Freedom From Most Bothersome Headache-Associated Symptom Feasible as Primary End Point

Using freedom from most bothersome symptom (MBS) associated with headache as a co-primary end point with freedom from pain is a feasible and desirable alternative to the traditional 4 co-primary end points, according to results published in Headache.

The phase 2b/3 ZOTRIP study evaluated adhesive dermally applied microarray (ADAM) zolmitriptan for the treatment of acute moderate to severe migraine compared with placebo (n=159). It was one of the first largest studies to incorporate MBS freedom as a co-primary end point with pain freedom. During the trial, the percentage of participants treated with ADAM zolmitriptan 3.8 mg who were pain-free and MBS-free at 2 hours post-dose was significantly higher compared with participants treated with placebo.

In their new study, the researchers performed a post-hoc analysis of data from the ZOTRIP study to compare how its end points compared with conventional end points of pain relief, nausea, photophobia, and phonophobia.

Of the participants, 79 reported photophobia as their MBS, 43 reported phonophobia, and 37 reported nausea.

Of the participants with photophobia as their MBS, 36% in the treatment group were pain-free at 2 hours compared with 14% in the placebo group (P =.02). Of these participants, 2-hour freedom from MBS was 67% in the treatment group and 35% in the placebo group (P<.01).

In participants with phonophobia as their MBS, 41% in the treatment group were pain-free at 2 hours compared with 14% in the placebo group (P =.05). Of these participants, 2-hour freedom from MBS was 55% in the treatment group and 43% in the placebo group (P =.45).

In participants with nausea as their MBS, 56% in the treatment group were pain-free at 2 hours compared with 16% in the placebo group (P=.01). Of these participants, 2-hour freedom from MBS was 89% in the treatment group and 58% in the placebo group (P=.04).

Only 28% of participants achieved MBS freedom without pain freedom, and only 1 participant achieved pain freedom but not MBS freedom.

“The major associated symptoms of migraine — photophobia, phonophobia, and nausea — are important for assessing a therapy’s effect on the migraine, but all symptoms are not always present,” the researchers wrote. “Therefore, requiring the elimination of a symptom that was never present and requiring a therapy to have a higher response rate than placebo in nausea freedom at 2 hours may require a large sample size per treatment group.”

Reference

Dodick DW, Tepper SJ, Friedman DI Gelfand AA, Kellerman DJ, Schmidt PC. Use of most bothersome symptom as a coprimary endpoint in migraine clinical trials: a post-hoc analysis of the pivotal ZOTRIP randomized, controlled trial. [published online May 21, 2018]. Headache. doi:10.1111/head.13327