Tolerability and Acceptance of Switching from Brand to Generic Glatiramer Acetate in Multiple Sclerosis.

Background: The costs of disease-modifying therapies (DMTs) for multiple sclerosis (MS) have increased interest in generic alternatives. Methods: This prospective and observational study aims to investigate the safety, tolerability, and acceptance of switching from brand glatiramer acetate (GA) 40 mg/mL three times per week (Copaxone®) to generic GA 40 mg/mL three times per week (Glatiramyl®). Conducted at the Neurocenter of Southern Switzerland from September 2020 to September 2021, the study enrolled 27 patients; 21 completed the study. Participants reported on local and systemic side effects three months before and after the switch, and on switch acceptance by means of visual analogue scales (from 0 to 10). Results: Results indicated that those on generic GA experienced fewer local (81.0% vs. 96.3%) and systemic (33.3% vs. 59.3%) adverse events than with the brand drug. The median intensity of local adverse events was 8 (4-20) on generic GA vs. 16 (9-22) on brand GA, while the median intensity of systemic adverse events was similar between generic and brand GA [0 (0-27) vs. 0 (0-21.5), respectively]. Seventy-one percent of participants rated their acceptance of generic GA as 7/10 or higher. Conclusions: The results suggest that switching from brand to generic GA 40 mg/mL is safe, well-tolerated, and accepted by patients with MS.

Clinic and genetic predictors in response to erenumab.

BACKGROUND AND PURPOSE: Erenumab (ERE) is the first anticalcitonin gene-related peptide receptor monoclonal antibody approved for migraine prevention. A proportion of patients do 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 [Migraine Disability Assessment scale] and Headache Impact Test-6), and use of abortive medications, during 3 months before and after ERE start were collected. Real-time polymerase chain reaction 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% responder patients (50-RESP) and 75% responder patients (75-RESP). 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 (odds ratio [OR] [95% confidence interval (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 with 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 significantly reduced MMDs. The 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-remitting (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 < .0001) and in secondary-progressive (SP) MS (from 0.34 to 0.06, p < .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.