Dataset Information

Early Management of OnabotulinumtoxinA Treatment in Chronic Migraine: Insights from a Real-Life European Multicenter Study.

ABSTRACT:

Introduction

OnabotulinumtoxinA (BT-A) quarterly was the first treatment approved specifically for chronic migraine (CM). It is unclear whether three cycles are better than two to assess early BT-A response.

Methods

We performed a retrospective analysis on real-life prospectively collected data in 16 European headache centers. All the centers provided data on patients treated with BT-A for CM over the first three cycles of treatment. For each treatment cycle we defined patients as "good responders" if reporting a ≥ 50% reduction in monthly headache days compared with the three months before starting BT-A, "partial responders" if reporting a 30-49% reduction in monthly headache days, and "non-responders" if reporting a < 30% reduction in monthly headache days or stopping the treatment before the third cycle.

Results

We included 2879 patients. Seven hundred and eighty-four (64.6%) of the 1213 patients reporting a good response during the first and/or the second cycle had a good response during the third cycle; 309 (49.3%) of the 627 patients reporting a partial response (but no good response) during the first and/or the second cycle had a good response during the third cycle; only 65 (6.3%) of the 1039 patients who did not respond during both the first two cycles achieved a good response during the third cycle. Multivariate analyses showed that partial or good response during the first or the second cycle were independently associated with good response during the third cycle.

Conclusions

Our data suggest that patients with CM responding to BT-A during the first two cycles will likely benefit from the third cycle of treatment, while the probability that non-responders to the first two cycles start responding during the third cycle is low. These results can help guide the individual decision to stop or continue treatment after the second cycle in patients who have not responded to the first two cycles.

SUBMITTER: Ornello R

PROVIDER: S-EPMC8119503 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionMigraine is mostly a female disorder because of its lower prevalence in men. Less than 20% of patients included in the available studies on migraine treatments are men; hence, the evidence on migraine treatments might not apply to men. The aims of the present study were to provide reliable information on the effectiveness of onabotulinumtoxinA (BT-A) for chronic migraine in men and to compare clinical benefits between men and women.MethodsWe performed a pooled patient-level gender-specific analysis of real-life data on BT-A for chronic migraine of patients followed-up to 9 months. We reported the 50% responder rates during each BT-A cycle, defined as percentage of reduction in monthly headache days (MHDs) compared to baseline, along with 75% and 30% responder rates. We also reported the mean decrease in MHDs and in days of acute medication use (DAMs) during each BT-A cycle as compared to baseline. We also evaluated the reasons for stopping the treatment within the third cycle.ResultsWe included an overall cohort of 2879 patients, 522 of whom (18.1%) were men. In men, 50% responder rates were 27.7% during the first BT-A cycle, 29.2% during the second, and 35.6% during the third cycle; in women, the corresponding rates were 26.6%, 33.5%, and 41.0%. In the overall cohort, responder rates did not differ between men and women during the first two cycles; during the third cycle, the distribution was different (P < 0.001) mostly because of higher rates of treatment stopping and non-responders in men. In the propensity score matched cohort, the trend was maintained but lost its statistical significance. Both men and women had a significant decrease in MHDs and in DAMs with BT-A treatment (P < 0.001). There were no gender differences in those changes with the only exception of MHD decrease which, during the third cycle, was lower in men than in women (7.4 vs 8.2 days, P = 0.016 in the overall cohort and 9.1 vs 12.5 days, P = 0.009 in the propensity score matched cohort). At the end of follow-up, 152 men and 485 women stopped BT-A treatment (29.1% vs 20.6%; P < 0.001). The relative proportion of patients stopping treatment because of inadequate response (less than 30% decrease in MHDs from baseline) was higher in men than in women (42.8% vs 39.6%), while the proportion of patients stopping because of adverse events was higher in women than in men (5.6% vs 0%; P = 0.031).ConclusionsOur pooled analysis suggests that the response to BT-A is significant in both men and women with a small gender difference in favor of women. Men tended to stop the treatment more frequently than women. We emphasize the need for more gender-specific data on migraine treatments from randomized controlled trials and observational studies.

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Project description:BackgroundChronic migraine (CM) is a disabling condition with high prevalence in the general population. Until the recent approval of monoclonal antibodies targeting the calcitonin gene-related peptide (Anti-CGRP mAbs), OnabotulinumtoxinA (BoNT-A) was the only treatment specifically approved for CM prophylaxis. Direct comparisons between the two treatments are not available so far.MethodsWe performed an observational, retrospective, multicenter study in Italy to compare the real-world effectiveness of Anti-CGRP mAbs and BoNT-A. Patients with CM who had received either treatment according to Italian prescribing regulations were extracted from available clinical databases. Efficacy outcomes included the change from baseline in monthly headache days (MHD), MIgraine Disability ASsessment test (MIDAS), and monthly acute medications (MAM) evaluated at 6 and 12 months of follow-up. The primary outcome was MHD change from baseline at 12 months. Safety outcomes included serious adverse events (SAE) and treatment discontinuation. Unadjusted and adjusted models were used for the analyses.ResultsTwo hundred sixteen potentially eligible patients were screened; 183 (86 Anti-CGRP mAbs; 97 BoNT-A) were included. One hundred seventy-one (80 Anti-CGRP mAbs; 91 BoNT-A) and 154 (69 Anti-CGRP mAbs; 85 BoNT-A) patients were included in the efficacy analysis at 6 and 12 months of follow-up, respectively. Anti-CGRP mAbs and BoNT-A both resulted in a mean MHD reduction at 6 (-11.5 and -7.2 days, respectively; unadjusted mean difference -4.3; 95%CI -6.6 to -2.0; p = 0.0003) and 12 months (-11.9 and -7.6, respectively; unadjusted mean difference -4.4; 95%CI -6.8 to -2.0; p = 0.0002) of follow-up. Similar results were observed after adjusting for baseline confounders. Anti-CGRP mAbs showed a significant MIDAS (-31.7 and -19.2 points, p = 0.0001 and p = 0.0296, respectively) and MAM reduction (-5.1 and -3.1 administrations, p = 0.0023 and p = 0.0574, respectively) compared to BoNT-A at 6 and 12 months. No SAEs were reported. One patient receiving fremanezumab discontinued treatment due to arthralgia. Treatment discontinuations, mainly for inefficacy, were comparable.ConclusionBoth Anti-CGRP mAbs and BoNT-A were effective in CM patients with Anti-CGRP mAbs presenting higher effect magnitude, with comparable safety. Still, BoNT-A remains a valuable option for CM patients with contraindications to Anti-CGRP mAbs or for frail categories who are candidates to local therapy with limited risk of systemic administration.

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Project description:Combination use of onabotulinumtoxinA and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) has the potential to be more effective than either therapy alone for migraine prevention. This retrospective, longitudinal chart review included adults with chronic migraine treated at one clinical site with ≥ 2 consecutive cycles of onabotulinumtoxinA and ≥ 1 month of subsequent combination treatment with CGRP mAbs. Charts at time of mAb prescription (baseline) and up to four visits ~ 3, 6, 9, and 12 months post-baseline were reviewed for safety, tolerability, and outcome measures (monthly headache days [MHDs], headache intensity, and migraine-related disability [MIDAS]). Of 300 charts reviewed, 257 patients met eligibility criteria (mean age: 50 years; 82% women). Average headache frequency was 21.5 MHDs before initiation of onabotulinumtoxinA and 12.1 MHDs before adding CGRP mAb therapy. Prescribed mAbs were erenumab (78%), fremanezumab (6%), and galcanezumab (16%). Over the entire study, patients discontinued CGRP mAb more frequently than onabotulinumtoxinA (23 vs. 3%). Adverse events occurred in 28% of patients, most commonly constipation (9%). Compared with onabotulinumtoxinA alone (baseline), MHDs decreased significantly at all visits (mean decrease: 3.5-4.0 MHDs over ~ 6-12 months of combination treatment); 45.1% of patients had clinically meaningful improvement in migraine-related disability (≥ 5-point reduction in MIDAS score) after ~ 6 months. In this real-world study, combination treatment with onabotulinumtoxinA and CGRP mAbs was well tolerated, with no new safety signals identified, and was associated with additional clinically meaningful benefits. More real-world and controlled trials should be considered to further assess safety and potential benefits of combination treatment. Video abstract: Real-world data suggests that CGRP inhibitors improve onabotulinumtoxinA efficacy for chronic migraine (MP4 20,067 kb).