The effect of galcanezumab for treating migraine headache was reduced following treatment cessation but did not return to baseline, and the persistence of clinical activity posttreatment was still deemed significant, according to a study published in Headache.
Long-acting monoclonal antibodies being explored for the treatment of migraine headache have a half-life of about 3 weeks and may be exploited as migraine preventive agents. The investigators of this study sought to assess the safety and efficacy of galcanezumab to prevent migraines after treatment cessation in adults with episodic migraine. The study included 740 patients with migraine headache from the EVOLVE-1 trial and 830 patients from the EVOLVE-2 trial who were randomly assigned 1:1:2 to receive galcanezumab 120 mg, galcanezumab 240 mg, or placebo. Galcanezumab and placebo treatments were administered subcutaneously once a month for 6 months. After treatment completion or discontinuation, participants were followed for another 4 months. Efficacy and safety outcomes were evaluated for the posttreatment period, including change from baseline in monthly migraine headache days, time-to-first loss of 50% response, proportion of patients initiating alternative migraine preventive treatments, quality of life measures, and adverse events.
Change in monthly migraine headache days from baseline to month 6 and month 10 decreased in both the galcanezumab 120 mg group (from 5.2 days at month 6 to 4.1 days at month 10) and the galcanezumab 240 mg group (from 5.3 days at month 6 to 3.8 days at month 10), and remained stable in the placebo group (from 3.4 days at month 6 to 3.3 days at month 10). Relative to baseline, the change in migraine days for the intervention groups was statistically significant at all time points. Compared with the placebo group, each dose group yielded statistically significant differences for each month except for galcanezumab 240 mg at month 10 (120 mg vs placebo: P<.001 months 1 to 6, P =.007 month 7, P =.044 month 8, P =.016 month 9, P =.042 month 10; 240 mg vs placebo: P <.001 months 1 to 7, P =.015 month 8, P =.021 month 9, P =.238 month 10).
Following cessation, time-to-first loss of 50% response increased over the posttreatment period and was similar for all groups. The proportion of participants who initiated alternative migraine preventive treatment was 1.6% of the EVOLVE-1 trial and 2.3% of the EVOLVE-2 trial, but there were no significant differences between intervention and placebo groups. Quality of life measures were greater in the galcanezumab groups vs placebo at month 6, but did not meet statistical significance at month 10. The most common adverse events posttreatment were upper respiratory tract infections; however, no treatment discontinuations were due to adverse events.
Limitations to the study included restricted enrollment criteria, which could prevent the generalizability of the results to more diverse populations, a predominantly Caucasian study population, and the fact that most patients had not failed 1 prior preventative.
The effect of galcanezumab treatment was reduced during the posttreatment period but did not return to baseline, and the reduction of monthly migraine days following treatment cessation was still significant. Galcanezumab was well tolerated and posttreatment persistence of clinical activity may have important implications for patients with migraine who need to stop medication temporarily or switch medications.
Stauffer VL, Wang S, Voulgaropoulos M, Skljarevski V, Kovacik A, Aurora SK. Effect of galcanezumab following treatment cessation in patients with migraine: results from 2 randomized phase 3 trials [published online April 3, 2019]. Headache. doi: 10.1111/head.13508