ABSTRACT
Background: High-efficacy (HE) disease-modifying therapies (DMTs) for Multiple Sclerosis (MS), such as anti-CD20 monoclonal antibodies - i.e., Ocrelizumab (OCR) and Rituximab - may worsen COVID-19 course. Preliminary data suggest that two doses of mRNA COVID-19 vaccine (RNA-Vax) reduce the risk of breakthrough/severe COVID-19 in patients with MS (pwMS) under treatment with HE-DMTs. Little is known about the protective effect of a third booster dose of RNA-Vax in pwMS treated with most commonly used HE-DMTs, such as Natalizumab (NTZ), Fingolimod (FNG), and OCR. Aim(s): To compare COVID-19 course and outcomes in pwMS on NTZ, FNG, and OCR after receiving the third dose of RNA-Vax. Method(s): Inclusion criteria were: >18 years old, being treated with NTZ/OCR/FNG since the first vaccine dose, diagnosis of COVID-19 after a third booster dose of RNA-Vax, not being treated with steroids within the month prior to any vaccine dose or COVID-19. Result(s): 232 pwMS (63 NTZ, 106 OCR, 63 FNG) from 17 Italian MS centers were included in the analysis. pwMS on NTZ (37+/-9) were younger than those on OCR (42+/-10, p=0.026) and FNG (43+/-11, p=0.006);EDSS was higher in pwMS on OCR (3.0, IQR=1.5-5.5) than those on FNG (2.0, IQR=1.0-3.0, p=0.017). COVID-19 was diagnosed 65+/-41 days after receiving the third booster dose. PwMS on OCR compared with those on NTZ showed more frequently (p<0.02-0.001): fever >38degreeC (53.8% vs 20.6%), cough (67% vs 36.5%), dyspnea (18.9% vs 3.2%), longer symptoms duration (9.5+/-8.7 vs 6+/-4.6 days), use of NSAIDs (74.5% vs 52.4%), oxygen (7.5% vs 0%), antibiotics (45.3% vs 14.3%). PwMS on OCR compared with those on FNG needed more frequently the use of oxygen (7.5% vs 1.6%, p=0.002). PwMS on FNG compared with those on NTZ showed more frequently (p<0.03-0.002): fever >38degreeC (39.7% vs 20.6%), cough (65.1% vs 36.5%), dyspnea (15.9% vs 3.2%). There were no differences between the 3 groups of pwMS regarding: COVID-19 treatment with steroids or monoclonal antibodies, hospitalization, and full recovery or death (0%). Discussion and Conclusion(s): Breakthrough COVID-19 after a third booster dose of RNA-Vax was more symptomatic in pwMS on OCR and FNG than those on NTZ. Nevertheless, no deaths were reported and the Covid-19 course in terms of full recovery and hospitalization rates was not different across different HE-DMTs. These results support the efficacy of a third booster dose of RNA-Vax in preventing severe COVID-19 (with hospitalization/ death) in pwMS treated with most common HE-DMTs.
ABSTRACT
Introduction: Since the beginning of the Sars-Cov-2 pandemic, several evidences have been gathered on the use of Disease Modifying Drugs (DMTs) in patients with Multiple Sclerosis (MS) .The introduction of the Sars-Cov-2 vaccine marked a turning point for MS patients, considered fragile patients. Aim(s):The objective of this study is to describe changes about the use of first-line DMTs in patients with a new diagnosis of MS, comparing the semester before and after the start of vaccination campaign for Sars-Cov-2. Method(s): The study included patients newly diagnosed with MS according to McDonald's 2017 criteria. The proportion of patients initiated into the use of Interferon Beta (IFN), Dimethylfumarate (DMF) and Teriflunamide (TERI) was defined as a proportion for the previous semester (October 2020- March 2021) and subsequent (April 2021-September 2021) to the avaibility of Sars- Cov-2 vaccine. The determinants of the choice of first-line DMTs were evaluated through regression analysis. Result(s): The study included 134 patients, including 40 (29.9%) male, average age of 38.3 +/- 12.3 years, disease duration of 3.0 +/- 4.6 years, average EDSS of 1.7 +/- 1.1. Among these, 75 (56%) patients started a first-line DMTs in the semester before the start of vaccination campaign [IFN 13 (9.7%), TERI 6 (4.5%), GA 28 (20.9%), DMF 28 (20.9%)], while 59 (44%) in the following semester [IFN 4 (3%), TERI 11(8.2%), GA 12 (8.9%) and DMF 32 (23.9%)]. A reduction of 40% and 53% respectively in the use of GA and IFN was observed in the semester following the start of the vaccination campaign. In contrast, an increase of 29 % in the use of TERI and 6% in the use of DMF respectively was reported in the same semester. The regression analysis shows the use of injection therapies (IFN, GA) being associated with female gender (p= 0.032) and with the previous semester to the availability of Sars- Cov-2 vaccine (p=0.006). In contrast, the use of TERI is associated with male gender (p=0.031) and with the following semester the introduction of the vaccine (p=0.05). About the use of DMF, a relationship with the post-introduction semester of the vaccine has been observed (p=0.037) the relapse rate in the previous 2 years is the strongest determinant in the choice of this treatment (p=0.001). Conclusion(s): Our data show how the start of the vaccination campaign for Sars-Cov-2 influenced the use of first-line immunotheraphies in patients with new diagnosis of MS.
ABSTRACT
OBJECTIVES: The present study aims to describe the evolution of teriflunomide use for multiple sclerosis (MS) in the clinical setting, in particular for naïve patients and young women. Predictors of treatment response were also investigated. METHODS: This was an independent, retrospective, real-world monocentric study. We analysed the use of teriflunomide from 2016 to 2020 in patients categorized as naïve or switchers, and assessed the variations in its use in men and women by age group. Clinical and MRI data of treated patients were evaluated, and NEDA-3 status at 24 and 36 months was defined. Determinants of therapeutic response were examined using regression analysis. RESULTS: The study included 319 MS patients exposed to teriflunomide [209 women (65.5%)]. Of these, 67 (21%) were naïve and 252 (79%) were switchers. A 20% increase of teriflunomide use in the naïve group in the past two years, particularly in 2020, the first year of global Sars-Cov-2 spread, was observed. An increase of teriflunomide use of more than 10% in young women under age 45 was also reported. NEDA-3 status was calculated for 204 patients after 24 months and was achieved in 120 (58.8%) of these ones. NEDA-3 was also achieved in 92/160 (56.8%) patients at 36 months. A lower ARR in the two years prior to teriflunomide treatment (p = 0.026), lower baseline age (p = 0.05), and lower EDSS score (p = 0.009) were associated with achievement of the NEDA-3. CONCLUSIONS: Our study confirms a major evolution in teriflunomide use in clinical settings, particularly for naïve patients and young women.