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

• Published in: Osteoarthritis and cartilage 2018-12, Vol.26 (12), p.1609-1618
• Main Authors: Jin, Y., Smith, C., Monteith, D., Brown, R., Camporeale, A., McNearney, T.A., Deeg, M.A., Raddad, E., Xiao, N., de la Peña, A., Kivitz, A.J., Schnitzer, T.J.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Calcitonin Gene-Related Peptide - antagonists & inhibitors; Celecoxib - therapeutic use; CGRP; Clinical trial; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Knee pain; Male; Middle Aged; Monoclonal antibody; Osteoarthritis; Osteoarthritis, Knee - complications; Osteoarthritis, Knee - drug therapy; Pain - drug therapy; Pain - etiology; Pain Management - methods; Pain Measurement - methods; Severity of Illness Index; Treatment Outcome
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2018.08.019

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. 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. The study was terminated after interim analysis suggested inadequate efficacy. Celecoxib significantly reduced WOMAC 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. This study failed to demonstrate sufficient statistical evidence that galcanezumab was efficacious for treating OA knee pain. NCT02192190.