Therapies targeting CGRP signaling for medication overuse headache

Abstract

Purpose of reviewMedication overuse headache (MOH) affects more than 60 million individuals worldwide causing enormous personal and social burden. Only repurposed drugs are available for MOH that share limited evidence for efficacy. The preclinical data suggesting that activation of the calcitonin gene-related peptide (CGRP) pathway is involved in headache chronification along with clinical evidence that monoclonal antibodies targeting CGRP (anti-CGRP mAbs) have good efficacy in preventing chronic migraine, triggered this review that aims to summarize the current data on the effectiveness and safety of mAbs against CGRP in MOH.Recent findingsPost hoc analyses of phase-3 trials of erenumab, fremanezumab, galcanezumab, and eptinezumab for the prevention of chronic migraine revealed that patients with MOH benefit from the treatment over placebo. Several real-world studies confirm the efficacy of erenumab and galcanezumab in patients with MO. However, all published trials evaluated treatments in patients with chronic migraine with MO collectively, not in patients with MOH exclusively.SummaryThe available data indicate that anti-CGRP mAbs represent a good mechanism-based and disease-specific therapeutical option with for MOH as long as detoxification and additional nonpharmaceutical interventions are operated. Future research should focus on long-term-controlled trials in MOH populations exclusively.

Consenso sobre anticuerpos monoclonales en migraña del Grupo de Estudio de Cefaleas de la Asociación Madrileña de Neurología

“…Parece que estos fármacos son igual de eficaces en este grupo de pacientes, reduciendo el consumo de analgésicos por su efecto en la disminución de la frecuencia y de la intensidad de las crisis. Este hecho también se explicaría por el potencial papel del CGRP en la propia fisiopatología de la cefalea por uso excesivo de analgésicos 57 .…”

Medication-Overuse Headache

“…46 Clinical trials assessing the efficacy of antibodies to CGRP or its receptor showed a treatment benefit for patients with MOH. 47 Subsequently, the oral small-molecule CGRP antagonists (gepants) rimegepant and atogepant were also shown to be efficacious in patients with chronic migraine and medication overuse. 48 Ubrogepant may confer a similar benefit, but the efficacy of lasmiditan in patients with MOH is as yet unclear.…”

New migraine drugs: A critical appraisal of the reason why the majority of migraine patients do not receive an adequate medication

“…It is very likely that gepants can also be used in patients with vascular diseases. Gepants might not lead to medication overuse and medication overuse headache (15). The main obstacle for the use of gepants is the very high price.…”