Efficacy, Safety, and Tolerability of Atogepant in Migraine Patients from the UAE

Why carry out this study? Real-world evidence on the effectiveness and safety of atogepant for migraine prevention has been reported in some western countries; however, this data is not available in the Middle East and North Africa (MENA) region, despite the high burden of migraine in the region and growing use of CGRP-targeted therapies. There is a clear unmet need for local and regional real-world data to evaluate treatment outcomes and tolerability of atogepant in patients with chronic and episodic migraine in the United Arab Emirates (UAE), the first country in the MENA region to approve the use of this medication. This study aimed to evaluate the effectiveness and safety of atogepant among patients with migraine headaches visiting an established headache clinic in UAE. What was learned from the study? Atogepant significantly reduced migraine days from 12 to 4, with 71% of patients achieving ≥ 50% reduction, and showed a favorable safety profile with 10.5% reporting mostly mild adverse events. This study provides the first real-world evidence from the UAE demonstrating that atogepant is effective and well tolerated in patients with migraine in a routine clinical practice. The findings support the use of atogepant as a preventive migraine therapy in the MENA region and highlight the need for larger multicenter prospective studies to further validate long-term outcomes and treatment strategies.

Among the 86 patients identified who were treated with atogepant, 59 met the inclusion criteria. Out those 59, 23 (39%) had chronic migraine and 36 (61%) had episodic migraine. The majority of patients were female 51 (86.4%), and most were Emirati nationals 41 (69%). Furthermore, patients aged 40–49 years represented the largest age group, comprising 24 individuals (40%). A total of 25 patients had comorbidities. Hypothyroidism was the most frequently reported condition (13%), followed by hyperlipidemia (7%). Polycystic ovarian syndrome, diabetes mellitus, hypertension, anxiety/depression, and asthma each accounted for 3% of the total comorbidity burden, whereas gastroesophageal reflux disease, irritable bowel syndrome, hyperthyroidism, endometriosis, and rheumatoid arthritis were less prevalent (2% each) (Table  1 ). Table 1 Demographics and basic characteristics of participants Characteristic N (%) Migraine type  Chronic migraine 23 (39%)  Episodic migraine 36 (61%) Sex  Female 51 (86.4%)  Male 8 (13.6%) Nationality  Emirati 41 (69%)  Non-Emirati 18 (31%) Age group (years)  < 20 3 (5.1%)  20–29 6 (10.2%)  30–39 18 (30.5%)  40–49 24 (40.7%)  50–59 6 (10.2%)  60–69 2 (3.4%) Comorbidity  Hypothyroidism 8 (13%)  Hyperlipidemia 4 (7%)  Polycystic ovarian syndrome (PCOS) 2 (3%)  Diabetes mellitus 2 (3%)  Hypertension 2 (3%)  Anxiety/depression 2 (3%)  Asthma 2 (3%)  Gastroesophageal reflux disease (GERD) 1 (2%)  Irritable bowel syndrome (IBS) 1 (2%)  Endometriosis 1 (2%)  Hyperthyroidism 1 (2%)  Rheumatoid arthritis 1 (2%) Demographics and basic characteristics of participants Among the 59 included patients, 14 completed 6 months of atogepant therapy, and an additional 11 completed treatment between 6 and 9 months, while 7 patients completed between 9 and 12 months. By 12 months, 3 patients had completed treatment. The remaining 24 patients continued therapy beyond 12 months, with 2 patients receiving atogepant for up to 24 months. The baseline mean MMDs for all patients were 12 (SD 8.1). For the primary endpoint, mean MMDs decreased to 4 (SD 5.2) at the most recent follow-up, representing a statistically significant reduction from baseline ( p  < 0.001). For secondary endpoints, mean MMDs decreased to 5 (SD 6.0) at 6 months and further to 4 (SD 3.8) at 12 months, with both time points demonstrating statistically significant reductions compared with baseline ( p  < 0.001 for both), consistent with the overall reduction in MMDs observed across follow-up (Fig.  2 ). At the most recent follow-up, 71% of patients achieved a ≥ 50% reduction in MMDs. Notably, 53% achieved a ≥ 75% reduction, and 13% achieved 100% reduction of MMDs (Fig.  3 ). Fig. 2 Changes in monthly migraine days (MMD) over time Fig. 3 MMD response rate Changes in monthly migraine days (MMD) over time MMD response rate We compared naïve and participants with previous preventive treatment (PPT) with regards to the changes in average MMD from baseline to last visit. Participants with PPT ( n  = 38) had an average MMD of 11.8 ± 8.8 at baseline which decreased to 4 ± 5.3 at the last visit. On the other hand, naïve participants ( n  = 21) had an average MMD of 13.5 ± 2.1 at baseline which decreased to 5 ± 4.2 at the last visit (Fig.  4 ). Figure  5 illustrates responders and non-responder rates for naïve patients and patients with PPT. The average treatment duration for 59 participants was 11.4 ± 4.8 months. Fig. 4 Naïve vs previous preventive treatment (PPT) participant changes in MMD from baseline to last visit Fig. 5 A breakdown of responders and non-responders rate for naïve patients and patients with 1 and multiple PPTs Naïve vs previous preventive treatment (PPT) participant changes in MMD from baseline to last visit A breakdown of responders and non-responders rate for naïve patients and patients with 1 and multiple PPTs Regarding safety, among the 59 patients who met the inclusion criteria, 9 (15%) experienced adverse events. The most common AE was constipation (56%), followed by nausea (22%), weight loss (22%), abdominal rash (11%), and fatigue (11%). Most participants who experienced side effects were aged 40–49 years (44%), followed by those aged 30–39 years (33%). Side effects were less common in younger age groups and were not reported in participants aged 50–69 years (Fig.  6 ). Fig. 6 Age of participants who experienced side effects Age of participants who experienced side effects Seven patients out of the 9 (78%) continued atogepant treatment after reporting an AE, while two participants (22%) discontinued atogepant treatment at the sixth (unspecified AE) and the ninth visits (severe constipation, fatigue) due to the side effects. See Table  2 for characteristics of participants who experienced side effects on atogepant treatment. Table 2 Characteristics of participants who experienced side effects on atogepant treatment ID Sex Side effect Severity Continued/discontinued Months 1 F Unspecified Unspecified Discontinued 6 2 F Constipation, nausea, perimenopausal symptoms Moderate Continued 5 3 M Nausea Unspecified Continued 2 4 F Abdominal rash Unspecified Continued 13 5 M Severe constipation Severe Continued 5 6 M Mild constipation Mild Continued 2 7 F Weight loss Unspecified Continued 1 8 F Constipation, weight loss Mild Continued 3 9 F Severe constipation and fatigue Severe Discontinued 9 Characteristics of participants who experienced side effects on atogepant treatment Sensitivity analyses confirmed the robustness of the primary efficacy results to the missing-data pattern (Supplementary Table S1). Under the most conservative BOCF analysis on the all-exposed population ( n  = 86), the mean reduction in MMD remained statistically significant (mean change 6.14, 95% CI 4.57–7.71; paired t (85) = 7.77, p  < 0.001). Under NRI, the ≥ 50%, ≥ 75%, and 100% responder rates were 48.8%, 37.2%, and 9.3%, respectively ( n  = 86). MI under MAR yielded a pooled mean MMD reduction of 7.81 (95% CI 6.15–9.47; pooled p  < 0.001) and pooled ≥ 50%, ≥ 75%, and 100% responder rates of 67.0%, 50.8%, and 17.1%, respectively. A tipping point analysis indicated that statistical significance would only be lost if the 27 excluded patients had, on average, worsened by approximately 12 MMD/month from baseline—an implausibly large deterioration in this clinical context. When safety was reanalyzed using the all-exposed population ( n  = 86), adverse events occurred in 9 patients (10.5%; 95% CI 5.6–18.7%), with 2 (2.3%) discontinuing because of AEs.

This real-world study demonstrates that atogepant is an effective, well-tolerated, and durable preventive treatment for migraine in a UAE clinical setting, including patients with prior preventive treatment failures. These findings are consistent with existing randomized and real-world evidence and further support the role of atogepant as a key component of contemporary migraine preventive therapy.

In this retrospective real-world study from the UAE, atogepant demonstrated substantial and sustained effectiveness in reducing MMDs in patients with migraine headaches. Treatment was associated with clinically meaningful reductions in migraine frequency over time, with high responder rates and a favorable tolerability profile. These results provide novel region-specific real-world evidence from the UAE, where published data on atogepant use in this region remains limited. The observed reduction in mean MMDs from baseline as compared to 6 months and the further improvement at longer follow-up are consistent with long-term efficacy patterns reported in the randomized 52-week trial, which showed sustained migraine frequency reduction with continued atogepant use [ 28 ]. Importantly, our ≥ 50% responder rate of 72% aligns with the responder rates reported in other real-world studies such as STAR and GIANT, which evaluated atogepant use in populations with prior preventive treatment failures [ 29 , 30 ]. The high proportion of patients achieving ≥ 75% reduction in MMDs and the 100% migraine days reduction is particularly clinically relevant, as higher responder thresholds have been shown to correlate more strongly with improvements in functional outcomes and migraine-specific quality of life [ 28 ]. Comparative efficacy analyses of CGRP-targeting therapies have demonstrated that atogepant provides migraine prevention benefits comparable to other CGRP pathway agents, including monoclonal antibodies, while offering the convenience of once-daily oral administration [ 31 ]. This oral dosing advantage may contribute to improved treatment adherence and persistence in real-world settings, particularly among patients who are reluctant to use injectable therapies or who have discontinued monoclonal antibodies [ 19 ]. Real-world multicenter studies have further demonstrated that atogepant remains an effective option in those patients with prior failure of anti-CGRP monoclonal antibodies, a finding that we have also observed in our study [ 30 ]. Atogepant was generally well tolerated in our study, with adverse events reported in 10.5% (9/86 in the all-exposed population; 15.3% in the final included cohort n  = 59) of patients, most commonly constipation and gastrointestinal symptoms, findings that are consistent with the established safety profile observed in clinical trials and long-term real-world studies [ 29 – 32 ]. Importantly, AEs were predominantly mild and did not appear to result in high rates of treatment discontinuation, reinforcing the favorable tolerability of atogepant observed across diverse populations and extended treatment durations. Furthermore, the absence of new or unexpected safety signals in our cohort further supports the long-term safety of CGRP receptor antagonism for migraine prevention [ 32 ]. Although our study primarily assessed migraine frequency, prior randomized and real-world studies have consistently demonstrated that reductions in MMDs with atogepant translate into meaningful improvements in patient-reported outcomes, including migraine-specific quality of life, daily activity performance, and headache-related disability. Given the high responder rates observed in our cohort, it is likely, although it was not measured, that similar functional and quality-of-life benefits were achieved, underscoring the clinical relevance of sustained migraine frequency reduction beyond numerical endpoints alone [ 28 – 30 ]. From a regional perspective, migraine remains underrecognized and undertreated in the Middle East, and real-world evidence supporting the use of newer and more effective preventive therapies remains limited [ 33 ]. Our findings provide region-specific data demonstrating that atogepant is effective and well tolerated in our population, supporting its integration into routine migraine preventive care in this setting and complementing existing international real-world evidence [ 30 – 32 , 34 ]. The once-daily oral administration, rapid onset of benefit, and favorable tolerability profile make atogepant a particularly attractive preventive option in populations where adherence to traditional oral preventives has been suboptimal [ 19 ]. This study has limitations inherent to its retrospective design, including reliance on medical record documentation and absence of a control group, which limits causal inference. Additionally, variability in follow-up duration reflects real-world practice and may introduce heterogeneity in outcome assessment. Furthermore, patients who discontinued atogepant early as a result of lack of efficacy or intolerance may be underrepresented in this cohort, potentially leading to an overestimation of treatment benefit. Nevertheless, the consistency of our findings with randomized controlled trials, long-term extension studies, and multicenter real-world cohorts strengthens the overall validity of our results [ 28 , 29 , 32 ]. To address potential bias from the 27 patients excluded from the primary efficacy analysis, four pre-specified sensitivity analyses were performed on the all-exposed population ( n  = 86): non-responder imputation, BOCF, MI under MAR (with Rubin’s rules pooling), and tipping point analysis (Supplementary Table S1). Across all approaches, the primary efficacy conclusion was unchanged, supporting the robustness of our findings. The MAR assumption underpinning the multiple-imputation analysis is justified by the documented administrative reasons for the exclusions, which were unrelated to atogepant response. Safety outcomes were additionally re-derived using the all-exposed population ( n  = 86) per best-practice guidance for retrospective safety reporting.

Migraine is a highly prevalent neurological disorder, affecting an estimated 1.1 billion people worldwide [ 1 ]. It is a major contributor to global disability, ranking as the second leading cause of years lived with disability (YLDs) and the leading cause of disability-adjusted life years (DALYs) among adult women [ 2 ]. Clinically, migraine is characterized by recurrent headache attacks accompanied by a range of associated symptoms, including photophobia, phonophobia, nausea, and vomiting [ 3 – 5 ]. In addition to its clinical burden, migraine is associated with significant social comorbidities [ 6 , 7 ], as well as a substantial economic burden on healthcare systems and society, which increases progressively with the need for additional or more complex therapeutic interventions [ 8 ]. According to the International Classification of Headache Disorders (ICHD-3), migraine is broadly categorized into episodic migraine (EM) and chronic migraine (CM) [ 9 ]. Distinguishing between these two types is an important element to assess the burden of the disease and influence the choices of treatment decisions [ 10 ]. Migraine prophylaxis aims to reduce the frequency, severity, and duration of attacks, while lowering the risk of medication overuse and its complications. The end goal is to improve patients’ quality of life by decreasing migraine attacks and their associated symptoms [ 11 ]. Despite the significant disability caused by migraine, only a minority (approximately 10–20%) of individuals eligible for preventive treatment, according to the 2021 American Headache Society consensus algorithm, are currently receiving migraine preventive medications [ 12 ]. Oral medications for migraine prevention are often associated with low adherence and persistence rates [ 13 ]. Low adherence may be attributed to the need for dose titration with the standard of care oral preventive treatments, which often require weeks to months to achieve maximum efficacy [ 14 ]. The trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP), a potent vasodilator, has been recognized as a key factor in the pathogenesis of migraine [ 15 , 16 ]. Drugs targeting the CGRP ligand and its receptor have emerged as a major focus in clinical practice. Among these are monoclonal antibodies, such as fremanezumab, which binds to CGRP, and erenumab, which binds to the CGRP receptor [ 17 , 18 ]. Gepants are non-peptide small molecules that bind to the CGRP receptor and have shown promise in preventing migraine attacks [ 19 ]. Unlike the monthly injectable monoclonal antibodies, gepants are available in various forms such as oral tablet, nasal spray, and orally disintegrating tablet (ODT) formulations [ 20 ]. Rimegepant, a gepant, is used for both acute and preventive management of migraine. However, since it is dosed every other day for prevention, adherence challenges may occur [ 21 ]. On the other hand, atogepant is a US Food and Drug Administration (FDA)-approved once-daily oral medication indicated for migraine prophylaxis and is the first oral therapy specifically developed for the preventive treatment of episodic migraine [ 22 ]. It is particularly suitable for individuals who prefer a daily oral regimen without the inconvenience of injectable treatments [ 23 ]. Multiple randomized phase 3 clinical trials have established the efficacy and favorable tolerability of atogepant for migraine prevention across both episodic and chronic migraine populations, with consistent reductions in monthly migraine days (MMDs) and sustained benefit demonstrated in long-term extension studies [ 24 – 27 ]. These trials provide robust evidence supporting atogepant as an effective CGRP receptor antagonist with a favorable safety profile. However, participants enrolled in randomized controlled trials are highly selected and managed under standardized conditions, which may limit the generalizability of these findings to routine clinical practice. Consequently, real-world studies are essential to evaluate the effectiveness, tolerability, and durability of atogepant in more heterogeneous patient populations, including those with comorbidities, prior preventive treatment failures, and variable adherence patterns. Since its approval in the United Arab Emirates (UAE) in January 2024, the effectiveness and tolerability of atogepant have not yet been established in this country. Given the increasing use of atogepant and the limited literature on its use in this region, this retrospective study aimed to evaluate the efficacy and tolerability of atogepant when used as preventive therapy in patients with episodic and chronic migraine who have previously failed response to standard treatments, CGRP mAbs, gepants, or who were naïve to atogepant.

This was a retrospective real-world study conducted at the American Center for Psychiatry and Neurology (ACPN), Abu Dhabi, UAE. The study evaluated the real-world efficacy, safety, and tolerability of atogepant for migraine prevention using routinely collected clinical data from electronic medical records. Data were reviewed for patients who initiated atogepant as part of our standard clinical care and were followed on a monthly basis for a minimum duration of 6 months. No study-specific interventions were performed, and treatment decisions, dosing, and follow-up schedules were determined by the treating neurologist according to routine clinical practice. This study was conducted in accordance with the Helsinki Declaration of 1964 and consistent with Good Clinical Practice (GCP). Compliance with all ethical guidelines, health authority regulations, and data privacy laws was ensured. Prior to the start of the study all relevant approvals were obtained from ACPN’s Institutional Review Board (IRB), and a waiver of informed consent from the corresponding ethics committee was obtained. To ensure transparency and accuracy all authors were given access to the study data. Eligible patients were adults aged ≥ 18 years with a diagnosis of episodic or chronic migraine according to the International Classification of Headache Disorders, third edition (ICHD-3), who initiated atogepant and continued therapy for at least 6 months. Data was reviewed from January 2024 to December 2025. Patients were required to have documented baseline MMDs prior to treatment initiation and at least one follow-up assessment of MMDs recorded at regular clinic visits. Out of a total of 86 patients who initiated treatment with atogepant, 59 patients met the inclusion criteria and were included in the analysis (Fig.  1 ). Those with insufficient documentation, or who discontinued atogepant before 6 months, or had incomplete follow-up visits were excluded. Patients received atogepant at a dose of 60 mg in accordance with the approved prescribing practices in the UAE. Fig. 1 Flowchart of participants included Flowchart of participants included The primary outcome was the change in MMDs from baseline to the most recent follow-up during atogepant treatment. Baseline MMDs were defined as the number of migraine days documented in the month preceding treatment initiation. Follow-up MMDs were extracted from clinical notes recorded during routine monthly follow-up visits based on patient-reported outcomes. Secondary outcomes included changes in MMDs at 6 and 12 months following atogepant initiation, as well as responder rates, defined as the proportion of patients achieving a clinically meaningful reduction in MMDs (≥ 50% reduction from baseline) at the most recent follow-up. Safety and tolerability were assessed descriptively based on adverse events (AEs) documented in medical records during follow-up visits, including gastrointestinal symptoms, fatigue, and other treatment-emergent adverse events. Treatment discontinuation and reasons for discontinuation were also recorded when available. Baseline demographic and clinical characteristics were summarized using descriptive statistics. Continuous variables were reported as mean ± standard deviation or median with interquartile range, as appropriate, and categorical variables were summarized as frequencies and percentages. For comorbidity analyses, percentages were calculated using the total number of reported comorbid conditions as the denominator. Changes in MMDs from baseline to follow-up were analyzed using paired t  tests for normally distributed data or Wilcoxon signed-rank tests for non-normally distributed data, as appropriate. The ≥ 50% responder rate was calculated at the last follow-up visit occurring ≥ 6 months after treatment initiation. Safety and tolerability outcomes were analyzed descriptively based on adverse events documented during follow-up. No formal hypothesis testing was performed for safety outcomes. A p  value < 0.05 was considered statistically significant. Twenty-seven patients (20 who received a single dose and discontinued for documented administrative reasons such as changes in insurance coverage or relocation, and 7 who had not reached the 6-month follow-up window by the December 2025 data cutoff) were excluded from the primary efficacy analysis. To assess the robustness of the primary analysis to this missing data, four pre-specified sensitivity analyses were performed on the all-exposed population ( n  = 86): (1) non-responder imputation (NRI), in which all 27 excluded patients were classified as non-responders for the binary responder-rate endpoints; (2) baseline observation carried forward (BOCF), in which each excluded patient’s follow-up monthly migraine days were set equal to their baseline value (zero change) for the continuous endpoint; (3) multiple imputation under the missing-at-random assumption (MI under MAR), in which follow-up MMD was imputed in m  = 20 imputations using a predictive linear- egression model that included baseline MMD, age, sex, migraine type, prior preventive treatment status, prior anti-CGRP monoclonal antibody exposure, and presence of any major comorbidity, with estimates pooled using Rubin’s rules; and (4) a tipping point analysis quantifying the magnitude of dropout deterioration that would be required to reverse the primary conclusion. The MAR assumption is supported by the documented administrative basis for missingness (insurance/travel and data cutoff censoring), neither of which depends on patient response to atogepant. Safety analyses were performed on the all-exposed population (all patients who received at least one dose of atogepant, n  = 86).

Below is the link to the electronic supplementary material. Supplementary file1 (DOC 32 KB) Supplementary file1 (DOC 32 KB)