Study to Compare the Efficacy and Cost-Effectiveness of Various Disease Modifying Drugs in the Management of Multiple Sclerosis in India- An Observational Study.

Background: Real-world data on the efficacy and cost-effectiveness of multiple sclerosis (MS) disease-modifying drugs (DMTs) is lacking in the Indian setting. The primary objective of this study was to evaluate the efficacy of DMTs, and the secondary objective was to evaluate cost-effectiveness and the quality of life (QoL) in these patients. Method: Seventy-four patients fulfilling study criteria were recruited in the retrospective observational study, of which 69 completed the study. Primary outcome was measured by annualized relapse rate (ARR), and secondary outcome was measured by WHOQOL-BREF scale, modified Kuppuswamy scale, and rating of DMT scale through a subjective questionnaire. Results: Patients on natalizumab, rituximab, and glatiramer acetate showed the highest reduction in ARR. The highest reduction of ARR (2.5) was produced by natalizumab and least by Peg-IFNß1a (0.5). In QoL analysis, teriflunomide group had the highest average score for both physical health (22.7, SD 4.7) and psychological (21.3, SD 4.0) domains, whereas natalizumab group had the lowest average score. Socio-economic status analysis showed DMF, IFNß 1a, peg-IFNß 1a, rituximab, and glatiramer acetate are affordable to the upper middle class and above, whereas natalizumab could be afforded only by high-class strata. Teriflunomide was most affordable annually. Study of adverse drug reactions showed natalizumab was very well tolerated by the study participants. Conclusion: Natalizumab, an infusion DMT, was highly effective in terms of reducing the ARR. Rituximab, an off-label DMT, was found to be very effective. Teriflunomide was overall an effective DMT in terms of affordability, QoL balance, and an acceptable ARR reduction.

Immune Reconstitution Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Review on Behalf of the EBMT Autoimmune Diseases Working Party.

Multiple sclerosis (MS) is a central nervous system (CNS) disorder, which is mediated by an abnormal immune response coordinated by T and B cells resulting in areas of inflammation, demyelination, and axonal loss. Disease-modifying treatments (DMTs) are available to dampen the inflammatory aggression but are ineffective in many patients. Autologous hematopoietic stem cell transplantation (HSCT) has been used as treatment in patients with a highly active disease, achieving a long-term clinical remission in most. The rationale of the intervention is to eradicate inflammatory autoreactive cells with lympho-ablative regimens and restore immune tolerance. Immunological studies have demonstrated that autologous HSCT induces a renewal of TCR repertoires, resurgence of immune regulatory cells, and depletion of proinflammatory T cell subsets, suggesting a "resetting" of immunological memory. Although our understanding of the clinical and immunological effects of autologous HSCT has progressed, further work is required to characterize the mechanisms that underlie treatment efficacy. Considering that memory B cells are disease-promoting and stem-like T cells are multipotent progenitors involved in self-regeneration of central and effector memory cells, investigating the reconstitution of B cell compartment and stem and effector subsets of immunological memory following autologous HSCT could elucidate those mechanisms. Since all subjects need to be optimally protected from vaccine-preventable diseases (including COVID-19), there is a need to ensure that vaccination in subjects undergoing HSCT is effective and safe. Additionally, the study of vaccination in HSCT-treated subjects as a means of evaluating immune responses could further distinguish broad immunosuppression from immune resetting.

Long term effect of delayed treatment on disability in patients with paediatric onset multiple sclerosis: A prospective Danish cohort study.

BACKGROUND: A consensus of early treatment with disease-modifying therapies (DMT) in multiple sclerosis (MS) has been reached based on several observational and experimental studies in adults. However, paediatric onset (PO)MS appears phenotypically different from adult onset MS, characterized by increased relapse rate and pronounced radiological activity on MRI. The objective of this study was to investigate the long-term consequences of delayed treatment start in POMS on disability in a real-world, population-based setting. METHODS: Based on prospectively collected data from The Danish Multiple Sclerosis Registry, we defined a cohort of MS patients with onset before the age of 18 years, who were born in 1980 or later, and started treatment with a DMT between 1998 and 2018. The POMS cohort was stratified according to treatment start within 2 years of onset (N = 140) or later (N = 151). Annualised relapse rate in each study group was compared using a negative binomial regression; and Cox proportional hazard model was used to estimate hazard ratios (HR) of time to sustained Expanded Disability Status Scale (EDSS) score 4, 6-month confirmed EDSS worsening and 6-month confirmed EDSS improvement, respectively, according to disease duration. RESULTS: The POMS cohort had a total median follow-up time of 7.7 years (interquartile range 4.6-11.6). There was no association between risk of relapses in patients with delayed treatment start compared to earlier treatment start. Patients starting on a DMT later than 2 years after onset had a 2.52-fold increased risk of reaching sustained EDSS 4 compared to those starting within 2 years of onset (HR=2.52, 95% confidence interval (CI)=1.01-6.34). For every year increment from onset to start of first DMT, the risk of reaching sustained EDSS 4 increased by 17% (HR=1.17, 95% CI=1.05-1.30). In line with this, the risk of reaching confirmed EDSS worsening was increased by 44% compared to those starting earlier, although not statistically significant (HR=1.44, 95% CI=0.95-2.19). Starting on a DMT later was associated with 61% decreased chance of confirmed EDSS improvement compared to those starting earlier (HR=0.39, 95% CI=0.26-0.59). For every year increment from onset to starting DMT, the risk of confirmed EDSS improvement decreased by 10% (HR=0.90, 95% CI=0.84-0.96). CONCLUSIONS: Delayed treatment start in this POMS cohort was associated with shorter time to reach sustained EDSS 4 and confirmed EDSS worsening, and decreased chance of reaching confirmed EDSS improvement, and thus support early treatment start in POMS patients.