Practical Evidence-Based Recommendations for Patients with Multiple Sclerosis Who Want to Have Children.

Multiple sclerosis (MS) management presently aims to reach a state of no (or minimal) evidence of disease activity. The development and commercialization of new drugs has led to a renewed interest in family planning, since patients with MS may face a future with reduced (or no) disease-related neurological disability. The advice of neurologists is often sought by patients who want to have children and need to know more about disease control at conception and during pregnancy and the puerperium. When MS is well controlled, the simple withdrawal of drugs for patients who intend to conceive is not an option. On the other hand, not all treatments presently recommended for MS are considered safe during conception, pregnancy and/or breastfeeding. The objective of the present study was to summarize the practical and evidence-based recommendations for family planning when our patients (women and men) have MS.Funding TEVA Pharmaceutical Brazil.

We know how to prescribe natalizumab for multiple sclerosis, but do we know how to withdraw it?

Natalizumab is a potent immunosuppressive monoclonal antibody used for the treatment of multiple sclerosis (MS). While definite guidelines for the safety of natalizumab prescriptions are available in all countries, there are no specific recommendations on how to withdraw the drug if the need arises. There are reports describing MS complications after natalizumab infusions were stopped. Most neurologists seem to stop natalizumab treatment according to their idea on how to best carry out the withdrawal. The present study shows the very different manners in which expert neurologists from 14 MS units in Brazil stopped natalizumab in their patients. The authors concluded that pharmacovigilance on natalizumab must persist after the drug is withdrawn in order to have enough data for adequate recommendations.

Long-term effects of exposure to disease-modifying drugs in the offspring of mothers with multiple sclerosis: a retrospective chart review.

INTRODUCTION: Multiple sclerosis (MS) mainly affects women of fertile age. To date, the only recommendation for women with MS intending to become pregnant is to stop all treatment. This recommendation reflects the concerns about the effects of disease-modifying drugs (DMDs) on the offspring. The objective of the present study was to assess the potential long-term effects of maternal exposure to DMDs on the offspring. METHOD: This was a retrospective study revising medical data on the offspring of women with MS. These women now have children aged at least 1 year and include a group of patients that were not exposed to any DMDs for at least 3 months prior to pregnancy and during the whole gestation (control group). Another group of patients had at least 2 weeks of exposure to DMDs, mainly to interferon beta or glatiramer acetate RESULTS: The women with MS participating in this study have children currently aged, on average, 6.6 years (range 1-39 years). There was no pattern of drug-related adverse events or complications in the children whose mothers were exposed to DMDs. No specific long-term adverse events were observed in the offspring of women with MS who were exposed to drugs during pregnancy. The profile of relevant diagnoses in their children was similar to that of children whose mothers had not been exposed to DMDs. CONCLUSIONS: The present retrospective study did not show a specific profile of long-term deleterious drug effects on children born from mothers who were exposed to drugs for MS treatment.

Long-term use of glatiramer acetate by 11 pregnant women with multiple sclerosis: a retrospective, multicentre case series.

BACKGROUND: Glatiramer acetate is a US FDA category B drug with regard to use by pregnant women with multiple sclerosis (MS). There are no data currently available for the continuous use of glatiramer acetate during pregnancy. OBJECTIVE: To assess the risks and benefits of glatiramer acetate used throughout pregnancy among women with active MS. DESIGN: Retrospective and multicentre case series. SETTINGS: Outpatient services of academic and private institutions caring for patients with MS in Brazil. PATIENTS: Eleven women with MS and their children were assessed. INTERVENTION: Retrospective evaluation of women with MS who received glatiramer acetate continuously for at least 7 months during pregnancy. This evaluation was performed by the neurologist responsible for the patient. Children aged 1 year and over, born to mothers who received glatiramer acetate during pregnancy, were assessed using the Denver II developmental screening test. MAIN OUTCOME MEASUREMENTS: Obstetric, neonatal and developmental outcomes. RESULTS: No drug-related obstetric complications were observed. No specific drug-related malformations, neonatal complications or developmental abnormalities were observed in the children. Postnatal MS relapse rates remained significantly lower than antenatal rates in these patients. CONCLUSIONS: No deleterious effects from glatiramer acetate were observed in these pregnant women with MS or in their offspring. No increment in postnatal relapse rate was observed. However, the use of glatiramer acetate during pregnancy should be restricted to the most difficult cases, in which the benefits clearly outweigh the risks.

Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations.

Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an inherited autosomal recessive deficiency of acid alpha-glucosidase (GAA), with predominant manifestations of skeletal muscle weakness. A broad range of studies have been published focusing on Pompe patients from different countries, but none from Brazil. We investigated 41 patients with either infantile-onset (21 cases) or late-onset (20 cases) disease by muscle pathology, enzyme activity and GAA gene mutation screening. Molecular analyses identified 71 mutant alleles from the probands, nine of which are novel (five missense mutations c.136T > G, c.650C > T, c.1456G > C, c.1834C > T, and c.1905C > A, a splice-site mutation c.1195-2A > G, two deletions c.18_25del and c.2185delC, and one nonsense mutation c.643G > T). Interestingly, the c.1905C > A variant was detected in four unrelated patients and may represent a common Brazilian Pompe mutation. The c.2560C > T severe mutation was frequent in our population suggesting a high prevalence in Brazil. Also, eight out of the 21 infantile-onset patients have two truncating mutations predicted to abrogate protein expression. Of the ten late-onset patients who do not carry the common late-onset intronic mutation c.-32-13T > G, five (from three separate families) carry the recently described intronic mutation, c.-32-3C > A, and one sibpair carries the novel missense mutation c.1781G > C in combination with known severe mutation c.1941C > G. The association of these variants (c.1781G > C and c.-32-3C > A) with late-onset disease suggests that they allow for some residual activity in these patients. Our findings help to characterize Pompe disease in Brazil and support the need for additional studies to define the wide clinical and pathological spectrum observed in this disease.