Lasmiditan is more effective compared to placebo in the patients with moderate to severe migraine disability regardless of their prior triptan response, researchers report at the 2018 PAINWeek conference.
Lasmiditan is a novel, centrally acting serotonin agonist with specificity for the 5-HT1F receptors.
In a combined post-hoc analysis of two phase III studies, the therapeutic benefit of lasmiditan in patients with moderate or severe migraine disability was “generally unaffected” by their prior triptan therapy response, according to Kerry Knievel, DO, of the Barrow Neurological Institute in Phoenix, and colleagues in a poster presentation at the 2018 PAINWeek conference.
In two randomized, double-blind phase III trials —SAMURAI and SPARTAN — oral lasmiditan bested placebo in the acute treatment of migraine. Both trials of the investigational drug studied adults with moderate to severe migraine disability (Migraine Disability Assessment score ≥11). In both studies, the percentage of patients who were migraine pain-free 2 hours after their first dose was significantly greater with 100 mg or 200 mg lasmiditan compared with placebo.
This post-hoc analysis examined whether a response to lasmiditan in SAMURAI and SPARTAN differed with how patients had responded to prior triptan therapy. It included placebo (n=429), 100 mg lasmiditan (n=382), and 200 mg lasmiditan (n=371) patients who had used triptans in the 3 months before the trials.
At baseline, these patients rated themselves as good, poor, or non-responders to their prior triptan therapy. Baseline characteristics generally were consistent between good and poor/non-responders.
- In the 200 mg lasmiditan group, the benefit of lasmiditan versus placebo did not vary significantly between triptan responder subgroups.
- In the 100 mg lasmiditan group, poor/non-responders showed a greater differential benefit than good responders in headache pain freedom and most bothersome symptom (MBS) freedom.
- The significant differences in headache pain freedom and MBS freedom at 2 hours between triptan good responders and poor/non-responders with lasmiditan 100 mg may reflect the numerically higher placebo response rates in good responders than in poor/non-responders (resulting from expectation bias).
- Numerically lower 100 mg lasmiditan response rates in good responders versus 200 mg lasmiditan also may have contributed to these findings.
- For each lasmiditan dose, the risk relative to placebo of experiencing a treatment-emergent adverse event was significantly lower for patients who had poor or no triptan response than it was for good responders.
- At the 100-mg dose, the OR of experiencing ≥1 adverse event was 3.2 for poor/non-responders responders compared with 6.5 (P=0.072) for good responders, relative to placebo.
- At the 200-mg dose, the OR was 3.8 for poor/non-responders and 8.1 (P=0.048) for good responders.
- Most treatment-emergent adverse events in SAMURAI and SPARTAN were mild to moderate.
The analysis had several limitations, the authors noted. Prior triptan response was a subjective assessment by the patient. There also was some variation in results between the individual SAMURAI and SPARTAN studies.
“Further work is needed, including more focused assessment of triptan response among those who had recently used the drugs or who had discontinued them in the past. More study is needed to better understand the findings, including the findings for treatment-emergent adverse events,” concluded the authors.