Michele Trimboli

Aim: Rimegepant is an effective acute migraine treatment, with limited evidence regarding its consistency across multiple migraine attacks. The primary aim is to assess rimegepant effectiveness across multiple migraine attacks. Methods: In this real-world, prospective, multicentric study we assessed participants who treated up to four different migraine attacks with rimegepant 75 mg orally disintegrating tablet. Data was collected every 30 min from migraine onset up to 2 h post dose using an electronic diary. Our primary outcome was 2-h pain freedom across all-treated attacks; secondary outcomes were: consistency of response (percentage of participants who achieved 2-h pain freedom in at least two treated attacks), safety and tolerability. Results: We enrolled 191 participants (80.1% females, age 44.8 [43.2–46.5] years, disease duration 28.4 [25.0–31.8] years, 27.7% with chronic migraine, 9.6 [8.9–10.9] baseline monthly migraine days-MMDs). We collected data from 377 migraine attacks (191 first-treated, 110 s-treated, 46 third-treated and 30 fourth-treated). Two-hour pain freedom was achieved in 44.6% (168/377) of treated attacks [39.3–49.6]. After correction for age, timing of rimegepant intake, baseline pain intensity, ongoing preventive treatment, and number of preventive drug classes that previously proved ineffective, 2-h pain freedom was associated with female sex (odds ratio (OR) = 2.3 [1.2–4.3], p = 0.012), no ongoing mAbs treatment (OR = 3.2 [1.6–6.4], p = 0.001), and lower MMDs (OR = 1.05 [1.0–1.1], p = 0.002). Consistency of response was 36.4% [27.3–45.5] (40/110). Participants reporting at least one adverse event were 11.5% (22/191). Conclusion: Our study confirms the effectiveness of rimegepant in nearly half of treated attacks and describe the consistency of response in a relatively large real-world population where one out of five participants achieved 2-h pain freedom in all-treated migraine attacks. No new safety signals were identified.

Background: The improved prevention of migraine, driven by the introduction of calcitonin gene-related peptide (CGRP)-targeted therapies, has prompted the International Headache Society (IHS) to propose new goals in migraine management. This study aimed to evaluate the safety and effectiveness of atogepant for migraine prevention over 24 weeks, in accordance with the IHS-defined goals. Methods: This is a multicenter, prospective, observational, real-world study on patients starting atogepant 60 mg for migraine prevention. We describe efficacy and safety outcomes at weeks 9–12 (T3) and 21–24 (T6) relative to baseline (T0) from the initiation of atogepant treatment. We also report the proportion of patients achieving migraine freedom, optimal, modest or insufficient control according to the IHS position paper categories. Results: One hundred twenty-eight ( n = 128) patients (63 (49.2%) with chronic migraine, 115 (89.9%) female, aged 48.3 ± 13.3 years) from 17 centers were analyzed. Monthly migraine days decreased from 16.5 ± 8.5 at T0 to 8.0 ± 8.4 at T3 ( p < 0.001 vs. T0) and 8.6 ± 9.2 at T6 ( p < 0001 vs. T0, p = 0.265 compared to T3). Overall, 64.8% of patients were responders (at least 50% reduction in monthly migraine days from T0) at T3 and 61.7% at T6; 81.9% of responders at T3 maintained the responder status at T6, while 24.4% of patients among non-responders at T3 became responders at T6. At T3 and T6, 39.1% of the entire cohort achieved at least optimal migraine control (20.6% in chronic migraine and 56.9% in episodic migraine). Conclusions: The STAR study demonstrates, in a real-world setting, the safety and the sustained effectiveness of atogepant 60 mg over 24 weeks and indicates that more than one-third of treated patients can achieve at least optimal disease control, with markedly better outcomes in episodic than in chronic migraine. Trial Registration: The study was preregistered on clinicaltrial.gov, NCT06414044.

Background: The International Headache Society has proposed new treatment goals for migraine prevention in real world, as a way to set higher standards of care. This study provides the first assessment of the proportion of individuals achieving them after 6 months of migraine-specific treatment with anti-CGRP monoclonal antibodies (MAbs). Methods: This was a prospective, real-world, European multicenter study, including adults with migraine treated with anti-CGRP MAbs (EUREkA cohort). We assessed the proportions of individuals in each treatment goal category–migraine freedom (no monthly migraine days [MMD]); optimal control (< 4 MMD), modest control (4–6 MMD); insufficient control (>6 MMD)–after 6 months of treatment. We also assessed the proportion of individuals with ≥50% reduction in MMD in the insufficient control group. Results: Of the 5818 individuals in the EUREkA cohort, 4963 had 6 months data. Of these, 82.3% (4086/4963) were females and the median age was 48.0 [40.0–55.0] years. At baseline, the median monthly headache days [MHD] and MMD were 20.0 [13.3–28.0] and 15.0 [10.0–20.0], respectively. All participants were classified as having insufficient headache control (>6 MMD) at baseline. At month 6, 6.9% (342/4963) had migraine freedom, 22.9% (1137/4963) optimal control, 24.6% (1223/4963) modest control and 45.6% (2261/4963) insufficient control. In the insufficient control group, 27.1% (613/2261) had ≥50% reduction in MMD. Conclusions: High standards of care, defined as optimal disease control or even migraine freedom, are achieved in real-world settings with anti-CGRP MAbs in approximately 30% of individuals with a high migraine burden. These findings highlight the need to expand global access to these treatments. Future studies should explore whether initiating migraine-specific preventive treatments earlier could further reduce residual migraine days in responders, enabling a larger proportion of patients to achieve optimal disease control.

Aim: To assess whether the timing of atogepant administration influences its tolerability and effectiveness over 12 weeks in patients with episodic and chronic migraine in a real-world setting. Methods: This is a post-hoc analysis of the STAR study, a prospective, Italian, multicenter study evaluating atogepant 60 mg for migraine prevention. Data were collected at baseline (T0) and after the first 12 weeks (T3) of treatment. Patients were grouped by administration timing (morning vs. evening) and by administration with or without food. Changes in monthly headache days (MHDs), monthly migraine days (MMDs), and Migraine Disability Assessment (MIDAS) were measured. Tolerability was evaluated via adverse events (AEs). Linear mixed-effects models (LMMs) were used. Results: Eighty-one patients (86% females, mean age 50.8 ± 13.7 years) were included. At T3, MMDs decreased from 16.6 to 9.7 (p < 0.001) and MHDs from 19.8 to 11.9 (p < 0.001); 60% of patients achieved ≥50% reduction in MMDs. AEs occurred in 34 (42%) participants. Atogepant was taken in the morning by 57% and in the evening by 43% of patients. Fifty-seven out of 81 participants (70.4%) took atogepant with food. No significant differences in MMDs, MHDs, or AEs emerged between morning and evening users. Evening users had higher baseline MIDAS scores (estimated marginal means [EMMs]: 69.9 vs. 39.9, p = 0.034) that showed a greater reduction compared to morning users ( F (1,63) = 6.29, p = 0.015), reaching similar final scores after 12 weeks (EMMs: 25.1 vs. 23.8). No difference in atogepant effectiveness and tolerability according to intake with or without food, except for a reduction in MHDs for patients who took atogepant without food (EMMs from 21.3 to 9.9 vs with food: EMMs from 18.4 to 12.7; F (1,79) = 8.553, p = 0.005). Conclusions: Atogepant significantly reduced migraine burden over 12 weeks in a real-world setting. Overall, the timing of atogepant administration did not affect its effectiveness or tolerability. However, a greater reduction in MIDAS scores was observed among evening users. Whether this reflects a pharmacological advantage or a ceiling effect remains unclear. Taking atogepant without food was associated with a significantly greater reduction in MHDs, whereas changes in MMDs and MIDAS scores did not differ between groups. Long-term and dedicated studies are needed to evaluate and confirm these findings. Trial Registration: The main study (STAR) was preregistered on clinicaltrial.gov, NCT06414044.

The aim of this study was to describe the long-term effectiveness and treatment persistence of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs) in migraine and to identify baseline factors associated with 2-year treatment continuation. A prospective observational multicenter registry-based study of anti-CGRP MAbs was conducted. We analyzed changes in monthly headache days (MHDs) at 24 months (M24) compared with baseline in those who reached M24 (ON-group). We analyzed patterns of response at 4 time points (6, 12, 18, and 24 months). We defined sustained response (SR) as a ≥50% reduction in MHDs at ≥3 of 4 time points. We compared baseline characteristics of the ON-group with those of the discontinuation group because of lack of effectiveness (OFF-group). A total of 1,340 individuals reached M24 (ON-group: median age 48.0 [41.0-55.0] years; 81.7% female). The median MHD at baseline was 20.0 (13.0-28.0) days. At M24, 60.4% of patients demonstrated ≥50% reduction in MHDs (809/1,340). The proportion of participants achieving SR at M24 was 53.8% (142/264). When compared with the ON-group (n = 1,340), the OFF-group (n = 1,057) showed statistically significant higher baseline MHDs (ON: 20.0 [13.0-28.0] vs OFF: 25.0 [16.0-28.0]) and a greater proportion of patients with aura (ON: 16.2% vs OFF: 22.9%), depression (ON: 22.8% vs OFF: 37.9%), and obesity (ON: 7.2% vs OFF: 19.1%) (p < 0.001). Sustained reductions in MHDs to anti-CGRP treatment at 2 years was observed. Delayed treatment onset, migraine with aura, depression, and obesity may negatively affect treatment persistence. This study provides Class IV evidence that, in patients with migraine, treatment with anti-CGRP MAbs is associated with sustained reductions in MHDs over a 24-month period.

Aim: The TACHIS study (from the ancient Greek adjective “ tachýs ” meaning rapid) aimed to evaluate eptinezumab effectiveness and tolerability in routine clinical practice, integrating patient-reported outcomes and use of International Headache Society (IHS)-endorsed categories of migraine control by treatment. Background: Eptinezumab is the only intravenous anti-calcitonin gene related peptide (CGRP) monoclonal antibody (mAb) approved for migraine prevention. While its efficacy has been demonstrated in RCTs, real-world evidence in patients with prior preventive treatment failures is still limited. Methods: TACHIS is a prospective, multicenter, observational study conducted in Italy. Adults with episodic or chronic migraine initiating eptinezumab were followed for 24 weeks. Primary outcomes included change from baseline in monthly migraine days (MMDs) and ≥50% responder rate. Secondary outcomes included changes from baseline in acute medication use, Migraine Disability Assessment (MIDAS) and Headache Impact Test-6 (HIT-6) and IHS-defined residual burden categories. Logistic regression identified factors of response status. Results: A total of 128 patients were included (82% female; 82% chronic migraine). MMDs decreased overall by 5.7 days (95% CI: −7.2 to −4.3) at week 12 and 6.9 (95% CI: −8.5 to −5.2) at week 24 (p < 0.001). A ≥ 50% response was achieved in 43.8% and 48.2% of patients at weeks 12 and 24, respectively. Over 40% of patients achieved optimal or modest migraine control. CGRP targeted therapy-naïve patients experienced significant greater benefit, though non-naïve patients also improved. Female sex and chronic migraine diagnosis were independently associated with response at 12 weeks. Adverse events were infrequent (4.7%) and mild, with no discontinuations due to safety concerns. Conclusions: Eptinezumab demonstrated effectiveness and tolerability in a real-world population of patients with migraine and prior preventive treatment failures. The integration of migraine control metrics provides a comprehensive evaluation of therapeutic impact and supports eptinezumab use in routine care. Trial Registration: The TACHIS study was preregistered on clinicaltrial.gov, NCT06409845.