Migraine evolution after the cessation of CGRP(-receptor) antibody prophylaxis: a prospective, longitudinal cohort study

Raffaelli, Bianca; Terhart, Maria; Overeem, Lucas Hendrik; Mecklenburg, Jasper; Neeb, Lars; Steinicke, Maureen; Reuter, Uwe

doi:10.1177/03331024211046617

Cited by 51 publications

(69 citation statements)

References 34 publications

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“…More recently, Raffaelli et al [ 16 ] confirmed that the cessation of mAbs targeting the CGRP pathway determines an increase in migraine frequency and acute medication intake in patients treated with mAbs targeting CGRP receptor (erenumab) or ligand (fremanezumab and galcanezumab). Moreover, the authors observed a faster MMDs increase in patients treated with the former than with the latter, probably related to the shorter elimination half-life of erenumab.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

“…This is a priori analysis. The sample size was considered in line with previous studies on the topic [ 16 – 20 ]. To achieve a power of 80% and a level of significance of 5% (two-sided), for detecting an effect size of 0.25 between paired variables, we calculated a sample size of at least 128 subjects.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2021

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“…have not yet been identified. Real-world studies, which allow the evaluation of patients generally excluded from most clinical trials (e.g., with several drug class failures), have mainly been focused on erenumab, the first anti-CGRP mAb to receive approval, following varying discontinuation periods from 1 to 4 months [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Predictors of sustained response and effects of the discontinuation of anti‐calcitonin gene related peptide antibodies and reinitiation in resistant chronic migraine

Iannone

Fattori

Benemei

et al. 2022

Euro J of Neurology

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Background and purpose: Guidelines for migraine prophylaxis suggest stopping medication after 6-12 months to reevaluate treatment appropriateness. The Italian Medicines Agency set a mandatory regulation to stop anti-calcitonin gene related protein (CGRP) pathway monoclonal antibody (anti-CGRP mAb) treatments for 3 months after 12 months of treatment. Herein, the effects of discontinuation and retreatment of anti-CGRP mAbs in resistant chronic migraine patients are assessed, evaluating predictive factors of sustained response.Methods: This was a monocentric prospective cohort study, enrolling 44 severe (resistant to ≥3 preventive treatments) chronic migraine patients (all with medication-overuse), treated with erenumab (54.5%) or galcanezumab (45.5%) for 12 months, who discontinued treatment for 3 months and then restarted for 1 month. Results:Overall, patients reported an increasing deteriorating trend during the 3 months of discontinuation. Monthly migraine days, number of analgesics, days with at least one analgesic used, a ≥50% response rate (reduction in monthly migraine days), and Migraine Disability Assessment Score and Headache Impact Test 6 total score, remained lower than baseline values, but increased compared to month 12 of treatment. All outcome measures decreased again during the month of retreatment. Patients who did not meet criteria for restarting treatment had a lower Migraine Disability Assessment Score (p = 0.03) and Headache Impact Test 6 (p = 0.01) score at baseline and better outcome measures during discontinuation compared to patients who restarted treatment. Conclusions:In most patients, the 3-month discontinuation of anti-CGRP mAbs resulted in progressive migraine deterioration that was rapidly reverted by retreatment. However, one-quarter of patients who reported better quality of life indices before treatment showed a sustained benefit during discontinuation and did not need retreatment.

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“…Recent real-world studies describe a worsening of migraine after the discontinuation of CGRP(−R) mAbs [ 19 , 20 ]. We reported a significant increase in monthly migraine days (MMD) already one month after the discontinuation of CGRP(−R) mAb therapy with a return to baseline levels after three months [ 21 ]. To date, no real-world data about health-related quality of life (HRQoL) after the cessation of mAb therapy exists.…”

Section: Introductionmentioning

confidence: 99%

Deterioration of headache impact and health-related quality of life in migraine patients after cessation of preventive treatment with CGRP(−receptor) antibodies

et al. 2021

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Background Migraine preventive treatment with CGRP(−receptor) monoclonal antibodies (mAbs) has a positive effect on patients’ health-related quality of life (HRQoL). The German treatment guidelines recommend discontinuing successful treatment with CGRP(−receptor) mAbs after 6–12 months. We aimed to evaluate headache-specific and generic HRQoL for three months after discontinuation of CGRP(−receptor) mAb treatment. Methods We conducted a prospective, longitudinal cohort study, including patients with migraine after 8–12 months of therapy with a CGRP(−R) mAb and before a planned discontinuation attempt. HRQoL was assessed at the time of the last mAbs injection (V1), eight weeks later (V2), and sixteen weeks later (V3). For headache-specific HRQoL, we used the Headache Impact Test-6 (HIT-6). Generic HRQoL was determined with the EuroQol-5-Dimension-5-Level (ED-5D-5L) form, and the Short-Form 12 (SF-12), which comprises a Physical Component Summary (PCS-12) and a Mental Component Summary (MCS-12). Questionnaires’ total scores were compared across the three observation points using nonparametric procedures. Results The study cohort consisted of n = 61 patients (n = 29 treated with the CGRP-receptor mAb erenumab and n = 32 with the CGRP mAbs galcanezumab or fremanezumab). The HIT-6 sum score was 59.69 ± 6.90 at V1 and increased by 3.69 ± 6.21 at V3 (p < 0.001), indicating a greater headache impact on patients’ lives. The mean total EQ-D5-L5 score declined from 0.85 ± 0.17 at V1 by − 0.07 ± 0.18 at V3 (p = 0.013). Both Mental and Physical Component Scores of the SF-12 worsened significantly during treatment discontinuation: The PCS-12 total score decreased by − 4.04 ± 7.90 from V1 to V3 (p = 0.013) and the MCS-12 score by − 2.73 ± 9.04 (p = 0.003). Changes in all questionnaires’ scores but the MCS-12 were already significant in the first month of the drug holiday (V2). Conclusions Our results show a significant decline in headache impact and generic HRQoL of migraine patients after treatment discontinuation of a CGRP(−R) mAb. The observed deterioration is above the established minimally clinically important differences for each of the questionnaires and can therefore be considered clinically meaningful. Monitoring HRQoL during a discontinuation attempt could facilitate the decision whether or not to resume preventive treatment with CGRP(−R) mAbs.

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Migraine evolution after the cessation of CGRP(-receptor) antibody prophylaxis: a prospective, longitudinal cohort study

Cited by 51 publications

References 34 publications

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

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

Predictors of sustained response and effects of the discontinuation of anti‐calcitonin gene related peptide antibodies and reinitiation in resistant chronic migraine

Deterioration of headache impact and health-related quality of life in migraine patients after cessation of preventive treatment with CGRP(−receptor) antibodies

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