The effectiveness of natalizumab vs fingolimod-A comparison of international registry studies.

BACKGROUND: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. METHODS: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. RESULTS: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. CONCLUSION: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.

Pharmacotherapeutic considerations in women with multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a chronically progressive disease of the central nervous system. The relapsing form of the disease predominantly affects women with onset between the ages 20 to 40 years. Therefore, timing, choice, and treatment options should take pregnancy planning into consideration to accommodate both the needs and safety of the mother and health of the fetus. AREAS COVERED: In this review, the authors discuss and summarize the recent evidence of different pharmacotherapeutic possibilities in the treatment of women with MS. EXPERT OPINION: There is evidence that disease modifying therapy reduces the risk of relapses and diminishes disability progression in people with relapsing MS. The disease is often diagnosed in the childbearing years, and thus pregnancy planning can possibly be a part of the pharmacotherapeutic considerations. The management of women planning pregnancy requires a balancing of risks. The clinician must consider the risks related to treatment discontinuation versus the risk of exposing the developing fetus to drugs that are potential fetotoxic. Randomized controlled trials of medication safety - if used during pregnancy, are prohibited for ethical reasons; hence, the evidence is continuously gathered from observational data, post-authorization studies and pregnancy registries.