Early (≤1-h) vs. late (>1-h) administration of frovatriptan plus dexketoprofen combination vs. frovatriptan monotherapy in the acute treatment of migraine attacks with or without aura: a post hoc analysis of a double-blind, randomized, parallel group study

Abstract

The early use of triptan in combination with a nonsteroidal anti-inflammatory drug after headache onset may improve the efficacy of acute migraine treatment. In this retrospective analysis of a randomized, double-blind, parallel group study, we assessed the efficacy of early or late intake of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex 25 and FroDex 37.5) vs. frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks. In this double-blind, randomized parallel group study 314 subjects with acute migraine with or without aura were randomly assigned to Frova, FroDex 25, or FroDex 37.5. Pain free (PF) at 2-h (primary endpoint), PF at 4-h and pain relief (PR) at 2 and 4-h, speed of onset at 60, 90, 120 and 240-min, and sustained pain free (SPF) at 24-h were compared across study groups according to early (≤1-h; n = 220) or late (>1-h; n = 59) intake. PF rates at 2 and 4-h were significantly larger with FroDex 37.5 vs. Frova (early intake, n = 71 FroDex 37.5 and n = 75 Frova: 49 vs. 32 % and 68 vs. 52 %, p < 0.05; late intake, n = 20 Frodex 37.5, and n = 18 Frova: 55 vs. 17 %, p < 0.05 and 85 vs. 28 %, p < 0.01). Also with FroDex 25, in the early intake group (n = 74) PF episodes were significantly higher than Frova. PR at 2 and 4-h was significantly better under FroDex 37.5 than Frova (95 % vs. 50 %, p < 0.001, 100 % vs. 72 %, p < 0.05) in the late intake group (n = 21). SPF episodes at 24-h after early dosing were 25 % (Frova), 45 % (FroDex 25) and 41 % (FroDex 37.5, p < 0.05 combinations vs. monotherapy), whereas they were not significantly different with late intake. All treatments were equally well tolerated. FroDex was similarly effective regardless of intake timing from headache onset.

Spotlight on frovatriptan: a review of its efficacy in the treatment of migraine

“…A further post hoc analysis of the study specifically evaluated the efficacy of frovatriptan plus dexketoprofen compared with monotherapy, when administered early (<1 hour after symptom onset) or late (>1 hour after onset). 27 Both early and late intake of the combination significantly improved pain-free and pain relief at 2 and 4 hours ( Figure 4 ), with the combination therapy similarly efficacious in treating acute migraine attack irrespective of the time of drug intake. 27 Furthermore, late intake of frovatriptan plus high-dose dexketoprofen proved efficient at managing the most severe and difficult attacks, decreasing the use of rescue medication, with 95% pain relief at 2 hours and 100% at 4 hours.…”

“… 27 Both early and late intake of the combination significantly improved pain-free and pain relief at 2 and 4 hours ( Figure 4 ), with the combination therapy similarly efficacious in treating acute migraine attack irrespective of the time of drug intake. 27 Furthermore, late intake of frovatriptan plus high-dose dexketoprofen proved efficient at managing the most severe and difficult attacks, decreasing the use of rescue medication, with 95% pain relief at 2 hours and 100% at 4 hours. This is noteworthy, as it lends support to the notion that the combination of triptan plus NSAIDs could potentially reduce the hazards of medication-overuse headaches and related adverse effects.…”

“…These results suggest that the differences in pharmacokinetic properties between frovatriptan and dexketoprofen may make the combination of these two agents particularly effective in migraine treatment, with dexketoprofen providing early pain relief while the longer half-life of frovatriptan reduces the risk of recurrence within 48 hours. 27 …”