Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis

Objective:To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort.Methods:Using data from the MSBase Registry, we included pregnancies conceived after 31 Dec 2010 from women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse, and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses.Results:We included 1998 pregnancies from 1619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% CI 0.27-0.32), fell to 0.19 (0.14-0.24) in third trimester, and increased to 0.59 (0.51-0.67) in early postpartum. Among women who used fingolimod or natalizumab, ARR before pregnancy was 0.37 (0.28-0.49) and 0.29 (0.22-0.37), respectively, and increased during pregnancy. Intrapartum ARR decreased with preconception dimethyl fumarate use. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (OR 0.76 per month [0.60-0.95], p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (HR 0.11 [0.04-0.32], p<0.0001). Breastfeeding women were less likely to relapse (HR 0.61 [0.41-0.91], p=0.016). 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum.Conclusion:Intrapartum and postpartum relapse probabilities increased among women with MS after natalizumab or fingolimod cessation. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 34 weeks gestation, with early re-initiation after delivery is an effective option to minimize relapse risks. Strategies of DMT use have to be balanced against potential fetal/neonatal complications.

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Comparative effectiveness of dimethyl fumarate in Multiple Sclerosis

10.21203/rs.3.rs-321622/v1 ◽

2021 ◽

Author(s):

Pauline Bosco-Levy ◽

Marc Debouverie ◽

Bruno Brochet ◽

Céline Louapre ◽

Elisabeth Maillard ◽

...

Keyword(s):

Multiple Sclerosis ◽

Negative Binomial ◽

Real Life ◽

Logistic Models ◽

Negative Binomial Regression ◽

Dimethyl Fumarate ◽

Population Based ◽

Disability Progression ◽

Real Life Setting ◽

Using Data

Abstract Objectives: To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse (ARR) and disability progression in multiple sclerosis (MS) compared to injectable immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real life setting. Methods: A population-based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between July 1, 2015 and December 12, 2017, with 4.5 years of database history and 1 to 3.5 years of follow-up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional Propensity Score. Negative binomial regression and a regression logistic models were used to estimate the relative risk (RR ± [95% CI]) of ARR and the Odds Ratio (OR ± [95% CI]) of disability progression, respectively. Results: Overall, 9 304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF- IMM, patients, 1679 DMF-TERI patients, and 376 DMF-FTY patients. DMF significantly reduced ARR compared to IMM (RR 0.72 [0.61 - 0.86]) and TERI (0.81 [0.68 - 0.96]). The risk of the progression of MS specific disability was not significantly different for any matched cohorts.Interpretation: DMF is associated with lower risk of relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM).

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Older Age at Multiple Sclerosis Onset Is an Independent Factor of Poor Prognosis: A Population-Based Cohort Study

Neuroepidemiology ◽

10.1159/000479516 ◽

2017 ◽

Vol 48 (3-4) ◽

pp. 179-187 ◽

Cited By ~ 19

Author(s):

Francis Guillemin ◽

Cédric Baumann ◽

Jonathan Epstein ◽

Philippe Kerschen ◽

Teresa Garot ◽

...

Keyword(s):

Multiple Sclerosis ◽

Poor Prognosis ◽

Cox Regression ◽

Late Onset ◽

Disease Onset ◽

Population Based ◽

Male Gender ◽

Disability Progression ◽

Relapsing Remitting ◽

Short Time

Background: Late-onset multiple sclerosis (LOMS) frequently features a primary progressive (PP) course, strongly predicting severe disability. In this population-based cohort, we estimated the prognostic role of age at multiple sclerosis (MS) onset, independent of PP course, on disability progression. Methods: The association of age at disease onset (adult, <50 years [AOMS], vs. late, ≥50 years [LOMS]) and time to Expanded Disability Status Scale (EDSS) score 4 and 6 was estimated by Cox regression modelling. Results: Among 3,597 patients, 245 had LOMS. Relapsing-remitting (RR) disease was less frequent with LOMS than AOMS (51.8 vs. 90.8%, p < 0.0001). PP course, LOMS and male gender predicted short time to EDSS 4 and 6. Worse outcome with LOMS (time to EDSS 4 and 6, HR 2.0 [95% CI 1.7-2.4] and 2.3 [1.9-2.9]) was independent of PP course or male gender. LOMS had greater impact on RR than PP disease (time to EDSS 4 and 6, HR 3.1 [2.3-4.0] and 4.0 [2.9-5.6]). Only LOMS predicted time from EDSS 4 to 6 (p < 0.0001). Conclusions: Late onset MS was strongly associated with poor prognosis, independent of initial disease course, in predicting the disability progression along time.

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Discontinuation of disease-modifying therapies in multiple sclerosis – Clinical outcome and prognostic factors

Multiple Sclerosis Journal ◽

10.1177/1352458516675751 ◽

2016 ◽

Vol 23 (9) ◽

pp. 1241-1248 ◽

Cited By ~ 22

Author(s):

Gabriel Bsteh ◽

Julia Feige ◽

Rainer Ehling ◽

Michael Auer ◽

Harald Hegen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Outcome ◽

Disease Activity ◽

Cox Regression ◽

Disability Progression ◽

Hazard Ratios ◽

Relapsing Remitting ◽

Disease Modifying ◽

Disease Modifying Treatment ◽

Relapsing Remitting Multiple Sclerosis

Background: Stable disease course may prompt consideration of disease-modifying treatment (DMT) discontinuation in relapsing–remitting multiple sclerosis (RRMS). Objective: To investigate the clinical outcome after DMT discontinuation and to identify predictive factors supporting decision-making. Methods: We included 221 RRMS patients, who discontinued DMT after ⩾12 months and had documented follow-up ⩾2 years after discontinuation. Hazard ratios (HRs) with 95% confidence intervals (CIs) regarding relapse and disability progression after DMT discontinuation were calculated from Cox regression models. Results: Age >45 years at discontinuation (HR = 0.47, CI = 0.23–0.95, p = 0.038), absence of relapses for ⩾4 years on DMT before discontinuation (HR = 0.29, CI = 0.10–0.82, p = 0.020) and absence of contrast enhancing lesions (HR = 0.46, CI = 0.28–0.78, p = 0.004) were independent predictors of absence of relapse after discontinuation. Age >45 years and absence of relapses ⩾4 years on DMT combined had an HR of 0.06 (CI = 0.01–0.44, p < 0.001). Higher Expanded Disability Status Scale (EDSS) at discontinuation, age >45 years and longer disease duration were significantly associated with disability progression after discontinuation. Conclusion: While freedom from further disease activity is generally unpredictable, there is a subset of patients (age ⩾45 years, DMT intake ⩾4 years without evidence of clinical or radiological disease activity) having a high likelihood of remaining relapse-free after DMT discontinuation. However, close clinical monitoring for recurrent disease activity is mandatory after discontinuing treatment.

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Pregnancy and multiple sclerosis in the DMT era: A cohort study in Western Austria

Multiple Sclerosis Journal ◽

10.1177/1352458518816614 ◽

2018 ◽

Vol 26 (1) ◽

pp. 69-78 ◽

Cited By ~ 5

Author(s):

Gabriel Bsteh ◽

Laura Algrang ◽

Harald Hegen ◽

Michael Auer ◽

Sebastian Wurth ◽

...

Keyword(s):

Multiple Sclerosis ◽

Binary Logistic Regression ◽

Disability Progression ◽

Early Postpartum ◽

Child Bearing ◽

Pregnancy And Postpartum ◽

Standardized Treatment ◽

Disease Modifying ◽

Personalized Approach ◽

Disease Modifying Treatment

Background: Multiple sclerosis (MS) predominantly affects women of child-bearing potential. Pregnancy in MS is still a controversial issue lacking standardized treatment recommendations. Objective: To examine the reciprocal effects of pregnancy, MS, and disease-modifying treatment (DMT). Methods: We analyzed 387 pregnancies in 239 women with relapsing remitting multiple sclerosis (RRMS) and ⩾1 pregnancy, establishment of diagnosis >1 year before conception, and ⩾2 years of follow-up after delivery. Relapse rates and Expanded Disability Status Scale (EDSS) scores were compared in the year before conception, during pregnancy, and 2 years postpartum. Binary logistic regression was used to investigate predictors of risk for relapses and disability progression during pregnancy and postpartum. Results: Risk of relapse and disability progression during pregnancy was predicted by pre-conception relapse activity, higher EDSS score at conception, use of highly effective disease-modifying treatment (H-DMT) pre-conception, and prolonged washout period. Postpartum relapse and disability progression was associated with relapse activity pre-conception and during pregnancy and use of H-DMT pre-conception. Early restart of DMT reduced the risk of postpartum relapse. Conclusion: A personalized approach in planning pregnancy in women with MS while on H-DMT needs to be adopted. It seems reasonable maintaining natalizumab closer to conception and restarting the drug early postpartum to reduce the considerable risk of disease reactivation during early pregnancy and after delivery.

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Comparative effectiveness of dimethyl fumarate in Multiple Sclerosis

10.22541/au.161633594.49088150/v1 ◽

2021 ◽

Author(s):

Pauline Bosco-Lévy ◽

Marc Debouverie ◽

Bruno Brochet ◽

Francis Guillemin ◽

Céline Louapre ◽

...

Keyword(s):

Multiple Sclerosis ◽

Negative Binomial ◽

Real Life ◽

Negative Binomial Regression ◽

Dimethyl Fumarate ◽

Population Based ◽

Disability Progression ◽

Logistic Regression Models ◽

Significant Difference ◽

Using Data

Objectives: To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse (ARR) and disability progression in multiple sclerosis (MS) compared to injectable immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real life setting. Methods: A population-based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between July 1, 2015 and December 12, 2017, with 4.5 years of database history and 1 to 3.5 years of follow-up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional Propensity Score. Negative binomial regression and a logistic regression models were used to estimate the relative risk (RR ± [95% CI]) of ARR and the Odds Ratio (OR ± [95% CI]) of disability progression, respectively. Results: Overall, 9 304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF- IMM, patients, 1679 DMF-TERI patients, and 376 DMF-FTY patients. DMF significantly reduced ARR compared to IMM (RR 0.72 [0.61 - 0.86]) and TERI (0.81 [0.68 - 0.96]) and did not show any significant difference when compared with FTY The risk of the progression of MS specific disability was not significantly different for any matched cohorts. Interpretation: DMF is associated with lower risk of relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM).

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Prediction of multiple sclerosis outcomes when switching to ocrelizumab

Multiple Sclerosis Journal ◽

10.1177/13524585211049986 ◽

2021 ◽

pp. 135245852110499

Author(s):

Michael Zhong ◽

Anneke van der Walt ◽

Jim Stankovich ◽

Tomas Kalincik ◽

Katherine Buzzard ◽

...

Keyword(s):

Multiple Sclerosis ◽

Dimethyl Fumarate ◽

Disability Progression ◽

Short Treatment ◽

Disease Modifying Therapy ◽

Treatment Gaps ◽

Relapsing Remitting ◽

Disease Modifying ◽

Cox Proportional Hazard Regression ◽

Relapsing Remitting Multiple Sclerosis

Background: Increasingly, people with relapsing-remitting multiple sclerosis (RRMS) are switched to highly effective disease-modifying therapies (DMTs) such as ocrelizumab. Objective: To determine predictors of relapse and disability progression when switching from another DMT to ocrelizumab. Methods: Patients with RRMS who switched to ocrelizumab were identified from the MSBase Registry and grouped by prior disease-modifying therapy (pDMT; interferon-β/glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod or natalizumab) and washout duration (<1 month, 1–2 months or 2–6 months). Survival analyses including multivariable Cox proportional hazard regression models were used to identify predictors of on-ocrelizumab relapse within 1 year, and 6-month confirmed disability progression (CDP). Results: After adjustment, relapse hazard when switching from fingolimod was greater than other pDMTs, but only in the first 3 months of ocrelizumab therapy (hazard ratio (HR) = 3.98, 95% confidence interval (CI) = 1.57–11.11, p = 0.004). The adjusted hazard for CDP was significantly higher with longer washout (2–6 m compared to <1 m: HR = 9.57, 95% CI = 1.92–47.64, p = 0.006). Conclusion: The risk of disability worsening during switch to ocrelizumab is reduced by short treatment gaps. Patients who cease fingolimod are at heightened relapse risk in the first 3 months on ocrelizumab. Prospective evaluation of strategies such as washout reduction may help optimise this switch.

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Real-World Comparative Cost-Effectiveness Analysis of Different Classes of Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis in Saudi Arabia

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182413261 ◽

2021 ◽

Vol 18 (24) ◽

pp. 13261

Author(s):

Yazed AlRuthia ◽

Bander Balkhi ◽

Sahar Abdullah Alkhalifah ◽

Salman Aljarallah ◽

Lama Almutairi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cost Effectiveness ◽

Annual Cost ◽

Dimethyl Fumarate ◽

Composite Outcome ◽

Disability Progression ◽

Disease Modifying Therapies ◽

Relapsing Remitting ◽

The Cost ◽

Relapsing Remitting Multiple Sclerosis

The very fact that multiple sclerosis (MS) is incurable and necessitates life-long care makes it one of the most burdensome illnesses. The aim of this study was to compare the cost-effectiveness of orally administered medications (e.g., fingolimod, dimethyl fumarate, and teriflunomide), interferon (IFN)-based therapy, and monoclonal antibodies (MABs) (e.g., natalizumab and rituximab) in the management of relapsing-remitting multiple sclerosis (RRMS) in Saudi Arabia using real-world data. This was a retrospective cohort study in which patients with RRMS aged ≥18 years without any other chronic health conditions with non-missing data for at least 12 months were recruited from the electronic health records of a university-affiliated tertiary care center. Multiple logistic regressions controlling for age, sex, and duration of therapy were conducted to examine the odds of disability progression, clinical relapse, MRI lesions, and composite outcome (e.g., relapse, lesion development on MRI, disability progression). The number of patients who met the inclusion criteria and were included in the analysis was 146. Most of the patients were female (70.51%) and young (e.g., ≤35 years of age). There were 40 patients on the orally administered agents (e.g., dimethyl fumarate, teriflunomide, fingolimod), 66 patients were on IFN-based therapy (e.g., Rebif®), and 40 patients were on monoclonal antibodies (e.g., rituximab and natalizumab). Patients on MABs had lower odds of the composite outcome (OR = 0.17 (95% CI: 0.068–0.428)). The use of orally administered agents was dominant (e.g., more effective and less costly), with average annual cost savings of USD −4336.65 (95% CI: −5207.89–−3903.32) and 8.11% higher rate of effectiveness (95% CI: −14.81–18.07) when compared with Rebif®. With regard to the use of MABs in comparison to Rebif®, MABs were associated with higher cost but a better rate of effectiveness, with an average additional annual cost of USD 1381.54 (95% CI: 421.31–3621.06) and 43.11% higher rate of effectiveness (95% CI: 30.38–61.15) when compared with Rebif®. In addition, the use of MABs was associated with higher cost but a better rate of effectiveness, with an average additional annual cost of USD 5717.88 (95% CI: 4970.75–8272.66) and 35% higher rate of effectiveness (95% CI: 10.0–42.50) when compared with orally administered agents. The use of MABs in the management of RRMS among the young patient population has shown to be the most effective therapy in comparison to both IFN-based therapy (e.g., Rebif®) and orally administered agents, but with higher cost. Orally administered agents resulted in better outcomes and lower costs in comparison to IFN-based therapy. Future studies should further examine the cost-effectiveness of different disease-modifying therapies for the management of RRMS using more robust study designs.

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