Erenumab more than doubles plasma CGRP levels

The calcitonin gene-related peptide (CGRP) receptor blocker erenumab is associated with a significant increase in CGRP levels in peripheral blood after 6 months of therapy in a real-life population of migraine patients. The efficacy and safety of erenumab was comparable with that in clinical trials.

Erenumab differs from the other available CGRP monoclonal antibodies by not blocking CGRP but its receptor. By doing this, one would expect the CGRP level to increase as a normal physiological reaction. Seemingly paradoxical, erenumab would in that case have a positive effect on migraine while causing CGRP levels to rise. Up until now, it was unknown what effect erenumab has on plasma CGRP levels, if any at all. Dr Nina Vashchenko (Sechenov First Moscow State Medical University, Russia) and her group set out to investigate this [1].

Included were 58 migraine patients who were treated with the CGRP monoclonal antibody erenumab. Of these, 50 were women and the average age was 44.6 ± 11.4 years. To assess CGRP levels, blood samples were obtained (not during a migraine attack) from the antecubital vein before and after 6 months of therapy. CGRP levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients had a headache diary and completed the Migraine Disability Assessment Scale (MIDAS), Hospital Anxiety and Depression Scale (HADS), and the Allodynia Symptom Checklist-12.

Of the 58 patients, 49 patients had chronic migraine and 28 had medication-overuse headache. During the study, 2 patients dropped out due to constipation and 42 continued treatment with erenumab for at least 6 months. The monthly number of headache days was 6.8 days after treatment compared with 21.6 days at baseline. Erenumab was more effective as acute migraine therapy than previous treatment in 31 patients (73.8%). Samples from 18 patients revealed that the mean plasma CGRP level was 21.29 pg/mL before treatment, which more than doubled to 59.94 pg/mL after treatment. It is unclear if this should be a cause of concern.

The efficacy and safety of erenumab was comparable with that in clinical trials. Dr Vashchenko added that of the patients who stopped erenumab therapy, those with higher elevated CRP levels during treatment saw their number of migraine days rise to baseline values relatively quickly.

1. Vashchenko N, et al. CGRP plasma levels in migraine patients before and after CGRP monoclonal antibodies therapy. OPR-049, EAN 2022, 25–28 April, Vienna, Austria.

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Posted on 22 August 20221 February 2024