To evaluate the relative efficacy and safety of Atzumi (STS101) compared with newly approved oral and intranasal migraine treatments using network meta-analysis.

A systematic search of major databases (to October 2025) identified randomized, placebo-controlled trials of adults with acute migraine. A frequentist random-effects NMA compared Atzumi (STS101), gepants, and triptans for 2-hour pain and MBS freedom, estimating pooled RRs with SUCRA ranking.

Twenty-two randomized controlled trials with approximately 15,400 participants were included. Across studies, a graded efficacy hierarchy was observed for 2-hour pain freedom (PF). Atzumi (STS101) achieved PF in 20.4% vs 17.5% with placebo (RR 1.17 [0.95–1.45]) and MBS freedom in 37.0% vs 32.5% (RR 1.14 [0.97–1.34]). Although not statistically superior at 2 hours, Atzumi showed PF rising to ~35% by 3–4 hours with sustained relief beyond 24 hours. In contrast, zavegepant 10 mg IN, ubrogepant 50 mg PO, and rimegepant 75 mg ODT achieved PF RRs of 1.49, 1.52, and 1.46, respectively, while sumatriptan 100 mg PO remained highest (1.88 [1.64–2.15]). SUCRA rankings for 2-hour PF were triptans 91%, gepants 69–73%, and Atzumi 47%, indicating modest early efficacy but durable late response. Safety favored Atzumi, with mild nasal discomfort (8.3%) and dysgeusia (3.7%), and no serious adverse events, compared with higher systemic AEs for oral triptans.

Atzumi (STS101) showed sustained efficacy beyond 3 hours with excellent tolerability, offering a safe non-oral option for acute migraine; overall study quality was high with low ROB 2.0.