Faculty Bibliography

Background/UNASSIGNED:Fingolimod is a daily oral medication used to treat relapsing multiple sclerosis (MS). Clinicians often adopt less frequent dosing for patients with profound drug-induced lymphopenia or other adverse events. Data on the effectiveness of alternate dose fingolimod are limited. Methods/UNASSIGNED:We conducted a multicenter, retrospective, observational study at 14 sites and identified 170 patients with MS taking alternate doses of fingolimod for ≥1 month. Clinical and radiologic outcomes were collected and compared during daily and alternate fingolimod dosing. Results/UNASSIGNED:< 0.001). Conclusions/UNASSIGNED:These data support the clinical strategy of alternate dosing of fingolimod in patients with good disease control but profound lymphopenia or other adverse events while on daily dose. Classification of Evidence/UNASSIGNED:This study provides Class IV evidence that for patients with MS on daily dose fingolimod with adverse events, alternate dose fingolimod is associated with disease activity similar to daily dose fingolimod.

We describe four patients who experienced optic neuritis (ON) and seizures and were found to have antibodies to myelin oligodendrocyte glycoprotein (MOG) in serum. The index case was a previously healthy 39-year-old man who developed steroid dependent ON and had a generalized seizure when steroids were tapered. He tested positive for antibodies to MOG. We have reviewed the charts of all 11 anti-MOG antibody positive patients in our practice and found that 4 patients, all of whom had experienced one or more episodes of ON, also had a generalized seizure during the course of their illness. In 2 patients - including the index case - seizure occurred during steroid taper and in 2 others at the time of an episode of acute disseminated encephalomyelitis (ADEM). Association of anti-MOG antibodies and relapsing demyelinating disorders of the central nervous system is increasingly recognized. Testing for anti-MOG antibodies should be considered in patients with optic neuritis and seizures, especially in those with who also have a history of ADEM.

Background: MS patients often stop disease-modifying therapy (DMT). MSBase, a 50,000-patient, global observational MS registry, provides a unique opportunity to identify predictors of relapses and disease progression after DMTs are stopped. Objectives: To identify predictors of relapse and confirmed disability progression after stopping DMTs. Methods: We included MS patients who, at the time of stopping DMT, were >=18 years and were on a DMT continuously for >=1 year. We also required that, after stopping DMT, each patient be followed for >2 years; did not restart DMT for > 6 months (to exclude therapy 'switchers'); and did not become pregnant for >1 year. Predictors of time to first relapse and 3-month confirmed progression (1.5 EDSS steps for baseline EDSS 0; 0.5-for baseline EDSS 6-6.5; 1-for all others) were analyzed using Cox proportional hazards regression. Hazard proportionality was assessed with scaled Schoenfeld residuals; p< 0.05 was considered significant. Results: We identified 4,842 patients in the MSBase who met our inclusion criteria (74% female; mean (SD) age 40.7 years (10.4); mean (SD) disease duration 11.6 years (7.7)). Median (IQR) EDSS at baseline was 3 (1.5, 5.5). The discontinued DMTs were: IFNb-1a sc in 28%; IFNb-1b-26%; IFNb-1a im-20%; glatiramer acetate 18%; natalizumab-6%; fingolimod 3%. Most common reasons for discontinuation, recorded for 48% patients, were adverse events (9%), inconvenience (7%) and intolerance (7%). Post-DMT follow up was 31,691 patient-years. Post-DMT annualized relapse rate (ARR) was 0.22 and was lowest post-IFNb-1b (ARR=0.19) and highest post-Natalizumab (ARR=0.32). Disability data was available for 2,678 patients. The incidence of post-DMT confirmed disability progression was 8.23 per 100 person-years (95% CI: 7.72, 8.76); it was lowest post-IFNb-1a (6.40 (5.45, 7.51)) and highest post-Natalizumab (12.55 (10.04, 15.69). DMT was restarted by 2,984 (61.6%) patients after a median (IQR) of 18.22 months (IQR 10.97, 36.60). For each DMT, we will present predictors of time to relapse and confirmed disability progression, and DMT restart based on Cox regression model. Conclusions: Understanding risk factors for post-DMT relapses and disability accumulation after cessation of DMTs may allow clinicians to identify patients at low risk of disease worsening, who may choose to safely discontinue a particular DMT, and those at high risk, who would be well advised to continue on therapy

BACKGROUND: Multiple sclerosis is a polysymptomatic disease. Little is known about relative contributions of the different multiple sclerosis symptoms to self-perception of health. OBJECTIVES: To investigate the relationship between symptom severity in 11 domains affected by multiple sclerosis and self-rated health. METHODS: Multiple sclerosis patients in two multiple sclerosis centers assessed self-rated health with a validated instrument and symptom burden with symptoMScreen, a validated battery of Likert scales for 11 domains commonly affected by multiple sclerosis. Pearson correlations and multivariate linear regressions were used to investigate the relationship between symptoMScreen scores and self-rated health. RESULTS: Among 1865 multiple sclerosis outpatients (68% women, 78% with relapsing-remitting multiple sclerosis, mean age 46.38 +/- 12.47 years, disease duration 13.43 +/- 10.04 years), average self-rated health score was 2.30 ('moderate to good'). Symptom burden (composite symptoMScreen score) highly correlated with self-rated health (r = 0.68, P < 0.0001) as did each of the symptoMScreen domain subscores. In regression analysis, pain (t = 7.00), ambulation (t = 6.91), and fatigue (t = 5.85) contributed the highest amount of variance in self-rated health (P < 0.001). CONCLUSIONS: Pain contributed the most to multiple sclerosis outpatients' perception of health, followed by gait dysfunction and fatigue. These findings suggest that 'invisible disability' may be more important to patients' sense of wellbeing than physical disability, and challenge the notion that physical disability should be the primary outcome measure in multiple sclerosis.