Clinic and genetic predictors in response to erenumab.

Zecca, Chiara; Cargnin, Sarah; Schankin, Christoph; Giannantoni, Nadia Mariagrazia; Viana, Michele; Maraffi, Isabella; Riccitelli, Gianna Carla; Sihabdeen, Shairin; Terrazzino, Salvatore; Gobbi, Claudio (2022). Clinic and genetic predictors in response to erenumab. European journal of neurology, 29(4), pp. 1209-1217. Wiley 10.1111/ene.15236

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BACKGROUND

Erenumab (ERE) is the first anti-calcitonin gene related peptide (CGRP) receptor monoclonal antibody approved for migraine prevention. A proportion of patients does not adequately respond to ERE.

METHODS

Prospective, multicenter study involving 110 migraine patients starting ERE 70 mg monthly. Baseline socio-demographics and migraine characteristics including mean monthly migraine days (MMDs), migraine-related burden (MIDAS and HIT-6 scales) and use of abortive medications during 3 months before and after ERE start were collected. Real-time PCR was used to determine polymorphic variants of calcitonin receptor-like receptor and receptor activity-modifying protein-1 genes. Logistic regression models were used to identify independent predictors for 50% (50-RESP) and 75% (75-RESP) responder patients.

RESULTS

At month 3, MMDs decreased from 17.2 to 9.2 (p<0.0001), 59/110 (53.6%) patients were 50-RESP, and 30/110 (27.3%) were 75-RESP. Age at migraine onset [OR (95%CI):1.062(1.008-1.120), p=0.024], number of failed preventive medications [0.753(0.600-0.946) p=0.015], and MIDAS score [1.011(1.002-1.020) p=0.017] were associated with 75-RESP. Among the genetic variants investigated, RAMP1 rs7590387 was found associated to a lower probability of being 75-RESP [per G allele OR (95%CI): 0.53(0.29-0.99), p=0.048], but this association did not survive adjustment for confounding clinical variables [per G allele, 0.55 (0.28-1.10), p=0.09].

CONCLUSIONS

In this real word study treatment with ERE significant reduced MMDs. Number of failed preventive medications, migraine burden, and age at migraine onset predicted response to ERE. Larger studies are required to confirm a possible role of RAMP1 rs7590387 as genetic predictor of ERE efficacy.

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