoriatic arthritis (PsA). The latter observation is instructive, and may provide a clue to important pathogenic differences between 2 outwardly similar forms of inflammatory arthritis.The study itself compared 3 different dose regimens of brodalumab (70 mg, 140 mg, and 210 mg) and placebo; doses were given every 2 weeks, with an additional loading dose at 1 week. The population studied was a typical methotrexate (MTX) inadequate responder population (∼80% female, 7–8 years of disease, Disease Activity Score28 ∼6.4, Health Assessment Questionnaire-Disability Index 1.4, and mean dose of MTX 17 mg/week). The primary endpoint selected was the ACR50 (American College of Rheumatology 50% improvement) response rate at Week 12. There was no benefit seen for any of the brodalumab doses over placebo, and no dose response seen for the 3 tested doses. None of the secondary endpoints were achieved either. This was in contrast to the brodalumab data in PsA, … Address correspondence to Dr. Ruderman. E-mail: e-ruderman{at}northwestern.edu ER -