Anti-CGRP monoclonal antibodies in chronic migraine with medication overuse: real-life effectiveness and predictors of response at 6 months

DOI: https://doi.org/10.1186/s10194-021-01328-1

Abstract-Summary In daily practice, anti-CGRP monoclonal antibodies (MAbs) may be useful in chronic migraine (CM) with medication overuse (MO), but data is limited.

We compared patients (1) with and without MO at baseline, (2) with and without ongoing MO after treatment, defining MO resolution as < 10 or 15 days/month of acute medication intake, according to analgesic type, during the 6-month treatment. Of 139 CM patients completing 6-month treatment with anti-CGRP MAbs,

71.2% (99/139) had MO at baseline.

After 6 months, patients with and without MO at baseline had significant and similar proportions of ≥50% reduction in migraine days/month (MO: 63.6% vs. non-MO: 57.5%, p = 0.500).

Reduction in headache frequency compared to baseline occurred in both MO-ongoing and MO-resolution group, although those who stopped overusing had a greater improvement (headache days/month: −13.4 ± 7.6 vs. –7.8 ± 7.2, p < 0.0001). In real-life anti-CGRP MAbs are as effective in CM patients with MO as in

patients without it and facilitate MO cessation.

Reduction in headache frequency and acute medication days/month occurs

regardless of whether patients stop overusing or not.

Introduction Medication overuse (MO) is defined as an acute medication intake of more than 10 or 15 days/month, according to the type of drug used, being present in more than 50% of chronic migraine (CM) patients [196].

Clinical trials with anti-CGRP MAbs included a small proportion of patients who were overusing acute medication, although they were not designed to evaluate this population.

We decided to analyze in a real-life clinical cohort the effectiveness of anti- CGRP MAbs after 6 months of treatment in patients with CM with and without MO, focusing on predictors of response.

700

4 Treatment

Methods From February 2019 to April 2021, we included consecutive patients who started treatment with anti-CGRP MAbs, following the criteria required by the Spanish government for anti-CGRP MAbs prescription (more than 8 migraine days, with failure of at least 3 migraine preventive medications, being onabotulinumtoxinA (BTX-A) one of them for CM) and in line with the European Headache Federation guideline on anti-CGRP MAbs use [197].

Patients completed an electronic headache diary (eDiary), starting 1 month prior to the first dose of anti-CGRP MAbs and throughout all treatment period to monitor headache frequency (migraine days/month-MDM; headache days/month-HDM) and severity.

We assessed statistical significance comparisons between MO resolution group (MO-R) and MO-ongoing group (MO-O) by Pearson’s chi-square when comparing categorical variables or Fisher’s exact test.

Included variables were either based on statistical significance from bivariate

tests (p ≤ 0.01) or considered clinically relevant (age and gender). Results At the time of the analysis, 44.0% (139/316) were CM patients who had completed 6 months of treatment (69.1% Erenumab and 30.9% Galcanezumab).

There were no differences in the proportions of MAbs (Erenumab vs.

Galcanezumab) used between patients with and without MO.

In regards to MO, 60.6% of patients (60/99) no longer satisfied MO definition

(MO-R) while 39.4% (39/99) kept overusing acute medication (MO-O).

The MO-O group had more anxiety in the Beck Anxiety Inventory scale (BAI)

(MO-R: 15.5[19.0] vs. MO-O: 22.0[20.0]; p = 0.020).

We also observed greater proportions of previous failure to onabotulinumtoxinA

in the MO-O group (MO-R: 33.3% vs. MO-O: 53.8%; p = 0.048).

Discussion In this prospective study, after 6 months of treatment with anti-CGRP MAbs, we observed that: First, ≥50% reduction in headache frequency for both MDM and HDM is similar regardless of the presence of MO at baseline.

Anti-CGRP MAbs help categorize MO into two profiles: (1) the MO-resolution group which represents patients whose overuse is directly related to migraine fre- quency, reducing days of acute medication intake by improving frequency with treatment; (2) the MO-ongoing group that includes patients where, despite a reduc- tion in MDM, other factors such as higher pain intensity possibly prevent from achieving a non-overuse behavior.

These MO profiles and possible predictors of MO resolution should be further evaluated by long-term real-life studies and larger cohorts of treated patients with anti-CGRP MAbs.

Our real-life study therefore supports the use of anti-CGRP drugs in patients with chronic migraine and MO with similar results as compared to those who do not overuse.

4.2 Preventive Treatment

701

Acknowledgement A machine generated summary based on the work of Caronna, Edoardo; Gallardo, Victor José; Alpuente, Alicia; Torres-Ferrus, Marta; Pozo-Rosich, Patricia. 2021 in The Journal of Headache and Pain.

The impact of anti-CGRP monoclonal antibodies in resistant migraine patients: a real-world evidence observational study