Background

Prolonged release (PR) fampridine is indicated for the improvement of walking in adult multiple sclerosis (MS) patients. Several studies have supported that PR-fampridine improves walking ability in this population; however, reported effects have varied widely across studies and study design.

Objectives

To conduct a systematic literature review (SLR) and meta-analysis (MA) to summarize the evidence on the efficacy and effectiveness of PR-fampridine in MS patients.

Methods

Following PRISMA guidelines, a systematic search of PubMed, EMBASE, YORK and Cochrane Library was conducted from January 1, 2006-April 1, 2019 to identify publications comparing the efficacy and effectiveness of PR-fampridine from Randomized Controlled Trials (RCTs) and observational studies (OBS). For RCTs, outcome measures include Timed 25-Foot Walk (T25FW) and 12-item Multiple Sclerosis Walking Scale (MSWS-12) responders and MSWS-12 scores; for OBS, T25FW walking time and MSWS-12 scores. In the MA, pooled estimates were derived using odds ratios (OR) and standardized mean differences (SMD) of both endpoints. Results from RCTs and OBS were reported separately using a random effects model.

Results

Of a total of 897 unique citations, 27 studies met all criteria for inclusion in the MA, 9 RCTs and 18 single-arm OBS. A pooled estimate based on T25FW responder data from 4 RCTs showed statistically significant improvements in walking ability in the PR-fampridine vs. placebo group; OR (95% CI): 4.8 (2.9-7.9), p<0.0005. Also, findings based on MSWS-12 responder data from 2 RCTs showed significant improvements in walking ability in the PR-fampridine group vs. placebo; OR (95% CI): 1.7 (1.1-2.5); p=0.011. A pooled estimate of mean MSWS-12 scores from 4 RCTs also showed significant improvements in the PR-fampridine vs. placebo group; OR (95% CI): 1.5 (1.2-1.9); p<0.0005. Summary estimates from OBS suggest a significant improvement vs. baseline on T25FW time derived from 9 studies showing that walking time was significantly improved vs. baseline; with SMD (95% CI): –0.31 (-0.479 to -0.146); p<0.0005. Also, the pooled estimate from MSWS-12 endpoint in 6 studies showed that walking ability was statistically improved vs. baseline; SMD (95% CI): -0.98 (-0.892 to -1.058); p<0.0005.

Conclusions

Across randomized and observational data, the use of PR-fampridine is consistently associated with significantly improved walking ability in MS patients measured by MSWS-12 or T25FW endpoints.

This study is funded by Biogen. Biogen funded the analyses for this abstract.

Background

Vitamin D is associated with inflammatory activity in MS, but it is less clear whether seasonal fluctuations of vitamin D levels can affect long-term prognosis in MS.

Objectives

We examined whether seasonal fluctuations of serum vitamin D levels were associated with long-term (10 years) disability scores in a well-defined group of adult Norwegian MS patients.

Methods

A cohort of 80 patients with relapsing-remitting MS completed a randomized controlled study on ω-3 fatty acids between 2004 and 2008. During the study period of 24 months, serum 25-hydroxyvitamin D (25[OH]D) were measured at 9 time points: at baseline, and then at month 1, 3, 6, 7, 9, 12, 18, and 24. A mean value per season (summer, fall, winter, spring) was calculated from these values. In 2017, a follow-up study was conducted, including disability assessment by the Expanded Disability Status Scale (EDSS). In linear regression models, we explored the association between dichotomized values of 25(OH)D (“above median” and “below median”) per season and the change in EDSS score 10 years later.

Results

The highest 25(OH)D levels were seen during summer (June-August: mean = 85.9 nmol/L, median = 81.0 nmol/L) when solar radiation peaks in Norway, and the lowest 25(OH)D levels were seen during spring (March-May: mean 55.8 nmol/L, median = 52.5 nmol/L). Higher 25(OH)D levels during winter, spring, and summer were significantly associated with less disability progression after 10 years in separate models adjusted for age, sex, and baseline EDSS score. However, in a model mutually adjusted for 25(OH)D levels for all four seasons, only spring levels remained significantly associated with disability progression. In this model, the EDSS change was 0.71 point (95% CI: 0.02 to 1.40) lower for patients with above compared to below median spring levels. The effect estimate remained similar after further adjusting for disease duration and disease-modifying treatment.

Conclusions

In our study population, low vitamin D levels during spring were significantly associated with greater long-term disability progression. This finding suggests that vitamin D supplements may be of extra importance during this season.

Background

People with multiple sclerosis (MS) have increased risk of depression and anxiety. It is not known if pregnancy and birth impact the risk of psychiatric symptoms in women with MS.

Objectives

To assess the occurrence, risk factors and prognosis of peripartum depression and anxiety in women with MS before and after diagnosis.

Methods

This study included women from the prospective Norwegian Mother, Father and Child Cohort study (MoBa) between 1999-2008. We used data from questionnaires at gestational weeks 18 and 30, and at 6 and 18 months postpartum. Self-reported data on depression and anxiety were recorded by Hopkins Symptom Checklist. Identification of women with MS was obtained from the Norwegian MS Registry, Norwegian Patient Registry and hospital records. The identified MS-women (n=546) were divided into 1) Pre-birth diagnosis (n=140), 2) Pre-birth onset with post-birth diagnosis (n=98) and 3) Post-birth onset (n=308). Thirty-five women were diagnosed with MS in the postpartum period. In group 2 and 3 the median follow-up time from birth until diagnosis was 7 years (range 0-17). The reference group consisted of women in MoBa without MS (n=111,267).

Results

Depression in gestational week 30 was more common among women with pre-birth diagnosis compared to the reference group (15% vs. 9%, OR 2.0 95% CI 1.2-3.1), adjusted for age, parity, overweight, socioeconomic factors and clustering among siblings. For those depressed in this group, the symptoms more often persisted to 6 months postpartum (77% vs. 38%, p=0.004), but the prognosis 18 months postpartum was similar. Women who were diagnosed with MS in the postpartum period had higher occurrence of depression compared to the reference group both 6 months (23% vs. 10%, p=0.023) and 18 months postpartum (42% vs. 13%, p<0.001). There was no significant difference in peripartum depression in women with post-birth diagnosis (group 2 and 3) compared to the reference group. Risk factors associated with depression in women with pre-birth diagnosis were adverse socioeconomic factors, history of physical and/or sexual abuse and pre-pregnancy psychiatric disease. There was no difference in peripartum anxiety between any of the MS groups and the reference group.

Conclusions

Women with diagnosed MS have an increased risk of depression in the third trimester. The burden of having a MS diagnosis seems to be the determinant for depression. Clinicians should be aware of postpartum depression in women diagnosed with MS in this period.