Comparing the relative and absolute effect of erenumab: is a 50% response enough? Results from the ESTEEMen study

Abstract

Background Monoclonal antibodies acting on the calcitonin gene-related peptide (CGRP) or its receptor have changed migraine preventive treatment. Those treatments have led to reconsidering the outcomes of migraine prevention. Available data mostly considered benefits in terms of relative efficacy (percent or absolute decrease in monthly migraine days [MMDs] or headache days compared with baseline). However, not enough attention has been paid to residual MMDs and/or migraine-related disability in treated patients. In the present study, we aimed at comparing the relative and absolute efficacy of erenumab. Methods ESTEEMen was a collaborative project among 16 European headache centers which already performed real-life data collections on patients treated with erenumab for at least 12 weeks. For the present study, we performed a subgroup analysis on patients with complete data on MMDs at baseline and at weeks 9-12 of treatment. Starting from efficacy thresholds proposed by previous literature, we classified patients into 0-29%, 30-49%, 50-74%, and ≥75% responders according to MMD decrease from baseline to weeks 9-12 of treatment. For each response category, we reported the median MMDs and Headache Impact test-6 (HIT-6) scores at baseline and at weeks 9-12. We categorized the number of residual MMDs at weeks 9-12 as follows: 0-3, 4-7, 8-14, ≥15. We classified HIT-6 score into four categories: ≤49, 50-55, 56-59, and ≥60. To keep in line with the original scope of the ESTEEMen study, calculations were performed in men and women. Results Out of 1215 patients, at weeks 9-12, 381 (31.4%) had a 0-29% response, 186 (15.3%) a 30-49% response, 396 (32.6%) a 50-74% response, and 252 (20.7%) a ≥75% response; 246 patients (20.2%) had 0-3 residual MMDs, 443 (36.5%) had 4-7 MMDs, 299 (24.6%) had 8-14 MMDs, and 227 (18.7%) had ≥15 MMDs. Among patients with 50-74% response, 246 (62.1%) had 4-7 and 94 (23.7%) 8-14 residual MMDs, while among patients with ≥75% response 187 (74.2%) had 0-3 and 65 (25.8%) had 4-7 residual MMDs. Conclusions The present study shows that even patients with good relative response to erenumab may have a clinically non-negligible residual migraine burden. Relative measures of efficacy cannot be enough to thoroughly consider the efficacy of migraine prevention.

Excellent Response to OnabotulinumtoxinA: Different Definitions, Different Predictors

“…The proportion of frequency-based excellent responders was about 4% and, indeed, this criterion is far more restrictive. Our data show that frequency-based criteria identify a lower proportion of responders than percent-based criteria; this finding is in line with what was found in a real-life study on erenumab [ 26 ]. The clinical consequence of this finding is that many patients on treatment with BT-A could benefit from combination treatments for the prevention of migraine.…”

“…The methods of this study have been previously published, since two more articles were derived from the analysis of the present dataset [ 26 , 27 ]; this is a pooled patient-level analysis of data from real-life studies on patients with CM treated with BT-A at 16 European headache centers. The centers potentially participating in the study were first identified through a MEDLINE search of the most recent publications on BT-A treatment for CM in Europe.…”

European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention – 2022 update

“…Combined treatment might be particularly suitable for patients achieving a substantial relative response (e.g. 50% reduction in monthly migraine days) with CGRP-mAbs with a relevant number of residual migraine or headache days [ 39 ]. Due to these considerations, the panel decided not to make an explicit statement either in favor or against combination therapy.…”

“…Much more complex is the issue of a CGRP-mAb switch for efficacy reasons. Indeed, there is a non-negligible proportion of individuals with migraine who do not have a clinical response after maintaining the treatment for an adequate period [ 39 , 60 ]. In those individuals with migraine, a switch to a different CGRP-mAb may represent an option.…”

Effectiveness of Transcranial Direct Current Stimulation and Monoclonal Antibodies Acting on the CGRP as a Combined Treatment for Migraine (TACTIC): Protocol for a Randomized, Double-Blind, Sham-Controlled Trial

“…However, both randomized controlled trials and real-life studies showed that up to one half of patients in clinical practice do not attain a 50% reduction in monthly migraine days from baseline even with those specific treatments and need further improvements in their migraine prevention. Besides, many patients, even if reporting a significant response to those drugs, may have a high number of residual monthly headache days resulting in a substantial impact on daily activities ( 27 ). The number of residual monthly migraine days after treatment, although clinically relevant, is not reported by the available studies ( 28 ).…”