Pregnancy-related relapses and breastfeeding in a contemporary multiple sclerosis cohort

ObjectiveTo determine whether women with multiple sclerosis (MS) diagnosed according to current criteria are at an increased risk of postpartum relapses and to assess whether this risk is modified by breastfeeding or MS disease-modifying therapies (DMTs), we examined the electronic health records (EHRs) of 466 pregnancies among 375 women with MS and their infants.MethodsWe used prospectively collected information from the EHR at Kaiser Permanente Southern and Northern California between 2008 and 2016 of the mother and infant to identify treatment history, breastfeeding, and relapses. Multivariable models accounting for measures of disease severity were used.ResultsIn the postpartum year, 26.4% relapsed, 87% breastfed, 36% breastfed exclusively for at least 2 months, and 58.8% did not use DMTs. At pregnancy onset, 67.2% had suboptimally controlled disease. Annualized relapse rates (ARRs) declined from 0.37 before pregnancy to 0.14–0.07 (p < 0.0001) during pregnancy, but in the postpartum period, we did not observe any rebound disease activity. The ARR was 0.27 in the first 3 months postpartum, returning to prepregnancy rates at 4–6 months (0.37). Exclusive breastfeeding reduced the risk of early postpartum relapses (adjusted hazard ratio = 0.37, p = 0.009), measures of disease severity increased the risk, and resuming modestly effective DMTs had no effect (time-dependent covariate, p = 0.62).ConclusionMost women diagnosed with MS today can have children without incurring an increased risk of relapses. Women with suboptimal disease control before pregnancy may benefit from highly effective DMTs that are compatible with pregnancy and lactation. Women with MS should be encouraged to breastfeed exclusively.

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Pregnancy and the Use of Disease-Modifying Therapies in Patients with Multiple Sclerosis: Benefits versus Risks

Multiple Sclerosis International ◽

10.1155/2016/1034912 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Raed Alroughani ◽

Ayse Altintas ◽

Mohammed Al Jumah ◽

Mohammadali Sahraian ◽

Issa Alsharoqi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Current Evidence ◽

Disease Modifying Therapies ◽

Increased Risk ◽

Pregnancy And Lactation ◽

Risk Of Disease ◽

Disease Reactivation ◽

Disease Modifying ◽

Adverse Pregnancy ◽

In Pregnancy

The burden of multiple sclerosis (MS) in women of childbearing potential is increasing, with peak incidence around the age of 30 years, increasing incidence and prevalence, and growing female : male ratio. Guidelines recommend early use of disease-modifying therapies (DMTs), which are contraindicated or recommended with considerable caution, during pregnancy/breastfeeding. Many physicians are reluctant to prescribe them for a woman who is/is planning to be pregnant. Interferons are not absolutely contraindicated during pregnancy, since interferon-βappears to lack serious adverse effects in pregnancy, despite a warning in its labelling concerning risk of spontaneous abortion. Glatiramer acetate, natalizumab, and alemtuzumab also may not induce adverse pregnancy outcomes, although natalizumab may induce haematologic abnormalities in newborns. An accelerated elimination procedure is needed for teriflunomide if pregnancy occurs on treatment or if pregnancy is planned. Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited. Increased relapse rates following withdrawal of some DMTs in pregnancy are concerning and require further research. The postpartum period brings increased risk of disease reactivation that needs to be carefully addressed through effective communication between treating physicians and mothers intending to breastfeed. We address the potential for use of the first- and second-line DMTs in pregnancy and lactation.

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Association between multiple sclerosis disease severity and adherence to disease-modifying therapies

Journal of Managed Care & Specialty Pharmacy ◽

10.18553/jmcp.2021.27.7.915 ◽

2021 ◽

Vol 27 (7) ◽

pp. 915-923

Author(s):

Adam Burkhard ◽

Joshua Toliver ◽

Karen Rascati

Keyword(s):

Multiple Sclerosis ◽

Disease Severity ◽

Disease Modifying Therapies ◽

Multiple Sclerosis Disease ◽

Disease Modifying

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Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis

Neurology ◽

10.1212/wnl.0000000000012753 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012753

Author(s):

Steve Simpson-Yap ◽

Edward De Brouwer ◽

Tomas Kalincik ◽

Nick Rijke ◽

Jan A Hillert ◽

...

Keyword(s):

Multiple Sclerosis ◽

Artificial Ventilation ◽

Dimethyl Fumarate ◽

Cross Sectional ◽

Icu Admission ◽

Disease Modifying Therapies ◽

Increased Risk ◽

External Consistency ◽

Disease Modifying ◽

Cross Sectional Design

Background:People with multiple sclerosis (MS) are a vulnerable group for severe COVID- 19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS.Methods:Data from 12 data-sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS-phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl-fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs) covariates were queried, alongside COVID-19 severity outcomes, hospitalisation, ICU admission, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression, adjusted for age, sex, MS-phenotype, and EDSS.Results:657(28.1%) with suspected and 1,683(61.9%) with confirmed COVID-19 were analysed. Among suspected+confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalised, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl-fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01- 2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39;aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.75,95%CI=1.29- 2.38; aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36;aOR=4.32,95%CI=2.27-8.23) but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab wereassociated with hospitalisation (aOR=1.86,95%CI=1.13-3.07; aOR=2.88,95%CI=1.68-4.92) and ICU admission (aOR=2.13,95%CI=0.85-5.35; aOR=3.23,95%CI=1.17-8.91), but only rituximab with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS-phenotype, and EDSS found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity.Conclusions:Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission. Despite the study’s cross-sectional design, the internal and external consistency of these results with prior studies suggests rituximab/ocrelizumab use may be a risk factor for more severe COVID-19.

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Use of Disease-Modifying Therapies in Pediatric Relapsing-Remitting Multiple Sclerosis in the United Kingdom

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000001008 ◽

2021 ◽

Vol 8 (4) ◽

pp. e1008

Author(s):

Omar A. Abdel-mannan ◽

Celeste Manchoon ◽

Thomas Rossor ◽

Justine-Clair Southin ◽

Carmen Tur ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Modifying Therapies ◽

Increased Risk ◽

Relapsing Remitting ◽

Relapse Time ◽

Disease Modifying ◽

Edss Score ◽

Remitting Multiple Sclerosis ◽

Time To Relapse ◽

Relapsing Remitting Multiple Sclerosis

ObjectivesTo compare the real-world effectiveness of newer disease-modifying therapies (DMTs) vs injectables in children with relapsing-remitting multiple sclerosis (RRMS).MethodsIn this retrospective, multicenter study, from the UK Childhood Inflammatory Demyelination Network, we identified children with RRMS receiving DMTs from January 2012 to December 2018. Clinical and paraclinical data were retrieved from the medical records. Annualized relapse rates (ARRs) before and on treatment, time to relapse, time to new MRI lesions, and change in Expanded Disability Status Scale (EDSS) score were calculated.ResultsOf 103 children treated with DMTs, followed up for 3.8 years, relapses on treatment were recorded in 53/89 (59.5%) on injectables vs 8/54 (15%) on newer DMTs. The ARR was reduced from 1.9 to 1.1 on injectables (p < 0.001) vs 1.6 to 0.3 on newer DMTs (p = 0.002). New MRI lesions occurred in 77/89 (86.5%) of patients on injectables vs 26/54 (47%) on newer DMTs (p = 0.0001). Children on newer DMTs showed longer time to relapse, time to switch treatment, and time to new radiologic activity than patients on injectables (log-rank p < 0.01). After adjustment for potential confounders, multivariable analysis showed that injectables were associated with 12-fold increased risk of clinical relapse (adjusted hazard ratio [HR] = 12.12, 95% CI = 1.64–89.87, p = 0.015) and a 2-fold increased risk of new radiologic activity (adjusted HR = 2.78, 95% CI = 1.08–7.13, p = 0.034) compared with newer DMTs. At 2 years from treatment initiation, 38/103 (37%) patients had MRI activity in the absence of clinical relapses. The EDSS score did not change during the follow-up, and only 2 patients had cognitive impairment.ConclusionNewer DMTs were associated with a lower risk of clinical and radiologic relapses in patients compared with injectables. Our study adds weight to the argument for an imminent shift in practice toward the use of newer, more efficacious DMTs in the first instance.Classification of EvidenceThis study provides Class IV evidence that newer DMTs (oral or infusions) are superior to injectables (interferon beta/glatiramer acetate) in reducing both clinical relapses and radiologic activity in children with RRMS.

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Clinical efficacy of teriflunomide over a fixed 2-year duration in the TOWER study

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217318775236 ◽

2018 ◽

Vol 4 (2) ◽

pp. 205521731877523 ◽

Cited By ~ 1

Author(s):

Mark S Freedman ◽

Julia Morawski ◽

Karthinathan Thangavelu

Keyword(s):

Multiple Sclerosis ◽

Clinical Outcomes ◽

Clinical Efficacy ◽

Phase 3 ◽

Comparative Analyses ◽

Disease Modifying Therapies ◽

Disease Modifying ◽

Intent To Treat ◽

Relapse Rates

Patients enrolled in the phase 3 TOWER study (NCT00751881) of teriflunomide had variable treatment durations (48–173 weeks). This has led to challenges when interpreting results in the context of other phase 3 trials of disease-modifying therapies for multiple sclerosis, which typically have a fixed 2-year duration. This communication reports clinical outcomes in TOWER over a fixed 2-year period. Reductions in annualised relapse rates and 12-week confirmed disability worsening associated with teriflunomide were comparable between overall intent-to-treat and fixed 2-year study populations in TOWER. Consistency in outcomes supports the inclusion of TOWER data in comparative analyses with other disease-modifying therapies. ClinicalTrials.gov: NCT00751881.

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Relapse Rates and Symptom Management Among Patients Receiving Natalizumab and other Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis

Value in Health ◽

10.1016/j.jval.2016.09.464 ◽

2016 ◽

Vol 19 (7) ◽

pp. A427

Author(s):

L Lee ◽

J Pike ◽

J Kendter ◽

D Campagnolo ◽

E Jones ◽

...

Keyword(s):

Multiple Sclerosis ◽

Symptom Management ◽

Disease Modifying Therapies ◽

Relapsing Remitting ◽

Disease Modifying ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis ◽

Relapse Rates

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Multiple Sclerosis, Disease-Modifying Therapies and COVID-19: A Systematic Review on Immune Response and Vaccination Recommendations

Vaccines ◽

10.3390/vaccines9070773 ◽

2021 ◽

Vol 9 (7) ◽

pp. 773

Author(s):

Verónica Cabreira ◽

Pedro Abreu ◽

Ricardo Soares-dos-Reis ◽

Joana Guimarães ◽

Maria José Sá

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Clinical Evidence ◽

Vaccine Response ◽

Response Dynamics ◽

Disease Modifying Therapies ◽

Vaccination Recommendations ◽

Increased Risk ◽

Disease Modifying ◽

Anti Cd20

Understanding the risks of COVID-19 in patients with Multiple Sclerosis (MS) receiving disease-modifying therapies (DMTs) and their immune reactions is vital to analyze vaccine response dynamics. A systematic review on COVID-19 course and outcomes in patients receiving different DMTs was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Emerging data on SARS-CoV-2 vaccines was used to elaborate recommendations. Data from 4417 patients suggest that MS per se do not portend a higher risk of severe COVID-19. As for the general population, advanced age, comorbidities, and higher disability significantly impact COVID-19 outcomes. Most DMTs have a negligible influence on COVID-19 incidence and outcome, while for those causing severe lymphopenia and hypogammaglobulinemia, such as anti-CD20 therapies, there might be a tendency of increased hospitalization, worse outcomes and a higher risk of re-infection. Blunted immune responses have been reported for many DMTs, with vaccination implications. Clinical evidence does not support an increased risk of MS relapse or vaccination failure, but vaccination timing needs to be individually tailored. For cladribine and alemtuzumab, it is recommended to wait 3–6 months after the last cycle until vaccination. For the general anti-CD20 therapies, vaccination must be deferred toward the end of the cycle and the next dose administered at least 4–6 weeks after completing vaccination. Serological status after vaccination is highly encouraged. Growing clinical evidence and continuous surveillance are extremely important to continue guiding future treatment strategies and vaccination protocols.

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Comparison of Disease-Modifying Therapies for the Management of Multiple Sclerosis: Analysis of Healthcare Resource Utilization and Relapse Rates from US Insurance Claims Data

PharmacoEconomics - Open ◽

10.1007/s41669-017-0035-2 ◽

2017 ◽

Vol 2 (1) ◽

pp. 31-41 ◽

Cited By ~ 5

Author(s):

Jacqueline Nicholas ◽

Aaron Boster ◽

Ning Wu ◽

Wei-Shi Yeh ◽

Monica Fay ◽

...

Keyword(s):

Multiple Sclerosis ◽

Resource Utilization ◽

Claims Data ◽

Healthcare Resource ◽

Healthcare Resource Utilization ◽

Insurance Claims ◽

Disease Modifying Therapies ◽

Insurance Claims Data ◽

Disease Modifying ◽

Relapse Rates

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Associations of DMT therapies with COVID-19 severity in multiple sclerosis

10.1101/2021.02.08.21251316 ◽

2021 ◽

Author(s):

Steve Simpson-Yap ◽

Edward De Brouwer ◽

Tomas Kalincik ◽

Nick Rijke ◽

Jan Hillert ◽

...

Keyword(s):

Multiple Sclerosis ◽

Artificial Ventilation ◽

Dimethyl Fumarate ◽

Mixed Effects ◽

Clinical Severity ◽

Vulnerable Group ◽

Icu Admission ◽

Disease Modifying Therapies ◽

Increased Risk ◽

Clinical Covariates

AbstractBackgroundPeople with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS.MethodsData from 12 data-sources in 28 countries were aggregated. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes, hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression.Results657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.75,95%CI=1.29-2.38; aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36; aOR=4.32,95%CI=2.27-8.23) but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.86,95%CI=1.13-3.07; aOR=2.88,95%CI=1.68-4.92) and ICU admission (aOR=2.13,95%CI=0.85-5.35; aOR=3.23,95%CI=1.17-8.91), but only rituximab with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death.ConclusionsUsing the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission, suggesting their use may be a risk factor for more severe COVID-19.

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