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Discontinuation of disease modifying therapies is associated with disability progression regardless of prior stable disease and age

Jakimovski, Dejan; Kavak, Katelyn S; Vaughn, Caila B; Goodman, Andrew D; Coyle, Patricia K; Krupp, Lauren; Gottesman, Malcolm; Edwards, Keith R; Lenihan, Michael; Perel, Allan; Zivadinov, Robert; Weinstock-Guttman, Bianca
BACKGROUND:Multiple sclerosis (MS) patients with stable disease course might view continued treatment as unnecessary. However, guidelines regarding treatment discontinuation are currently lacking. OBJECTIVE:To assess the clinical course after treatment discontinuation in MS patients with long disease duration. METHODS:Patients who discontinued disease-modifying treatments (DMTs) and not resume treatment (n = 216) were extracted from New York State MS Consortium (NYSMSC) and followed across three time points (average 4.6 years). Stable course was defined as no change in Expanded Disability Status Scale (EDSS) scores (<1.0 increase if EDSS<6.0 or <0.5-point increase if EDSS≥6.0) from baseline (time 1) to DMT discontinuation (time 2). Both stable and worsening MS patients were later assessed again after the DMT discontinuation (time 3). Additional analyses were performed based on disease subtype, type of medication, age cut-off of 55 and EDSS of 6.0. RESULTS:From the cohort of 216 MS patients who discontinued DMT, 161 (72.5%) were classified as stable before DMT discontinuation. After DMT discontinuation, 53 previously stable MS patients (32.9%) experienced disability worsening/progression (DWP). 29.2 and 40% of previously stable RRMS and SPMS respectively had DWP after DMT discontinuation. Over two years after DMT discontinuation, the rate of DWP was similar between patients younger or older than 55 years (31.1% vs 25.9%, respectively). MS patients with EDSS≥6.0 had greater DWP when compared to less disabled patients while remaining on therapy as well as after discontinuation (40.7% vs 15.4%, p < 0.001 and 39.6% vs 15.2%, p < 0.001, respectively). CONCLUSION/CONCLUSIONS:MS patients with stable disease course experience DWP after treatment discontinuation, with no clear relation to age and disease subtype. Patients with EDSS≥6.0 are at higher risk for DWP.
PMID: 34915316
ISSN: 2211-0356
CID: 5099592

COVID-19 outcomes in MS: Observational study of early experience from NYU Multiple Sclerosis Comprehensive Care Center

Parrotta, Erica; Kister, Ilya; Charvet, Leigh; Sammarco, Carrie; Saha, Valerie; Charlson, Robert Erik; Howard, Jonathan; Gutman, Josef Maxwell; Gottesman, Malcolm; Abou-Fayssal, Nada; Wolintz, Robyn; Keilson, Marshall; Fernandez-Carbonell, Cristina; Krupp, Lauren B; Zhovtis Ryerson, Lana
OBJECTIVE:To report outcomes on patients with multiple sclerosis (MS) and related disorders with coronavirus disease 2019 (COVID-19) illness. METHODS:From March 16 to April 30, 2020, patients with MS or related disorders at NYU Langone MS Comprehensive Care Center were identified with laboratory-confirmed or suspected COVID-19. The diagnosis was established using a standardized questionnaire or by review of in-patient hospital records. RESULTS:We identified 76 patients (55 with relapsing MS, of which 9 had pediatric onset; 17 with progressive MS; and 4 with related disorders). Thirty-seven underwent PCR testing and were confirmed positive. Of the entire group, 64 (84%) patients were on disease-modifying therapy (DMT) including anti-CD20 therapies (n = 34, 44.7%) and sphingosine-1-phosphate receptor modulators (n = 10, 13.5%). The most common COVID-19 symptoms were fever and cough, but 21.1% of patients had neurologic symptom recrudescence preceding or coinciding with the infection. A total of 18 (23.7%) were hospitalized; 8 (10.5%) had COVID-19 critical illness or related death. Features more common among those hospitalized or with critical illness or death were older age, presence of comorbidities, progressive disease, and a nonambulatory status. No DMT class was associated with an increased risk of hospitalization or fatal outcome. CONCLUSIONS:Most patients with MS with COVID-19 do not require hospitalization despite being on DMTs. Factors associated with critical illness were similar to the general at-risk patient population. DMT use did not emerge as a predictor of poor COVID-19 outcome in this preliminary sample.
PMID: 32646885
ISSN: 2332-7812
CID: 4518282

Anti-John Cunningham virus antibody index levels in multiple sclerosis patients treated with rituximab, fingolimod, and dimethyl fumarate

Farley, Stephen; Gottesman, Malcolm H; Friedman-Urevich, Sharon; Ye, Janin; Shen, Mark; Grueneberg, Denise; Martone, Lorraine; Calixte, Rose
Background/UNASSIGNED:Progressive multifocal leukoencephalopathy (PML), a potentially fatal demyelinating disease caused by the John Cunningham virus (JCV), can occur as a complication of treatment with rituximab, fingolimod, and dimethyl fumarate. The primary objective of this study was to determine changes in anti-JCV antibody index values in multiple sclerosis (MS) patients treated with these three medications. Second, we explored the relationship between absolute lymphocyte count (ALC), anti-JCV antibody index values, and various patient characteristics. Methods/UNASSIGNED:In this retrospective chart review, we evaluated changes in JCV serology and ALC in 172 MS patients treated with fingolimod, rituximab, or dimethyl fumarate (2013-2016). Only those with known anti-JCV antibody and ALC values before starting the study medications were included. Subsequent values were obtained on an ad hoc basis throughout the study. Results/UNASSIGNED:= 0.014, respectively). A non-significant decreasing trend in anti-JCV antibody index values occurred in patients treated with dimethyl fumarate. Notably, there was no relationship between ALC and anti-JCV antibody index values for patients treated with rituximab, fingolimod, or dimethyl fumarate. Conclusions/UNASSIGNED:Anti-JCV antibody index values significantly decreased in MS patients treated with fingolimod and rituximab; however, this did not occur with dimethyl fumarate. Fingolimod and rituximab may impair the humoral response to the JCV. Nevertheless, a declining anti-JCV antibody index in MS patients treated with fingolimod or rituximab should not necessarily be interpreted as correlating with a decreased risk for PML.
PMID: 31528397
ISSN: 2229-5097
CID: 4115582

Discontinuation of Disease Modifying Therapies in Stable MS Patients is Associated with Disability Progression Regardless of Age [Meeting Abstract]

Weinstock-Guttman, Bianca; Kavak, Katelyn; Vaughn, Caila; Goodman, Andrew; Coyle, Patricia; Krupp, Lauren; Gottesman, Malcolm; Edwards, Keith; Lenihan, Michael; Perel, Allan; Zivadinov, Robert
ISSN: 0028-3878
CID: 3561632

Smelf-reported fatigue and lower limb problems predictive of conversion to secondary progressive multiple sclerosis in an aging sample of patients [Meeting Abstract]

Vaughn, C; Kavak, K; Bushra, A; Noyes, E; Edwards, K; Goodman, A; Coyle, P; Krupp, L; Jubelt, B; Gottesman, M; Benedict, R; Weinstock-Guttman, B
Objective: To investigate patient reported outcomes predictive of conversion to SPMS in an aging sample of MS patients. Background: The secondary progressive (SP) phase of multiple sclerosis (MS) is characterized by a progressive accumulation of neurological disability, preceded by a relapsing remitting (RR) disease course. Older age at disease onset, high frequency of relapses and male sex have frequently been found to be predictive of a higher risk of disease conversion. Design/Methods: Subjects are part of the New York State Multiple Sclerosis Consortium (NYSMSC). Patients with an RRMS disease type at study enrollment, age 50 or over, with a disease duration of at least 15 years were selected for this study (n=155). Chi-squared tests and logistic regression modelling were used to investigate the predictive value of patient reported outcomes at study enrollment and conversion to SPMS at year 5. Results: Five years after study enrollment (median disease duration=22 years), 47 (30.3%) RRMS subjects progressed to SPMS. Those who converted were older at study enrollment (54.8 vs 52.1, p=.01), and had a higher Kurtzke Expanded Disability Status Scale (EDSS) at both baseline (3.5 vs 2.6, p<.001), and at year 5 (5.6 vs 3.0, p<.001). Patients who progressed at year 5 were more likely to report lower limb problems at baseline (53.2% vs 21.5%, OR: 3.0, p<.001), and were more likely to report some degree of fatigue (91.5% vs 68.2%, OR: 4.2, p=.004), compared to those who did not progress, even after adjusting for age, disease duration and EDSS. Fatigue and lower limb problems were strongly correlated (p-value=0.001). Conclusions: Fatigue and lower limb problems at baseline were predictive of a higher chance of conversion after 5 years of follow-up. Targeting patients with these symptoms may result in more successfully predicting patients at higher risk of disease conversion and subsequently tailoring therapeutic strategies
ISSN: 1526-632x
CID: 2608752

JC Titers in Multiple Sclerosis (MS) Patients Treated With Rituximab, Fingolimod and Dimethyl Fumarate at an American MS center [Meeting Abstract]

Gottesman, Malcolm H.; Farley, Stephen; Friedman-Urevich, Sharon; Ye, Janin; Grueneberg, Denise; Martone, Lorraine
ISSN: 1352-4585
CID: 3486102

Alteration of Thyroid Function Tests Caused by High Dose Biotin Treatment; A Case Report [Meeting Abstract]

Gottesman, Malcolm H.; Martone, Lorraine; Friedman-Urevich, Sharon; Grueneberg, Denise
ISSN: 1352-4585
CID: 3486092

Pregnancy decision-making and related outcomes among women with MS enrolled in the New York state multiple sclerosis consortium [Meeting Abstract]

Vaughn, C B; Kavak, K; Nadeem, M; Zakalik, K; Teter, B; Coyle, P; Krupp, L; Hyland, M; Jubelt, B; Gottesman, M; Edwards, K; Weinstock-Guttman, B
Background: Pregnancy is a period of relative disease quiescence for a majority of women with multiple sclerosis (MS). Though the use of disease modifying therapies (DMTs) is discouraged during pregnancy, specific recommendations with respect to breastfeeding or timing of cessation of DMT use as well as reinitiation of DMT postpartum are often unclear. Objective: Our primary objective is to examine the pregnancy making decisions of women with MS enrolled in the New York State MS Consortium (NYSMSC) and the associations with clinical outcomes. Methods: 800 women enrolled in the NYSMSC were mailed a questionnaire inquiring on reproductive history and reproductive decision-making. Longitudinally collected information including demographics, disease characteristics (MS type, relapses), EDSS, DMT history, and patient-reported outcomes are available from the 20-year ongoing prospective NYSMSC registry. Results: To date, 477 questionnaires have been received. Of the 365 women who responded to specific pregnancy questions, 97 (26.6%) reported at least one pregnancy or pregnancy attempt after diagnosis of MS. Of those who attempted pregnancy post- MS diagnosis, 64 (66%) reported at least one successful pregnancy, while 21 (21.7%) reported that they were unable to conceive, and several were still trying. The majority of women (61.1%) resumed the same DMT they had been taking before their pregnancy, and 65.4% resumed DMT use within 6 months of delivery. Ten women (10.3%) reported relapses during pregnancy. There were no significant differences in age or DMT use between women who reported relapses and women who did not. Women who reported relapses during pregnancy were also more likely to report relapses in the 12 months prior to the pregnancy (p=0.020). Sixteen women reported a relapse in the 12 months before pregnancy; of those, 11 (68.8%) also reported relapses in the 12 months after pregnancy. Of the 55 women who did not have a relapse in the 12 months before pregnancy; 15 (29.1%) reported having a relapse in the 12 months after pregnancy. The difference between the two groups was significant (p-value=0.004). Conclusion: A substantial portion of women with MS will intend to become pregnant after their MS diagnosis. As such, it is essential that evidence-based information is available to young women with MS. Additional analyses will be presented in a larger sample with respect to the effect and type of DMT used before and after pregnancy on relapses
ISSN: 1477-0970
CID: 2277012

Factors associated with benign multiple sclerosis in the New York State MS Consortium (NYSMSC)

Zivadinov, Robert; Cookfair, Diane L; Krupp, Lauren; Miller, Aaron E; Lava, Neil; Coyle, Patricia K; Goodman, Andrew D; Jubelt, Burk; Lenihan, Michael; Herbert, Joseph; Gottesman, Malcolm; Snyder, David H; Apatoff, Brian R; Teter, Barbara E; Perel, Allan B; Munschauer, Frederick; Weinstock-Guttman, Bianca
BACKGROUND: This retrospective analysis explored prognostic factors associated with a benign multiple sclerosis (BMS) disease course at baseline and over the 4-year follow-up. METHODS: Patients from the centralized New York State Multiple Sclerosis Consortium registry were classified as having BMS according to 3 different criteria centered on disease duration and disability. Additional analyses explored prognostic factors associated with BMS using the most conservative disability criteria (Expanded Disability Status Scale /=10 years). RESULTS: Among 6258 patients who fulfilled eligibility criteria, 19.8 % to 33.3 % were characterized as having BMS, at baseline depending on classification criteria used. Positive prognostic factors for BMS at baseline included female sex (p < 0.0001) and younger age at onset (p < 0.0001); negative prognostic factors included progressive-onset type of MS and African-American race. Of the 1237 BMS patients (per most conservative criteria), 742 were followed for a median of 4 years to explore effect of disease-modifying treatment (DMT) on benign status. DMT (p = 0.009) and longer disease duration (p = 0.007) were the only significant positive predictors of maintaining BMS at follow-up. The protective effect was stronger for patients taking DMT at both enrollment and follow-up (OR = 0.71; p = 0.006). CONCLUSIONS: There is a need for development of more reliable prognostic indicators of BMS. Use of DMT was significantly associated with maintaining a benign disease state.
PMID: 27416843
ISSN: 1471-2377
CID: 2180222

Higher weight in adolescence and young adulthood is associated with an earlier age at multiple sclerosis onset

Kavak, Katelyn S; Teter, Barbara E; Hagemeier, Jesper; Zakalik, Karen; Weinstock-Guttman, Bianca; [Edwards, K; Goodman, A; Gottesman, M; Herbert, J; Kister, I; Jubelt, B; Coyle, P; Krupp, Lauren, B; Lenihan, M; Gerber, A; Parel, A; Zivadinov, R; Granger, C]
BACKGROUND: Growing evidence suggests an association between adolescent obesity and increased risk of multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to investigate whether weight or body mass index (BMI) in adolescence and young adulthood was associated with age at MS symptom onset. METHODS: Our cohort is comprised of a sub-group of 184 women enrolled in the New York State MS Consortium registry. Individuals were asked to recall their weight at the time of first menstruation and at age 25. BMI was calculated accordingly for age 25. Regression analyses were carried out to investigate the association between weight or BMI and age at onset. RESULTS: Weight at menarche was significantly related to younger age at symptom onset (beta = -0.073, p = 0.001). These results were also found at age 25 for weight (beta = -0.080, p < 0.001) and BMI (beta = -0.448, p = 0.001). Significantly earlier disease onset (26.9 years +/-9.9) was observed in individuals who were overweight at 25 compared to those who were not overweight (32.1 years +/-9.2, p = 0.006). CONCLUSIONS: Women who reported higher weight in adolescence and BMI in early adulthood were younger at MS onset. Future research should investigate whether there is a causal link between body weight and MS, as prevention lifestyle and dietary interventions could be implemented.
PMID: 25392327
ISSN: 1477-0970
CID: 2237042