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. Supplementary Information The online version contains supplementary material available at 10.1007/s40122-021-00264-x.

Real-World Evidence for the Safety and Efficacy of CGRP Monoclonal Antibody Therapy Added to OnabotulinumtoxinA Treatment for Migraine Prevention in Adult Patients With Chronic Migraine

“…These findings are consistent with the results of other realworld studies evaluating the safety and efficacy of combination treatment with onabotulinumtoxinA and a CGRP mAb. The recent publication of a similar study by Blumenfeld et al (36) showed a 3.5-4 day reduction in MHD over 6-12 months of combination treatment after an initial mean reduction from 21.5 MHD to 12.1 MHD with onabotulinumtoxinA alone. A retrospective analysis by Armanious et al (33) recently demonstrated a 6.8-8.1 reduction in MHD in patients with CM who received 1-3 months of combination treatment with erenumab and onabotulinumtoxinA.…”

“…The safety profile of combination treatment in this real-world study is consistent with that observed in prior analyses of each treatment alone and other real-world studies of CGRP mAbs added to onabotulinumtoxinA treatment for CM. In a similar study of combination preventive treatment of CM with onabotulinumtoxinA and a CGRP mAb by Blumenfeld et al ( 36 ) 28% of patients experienced an AE; the only one reported by ≥5% of patients was constipation. Another retrospective chart review of patients prescribed a CGRP mAb while receiving onabotulinumtoxinA for CM by Cohen et al ( 34 ) reported that AEs occurred in 8.5% of patients and included constipation, injection site reaction, and/or fatigue.…”

“…To date, no prospective clinical trials and only a limited number of real-world studies have examined this treatment approach (33)(34)(35)(36)(37)(38). The AHS position statement reports that combination treatment with onabotulinumtoxinA and a CGRP mAb is probably effective, and CGRP therapy may be added to one or more established treatments based on clinical judgment provided the risk of drug-antibody interactions is considered minimal or non-existent (10,11).…”

“…Preclinical data show that onabotulinumtoxinA and CGRP mAbs prevent the activation of different types of pain fibers involved in migraine: onabotulinumtoxinA primarily prevents the activation of unmyelinated C-fibers (30) and CGRP mAbs mainly prevent the activation of thinly myelinated Aδ-fibers (29). Real-world studies have provided initial evidence of clinical benefit with the addition of a CGRP mAb to onabotulinumtoxinA treatment for CM (33)(34)(35)(36)(37)(38).…”

Calcitonin Gene-Related Peptide (CGRP)-Targeted Monoclonal Antibodies and Antagonists in Migraine: Current Evidence and Rationale

“…On a smaller subset study population (n = 66) with quantifiable MHD data, patients receiving combined therapy have decreased 5.7 MHDs from onabot alone ( p < 0.001) and a total decrease of 16.6 MHDs (64.5% reduction from baseline, p < 0.001). Blumenfeld et al assessed 257 patients receiving concurrent onabot and CGRP-mAb therapy, reporting a MHD decrease of 3.5–4.0 [ 139 ]. Additionally, patients reported a mean decrease in Migraine Disability Assessment (MIDAS) scores of 6.1–11.1 points.…”