Background

Many women with multiple sclerosis (MS) report fluctuating symptoms across their menstrual cycle. Oral contraceptives (OCs) alter hormonal levels across the menstrual cycle. While cyclic OCs administer hormones for 21 days, followed by a week of placebo, continuous OCs can administer continuous doses of hormones for up to 3 months. Previous studies have suggested that OC use is associated with lower MS-related inflammation. We hypothesized that due to reduced hormonal fluctuations, women with MS might experience less inflammatory activity (clinical relapses+MRI) on continuous OCs than on cyclic OCs.

Methods

We performed a retrospective analysis of prospectively collected data. For women with MS aged 18-50 seen at the UCSF Center for MS and Neuroinflammation, we extracted data on OC use from the Electronic Medical Records (EMR). All variables were confirmed using manual clinical chart review. We identified 19 women with relapsing forms of MS on continuous OCs and matched them (2:1 when possible) to women on cyclic OCs for OC formulation, age, MS duration and DMT type. Inflammatory activity in the two groups was then compared using log-rank tests (time to new relapse, new T2-weighted lesion formation, and gadolinium-enhancing lesion formation) and t-tests (annualized relapse rate). We also performed subgroup analyses in women with at least 1 year (N = 28) and 2 years (N = 21) of clinical observation. A power calculation was performed.

Results

There was no difference in time to relapse (p = 0.50) between continuous and cycling OC users. However, continuous OC users showed a statistical trend to longer time to T2 lesion formation (p = 0.09) and longer time to contrast-enhancing lesion formation (p = 0.05). In patients with at least 1 year of observation, there was a significant difference in time to T2 lesion formation (p = 0.03) and time to contrast-enhancing lesion formation (p = 0.02).

Conclusion

In this exploratory study, women on continuous OCs showed a trend towards less inflammatory activity on MRI relative to women on cyclic OCs. This difference was not reflected in relapse rates. We estimate that 342 patients would be required for an adequately powered cohort study to evaluate such an effect. Our findings provide reassurance that for women using continuous OCs to alleviate menstrual fluctuations in symptoms, there is not an increase in MS-related inflammatory activity.

Background

Vitamin K antagonist (VKA)-associated intracerebral hemorrhages (ICHs) are more likely to expand and are associated with higher mortality than primary ICH. Prompt reversal of anticoagulant effect with prothrombin complex concentrate (PCC) may promote hemostasis and decrease hematoma expansion. The aim of this study was to evaluate the impact of an electronic order set designed to standardize and facilitate more timely reversal of coagulopathy in VKA-associated ICH.

Methods

We identified all adults who received PCC for VKA-associated ICH from June 2012 to June 2015 at University of California San Francisco Medical Center, which included a period before and after an electronic order set became available in 2014. We abstracted baseline demographics and clinical data from electronic health records. The primary outcome was time from radiographic identification of ICH to administration of PCC.

Results

Thirty-one patients received PCC for VKA-associated ICH, including 17 patients before and 14 patients after the order set became available. Baseline demographics and clinical features were similar. Order set use was associated with a significant decrease in the time from identification of ICH on imaging to the administration of PCC (median 83 vs 45 minutes; P = .02), more accurate dosing (29.4% vs 92.9%; P < .01), and a shorter time from the PCC order to follow-up international normalized ratio (INR) testing (median 164 vs 85 minutes, P = .001).

Conclusion

An electronic order set for administering PCC for VKA-associated ICH was associated with significantly faster time to PCC administration and increased dosing accuracy.

Objective

To evaluate the safety of rituximab treatment before and during pregnancy in women with MS and neuromyelitis optica spectrum disorders (NMOSDs) who may be at risk of relapses by performing a systematic literature review combined with a retrospective single-center case series.

Methods

Studies were systematically identified in the PubMed, Google Scholar, and EMBASE using the key terms "pregnancy" and "rituximab"; 22 articles were included for review (>17,000 screened). Then, patients with MS and NMOSD from 1 center (University of California, San Francisco) exposed to rituximab before conception were identified through medical record review.

Results

Systematic review: We identified 102 pregnancies with rituximab use within 6 months of conception: 78 resulted in live births and 12 in spontaneous abortions. Of 54 live births with reported gestational age, 31 occurred at term (37 weeks+) and 2 before 32 weeks. When checked, B-cell counts were low in 39% of newborns and normalized within 6 months. Case series: we identified 11 pregnancies (1 ongoing) in 10 women (7 MS and 3 NMOSD) treated with rituximab within 6 months of conception. All completed pregnancies resulted in term live births of healthy newborns (1 lost to follow-up at term). No maternal relapses occurred before/during pregnancy; 1 occurred postpartum (NMOSD).

Conclusion

No major safety signal was observed with rituximab use within 6 months of conception. Beyond the need for monitoring neonatal B cells, these observations support prospectively monitoring a larger patient cohort to determine whether rituximab may safely protect women with MS and NMOSD who are planning a pregnancy against relapses.