High persistence and low adverse events burden in cladribine treated MS patients from Argentina.

BACKGROUND: Early initiation with high efficacy therapies seems to be better than an escalation approach in terms of disability prevention in patients with relapsing-remitting MS (RRMS). Although efficacy and safety of cladribine tablets have been shown in clinical trials, real-world evidence (RWE) studies from Latin America are scarce. OBJECTIVE: To describe the baseline characteristics of patients enrolled in the Argentina Patient Support Program (PSP) for cladribine tablets (Adveva®), with at least 1 treatment course, evaluate treatment persistence, adverse event reports from PSP patients and reported relapses characterization. METHODS: Anonymized data routinely collected by Adveva® team of patients that received the first dose of cladribine from April 16th 2018 to March 31st 2021 were analyzed. Treatment persistence was defined as the percentage of patients that initiated year 2 (Y2) from the population of patients with elapsed time since year 1 (Y1) cladribine tablet initiation of at least 18 months. In addition, using the pharmacovigilance data, reported adverse events and the time elapsed from treatment initiation to relapse were analyzed. RESULTS: The present analysis included 269 patients (mean age: 41.7 ± 16 years) that had initiated Y1 of cladribine tablets treatment between April 16th 2018 and March 31st 2021. Although only 29.4% (79/269) of our population was treatment naïve, the ratio of naïve/switch patients that initiated cladribine tablets increased from April 2018-March 2019 to April 2020-March 2021. From the 110 patients with elapsed time since treatment initiation ≥18 months, 101 patients initiated Y2 indicating a persistence level of 91.8%. During follow-up, 425 adverse events were reported, mainly MS relapse (8.9%, 38/425), fatigue (3.8%, 16/425) and headache (3.5%, 15/425). Lymphopenia and infections were rarely reported by RRMS patients treated with cladribine tablets. MS relapse was more frequently reported in patients switching from a previous treatment (87.5%, 27/32) than in the naïve cohort (12.5%, 5/32). CONCLUSIONS: The first real life experience in RRMS patients from Latin America demonstrated that the Adveva® enrolled support program patients have a high persistence level to oral treatment with cladribine tablets. Our results also confirmed the known safety profile of cladribine tablets, with a low incidence of lymphopenia and infections.

Disease activity impacts disability progression in primary progressive multiple sclerosis.

BACKGROUND: Although solid information on the natural history of primary progressive multiple sclerosis (PPMS) is available, evidence regarding impact of disease activity on PPMS progression remains controversial. OBJECTIVE: To describe the clinical characteristics, presence or absence of MRI activity, and natural history of a PPMS cohort from two referral centers in Argentina and assess whether clinical and/or radiological disease activity correlated with disability worsening. METHODS: Retrospective study conducted at two MS clinics in Buenos Aires, Argentina, through comparative analysis of patients with and without evidence of disease activity. RESULTS: Clinical and/or radiologic activity was presented in 56 (31%) of 178 patients. When stratified by age at onset, we found that for every 10 years of increase in age at onset, risk of reaching EDSS scores of 4 and 6 increased by 26% and 31%, respectively (EDSS 4: HR 1.26, CI 95%: 1.06-1.50; EDSS 6: HR 1.31, CI 95%: 1.06-1.62). Patients who presented clinical exacerbations reached EDSS scores of 6, 7 and 8 faster than those without associated exacerbations (p = 0.009, p = 0.016 and p = 0.001, respectively). Likewise, patients who presented gadolinium-enhancing lesions during the course of disease reached EDSS scores of 7 earlier (p = 0.002). CONCLUSION: Older age at onset and presence of clinical and/or radiological disease activity correlated with accelerated disability progression in this cohort of PPMS patients.

Evolution of multiple sclerosis prevalence and phenotype in Latin America.

BACKGROUND: Literature regarding MS epidemiology and phenotype is scarce but has increased markedly over the past years. The objective of the present work is to assess the evolution of the prevalence and phenotype of MS in Latin America during recent years. METHODS: Review of literature. RESULTS: MS prevalence levels are low to medium in Latin America, although these have increased in recent years. A small latitudinal gradient has also been observed, but exceptions to this rule exist, suggesting other genetic and environmental factors ultimately influence regional prevalence rates. One of the distinctive features of the region is the complex genetic admixture arising from multiple divergent population ancestries in different countries including: Native Americans, Caucasians and Africans. Another variable which would lower MS risk in the region could be a protective effect linked to exposure to certain infections, such as parasites. Despite differences in MS epidemiology, Latin American patients show an MS phenotype very similar to that of Caucasian patients, and a progressively increasing female gender ratio as has been described worldwide. CONCLUSION: MS epidemiology in Latin American patients has distinctive features. Both, prevalence and incidence, are increasing.

TRPM4 mRNA expression levels in peripheral blood mononuclear cells from multiple sclerosis patients.

Recent studies have suggested a role of the cation channel TRPM4 in mediating neurodegeneration in experimental autoimmune encephalomyelitis and multiple sclerosis (MS). We aimed to extrapolate central nervous system findings to the blood compartment by determining TRPM4 expression in peripheral blood mononuclear cells from 12 healthy controls (HC) and 64 untreated MS patients. TRPM4 mRNA expression levels were comparable between HC and MS patients with primary progressive MS (n=17), secondary progressive MS (n=19), and relapsing-remitting MS during clinical remission (n=21) and relapses (n=7). These findings do not support a role of TRPM4 in the peripheral blood compartment of MS patients.