Multiple sclerosis (MS) is a chronic immune-mediated, inflammatory, neuro-degenerative disease of the central nervous system, prevalent in women of reproductive age. Today, many women want to start a ...family after MS diagnosis. There are over 20 treatments for MS, and safely navigating family planning is important. We review updated information on family planning, preconception, and peri-partum considerations, and reproductive concerns in special populations with MS.
There are no MS-related restrictions on any available and appropriate contraceptive method in women with MS. The question of MS and pregnancy outcomes following assisted reproduction, remains somewhat unsettled. In many studies, no elevated relapse risk is confirmed regardless of the type of fertility treatment. MRI status may offer better assessment of postpartum disease stability than relapse rate alone. Ongoing effective MS treatments during fertility assistance and before pregnancy, can further reduce the relapse risk. B-cell depleting therapies are emerging as safe and effective treatments for peripartum MS patients.
Patients with MS should receive accurate support and counseling related to their reproductive options. The general outlook on pregnancy and MS remains positive. The ever-increasing therapeutic complexity of MS calls for ongoing education and updated guidance for neuroimmunology and obstetrics healthcare providers.
The availability of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), provides hope towards mitigation of the coronavirus disease 2019 (COVID-19) pandemic. Vaccine ...safety and efficacy has not been established in individuals with chronic autoimmune diseases such as multiple sclerosis (MS). Anecdotal reports suggest that the vaccines may be associated with brain, spinal cord, peripheral nervous system, and cardiac inflammation. Based on the high morbidity and unpredictable course of COVID-19, and the need to achieve herd immunity, vaccination has been recommended for patients with MS. We report clinical and MRI features of seven individuals who received the Moderna (
n =
3) or Pfizer (
n =
4) SARS-CoV-2 mRNA vaccines. Within one to 21 days of either the first (
n =
2) or second (
n =
5) vaccine dose, these patients developed neurologic symptoms and MRI findings consistent with active CNS demyelination of the optic nerve, brain, and/or spinal cord. Symptoms included visual loss, dysmetria, gait instability, paresthesias, sphincter disturbance, and limb weakness. Age ranged from 24 to 64 (mean 39.1) years; five were woman (71.4%). The final diagnosis was exacerbation of known stable MS (
n =
4, two were receiving disease-modifying therapy at the time of vaccination), new onset MS (
n =
2), or new onset neuromyelitis optica (
n =
1). All responded to corticosteroid (
n =
7) or plasma exchange (
n =
1) therapy, with five returning to baseline and two approaching baseline. Large prospective studies are required to further investigate any possible relationship between COVID-19 vaccines and acute CNS demyelination.
•All phase III DMT trials in MS lack data on baseline sex differences in demographic and clinical characteristics.•Most phase III DMT trials in MS did not perform pre-specified sex-specific efficacy ...or adverse events analysis.•Few recent DMT trials in MS performed post-hoc sex-specific efficacy and adverse events analysis.•Post-menopausal women or older men are not included or analyzed separately in DMT clinical trials.•High quality data of sex steroid MS therapies is lacking.
Despite established sex differences in multiple sclerosis (MS) risk and course, sex-specific efficacy and toxicity of existing MS therapies, and possible sex-specific therapeutic approaches, remain underexplored. We systematically reviewed published sex differences from Phase III pivotal trials for FDA or EMA-approved MS disease modifying therapies (DMTs), along with additional information from pharmaceutical companies, for pre-specified or post-hoc baseline characteristics, efficacy and safety outcomes by sex, and sex-specific concerns. Then, we reviewed trials testing hormonal therapies in MS. None of the Phase III clinical trials performed baseline sex-specific analyses or were powered to evaluated DMTs in menopausal/older populations. Some recent trials performed pre-specified or post-hoc stratification of outcomes by sex. Sex-specific hormonal intervention trials were limited. Adequately powered, pre-specified analyses accounting for baseline sex and age are required to maximize safety and efficacy in specific patient populations.
To evaluate relapse rates and disease-modifying drug (DMD) treatment in US women with multiple sclerosis (MS) and a live birth.
This retrospective administrative claims database study used US ...commercial health plan data from women with MS and a live birth from January 1, 2006, to June 30, 2015. Relapses and DMD treatment were evaluated 1-year prepregnancy, during pregnancy, during puerperium (6 weeks postpregnancy), and 1-year postpregnancy. Relapse was defined as MS-related hospitalization, emergency room visit, or outpatient visit with corticosteroid prescription within 7 days. Generalized estimating equation models for longitudinal data tested for differences between prepregnancy vs the other time periods.
A total of 2,158 patients were eligible. The odds of relapse declined during pregnancy (odds ratio OR 0.623, 95% confidence interval CI 0.521-0.744;
< 0.0001), increased during puerperium (OR 1.710, 95% CI 1.358-2.152;
< 0.0001), and ended at a higher level during the last 3 postpartum quarters (OR 1.216, 95% CI 1.052-1.406;
= 0.0081). The proportion of women with DMD treatment was rather low overall: approximately 20% prepregnancy, bottoming to 1.9% during the second trimester, and peaking at 25.5% 9 to 12 months postpartum. DMD treatment declined significantly during pregnancy (OR 0.171, 95% CI 0.144-0.203;
< 0.0001), remained lower during puerperium (OR 0.361, 95% CI 0.312-0.418;
< 0.0001), and ended at a higher level during the last 3 postpartum quarters (OR 1.259, 95% CI 1.156-1.371;
< 0.0001).
The rate of MS relapse decreased during pregnancy, increased 6 months postpartum, and decreased 6 to 12 months postpartum. DMD treatment was uncommon in the year before pregnancy, further decreased immediately prepregnancy and during pregnancy, and increased postpartum.
To compare pregnancy prevalence and complications in women with and without multiple sclerosis (MS).
This retrospective US administrative claims study used data from January 1, 2006, to June 30, ...2015. All data for women with MS were included. A nationally representative 5% random sample from approximately 58 million women without MS was used to compute the dataset. Annual pregnancy rates, identified via diagnosis/procedure codes and adjusted for covariates, were estimated via logistic regression. Claims for pregnancy and labor/delivery complications were compared using propensity score matching.
From 2006 to 2014, the adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%; the adjusted proportion without MS and with pregnancy decreased from 8.83% to 7.75%. The difference in linear trend (0.17% increase and 0.15% decrease in per-annum pregnancy rates) was significant (
statistic = 7.8;
< 0.0001). After matching (n = 2,115 per group), a higher proportion of women with MS than without had claims for premature labor (31.4% vs 27.4%;
= 0.005), infection (13.3% vs 10.9%;
= 0.016), cardiovascular disease (3.0% vs 1.9%;
= 0.028), anemia/acquired coagulation disorders (2.5% vs 1.3%;
= 0.007), neurologic complications (1.6% vs 0.6%;
= 0.005), sexually transmitted diseases (0.4% vs 0.1%;
= 0.045), acquired fetal damage (27.8% vs 23.5%;
= 0.002), and congenital fetal malformations (13.2% vs 10.3%;
= 0.004).
Pregnancy rates in this population of women with MS have been increasing. High rates of claims for several peripartum complications were observed in women with and those without MS. Claims data provide knowledge of interactions patients have with the health care system and are valuable initial exploratory analyses.
For women with multiple sclerosis (MS) who become pregnant, the risks and benefits of ongoing therapy for the health of both the mother and the fetus must be carefully considered. Based on a ...literature review and our MS center’s standard practices, we provide guidance to aid clinical decision making in the absence of clear evidence-based clinical practice guidelines. Women seeking to achieve pregnancy should generally discontinue disease-modifying therapy use prior to attempting conception. For example, the immunosuppressant mitoxantrone is teratogenic and should be prescribed only with the assurance of effective contraception. Conception should be discouraged for patients on fingolimod, because of the limited information available on human pregnancy outcomes. Current evidence, including data from pregnancy registries for glatiramer acetate (GA), interferon beta-1a (IFNβ-1a), and natalizumab, has not shown specific patterns of malformations suggesting teratogenicity. Pregnancy registry data have not been published for IFNβ-1b. During breastfeeding, intravenous immunoglobulin and corticosteroids are generally safe and may be associated with a reduction in postpartum relapses; however, a washout period is recommended between corticosteroid administration and the resumption of breastfeeding. Clinical data on the use of IFNβ, GA, and natalizumab during lactation are limited. Mitoxantrone is contraindicated during breastfeeding, and fingolimod should be avoided in nursing mothers, because of a lack of data.
Reproductive Issues in MS Houtchens, Maria K; Kaplan, Tamara B
Seminars in neurology,
12/2017, Volume:
37, Issue:
6
Journal Article
Peer reviewed
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, predominantly affecting women of childbearing age. Therefore, issues of conception, pregnancy, and delivery are of ...significant importance to patients and treating physicians. We discuss immunologic and clinical effects of pregnancy on the course of MS including both immunosuppression on a local level and a heightened state of immunocompetence on a global level. Clinical outcomes of the Pregnancy in Multiple Sclerosis trials are reported. We analyze and update the available data on safety and efficacy of immunomodulating MS treatments and symptomatic treatments for pregnant and lactating women, and address specific issues of MS management at the time of pregnancy. We review the data related to estrogen-based MS therapies currently or previously in trials. Pregnancy does not appear to be associated with adverse outcomes in MS patients. Some evidence suggests possible beneficial effects, although clear prospective data of sufficient length and quality are limited. Long-term relapse rates or disability progression do not seem to be affected by pregnancy in MS patients. The use of immunosuppressive or immunomodulatory agents in pregnancy is not routinely advisable but could be considered under special circumstances.
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