Safety of Rimegepant, an Oral CGRP Receptor Antagonist, Plus CGRP Monoclonal Antibodies for Migraine

Abstract

Objective Evaluate the safety and tolerability of oral rimegepant when used for acute treatment concomitantly with a monoclonal antibody (mAb) targeting the calcitonin gene‐related peptide (CGRP) ligand or receptor (CGRP mAb) for the preventive treatment of migraine. Background The efficacy of CGRP mAbs for the preventive treatment of migraine and the small molecule CGRP receptor antagonist rimegepant for acute treatment has been demonstrated in randomized controlled clinical trials. Over the past few years, the US Food and Drug Administration has approved 4 CGRP mAbs for the preventive treatment of migraine and 2 small molecule CGRP receptor antagonists for the acute treatment of migraine. A previous case report of 2 patients receiving concomitant treatment with rimegepant and erenumab suggested that rimegepant may be safely used as acute treatment in patients who are also receiving a preventive regimen involving CGRP mAbs. We report here 13 additional patients with migraine who simultaneously used rimegepant and either erenumab, fremanezumab, or galcanezumab and assess the rate of on‐treatment adverse events (AEs). Methods This was a substudy nested within a multicenter, open‐label, long‐term safety study in adults with 2‐14 monthly migraine attacks of moderate to severe pain intensity. A subgroup experiencing 2‐8 monthly attacks and taking a stable dose of a CGRP mAb also took rimegepant 75 mg as needed up to once daily for acute treatment for 12 weeks. Results The 13 patients (11 women [85%]; mean age 49.9 years) enrolled in the substudy were being treated with CGRP mAbs (erenumab [n = 7], fremanezumab [n = 4], or galcanezumab [n = 2]). Mean (SD) time in the rimegepant treatment period was 9.6 (4.6) weeks. Mean (SD) 4‐week rimegepant exposure was 7.8 (5.5) doses; a total of 224 doses were taken. Five (38%) patients reported ≥1 on‐treatment AE. Of these, 2 (15%) patients had mild or moderate nasopharyngitis; no other AEs occurred in ≥2 patients. Three patients had AEs of mild or moderate severity that were considered potentially treatment‐related. No patients had serious AEs, AEs leading to discontinuation, or aminotransferase levels >3× the upper limit of normal. Conclusion Rimegepant, when used as an oral acute treatment in patients receiving CGRP mAbs as preventive treatment, was well tolerated; no safety issues were identified. Studies involving larger patient populations are needed to confirm these findings.

Real‐world efficacy, tolerability, and safety of ubrogepant

“…1,2,11,12 A recent study reported no safety issues of using rimegepant in 13 patients that were on a CGRP mAb. 13 The results of the 62 (58.5%) patients that were concurrently using a CGRP mAb in our study support the efficacy of ubrogepant in this population given there was no difference on the "good responder" rate compared to those who were not on a CGRP mAb, 25 (41%) versus 25 (56.8%) patients, p = 0.11. The lack of complete, sustained blockade of the CGRP pathway of ligand or receptor-targeted CGRP mAbs may account for the therapeutic benefit of ubrogepant in these patients.…”

Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of New Anti-Migraine Drugs—Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies

“…In such an event, rimegepant should be discontinued. In addition, no serious adverse events, including hepatotoxicity, were reported [71][72][73][74][75][76][77][78][79][80][81].…”

“…Rimegepant has not been administered to patients with end-stage renal disease (CLcr < 15 mL/min) or to patients on dialysis; therefore, its use should be avoided in these patients. No dosage adjustment of rimegepant is required for patients with mild, moderate, or severe renal impairment [69,76,77,79,80].…”

Neues in der Migränetherapie

“…Aus diesem Grund führen die jeweiligen FDA und EMA Zulassungen diesbezüglich auch keine Einschränkungen auf. Selbst bei einer Kombination von Gepanten mit monoklonalen CGRP/CGRP-Rezeptorantikörpern sind keine Hinweise auf ein erhöhtes Ischämierisiko aufgefallen [53].…”