A Retrospective Evaluation of Over-the-Counter Products Versus Recently Approved Oral Prescription Products for Episodic Migraine

Abstract Title: A Retrospective Evaluation of Over-the-Counter Products Versus Recently Approved Oral Prescription Products for Episodic Migraine

Background: Combination analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), triptans, ergots, and opioids have long been the mainstay of episodic migraine treatment. A study examining a sample of migraine sufferers (n= 568) representative of the larger United States (US) population found that 49% use over-the-counter (OTC) products alone and another 23% combine them with prescription (Rx) products to treat their episodic migraine. In recent years, the treatment paradigm for episodic migraine has changed to include new classes of oral Rx products: gepants and selective 5-HT agonists. However, no head-to-head comparisons between these new Rx products and current OTC migraine products presently exist.

Purpose/Objectives: The purpose of this analysis is to evaluate how the existing OTC products indicated for episodic migraine in the US (the triple combination of acetaminophen, aspirin and caffeine [AAC], and ibuprofen [IBU]) compare with the recently approved classes of oral Rx products (gepants and selective 5-HT agonists).

Method: This is a retrospective evaluation of published pivotal episodic migraine studies for comparison with the approved migraine doses of IBU (400mg), AAC (500mg/500mg/130mg), gepants (rimegepant [RIM] 75mg and ubrogepant [UBR] 50mg), and 5-HT agonist lasmiditan [LAS](100mg) compared to placebo.

Studies with standard clinical trial endpoints to assess the products’ efficacy in episodic migraine were reviewed. Primary efficacy endpoints were defined as measures of headache “pain-relief” (% of patients who reported pain reduction from “severe/moderate pain” to “mild/no pain”) and “pain-freedom” (% of patients who reported “severe/moderate pain” to “no pain”) 2 hours post-dose. Secondary endpoints included time to pain-freedom, need for supplemental medication, reduction in nausea, photophobia, phonophobia, and sustained pain-relief for 24 hours.

Search parameters were limited to pivotal, placebo-controlled studies conducted with adults in the US. Two IBU, three AAC, one RIM, two UBR, and two LAS studies met the inclusion criteria.

Results: At 2-hours post-dose, all OTC and Rx products significantly improved pain-relief and pain-freedom compared to placebo. For OTC, the pain-relief and pain-freedom achieved by AAC 500mg/500mg/130mg was (59.3% vs ∆26.5% and 20.8% vs ∆13.7%) and by solubilized-IBU 400mg (72.3% vs ∆22.3% and 27.7% vs ∆14.3%) respectively. Similarly for Rx, pain-relief provided by RIM 75mg, UBR 50mg, and LAS 100mg was (59.3% vs ∆16.0%), (61.7% vs ∆13.1%), (62.1% vs ∆17.2%) and pain-freedom was (21.2% vs ∆10.3%), (20.5% vs ∆7.5%), and (29.8% vs ∆11.5%) respectively. IBU-tablets had lower pain-relief (40.8% vs ∆12.7%) and pain-freedom (13.9% vs ∆6.2%) than other products.

Conclusions: OTC and newly approved oral Rx products demonstrated statistically significant better responses on both primary endpoints of 2 hour pain relief and pain freedom compared to placebo, confirming their ability to treat episodic migraine, even though some differences in response at 2 hours post-dose between types of medications did exist. However, OTC treatments continue to be an important front-line option for episodic migraine. AAC and IBU have a long history of use and an established role in treating episodic migraine as recognized in the American Headache Society migraine treatment guidelines.i OTC treatments offer convenience and affordability when compared to the newer oral Rx products. Use of OTC products is and should remain an important part of an integrated healthcare approach for episodic migraine with the newer oral Rx therapeutic approaches for treatment.

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