Efficacy of early vs. late use of frovatriptan combined with dexketoprofen vs. frovatriptan alone in the acute treatment of migraine attacks with or without aura

Abstract

Early triptan use after headache onset may help improve the efficacy of acute migraine treatment. This may be particularly the case when triptan therapy is combined with a nonsteroidal anti-inflammatory drug (NSAID). The objective of this is to assess whether the combination of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex25 and FroDex37.5) is superior to frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks in patients who took the drug within 30 min from the onset of pain (early use) or after (late use). A total of 314 subjects with a history of migraine with or without aura were randomized into a double-blind, multicenter, parallel group, pilot study to Frova, FroDex25 or FroDex37.5 and were required to treat at least one migraine attack. In the present post hoc analysis, traditional migraine endpoints were compared across study drugs for subgroups of the 279 patients of the full analysis set according to early (n = 172) or late (n = 107) drug use. The proportion of patients pain free at 2 h in the early drug use subgroup was 33 % with Frova, 50 % with FroDex25 and 51 % with FroDex37.5 mg (p = NS combinations vs. monotherapy), while in the late drug use subgroup was 22, 51 and 50 % (p < 0.05 FroDex25 and FroDex37.5 vs. Frova), respectively. Pain-free episodes at 4 h were 54 % for early and 34 % for late use of Frova, 71 and 57 % with FroDex25 and 74 and 68 % with FroDex37.5 (p < 0.05 for early and p < 0.01 for late use vs. Frova). The proportion of sustained pain free at 24 h was 26 % under Frova, 43 % under FroDex25 mg and 40 % under FroDex37.5 mg (p = NS FroDex25 or 37.5 vs. Frova) in the early drug intake subgroup, while it was 19 % under Frova, 43 % under FroDex25 mg and 45 % under FroDex37.5 mg (p < 0.05 FroDex25 and FroDex37.5 vs. Frova) in the late drug intake subgroup. Risk of relapse at 48 h was similar (p = NS) among study drug groups (Frova: 25 %, FroDex25: 21 %, and FroDex37.5: 37 %) for the early as well as for the late drug use subgroup (14, 42 and 32 %). FroDex was found to be more effective than Frova taken either early or late. The intrinsic pharmacokinetic properties of the two single drug components made FroDex combination particularly effective within the 2–48-h window from the onset of the acute migraine attack. The efficacy does not seem to be influenced by the time of drug use relative to the onset of headache.

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

“…FroDex late intake decreased the use of rescue medications in respect of monotherapy, thus confirming our previous results with late intake after 30-min [12]. Thus, the combination of triptan plus NSAIDs could reduce the risk of medication-overuse headaches and related adverse drug effects [11,16].…”

“…The combination was more effective than monotherapy on pain free at 2-h regardless of timing and dosing, confirming evidence from the main study [10] and from a previous post hoc analysis assessing the efficacy of the drug taken 30-min before or after pain onset [12]. The early intake of FroDex 25 mg increased pain-free activity at 2 and 4-h compared to Frova.…”

“…In our previous post hoc analysis in which we defined as ''early'' the intake within 30-min from headache onset, we observed a significant improvement on pain free at 2-h activity in the late intake group (FroDex 25 51 % vs. Frova 22 %, p \ 0.005, FroDex 37.5 50 % vs. Frova 22 %, p \ 0.005), while in the early intake group the difference in favor of the combination did not achieve the statistical significance [12]. Here, even the early intake resulted significantly more efficient than monotherapy at promoting pain-free activity at 2 and 4-h. FroDex intake after 30-min but within 1-h from headache onset may have major and longer benefits than triptan monotherapy on pain control, even with lower NSAID dosing.…”

“…Therefore, a retrospective analysis from the aforementioned randomized study was performed to analyze whether drug use within 30-min from headache pain onset may affect combination efficacy. The timing of drug intake relative to the onset of headache did not seem to influence clinical benefits of frovatriptan plus dexketoprofen [12]. The combination was confirmed as similarly effective at treating acute migraine attacks either with early or late administration.…”

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

“…The efficacy of the combination of frovatriptan and the NSAID dexketoprofen has also recently been investigated. 26 – 28 …”