Supplementary file 1_Comparative efficacy of AAC and ibuprofen versus lasmiditan, ubrogepant, and rimegepant for the acute treatment of episodic migraine in adults: a systematic review and network meta-analysis.docx

Compared with placebo, acetaminophen, aspirin, and caffeine (AAC) combination showed superior 2 h pain relief (RR, 1.76; 95% CI, 1.61–1.94; p-score = 0.96), followed by ibuprofen 400 mg and 200 mg. For 2 h pain freedom, AAC, ibuprofen 400 mg, and lasmiditan 200 mg showed broadly comparable favorable effects versus placebo, with similar RRs and p-scores. AAC also produced the greatest reductions in photophobia and phonophobia at 2 h (photophobia: RR, 1.99; 95% CI, 1.62–2.45; p-score = 0.97; phonophobia: RR, 1.53; 95% CI, 1.28–1.84; p-score = 0.89), while ibuprofen Liquigel 400 mg provided additional meaningful benefit.

For nausea, rimegepant 75 mg demonstrated the strongest effect (RR, 1.15; 95% CI, 1.08–1.22; p-score = 0.85), followed by ibuprofen Liquigel 400 mg and AAC.</p>Conclusion<p>In this NMA, OTC therapies showed meaningful efficacy and favorable safety for acute episodic migraine versus placebo, with ibuprofen and AAC demonstrating consistent benefits across 2 h pain and secondary outcomes. These findings support their use as effective, accessible options alongside newer oral agents.

Larger trials and patient-level analyses are needed to refine efficacy, optimize dosing, and personalize migraine management.</p>Systematic review registration<p>crd.york.ac.uk/PROSPERO/view/CRD420261325571, Identifier CRD420261325571.</p>