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Switching OnabotulinumtoxinA to Monoclonal Anti-CGRP Antibodies in Drug-Resistant Chronic Migraine

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Abstract

Background

OnabotulinumtoxinA (BTX-A) and anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (anti-CGRP mAbs) are approved drugs for chronic migraine (CM), a difficult-to-treat condition. Optimization of CM patient management by choosing the best options and determining appropriate time for switching or adding concomitant treatments are highly needed.

Objective

Evaluate clinical response to anti-CGRP mAbs in patients who switched from BTX-A due to ineffectiveness defined by different cut-offs and assess the retention rate, effectiveness, and safety of both drugs within the first 9 months of treatment.

Methods

A monocentric, cohort study, enrolling patients with CM, resistant to several preventive treatments, first treated with BTX-A and then with anti-CGRP mAbs with two observational phases of 9 months preceded by respective baseline. First, the retention rate and effectiveness of both treatments were measured in all patients. A second analysis assessed effectiveness in patients stratified according to <50 or <30% response rate to BTX-A. The absolute change from baseline in monthly headache days (MHDs), response rate, analgesic use, and persistence in medication overuse (MO) at 3, 6, and 9 months of treatment were recorded. Last observation carried forward (LOCF) analyses, including all patients and assuming no further changes after discontinuation, were performed for all outcomes.

Results

Of the 78 enrolled patients (80.8% female, and 89.7% with MO at baseline), 32 (41.0%) received erenumab, 32 (41.0%) galcanezumab, and 14 (18.0%) fremanezumab. Retention rate was 62.2 and 91.0% for BTX-A and 76.9 and 96.2%, for anti-CGRP mAbs at 3 and 9 months of treatment, respectively. At 9 months of treatment, 22.4% of BTX-A patients and 65.0% of anti-CGRP mAbs patients achieved a ≥50% response rate. Anti-CGRP mAbs reduced MHDs, AMN, and AMDs, and decreased the number of MO patients at 9 months. In patients stratified according to <50 or <30% response rate to BTX-A, response rate (≥50% response at 9 months) to anti-CGRP was 62.9 and 57.9%, respectively. LOCF analyses confirmed these findings. No serious adverse events (AEs) were recorded and only two patients discontinued treatment due to AEs.

Conclusions

Difficult-to-treat CM patients who discontinued BTX-A and received anti-CGRP mAbs showed a substantial clinical improvement in migraine-related outcomes. Switching to an anti-CGRP mAb appears to be a viable option in patients with insufficient response after the first 2 cycles with BTX-A. The appropriate variables, cut-offs, and timing to define ineffectiveness and the best time to switch or combine therapies for difficult-to-treat CM need to be investigated further.

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Acknowledgements

The “Società Italiana per lo Studio delle Cefalee” (SISC) is acknowledged for the “Registro Italiano delle Cefalee (RICe)”.

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Authors and Affiliations

  1. Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Viale Pieraccini 6, Florence, Italy

    Luigi Francesco Iannone, Davide Fattori, Martina Marangoni, Alberto Chiarugi & Pierangelo Geppetti

  2. Headache Center and Clinical Pharmacology Unit, Careggi University Hospital, Florence, Italy

    Luigi Francesco Iannone, Silvia Benemei, Alberto Chiarugi, Pierangelo Geppetti & Francesco De Cesaris

Authors
  1. Luigi Francesco Iannone
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  2. Davide Fattori
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Corresponding author

Correspondence to Pierangelo Geppetti.

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Funding

This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

PG: received personal fees from Allergan, Eli Lilly, Novartis, Amgen, TEVA; Grants from Amgen, TEVA, Eli-Lilly, Allergan, Chiesi; Scientific Advisory Board, Endosome Therapeutics; Founding scientist of FloNext srl, Spinoff of the University of Florence. FDC received personal fees from TEVA, Eli Lilly, Novartis. LFI received personal fees from Eli-Lilly. Other authors have no conflicting interests.

Data availability

The data collected and analyzed for the current study are available from the corresponding author on reasonable request.

Ethics

The study was approved as a part of the Registro Italiano Cefalee (RICe) study by the local Ethics committee (Studio RICe, 14591_oss).

Consent to participate

Informed consent was obtained from each patient.

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Not applicable.

Code availability

Not applicable.

Author contributions

PG, LFI, and FDC designed the study; LFI, DF, MM, SB, AC, FDC, and PG performed the research; LFI, PG, AC, and FDC analyzed and interpreted the data. PG, DF, MM, SB, AC, and FDC critically revised the draft manuscript. All authors critically reviewed the manuscript, agree to be fully accountable for ensuring the integrity and accuracy of the work, and read and approved the final manuscript.

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Iannone, L.F., Fattori, D., Marangoni, M. et al. Switching OnabotulinumtoxinA to Monoclonal Anti-CGRP Antibodies in Drug-Resistant Chronic Migraine. CNS Drugs 37, 189–202 (2023). https://doi.org/10.1007/s40263-022-00983-5

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