Discontinuing monoclonal antibodies targeting CGRP pathway after one-year treatment: an observational longitudinal cohort study

Fabrizio Vernieri, Nicoletta Brunelli, Roberta Messina, Carmelina Maria Costa, Bruno Colombo, Paola Torelli, Simone Quintana, Sabina Cevoli, Valentina Favoni, Florindo d'Onofrio, Gabriella Egeo, Renata Rao, Massimo Filippi, Piero Barbanti, Claudia Altamura, Fabrizio Vernieri, Nicoletta Brunelli, Roberta Messina, Carmelina Maria Costa, Bruno Colombo, Paola Torelli, Simone Quintana, Sabina Cevoli, Valentina Favoni, Florindo d'Onofrio, Gabriella Egeo, Renata Rao, Massimo Filippi, Piero Barbanti, Claudia Altamura

Abstract

Background: Monoclonal antibodies anti-calcitonin gene-related peptide (mAbs anti-CGRP) pathway are effective and safe on migraine prevention. However, some drug agencies limited these treatments to one year due to their high costs. This study aimed at evaluating the effect of discontinuing mAbs anti-CGRP on monthly migraine days (MMDs) and disability in high-frequency episodic (HFEM) and chronic migraine (CM) patients.

Methods: This observational longitudinal cohort study was conducted at 10 Italian headache centres. Consecutive adult patients were followed-up for three months (F-UP1-3) after discontinuation of a one-year erenumab/galcanezumab treatment. The primary endpoint was the change in F-UP MMDs. Secondary endpoints included variation in pain intensity (Numerical Rating Scale, NRS), monthly acute medication intake (MAMI), and HIT-6 scores. We also assessed from F-UP1 to 3 the ≥50% response rate, relapse rate to CM, and recurrence of Medication Overuse (MO).

Results: We enrolled 154 patients (72.1% female, 48.2 ± 11.1 years, 107 CM, 47 HFEM); 91 were treated with erenumab, 63 with galcanezumab. From F-UP1 to F-UP3, MMDs, MAMI, NRS, and HIT-6 progressively increased but were still lower at F-UP3 than baseline (Friedman's analysis of rank, p < .001). In the F-UP1-3 visits, ≥50% response rate frequency did not differ significantly between CM and HFEM patients. However, the median reduction in response rate at F-UP3 was higher in HFEM (- 47.7% [25th, - 79.5; 75th,-17.0]) than in CM patients (- 25.5% [25th, - 47.1; 75th, - 3.3]; Mann-Whitney U test; p = .032). Of the 84 baseline CM patients who had reverted to episodic migraine, 28 (33.3%) relapsed to CM at F-UP1, 35 (41.7%) at F-UP2, 39 (46.4%) at F-UP3. Of the 64 baseline patients suffering of medication overuse headache ceasing MO, 15 (18.3%) relapsed to MO at F-UP1, 26 (31.6%) at F-UP2, and 30 (42.3%, 11 missing data) at F-UP3. Lower MMDs, MAMI, NRS, and HIT-6 and higher response rate in the last month of therapy characterized patients with ≥50% response rate at F-UP1 and F-UP3 (Mann-Whitney U test; consistently p < .01).

Conclusion: Migraine frequency and disability gradually increased after mAbs anti-CGRP interruption. Most patients did not relapse to MO or CM despite the increase in MMDs. Our data suggest to reconsider mAbs anti-CGRP discontinuation.

Keywords: Calcitonin gene-related peptide; Discontinuation; Migraine treatment; Monoclonal antibodies; Real-world.

Conflict of interest statement

Fabrizio Vernieri received travel grants, honoraria for advisory boards, speaker panels, or clinical investigation studies from Allergan, Amgen, Angelini, Eli-Lilly, Lundbeck, Novartis, and Teva.

Roberta Messina received honoraria as speaker from Novartis, Eli Lilly, and Teva.

Bruno Colombo received travel grants, honoraria for advisory boards, speaker panels, or clinical investigation studies from Novartis, Teva, Eli-Lilly Lusofarmaco Paola Torelli received travel grant, honoraria as a speaker, or for participating in advisory boards from Novartis, Teva, Eli Lilly, and Allergan.

Sabina Cevoli received travel grants, honoraria for advisory boards, speaker panels or clinical investigation studies from Novartis, Teva, Lilly, Allergan, Ibsa, Amgen and Lundbeck.

Valentina Favoni received honoraria as speaker or for participating in advisory boards from Ely-Lilly, Novartis and Teva.

Florindo d’Onofrio received grants and honoraria from Lilly, Teva, Novartis, Neopharmed.

Gabriella Egeo received travel grants and honoraria from Eli-Lilly, Novartis, New Penta and Ecupharma.

Renata Rao received honoraria for speaker panels from Teva, Lilly, Novartis.

Massimo Filippi is the Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and AriSLA (Fondazione Italiana di Ricerca per la SLA).

Piero Barbanti received travel grants, honoraria for advisory boards, speaker panels or clinical investigation studies from Alder, Allergan, Angelini, Bayer, ElectroCore, Eli-Lilly, GSK, Lusofarmaco, MSD, Novartis, Stx-Med, Teva, Visufarma, Zambon.

Claudia Altamura received travel grants and honoraria from Novartis, Eli Lilly, Lusofarmaco, Laborest, Allergan, Almirall.

Nicoletta Brunelli, Simone Quintana and Carmelina Maria Costa have nothing to disclose.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
The frequencies of patients with ≥50% response rate at the last month of therapy with mAbs anti-CGRP pathway and at the three-months of discontinuation in CM and HFEM
Fig. 2
Fig. 2
The frequency of patients having at least 8 MMDs in the three months of mAbs anti-CGRP pathway discontinuation in CM and HFEM patients
Fig. 3
Fig. 3
The median value (95% CI bars) of MMDs percentual reduction in the last month of therapy in patients relapsing to

Fig. 4

The frequency of patients relapsing…

Fig. 4

The frequency of patients relapsing to CM (A) and MO (B) MMDs in…

Fig. 4
The frequency of patients relapsing to CM (A) and MO (B) MMDs in the three months of mAbs anti-CGRP pathway discontinuation
Fig. 4
Fig. 4
The frequency of patients relapsing to CM (A) and MO (B) MMDs in the three months of mAbs anti-CGRP pathway discontinuation

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