Low-Dose DFN-11 Successful in Relieving Severe and Moderate Acute Migraine Pain

Stephen Landy, MD, neurologist, Baptist Medical Group

Stephen Landy, MD

A 3-mg, low-dose sumatriptan injection, dubbed DFN-11, was shown to relieve both pain and the most bothersome symptom similarly in acute attacks of moderate and severe pain intensity in patients with migraine.¹

Led by Stephen Landy, MD, neurologist, Baptist Medical Group, the investigators reported that in a cohort of 268 patients, DFN-11 reported significantly higher rates of pain freedom at 2 hours compared with placebo (P = .002) as well as pain relief at 2 hours (P = .018) compared to placebo. Additionally, the rates of freedom from the most bothersome symptom in post hoc analysis were also significantly higher when compared to placebo (P = .021).

The study data, which were analyzed from the RESTOR study, were presented in a poster at the 2019 American Headache Society (AHS) Annual Meeting, July 11-14, 2019, in Philadelphia, Pennsylvania.

Landy and colleagues wrote that “subjects with at least 12 months of episodic migraine (2 to 6 attacks per month on average), with no more than 14 headache days per month, and at least 48 headache-free hours between attacks, were randomized 1:1 to DFN or placebo in the double-blind period.” In total, 119 patients were randomized to placebo and 111 to DFN-11, with 104 in each treatment arm (208 total) having data post-dose.

The patients were instructed to self-administer DFN-11 to treat migraine attacks at moderate or severe pain intensity, defined as 2 or 3 on a rating scale of 0 to 3, and record real-time pain intensity and symptoms pre-dose and post-dose in an electronic diary.

The pain-freedom rates at 2 hours for the treatment arm and placebo arms, respectively, were 51% and 30.8%, while pain-relief was achieved by 76% and 61.5%, respectively. At 2 hours post-dose, 641% of the DFN-11 arm experienced freedom from their most bothersome symptom (nausea, photophobia, or phonophobia) compared to 48.1% in the placebo arm (P = .031).

Pain intensity was measured prior to the dose administration, with 78% (n = 68) of the DFN-11 group reporting moderate pain and 22% (n = 19) reporting sever pain. In the placebo group, the distribution similar between moderate and severe.

Of those in the DFN-11 group, 52.9% of the moderate pain subgroup reported pain-freedom at 2 hours while 47.4% in the severe pain subgroup achieved pain freedom. With regard to pain relief at 2 hours, this outcome was achieved by 77.9% of the moderate pain group and 68.4% of the severe pain group. As for freedom from the most bothersome system in the moderate and severe pain subgroups of the DFN cohort, freedom was achieved post dose by 62.3% and 70.6%, respectively.

“Placebo response rates at 2 hours post-dose for subjects with moderate pain pre-dose were higher vs. subjects with sever pre-dose pain intensity for all 3 measures,” Landy and colleagues detailed. “The overall therapeutic gain appears to be greater for severe [pain intensity].”

The investigators noted that the efficacy of DFN-11 has been established previously in the acute treatment of migraine in the aforementioned phase 3 study, RESTOR. In that trial, those treated with DFN-11 reported significantly higher rates of pain-freedom at 2 hours post-dose (P =  .0023), as well as higher proportions of patients who were pain-free at 30, 60, and 90 minutes post-dose (P ≤.0195). Additionally, at 2 hours post-dose, DFN-11 was also significantly superior to placebo for freedom from photophobia (P  = .0056) and phonophobia (P = .0167).²

Safety and tolerability in the RESTOR study were considered good. In total, 33.3% (37 of 111 patients) of those who received DFN-11 and 13.4% (16 of 119) of those who received placebo experienced at least 1 treatment-emergent adverse event (AE). The most common AEs for the DFN-11 group and placebo group, respectively, were injection site swelling (7.2% vs 0.8%) and pain (7.2% vs 5.9%). Chest discomfort was about half as common in the DFN-11 treatment group (0.9%) as it was in the placebo group (1.7%).

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REFERENCES

1. Landy S, Munjal S, Brand-Schieber E, Rapoport A. The effect of migraine headache intensity on the efficacy of low-dose (3 mg) sumatriptan injection (DFN-11) in the acute treatment of episodic migraine attacks: from the RESTOR study. Presented at: 2019 American Headache Society Annual Meeting; July 11-14, 2019; Philadelphia, PA. Poster P156.

2. Landy S, Munjal S, Brand-Schieber E, Rapoport AM. Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: a multicenter, randomized, double-blind, placebo-controlled study. J Headache Pain. 2018;19(1):69. doi: 10.1186/s10194-018-0881-z.