Real-World Evidence for Control of Chronic Migraine Patients Receiving CGRP Monoclonal Antibody Therapy Added to OnabotulinumtoxinA: A Retrospective Chart Review

Abstract

Introduction: 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.

Methods: 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]).

Results: 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.

Conclusions: 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).

Keywords: CGRP receptor; Chronic daily headache; Chronic headache; Combination therapy; Migraine headache; Preventive treatment; Type A botulinum toxins.

Fig. 1

Study design. ^aNot all patients had four visits or 12 months of data. ^bBaseline assessments for outcome measures (e.g., headache day frequency, headache intensity, disability) were collected from the visit at which the CGRP mAb was prescribed and reflect patient assessments during approximately 1–3 months prior to initiation of the CGRP mAb. ^cCGRP mAbs were self-administered by subcutaneous injection. Per label, erenumab and galcanezumab are administered once monthly, and fremanezumab is administered once every 3 months. ^dOnabotulinumtoxinA treatment is not always administered per label. CGRP calcitonin gene–related peptide, mAb monoclonal antibody, MIDAS Migraine Disability Assessment

Fig. 2

Analysis cohorts for primary analysis and sensitivity analysis (AHS CGRP mAb cohort [31]). ^aOther reasons for exclusion included negative time from migraine diagnosis to index date; negative time from first onabotulinumtoxinA injection to index date; headache frequency of 45/30 days recorded at index; and data available for only one visit (visit 4). AHS American Headache Society, CGRP calcitonin gene–related peptide, CM chronic migraine, HIT-6 6-item Headache Impact Test, mAb monoclonal antibody, MIDAS Migraine Disability Assessment

Fig. 3

Change in monthly headache frequency during combination therapy with onabotulinumtoxinA and a CGRP monoclonal antibody. a Mean change from baseline and b percentage of patients with a ≥ 50% reduction from baseline in monthly headache frequency in the primary analysis cohort. c Mean change from baseline and d percentage of patients with a ≥ 50% reduction from baseline in monthly headache frequency in the AHS CGRP mAb cohort. AHS American Headache Society, CGRP calcitonin gene–related peptide, CI confidence interval, mAb monoclonal antibody

Fig. 4

Change in migraine-associated disability during combination therapy with onabotulinumtoxinA and a CGRP monoclonal antibody. a Mean change from baseline in MIDAS score, b percentage of patients with a ≥ 5-point reduction in MIDAS score, and c percentage of patients with a ≥ 30% improvement from baseline in MIDAS score in the primary analysis cohort. d Mean change from baseline in MIDAS score, e percentage of patients with a ≥ 5-point reduction in MIDAS score, and f percentage of patients with a ≥ 30% improvement from baseline in MIDAS score in the AHS CGRP mAb cohort. AHS American Headache Society, CGRP calcitonin gene–related peptide, CI confidence interval, mAb monoclonal antibody, MIDAS migraine disability assessment