CGRP blockade by galcanezumab was not associated with reductions in signs and symptoms of knee osteoarthritis in a randomized clinical trial

Objective: This study tested whether galcanezumab, a humanized monoclonal antibody with efficacy against migraine, was superior to placebo for the treatment of mild or moderate osteoarthritis (OA) knee pain. Method: In a multicenter, double-blind, placebo-and celecoxib-controlled trial, patients with moderate to severe OA pain were randomized to placebo; celecoxib 200 mg daily for 16 weeks; or galcanezumab 5, 50, 120, and 300 mg subcutaneously every 4 weeks, twice. The primary outcome was change from baseline at Week 8 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore measured by 100 mm visual analog scale (VAS). The trial was considered positive if >1 dose of galcanezumab demonstrated >= 95% Bayesian posterior probability of superiority to placebo and >= 50% posterior probability of superiority to placebo by >= 9 mm. A planned interim analysis allowed termination of the study if posterior probability of superiority to placebo by >= 9 mm was <= 5%. Secondary endpoints included WOMAC function subscore and Patient Global Assessment (PGA) of OA. Safety and tolerability were also assessed. Results: The study was terminated after interim analysis suggested inadequate efficacy. Celecoxib significantly reducedWOMAC pain subscore compared with placebo [-12.0 mm; 95% confidence interval (CI) -23 to -2 mm]. None of the galcanezumab arms demonstrated clinically meaningful improvement (range: 1.5 to -5.0 mm) or met the prespecified success criteria. No improvement in any secondary objective was observed. Galcanezumab was well tolerated by OA patients. Conclusions: This study failed to demonstrate sufficient statistical evidence that galcanezumab was efficacious for treating OA knee pain. Study identification: NCT02192190. (c) 2018 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.