Early and sustained efficacy of fremanezumab over 24-weeks in migraine patients with multiple preventive treatment failures: the multicenter, prospective, real-life FRIEND2 study

Abstract

Background To verify the long-term (24-week) efficacy, safety, and tolerability of fremanezumab in real-life patients with high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM: ≥ 15 days/month), and multiple preventive treatment failures. Methods This is a prospective, cohort, real-life study at 28 headache centers on consecutive patients affected by HFEM or CM with multiple preventive treatment failures who were prescribed subcutaneous fremanezumab (225 mg monthly/675 mg quarterly) for ≥ 24 weeks. Primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM at weeks 21–24 compared to baseline. Secondary endpoints encompassed changes in monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS, HIT-6 and MIDAS scores at the same time interval. Changes in MMDs/MHDs, monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS and HIT-6 scores at week 4 were also monitored. Results Four hundred ten patients who had received ≥ 1 dose of fremanezumab were considered for safety analysis while 148 patients treated for ≥ 24 weeks were included in the efficacy analysis. At weeks 21–24, fremanezumab significantly (p < 0.001) reduced MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM compared to baseline. The proportions of ≥ 50%, ≥ 75% and 100% responders at weeks 21-24were 75.0%, 30.8%, 9.6% (HFEM), and 72.9, 44.8 and 1% (CM). A significant (p < 0.001) decrease in MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM was already present at week 4. The proportions of ≥ 50%, ≥ 75%, and 100% responders at week 4 were 67.6%, 32.4%, 11.8% (HFEM) and 67.3%, 40%, 1.8% (CM). CM remitted to episodic migraine and medication overuse to no-medication overuse in 83.3 and 75% of patients at week 24, and in 80 and 72.4% at week 4. Adverse events were rare (2.4%), mild and transient. No patient discontinued treatment for any reason. Conclusions Fremanezumab is characterized by an early and sustained efficacy in HFEM and CM patients with multiple preventive treatment failures in real-life, revealing an optimal safety and tolerability profile.

Real-world experience with monthly and quarterly dosing of fremanezumab for the treatment of patients with migraine in Japan

“…Additionally, the efficacy of fremanezumab has been demonstrated in several real-world studies in Europe and the United States (7)(8)(9). Barbanti et al reported the effectiveness of fremanezumab in patients with chronic and highfrequency episodic migraine in multicenter real-world studies for 3 and 6 months (7,10). However, the clinical evidence for fremanezumab in migraine prophylaxis in Asia is limited to randomized controlled trial (RCT) results and post hoc analyses (11)(12)(13)(14), and more clinical evidence from real-world studies is needed, especially in Asian migraine patients with various clinical backgrounds.…”

Real-world effectiveness of fremanezumab for the preventive treatment of migraine: Interim analysis of the pan-European, prospective, observational, phase 4 PEARL study

“…Additionally, post-marketing data identified an association between erenumab and elevated blood pressure, leading to hypertension being added to the Warnings and Precautions section of the prescribing information (27). Previously published real-world fremanezumab data have not revealed any new safety signals (16,18), and this interim analysis of PEARL reported few AEs with fremanezumab; one participant experienced a drug-related serious AE (dysphonia), and 2.2% of participants discontinued treatment due to AEs. Fremanezumab-related constipation was reported as an adverse event in 3.0% of participants; this is markedly lower than with other mAbs targeting CGRP or its receptor observational study results.…”

“…While early RWE data on the effectiveness, safety, and tolerability of fremanezumab were collected retrospectively on a relatively small number of participants (16), prospective studies have followed, enrolling larger cohorts for a longer duration. For example, the FRIEND study was conducted across 28 Italian headache centers and demonstrated the effectiveness of fremanezumab in reducing MMD and other effectiveness endpoints through week 24 in 148 participants with high-frequency EM and CM who were not previously exposed to antibodies targeting CGRP (18). In contrast, PEARL includes participants from 11 European countries with diverse demographics, generating the largest real-world data pool available for fremanezumab from participants with varied ages, nationalities, ethnic backgrounds, comorbidities, and concomitant medications.…”

“…Regulatory authorities have also recognized the importance of real-world evidence in drug development and monitoring, as well as in decision-making for regulation and assessment (14). However, the currently available RWE on the effectiveness, safety, and tolerability of fremanezumab for the prevention of migraine is limited, with most studies being retrospective or conducted across only one or two countries (15–21). Therefore, large scale, prospective, multicenter, multi-country, real-world studies of fremanezumab are needed to complement the evidence generated from RCTs.…”

Patterns of anti‐CGRP mAbs use and variation of triptan consumption following treatment initiation: A descriptive drug utilization study in the Tuscany region, Italy

“…In Italy, despite being one of the leading countries in conducting real-world, multicenter, prospective studies on anti-CGRP mAbs, the available evidence is based on studies with relatively small patient samples and a maximum follow-up duration of 12 months from anti-CGRP mAb initiation. [19][20][21][22][23][24][25][26] Moreover, to the best of our knowledge, only prospective studies based on primary data collection and/or medical records from headache centers have been performed in Italy to date. [19][20][21][22][23][24][25][26] Herein, we describe the real-world utilization pattern of anti-CGRP mAbs in a large sample of the Italian population using information captured in the regional administrative health-care databases (ARS) of Tuscany.…”