Long‐term (48 weeks) effectiveness, safety, and tolerability of erenumab in the prevention of high‐frequency episodic and chronic migraine in a real world: Results of the EARLY 2 study

Abstract

Objective To evaluate the long‐term effectiveness, safety, and tolerability of erenumab in a real‐world migraine population, looking for putative predictors of responsiveness. Background Erenumab proved to be effective, safe, and well tolerated in the prevention of episodic migraine (EM) and chronic migraine (CM) in long‐term extension studies of double‐blind, placebo‐controlled trials in patients with no more than two (EM) or three (CM) prior preventive treatment failures. Methods A 48‐week, multicenter, longitudinal cohort real‐life study was conducted at 15 headache centers across eight Italian regions between December 20, 2018 and July 31, 2020. We considered all consecutive patients with high‐frequency episodic migraine (HFEM) or CM aged 18–65 years. Each patient was treated with erenumab 70 mg, administered monthly. The dose was switched to 140 mg in nonresponders and in responders who had become nonresponders for at least 4 weeks. Change in monthly migraine days (MMDs) or monthly headache days (MHDs) at Weeks 45–48 compared with baseline was the primary efficacy endpoint. Secondary endpoints encompassed variation in monthly analgesic intake, achievement of a ≥50%, ≥75%, or 100% reduction in migraine or headache days, and any change in the Visual Analogue Scale (VAS) and Headache Impact Test‐6 scores (HIT‐6) during the same time interval. Results A total of 242 patients with migraine received at least one dose of erenumab 70 mg and were considered for safety analysis, whereas 221 received a monthly erenumab dose for ≥48 weeks and were included in the effectiveness and safety analysis set. All patients had previously been treated unsuccessfully with ≥3 migraine‐preventive medication classes. From baseline to Weeks 45–48, erenumab treatment reduced MMD by 4.3 ± 5.3 (mean ± SD) in patients with HFEM, and MHD by 12.8 ± 8.9 (mean ± SD) in subjects with CM. VAS and HIT‐6 scores were decreased by 1.8 ± 1.9 (mean ± SD) and 12.3 ± 11 (mean ± SD) in HFEM, and by 3.0 ± 2.2 (mean ± SD) and 13.1 ± 11.2 (mean ± SD) in CM. Median monthly analgesic intake passed from 11.0 (interquartile range [IQR] 10.0–13.0) to 5 (IQR 2.0–8.0) in HFEM and from 20.0 (IQR 15.0–30.0) to 6.0 (IQR 3.8–10.0) in CM. The ≥50% responders were 56.1% (32/57) in HFEM and 75.6% (124/164) in CM; ≥75% responders were 31.6% (18/57) and 44.5% (73/164); and 100% responders were 8.8% (5/57) and 1.2% (2/164), respectively. At Week 48, 83.6% (137/164) of patients with CM had reverted to EM. Erenumab was safe and well tolerated. Responsiveness to erenumab was positively associated with cutaneous allodynia (OR: 5.44, 95% CI: 1.52–19.41; p = 0.009) in HFEM. In patients with CM, ≥50% responsiveness was positively associated with male sex (OR: 2.99, 95% CI: 1.03–8.7; p = 0.044) and baseline migraine frequency (OR: 1.12, 95% CI: 1.05–1.20; p = 0.001) and negatively associated with psychiatric comorbidities (OR: 0.37, 95% CI: 0.15–0.87; p = 0.023) and prior treatment failures (OR: 0.77, 95% CI: 0.64–0.92; p = 0.004). Conclusions Long‐term (48‐week) erenumab...

Discontinuing monoclonal antibodies targeting CGRP pathway after one-year treatment: an observational longitudinal cohort study

“…Although their numerous limitations, they have the advantage of better representing the population we usually have to deal with in our everyday clinical practice. Different RWE about mAbs has provided several helpful data to improve migraine patients’ management with these new treatments [ 8 , 9 , 32 ]. We have to consider real-life experiences to improve our clinical practice, having the possibility to choose the best management beyond the a priori imposed rules.…”

“…This observational longitudinal cohort study was conducted as part of two observational longitudinal multicentric studies on the real-life use of erenumab (the EARLY—ErenumAb in Real Life in ItalY—study) [ 8 ] and galcanezumab (the GARLIT—GalcanezumAb in Real Life in ITaly—study) [ 9 ], in 10 third level headache centres in Italy.…”

“…They were not previously involved in any randomized clinical mAbs anti-CGRP trial. Data collection of the EARLY and GARLIT studies is described elsewhere [ 8 , 9 ]. The present paper considered the 12-month treatment and 3-month suspension interval regarding erenumab and galcanezumab patients’ data from the treatment phase on direct hospital dispensation.…”

“…Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP), i.e., mAbs anti-CGRP pathway, opened a new era in migraine prevention [ 1 ]. Randomized clinical trials (RCTs) demonstrated excellent effectiveness and safety of these treatments [ 2 – 7 ], and increasing real-world studies have confirmed this evidence in real life [ 8 , 9 ]. International drug agencies have approved mAbs anti-CGRP to prevent episodic and chronic migraine in adults since 2018.…”

Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity

“…In the only study assessing potential sex differences in the effects of CGRP within the LOC system, Allen and Luebke (2017) reported no functional differences between male and female CGRP-null mice. The lack of sex differences in that mouse study contrasts with sex differences in CGRP immunoreactivity observed in other tissues from rat and from human (Valdemarsson et al, 1990;Herbison and Spratt, 1995;Ji et al, 2019), with sex differences in humans potentially explaining sex differences in the efficacy of antimigraine medications that target CGRP receptors (Barbanti et al, 2021;de Vries Lentsch et al, 2021).…”