Faculty Bibliography

BACKGROUND/UNASSIGNED:Multiple sclerosis (MS) is a neuroinflammatory disease with debilitating manifestations that may predispose patients to hip fracture and osteoarthritis, and may affect recovery from total hip arthroplasty (THA). With increased longevity of MS patients and growth in demand for arthroplasty in this population, it is important to understand outcomes of THA in patients with MS. AIM/UNASSIGNED:We sought to compare outcomes of THA among persons with MS and without MS. METHODS/UNASSIGNED:International Classification of Diseases, Ninth Revision Procedure Coding System (ICD-9-PCS) codes for hip arthroplasty (815.1) were used to identify all patients in the New York Statewide Planning and Research Cooperative System (SPARCS) database who underwent THA between 2000 and 2014. Patients with MS, the primary exposure, were identified using ICD-9-Clinical Modification (CM) code 340. The study outcomes of length of stay (days), discharge disposition, index admission mortality, 90-day readmission, 1-year revision arthroplasty, and 1-year all-cause mortality were evaluated using multivariable regression analyses inclusive of basic demographics, admission source, disposition, payer, comorbidity, and socioeconomic status (SES). RESULTS/UNASSIGNED: = 0.035). However, MS patients had similar risk for 90-day readmission and one-year all-cause mortality as compared with non-MS patients. CONCLUSIONS/UNASSIGNED:Although patients with MS who underwent THA had a 90-day complication risk that was similar to those without MS, the risk for requiring revision surgery was more than 2-fold higher. Additional studies are needed to understand the reasons for revision surgery and for developing strategies to mitigate the risk of complications.

BACKGROUND:The risk of SARS-CoV-2 infection and severity with disease modifying therapies (DMTs) in multiple sclerosis (MS) remains unclear, with some studies demonstrating increased risks of infection with B-cell-depleting (anti-CD20) therapies and severity, while others fail to observe an association. Most existing studies are limited by a reliance on 'numerator' data (i.e., COVID-19 cases) only. OBJECTIVE:To assess the risks of COVID-19 by DMT, this study aimed to assess both 'numerator' (patients with SARS-CoV-2 infection) and 'denominator' data (all patients treated with DMTs of interest) to determine if any DMTs impart an increased risk of SARS-CoV-2 infection or disease severity. METHODS:We systematically reviewed charts and queried patients during clinic encounters in the NYU MS Comprehensive Care Center (MSCCC) for evidence of COVID-19 in all patients who were on the most commonly used DMTs in our clinic (sphingosine-1-phosphate receptor (S1P) modulators (fingolimod/siponimod), rituximab, ocrelizumab, fumarates (dimethyl fumarate/diroximel fumarate), and natalizumab). COVID-19 status was determined by clinical symptoms (CDC case definition) and laboratory testing where available (SARS-CoV-2 PCR, SARS-CoV-2 IgG). Multivariable analyses were conducted to determine predictors of infection and severe disease (hospitalization or death) using SARS-CoV-2 infected individuals per DMT group and all individuals on a given DMT as denominator. RESULTS:We identified 1,439 MS patients on DMTs of interest, of which 230 had lab-confirmed (n = 173; 75.2%) or suspected (n = 57; 24.8%) COVID-19. Infection was most frequent in those on rituximab (35/138; 25.4%), followed by fumarates (39/217; 18.0%), S1P modulators (43/250; 17.2%), natalizumab (36/245; 14.7%), and ocrelizumab (77/589; 13.1%). There were 14 hospitalizations and 2 deaths. No DMT was found to be significantly associated with increased risk of SARS-CoV-2 infection. Rituximab was a predictor of severe SARS-CoV-2 infection among patients with SARS-CoV-2 infection (OR 6.7; 95% CI 1.1-41.7) but did not reach statistical significance when the entire patient population on DMT was used (OR 2.8; 95% CI 0.6-12.2). No other DMT was associated with an increased risk of severe COVID-19. CONCLUSIONS:Analysis of COVID-19 risk among all patients on the commonly used DMTs did not demonstrate increased risk of infection with any DMT. Rituximab was associated with increased risk for severe disease.

BACKGROUND/UNASSIGNED:The MSBase prediction model of treatment response leverages multiple demographic and clinical characteristics to estimate hazards of relapses, confirmed disability accumulation (CDA), and confirmed disability improvement (CDI). The model did not include Multiple Sclerosis Severity Score (MSSS), a disease duration-adjusted ranked score of disability. OBJECTIVE/UNASSIGNED:To incorporate MSSS into the MSBase prediction model and compare model accuracy with and without MSSS. METHODS/UNASSIGNED:The associations between MSSS and relapse, CDA, and CDI were evaluated with marginal proportional hazards models adjusted for three principal components representative of patients' demographic and clinical characteristics. The model fit with and without MSSS was assessed with penalized r2 and Harrell C. RESULTS/UNASSIGNED:A total of 5866 MS patients were started on disease-modifying therapy during prospective follow-up (age 38.4 ± 10.6 years; 72% female; disease duration 8.5 ± 7.7 years). Including MSSS into the model improved the accuracy of individual prediction of relapses by 31%, of CDA by 23%, and of CDI by 24% (Harrell C) and increased the amount of variance explained for relapses by 49%, for CDI by 11%, and for CDA by 10% as compared with the original model. CONCLUSION/UNASSIGNED:Addition of a single, readily available metric, MSSS, to the comprehensive MSBase prediction model considerably improved the individual accuracy of prognostics in MS.