ABSTRACT
Introduction: Real-world evidence studies regarding the effectiveness and safety of disease-modifying therapies are useful for clinical practice and for assessing the risk-benefit of some health policy interventions. Objective(s): To evaluate safety and effectiveness outcomes in year 1 and year 2 in patients receiving antiCD20 monoclonal antibodies. Method(s): Longitudinal observational study of MS patients under regular care at the Programa de Esclerosis Multiple UC in Chile who received at least one dose of ocrelizumab or rituximab between June 2018 and April 2022. Result(s): A total of 229 patients were included, 219 using Ocrelizumab and 10 using Rituximab. 163 patients had relapsingremitting MS (RRMS), 68% female, mean age at antiCD20 34.3+8.5 years, mean disease duration 5.6+5.4 years, and median baseline EDSS 1.5(0-6.0). 35 had primary progressive MS (PPMS), 54% female, mean age at antiCD20 47+12 years, mean disease duration 6.3+6.3 years and median EDSS 4.0(1.0-7.0). 31 had secondary progressive MS (SPMS), 64% female, mean age at antiCD20 50.4+9.7 years, mean disease duration 16.4+10.1 years and median EDSS 6.0(1.0-7.0). Before antiCD20, mean annualized relapse rate (ARR) was 0.7+0.5 for RRMS, and 0.2+0.4 for PPMS and SPMS patients, and MRI activity (newT2/Gd+) was observed in 84.8% of RRMS, 60% of PPMS and 40.7% of SPMS patients. Mean ARR in years 1 and 2 was 0 in RRMS and PPMS, 0.05+0.2 in year 1 and 0 in year 2 for SPMS. NewT2/Gd+ in years 1 and 2 were observed in 11.4% and 8.3% in RRMS, 21.4% and 0 in PPMS, and 0 in SPMS. Year 1 and 2 EDSS progression was observed in 0% and 3.6% of RRMS, 0 and 15.4% in PPMS, and 18.1% and 21.4% in SPMS. Years 1 and 2 NEDA3 was obtained in 82.6% and 94.6% of RRMS, 70% and 87.5% of PPMS and 90% and 87.5% of SPMS. Infusion Reactions were observed in 35% during the first dose, decreasing with each infusion (13.5% in the fourth infusion), all were considered mild. The most frequent year 1 adverse event were COVID-19 (n=5), upper tract infection (n=4), diarrhoea (n=4) and urinary tract infection (n=4). The most frequent year 2 adverse events were COVID-19 (n=4) and skin infection (n=3). One patient with previous history of breast cancer developed a tumour recurrence during the second year of treatment. Conclusion(s): This study supports robust effectiveness outcomes in a real-world cohort, with a consistent safety profile in patients receiving care at a specialized MS Unit.
ABSTRACT
Background: Vaccination strategies against SARS-CoV-2 have been implemented worldwide. Safety and effectiveness outcomes in special populations, such as MS patients receiving diseasemodifying therapy (DMT) may guide future recommendations. Objectives: To assess the safety and seroconversion (SC) rates of mRNA (Pfizer-BioNtech) and inactivated (Sinovac-CoronaVac) vaccines in patients with MS in Chile. Methods: Multicentric, prospective, observational study including patients from 4 tertiary centres. Humoral immune response was determined at least 4 weeks after the second dose of either vaccine, by assessing IgG against spike 1 (S1) and nucleocapsid (N) proteins (ECLIA Cobas, Roche) and events supposedly attributable to vaccination (AESAV) were collected. Subgroup comparisons according to DMT and type of vaccine were also performed. Results: A total of 115 patients were included (71% women, mean age 41+11 years, mean disease duration 8+6 years, 83% RRMS, median EDSS 2.0 (range 0-7.5)). Humoral immune response rates of the whole sample were 67% (100% for S1 and 16% for N). Thirty percent of the patients received mRNA vaccine, and SC was significantly higher in this group compared to the inactivated vaccine (81% vs. 61%, p=0.04). Interferon beta/ glatiramer acetate were used by 4% of the patients (100% SC), teriflunomide/dimethylfumarate 8% (100% SC), fingolimod 11% (92% SC), cladribine 7% (88% SC), natalizumab 6% (100% SC), ocrelizumab/rituximab 57% (45% SC, 58% with mRNA and 38% with inactivated vaccine), alemtuzumab 5% (100% SC), and 2% without DMT (100% SC). The most frequent AESAV were local pain (16%), myalgia (13%), headache (11%), and mild fever (3%). Two mild relapses with the inactivated vaccine were observed within the 8 weeks after the first dose. By the time of this report, 3 patients developed COVID- 19 after full vaccination (1 fingolimod, positive IgG-S1, mild COVID19;1 natalizumab, positive IgG-S1, mild COVID19;1 rituximab, negative IgG-S1, required hospitalization and 1 day of non-invasive mechanical ventilation). Conclusions: Vaccination with mRNA and inactivated vaccines appear to be safe in patients with MS, with less than 2% risk of relapse after vaccination. Higher seroconversion rates were observed using the mRNA vaccine. Humoral immune response rate is lower in patients using antiCD20. Determining cellular response and clinical effectiveness on preventing SARS-CoV-2 infection or severe COVID-19 is still needed to be determined.