Benefit-Risk Assessment of Galcanezumab Versus Placebo for the Treatment of Episodic and Chronic Migraine Using the Metrics of Number Needed to Treat and Number Needed to Harm

Abstract

Introduction: Subcutaneous galcanezumab was an effective, well-tolerated preventive treatment for adults with episodic (EM) or chronic migraine (CM) in 4 phase 3 randomized controlled trials: EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER. Number needed to treat (NNT) and to harm (NNH) are metrics of effect size used to evaluate benefit-risk profiles. This study evaluated NNT, NNH, and benefit-risk profiles (measured as likelihood to be helped or harmed, LHH) of galcanezumab 120 mg versus placebo in patients with EM or CM.

Methods: Primary efficacy outcomes were responses defined as ≥ 30%, ≥ 50%, and ≥ 75% reductions from baseline in number of monthly migraine headache days in patients with EM (EVOLVE-1; EVOLVE-2; CONQUER) and CM (REGAIN; CONQUER); corresponding NNTs to achieve respective responses; and corresponding NNHs for discontinuations due to adverse events (DCAEs) among the safety population. Secondary efficacy outcomes were responses for patients with ≥ 2 failed prior preventive treatments due to lack of efficacy and/or for tolerability reasons. All LHHs were based on ≥ 50% response and DCAEs.

Results: During double-blind treatment periods with galcanezumab 120 mg, NNT to achieve ≥ 30% and ≥ 50% responses ranged from 4 to 10 and NNT to achieve ≥ 75% responses ranged from 5 to 23 in individual trials. NNH ranged from 93 to 1000, while LHH ranged from 18.6 to 104.6. NNTs were generally more robust among patients with EM than with CM; however, in patients with failure of ≥ 2 prior preventive treatments, NNTs to achieve ≥ 30% and ≥ 50% responses were similar between patients with CM and EM. NNHs were imputed as 1000 for both migraine types. Resulting LHHs were 178.8 (EM) and 127 (CM).

Conclusion: Across 4 trials, galcanezumab 120 mg demonstrated a favorable benefit-risk profile versus placebo, based on low NNTs to achieve response and high NNHs associated with DCAEs. LHH values consistently far exceeded 1.

Trial registration numbers: EVOLVE-1: ClinicalTrials.gov identifier, NCT02614183; EVOLVE-2: ClinicalTrials.gov identifier, NCT02614196; REGAIN: ClinicalTrials.gov identifier, NCT02614261; CONQUER: ClinicalTrials.gov identifier, NCT03559257.

Keywords: Benefit–risk profile; Chronic migraine; Effect size; Episodic migraine; Galcanezumab; Likelihood of help versus harm; Number needed to harm; Number needed to treat.