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

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.

Resumption of migraine preventive treatment with CGRP(-receptor) antibodies after a 3-month drug holiday: a real-world experience

“…This data is relevant for clinical practice as most patients treated with a CGRP(-R) mAb in Europe undergo a drug holiday after 6–12 months as recommended by national and international guidelines, or even forced by the healthcare systems of some countries [ 14 , 15 , 19 ]. Recent studies have focused on migraine progression after treatment discontinuation.…”

“…In the study by Gantenbein et al, half of patients reached after three months of treatment pause a number of MMD comparable to the baseline phase [ 15 ]. Vernieri et al also reported a gradual increase of MMD following cessation of treatment with erenumab and galcanezumab: After three months of drug holiday the 50% responder rates decreased from > 70% to < 30% [ 19 ]. Similarly, in the parent study of this analysis, we showed a significant increase of migraine frequency over time after CGRP(-R) mAbs treatment cessation [ 17 ], which is also observed in this subgroup analysis.…”

“…Moreover, mAbs long-term data over several years demonstrated a consistent good efficacy and tolerability [ 30 ]. Given the recent evidence on migraine deterioration during discontinuation attempts [ 15 – 17 , 19 ], the need for periodical treatment interruptions remains a matter of discussion.…”

Conversion from chronic to episodic migraine in patients treated with galcanezumab in real life in Italy: the 12-month observational, longitudinal, cohort multicenter GARLIT experience

“…Once the frequency of migraine attacks decreases, patients are more likely to lead a healthier lifestyle and be less impacted by the fear of pain and psychosocial stress [ 33 ]. This indirect advantage exerted by mAb targeting the CGRP pathway is also supported by the no-return to the baseline condition after 3 months of suspension [ 34 ].…”

Treatment of resistant chronic migraine with anti-CGRP monoclonal antibodies: a systematic review

“…Despite the majority of patients with chronic migraine reverted to episodic migraine after one year of treatment, data collected by these authors demonstrated that, in most patients, the therapeutic effect does not persist after anti-CGRP mAb discontinuation. For this reason, anti-CGRP mAb cannot be considered disease-modifying treatments, at least not after a one-year period of use [ 75 ]. It would be necessary to observe the clinical course of patients withdrawing the therapy with these biological drugs after longer treatment periods.…”