Migraine Headache Day Response Rates and the Implications to Patient Functioning: An Evaluation of 3 Randomized Phase 3 Clinical Trials of Galcanezumab in Patients With Migraine

Abstract

Objective: This post hoc study investigated the relationship between patient response in terms of migraine headache day reduction and patient-reported outcomes of health-related quality of life (HRQoL) and disability categories.

Background: Migraine causes considerable disease-related disability and negatively impacts HRQoL of patients. Calcitonin gene-related peptide inhibitors improve these outcomes and may eliminate disability due to migraine in some patients.

Methods: Analyses used data from 3 double-blind, placebo (PBO)-controlled, phase 3 studies in adults with episodic migraine (EM) (EVOLVE-1: N = 858 and EVOLVE-2: N = 915) or chronic migraine (CM) (REGAIN: N = 1113). Patients were randomized 2:1:1 to subcutaneous injection of PBO, galcanezumab (GMB) 120 mg, or GMB 240 mg once monthly for 6 months in EVOLVE-1 and -2 and for 3 months in REGAIN. Primary endpoint was overall mean change from baseline in monthly migraine headache days. Patients were divided into 4 response-level groups based on percent change from baseline (<30%, ≥30% to <50%, ≥50% to <75%, ≥75%). Patient-reported outcomes included the 14-item Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ) and Migraine Disability Assessment (MIDAS) questionnaire.

Results: Among patients with migraine, mean improvements from baseline in MSQ domain scores increased with each successive level of migraine headache day response. On a 100-pt scale, increases in Role Function-Restrictive score in EM were 16.8 and 36.0 at the <30% and ≥75% response levels, respectively, and for CM were 10.7 and 46.5. Similar patterns in scores were observed for the Role Function-Preventive and Emotional Function domains. Examination of improvement in MSQ item score by treatment group showed that, in patients with EM, approximately 10 to 20% more GMB-treated patients (N = 796 for GMB 120 mg and GMB 240 mg) had improvements in all 14 MSQ items compared with PBO-treated patients (N = 773) (all P < .001). In patients with CM, 3 to 16% more GMB-treated patients (N = 507) had improvements in the 14 MSQ items compared with PBO (N = 494), though differences were statistically significant in only 19 of 28 comparisons. At baseline, mean MIDAS scores (EM, 33.1; CM, 67.2) indicated severe mean disability for patients with EM and very severe disability for patients with CM. Among patients with EM, 215 of 425 (50.6%) of those treated with GMB 120 mg and 212 of 413 (51.3%) treated with 240 mg had little/no disability due to migraine after 6 months (PBO: 277 of 832 (33.3%), P < .001 for both). Among patients with CM, 50 of 254 (19.7%) of those treated with GMB 120 mg and 54 of 258 (20.9%) treated with 240 mg reached the level of little/no disability after 3 months of treatment (PBO: 70 of 504 (13.9%), P = .045 for 120 mg, P = .017 for 240 mg).

Conclusions: Because migraine greatly impairs an individual's ability to participate in activities of daily living, measurements of HRQoL are essential in clinical research. This study showed that function in daily life, as measured by MSQ score, improved as migraine headache days were reduced and that GMB-treated patients were more likely to see improvement in MSQ item scores compared with PBO-treated patients. Elimination of migraine-related disability was also more frequent in GMB-treated patients compared with placebo-treated patients.

Keywords: calcitonin gene-related peptide; chronic migraine; episodic migraine; galcanezumab; patient-reported outcomes.

Fig. 1

Patients were grouped by response rates based on their percent decrease from baseline in monthly migraine headache days. Response groups included both galcanezumab‐ and placebo‐treated patients. Mean change from baseline in unscaled Migraine‐Specific Quality of Life Questionnaire version 2.1 (MSQ) item scores (range 1‐6 for each item) were calculated for each response group. Points represent the mean change in score for individual items from the role function‐restrictive (RF‐R), role function‐preventive (RF‐P), and emotional function (EF) domains of the MSQ for response groups from EVOLVE‐1 and ‐2 (1a) and REGAIN (1b). Error bars show standard error of mean (SEM). Abbreviated content of MSQ items: 1. Migraine interfered with how dealt with family. 2. Migraine interfered with leisure activities. 3. Difficulty performing work or daily activities due to migraine. 4. Kept from getting much done at work or home due to migraine. 5. Migraine limited ability to concentrate at work or for an activity. 6. Migraine made too tired for work or activities. 7. Migraine limited the days felt energetic. 8. Skipped work or activity due to migraine. 9. Often needed help in handling routine tasks. 10. Stopped work or activity due to migraine. 11. Not gone to social activity due to migraine. 12. Felt frustrated due to migraine. 13. Felt like a burden due to migraine. 14. Afraid to disappoint others due to migraine.Pvalues across response groups were <.001 for all MSQ items in both episodic and chronic migraine populations.

Fig. 2

Patients from EVOLVE‐1 and ‐2 (3a) and REGAIN (3b) were grouped into baseline Migraine Disability Assessment (MIDAS) disability categories using baseline total MIDAS score. Bars show percentages of patients who were in the “little/no disability” category at the trial endpoint (Month 6 for EVOLVE‐1 and ‐2 and Month 3 for REGAIN) for baseline disability categories of “moderate,” “severe,” and “very severe,” as well as all patients together, by treatment. The “all patients” group also included patients with baseline MIDAS categories of “mild” and “little/no” disability. Galcanezumab (GMB).*P < .05, **P < .01, ***P < .001 vs placebo (PBO) by Fisher’s exact test.