Effectiveness and tolerability of atogepant as preventive treatment in resistant individuals with chronic migraine: Six-month real-world evidence

Abstract

Background The discovery of calcitonin gene-related peptide (CGRP) as a key player in migraine pathophysiology has revolutionized the approach to preventive treatment. Atogepant, an oral small-molecule CGRP receptor antagonist, has shown promising efficacy in randomized controlled trials (RCTs) for both episodic and chronic migraine. However, real-world evidence, particularly in individuals with chronic migraine and multiple preventive treatment failures, remains limited. This study is aimed to evaluate the effectiveness, safety, and tolerability of daily atogepant 60 mg in a homogeneous cohort of resistant individuals with chronic migraine over a 24-week period to extend the short-term observation assessed in previous real-world studies. Methods In the present real-world, prospective, monocentric study, a total of 100 participants (93% female; mean ± SD, age 43 ± 11 years) with chronic migraine with at least three previous treatment failures without medication overuse headache were consecutively recruited and received atogepant 60 mg daily for six months. All participants had failed a median of six previous preventive treatments, including CGRP-monoclonal antibodies (mAbs) (68%) and onabotulinumtoxin-A (BoNT-A) (14%). Primary outcomes included change in monthly migraine days (MMDs) and greater than 50% responder rate at 12 and 24 weeks. Secondary outcomes included changes in monthly headache days (MHDs), acute medication intake (MAMI), headache impact (Headache Impact Test (HIT-6)), anxiety and depression (Hospital Anxiety and Depression Scale (HADS)) and patient satisfaction (Patient's Global Impression of Change (PGIC)), change in MMDs, demographic and clinical features associated with greater than 50% responder rate, as well as effectiveness in individuals with previous CGRP-mAbs failure. Treatment-emergent adverse events (TEAEs) were also recorded. Results At weeks 12 and 24, MMDs were reduced by 5.6 and 7.1 days from baseline, respectively (p < 0.001), while 45% and 53% of participants achieved a ≥ 50% reduction in MMDs. Significant improvements were also seen in MHDs (−8.1 days), MAMI (−5.1 days) and HIT-6 scores (−6.2 points). Conversion from chronic to episodic migraine occurred in 60% of participants. PGIC results showed that 69% of participants reported feeling “much” or “very much” better. Logistic regression identified higher socioeconomic status (odds ratio = 2.87) as a positive predictor and previous CGRP-mAb failure (odds ratio = 0.38) as a negative predictor of treatment response. Nevertheless, among individuals with more than one CGRP-mAb failure, 47% achieved a ≥50% reduction in MMDs. TEAEs were reported by 53% of participants, with constipation (28%) and fatigue (16%) being the most common. Conclusions Atogepant 60 mg daily demonstrated meaningful clinical benefit and good tolerability in real-world individuals with treatment-resistant chronic migraine over a 24-week period. These findings extend data from RCTs and real-world studies limited to 12-week period of observation, supporting atogepant as an effective option even in individuals with prior CGRP-mAb failure.