Shift from chronic to episodic migraine frequency in a long-term phase 3 study of galcanezumab

Abstract

Background: Chronic migraine (CM) is a highly disabling form of migraine in which patients have ≥ 15 headache days per month, of which at least 8 have the features of migraine. Galcanezumab is a monoclonal antibody to calcitonin gene-related peptide which is approved for the preventive treatment of migraine. Ability to convert patients from chronic migraine frequency to episodic migraine (EM) frequency is a clinically relevant and desirable outcome when prescribing preventive treatments to patients with CM.

Methods: Patients aged 18-65 years with an ICHD-3β diagnosis of CM were randomized 2:1:1 to receive monthly injections of placebo (N = 558), galcanezumab 120 mg with a 240-mg loading dose (N = 278), or galcanezumab 240 mg (N = 277) during a 3-month double-blind period of the phase 3 REGAIN trial. Patients could subsequently enter a 9-month open-label extension in which they received galcanezumab 120 mg or 240 mg/month per investigator's discretion. In this post-hoc analysis, we assessed the percentages of patients who shifted to EM (< 8 migraine headache days or < 15 headache days/month), low frequency EM (LFEM; <8 migraine headache days/month), and very low frequency EM (VLFEM; <4 migraine headache days/month) for at least 3 consecutive months. Double-blind percentage comparisons versus placebo represent modeled estimates from raw rates.

Results: At baseline, patients had a mean of 19.4 migraine headache days per month (SD = 4.5) and 21.4 headache days per month (SD = 4.1). During the 3-month double-blind treatment period, a greater percentage of galcanezumab-treated patients shifted to EM frequency and maintained it across all 3 months (31.5%) than did placebo-treated patients (19.8%, p < 0.001). Among galcanezumab-treated patients across the entire 12-month trial, 65.1% shifted from CM to EM frequency, with 44.2% shifting to LFEM and 21.5% shifting to VLFEM for ≥ 3 consecutive months. Proportions of patients shifting from CM to EM frequency for ≥ 3 consecutive months and until last patient visit were: 55.0% to EM; 33.4% to LFEM; 13.9% to VLFEM.

Conclusion: These results suggest that galcanezumab helped a majority of patients convert from chronic to episodic migraine frequency over the course of this 12-month study.

Trial registration: Clinicaltrials.gov NCT02614261, first registered November 25, 2015.

Keywords: Calcitonin gene-related peptide; Chronic migraine; Episodic migraine; Galcanezumab; Migraine prevention.

Fig. 1

Percentage of patients shifting from CM to EM frequency during the 3-month double-blind treatment period. The percentage of patients shifting to EM frequency is shown at Month 3 (A) and at all 3 Months (B). EM is defined as < 8 migraine headache days/month or < 15 headache days/month, LFEM as < 8 migraine headache days/month, and VLFEM as < 4 migraine headache days/month. Thus, EM includes LFEM and VLFEM, and LFEM includes VLFEM. *p < 0.05, **p < 0.01, ***p < 0.001 (vs. placebo). Abbreviations: EM, episodic migraine, LFEM, low frequency episodic migraine; VLFEM, very low frequency episodic migraine

Fig. 2

Percentage of patients shifting from CM to EM frequency during the 12-month study. The percentage of patients is shown who maintained a shift to EM frequency from CM for ≥ 3 consecutive months on galcanezumab during the 12-month study (double-blind and OLE periods) (A) and who maintained that ≥ 3-month shift to EM frequency until their endpoint (B). Bars are labeled based on the randomized treatment group assigned at the start of the 3-month double-blind period. Patients who were on placebo during the double-blind period and received galcaneumab during the OLE period only have data from the OLE included in this analysis and are labelled as “From previous placebo.” The “All galcanezumab” group includes all patients who received galcanezumab in either the double-blind or OLE periods, regardless of previous randomized group. EM is defined as < 8 migraine headache days/month or < 15 headache days/month, LFEM as < 8 migraine headache days/month; and VLFEM as < 4 migraine headache days/month. Thus, EM includes LFEM and VLFEM, and LFEM includes VLFEM. Abbreviations: EM, episodic migraine, LFEM, low frequency episodic migraine; OLE, open-label extension; VLFEM, very low frequency episodic migraine

Fig. 3

The distribution of non-overlapping headache frequency categories during the 12-month study. The distribution shown is based on unique categories defined by frequency of migraine headache days that were achieved for at least 3 consecutive months (A) and for at least 3 consecutive months and maintained until the patient’s endpoint (B). The percentage of all patients who shifted to < 4 migraine headache days/month, ≥ 4 migraine headache days/month but < 8 migraine headache days/month, and ≥ 8 migraine headache days/month, but < 15 headache days/month, as well as those who had CM frequency throughout, are shown for the proportion of patients who had a shift for ≥ 3 consecutive months (A) and for those who maintained that shift for ≥ 3 consecutive months and until the patient’s endpoint (B). Abbreviations: CM, chronic migraine; EM, episodic migraine; HDs, headache days; LFEM, low frequency episodic migraine; MHDs, migraine headache days; OLE, open-label extension; VLFEM, very low frequency episodic migraine