Clinic and genetic predictors in response to erenumab.

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

Treatment of multiple sclerosis with rituximab: A multicentric Italian-Swiss experience

Background: Rituximab, an anti-CD20 monoclonal antibody leading to B lymphocyte depletion, is increasingly used as an off-label treatment option for multiple sclerosis (MS). Objective: To investigate the effectiveness and safety of rituximab in relapsing\u2013remitting (RR) and progressive MS. Methods: This is a multicenter, retrospective study on consecutive MS patients treated off-label with rituximab in 22 Italian and 1 Swiss MS centers. Relapse rate, time to first relapse, Expanded Disability Status Scale (EDSS) progression, incidence of adverse events, and radiological outcomes from 2009 to 2019 were analyzed. Results: A total of 355/451 enrolled subjects had at least one follow-up visit and were included in the outcome analysis. Annualized relapse rate significantly decreases after rituximab initiation versus the pre-rituximab start year in RRMS (from 0.86 to 0.09, p &lt;.0001) and in secondary-progressive (SP) MS (from 0.34 to 0.06, p &lt;.0001) and had a slight decrease in primary-progressive (PP) MS patients (from 0.12 to 0.07, p = 0.45). After 3 years from rituximab start, the proportion of patients with a confirmed EDSS progression was 14.6% in the RRMS group, 24.7% in the SPMS group, and 41.5% in the PPMS group. No major safety concerns arose. Conclusion: Consistently with other observational studies, our data show effectiveness of rituximab in reducing disease activity in patients with MS