Efficacy of oral ketoprofen in acute migraine: a double‐blind randomized clinical trial.

Abstract

Neurology. 2002 Jun 11;58(11):1660‐1665Background: Certain nonsteroidal anti‐inflammatory drugs are effective in the acute treatment of migraine attacks. The authors report a double‐blind, placebo‐controlled, randomized cross‐over trial of a dual‐release formulation of oral ketoprofen in the acute treatment of migraine attacks.Methods: The authors compared the efficacy of two doses of ketoprofen (75 or 150 mg) with that of placebo (primary analysis) and zolmitriptan 2.5 mg (secondary analysis) on one to four consecutive attacks in 235 intent‐to‐treat patients (out of 257 randomized patients) with migraine with or without aura. The principal efficacy outcome was headache relief (reduction in headache severity from severe or moderate to mild or absent at 2 hours).Results: Results are based on 838 attacks with a severe or moderate headache that were evaluable at 2 hours. Relief was reported for 62.6% of headaches treated with ketoprofen 75 mg, 61.6% with ketoprofen 150 mg, and 66.8% with zolmitriptan. The difference between the three active treatments and placebo (27.8% relief) was highly significant, both tests of ketoprofen vs placebo being globally controlled at a 5% level for the type I error (primary analysis). Headaches at 2 hours disappeared more frequently for the active treatments than for placebo. The authors also demonstrated efficacy on most other secondary outcomes. The tolerance of ketoprofen was good (similar to that of placebo).Conclusions: Oral ketoprofen (75 mg or 150 mg) in a dual‐release formulation is an effective and well‐tolerated drug in the acute treatment of migraine attacks.Comment: Almost none of the studies comparing triptans to nonsteroidal anti‐inflammatory drugs (NSAIDs) or non‐triptans show a superiority for triptans for the primary endpoint of headache response at 2 hours. Most of the studies show a superiority for triptans over NSAIDs for the secondary endpoint of pain‐free at 2 hours. Pain‐free response appears linked to sustained pain‐free response, that is to the migraine not recurring. Dr. Julio Pascual's prospective study (Pascual J, Fite B, Lopez‐Gil A. Comparison of triptan tablet consumption per attack: a prospective study of migraineurs in Spain. Headache. 2002;42:93‐98) on tablet consumption per attack in Spain found that non‐triptan tablet use per attack was always higher than triptan use. Dr. Jean Schoenen has raised the issue that this may be due to inadequate doses for the NSAIDs. However, in the aspirin‐metoclopramide vs sumatriptan studies (eg, Tfelt‐Hansen P, Henry P, Mulder LJ, Scheldewaert RG, Schoenen E, Chazot G. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet. 1995;346:923‐926) the 1000‐mg dose of aspirin seems adequate, and yet pain‐free numbers favored sumatriptan. It is possible that the key difference in NSAIDs versus triptans is not in the ability to give relief, but in the ability to yield a sustained pain‐free result. The probable superiority of triptans in this regard might reduce the likely need for re‐dosing in an attack, and decrease the risk for medication overuse headache. Further studies comparing triptans and non‐triptans should use pain‐free, sustained pain‐free, and number of doses per attack as primary endpoints rather than headache response. SJT