Clinical Edge Journal Scan

Clinical Edge Journal Scan Commentary: Multiple Sclerosis March 2022

Dr. Gudesblatt scans the journals, so you don’t have to!

Publish date: February 23, 2022

Mark Gudesblatt, MD

Clinical Edge Journal Scan: Multiple Sclerosis March 2022 (1 of 11)

Clinical Edge Journal Scan Commentary: Multiple Sclerosis March 2022
Third COVID-19 vaccine dose shows benefit in MS patients with a weak response after 2 doses
Multiple sclerosis relapses are prevalent after natalizumab cessation during pregnancy
Multiple sclerosis: Evidence spanning 3 decades finds no influence of DMTs on neoplasm incidence
Differential impact of multiple sclerosis therapies on SARS-CoV-2 vaccine-induced immune response
Multiple sclerosis: Excellent response to SARS-CoV-2 vaccine in patients with MS
High or increasing sNfl level predictive of impending relapses in active multiple sclerosis
sNfL and disease course in progressive MS without acute inflammation: Is there a link?
Primary progressive MS: No difference in efficacy between rituximab and ocrelizumab in real world
Early decline in lymphocyte count best predicts DMF-associated lymphopenia in relapsing MS
Web-based mindfulness program improves depressive symptoms in MS

Mark Gudesblatt, MD

There are multiple effective disease modifying therapies (DMT) available from which to choose to treat people with multiple sclerosis (PwMS). The patient and prescribing clinician’s DMT choices are both affected by multiple factors in the real-world including cost, insurance step plan, and coverage, as well as frequency, route of administration, and traditional risk/benefit perceptions. Despite the multiple issues to address, concerns related to how to weigh DMT choice with the ongoing viral pandemic and how to assess the impact of choice on patient safety from Covid-19 infection, re-infection and protection from vaccination response, or need to repeat vaccination in what appears to be continually mutating Covid-19 remains both complicated and uncertain. The importance of additional information regarding these concerns and incorporating this data into the shared decision-making process remains a topic of great interest. As reviewed last month, vaccination response can vary along DMT choice and class. PwMS who were untreated or received “immunomodulatory DMT” (IM-DMT) showed excellent seroconversion rates after SARS-CoV-2 vaccination; however, Bsteh G et al found that “immunosuppressive DMT” (IS-DMT) was associated with lower seroconversion rates. For these PwMS (N = 456) 3 months after vaccination seroconversion occurred in 96.7% of untreated PwMS (N = 91), 97.1% of IM-DMT treated PwMS (N = 139), and 61.1% of IS-DMT treated PwMS(N = 226) compared with 97.4% of healthy control individuals (N = 116) ( P < .001), with IS-DMT being the only significant predictor of poorer seroconversion (odds ratio 0.04; P < .001). Another study specifically exploring both varied DMT and quantitative response noted that spike receptor-binding domain (RBD) immunoglobulin G (IgG) levels following SARS-CoV-2 vaccination were higher in PwMS treated with dimethyl fumarate (DMF) (N = 5) or natalizumab (N = 6) vs. healthy controls (N = 13). However, RBD IgG levels were significantly lower in patients receiving sphingosine-1-phosphate receptor modulators (S1P) (N = 7) or anti-CD20 monoclonal antibody (mAb) (rituximab, n = 13, or ocrelizumab, n = 22). Post-vaccination spike RBD IgG levels were significantly higher in PwMS treated with DMF ( P = .038) and natalizumab ( P < .0001) than in healthy controls, whereas patients receiving S1P ( P = .01), rituximab ( P = .002), or ocrelizumab ( P = .0004) showed significantly reduced RBD IgG levels. However, a Norwegian study demonstrated that incorporating a third dose of COVID-19 mRNA vaccine increased the levels of anti-SARS-CoV-2 spike RBD immunoglobulin G (IgG) antibodies in PwMS (N = 130) treated with anti-CD20 therapy (N = 101) or fingolimod (N = 29) who previously had had a weak humoral response after 2 doses of mRNA COVID-19 vaccine. After re-vaccination , the mean levels of anti-SARS-CoV-2 spike RBD IgG titers increased significantly in both anti-CD20 (75.7 arbitrary units [AU]; P < .001) and fingolimod (29.6 AU; P = .006) treated groups without serious adverse events recorded. A decline in mean absolute lymphocyte count (ALC) of ≥21.2% within the first 3 months of treatment with DMF in PwMS increased the risk for DMF associated-lymphopenia by 6.5-fold (adjusted hazard risk [aHR] 6.503), whereas a decline of ≥40.2% increased the risk for severe lymphopenia by 12.67-fold (aHR 12.67; both P < .0010). The impact of DMF lymphopenia on vaccine response is unknown at the present. The take home practical message for the treating MS clinician is to include considerations of vaccine response in the shared decision making (SDM) process of patient centric DMT choice and monitor ALC impact. Including baseline anti-SARS-CoV-2 spike RBD information proactively at the time of DMT choice might be of importance in SDM. This varied vaccination response and treatment strategies continue to be an evolving and important area of DMT choice impact for long term safety of PwMS beyond relapse and Expanded Disability Status Scale (EDSS).

Clinical Edge Journal Scan Commentary: Multiple Sclerosis March 2022

Dr. Gudesblatt scans the journals, so you don’t have to!

Clinical Edge Journal Scan: Multiple Sclerosis March 2022 (1 of 11)

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Clinical Edge Journal Scan: Multiple Sclerosis March 2022 (1 of 11)