EDSS Change Research Articles

Real-life use of oral disease-modifying treatments in Austria.

ObjectivesTo compare the efficacy, frequencies and reasons for treatment interruption of fingolimod, dimethyl fumarate (DMF) or teriflunomide in a nationwide observational cohort using prospectively collected data.Materials and methodsTwo cohorts of patients with relapsing‐remitting multiple sclerosis (RRMS) starting treatment with fingolimod, dimethyl fumarate or teriflunomide documented in the Austrian MS Treatment Registry (AMSTR) since 2014 and either staying on therapy for at least 12 months (12m cohort) or having at least one follow‐up visit (total cohort). The 12m cohort included 664 RRMS patients: 315 in the fingolimod, 232 in the DMF and 117 in the teriflunomide group. Multinomial propensity scores were used for inverse probability weighting to correct for the bias of this non‐randomised registry study.ResultsEstimated mean annualized relapse rates (ARR) over 12 months were 0.21 for fingolimod, 0.20 for DMF and 0.19 for teriflunomide treatment, causing an incidence rate ratio (IRR) of 1.01 for fingolimod vs DMF (P = 0.96) and 0.92 for teriflunomide vs DMF (P = 0.84). No differences were found regarding the probability for experiencing a relapse, EDSS change, EDSS progression and EDSS regression, except regarding less sustained EDSS progression for 12 weeks concerning DMF vs fingolimod (P = 0.02). The hazard ratio for treatment interruption comparing fingolimod vs DMF was 1.03 (P = 0.86) and 1.07 comparing teriflunomide vs DMF (P = 0.77).ConclusionsIn the AMSTR, there was no difference concerning ARR, probability for a relapse, EDSS change, treatment interruption, EDSS progression or regression between oral DMTs, except regarding less sustained EDSS progression for 12 weeks concerning DMF vs fingolimod.

PACTRIMS 2018

Background: In CARE-MS II (NCT00548405), 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months [M] later: 3 days) significantly improved clinical/MRI outcomes versus SC IFNB-1a over 2 years (y) in RRMS patients with inadequate response to prior therapy. Efficacy was maintained in a 4-y extension (NCT00930553), wherein patients could receive additional alemtuzumab (12 mg/day; 3 days; ⩾12M apart) as needed for disease activity or other disease-modifying therapy (DMT). Patients could continue in an additional 5-y extension (TOPAZ; NCT02255656). Aims: To evaluate 8-y efficacy/safety of alemtuzumab in CARE-MS II patients. Methods: At investigator’s discretion, patients in TOPAZ can receive as-needed additional alemtuzumab (⩾12M apart; no criteria) or other DMT (any time). Results: 300/435 (69%) patients completed TOPAZ Y2 (Y8 after initiating alemtuzumab); 44% received neither additional alemtuzumab nor another DMT. At Y8, annualised relapse rate was 0.18, 85% were relapse-free, 70% had stable/improved EDSS versus baseline, and mean EDSS change was 0.17. Through Y8, 64% were free of 6-month confirmed disability worsening, and 47% achieved 6-month confirmed disability improvement. In Y8, 58% achieved no evidence of disease activity, and 70% were free of MRI disease activity. Median percent brain volume loss (BVL) from baseline through Y8 was –1.06%; BVL was –0.19% or less annually in Y3–8. Safety remained consistent through Y8, with no new immune thrombocytopenia or nephropathy cases. Conclusion: Efficacy of alemtuzumab on clinical, MRI, and BVL outcomes was maintained through Y8 in absence of continuous treatment in CARE-MS II patients, with a consistent and manageable safety profile.

A Comparison Study of Efficacy and Safety of a Biosimilar Form of Intramuscular Βeta-interferon I-a Versus the Reference Product: A Randomized Controlled Clinical Trial in Iran.

We compared the efficacy and safety of a biosimilar form of beta-interferon-1a (Actovex) versus the reference product in the treatment of relapsing remitting multiple sclerosis (RRMS). In a double blind, randomized phase 3 clinical trial, we evaluated 138 patients with RRMS that were allocated to receive the biosimilar medication and the reference treatment (30 μg intramuscular, weekly for one year). We investigated changes in EDSS, relapse rate and MRI changes within one year. In sixty-nine patients who were allocated to each arm and analyzed mean age and its standard deviation was 32.4 ± 8.8 and 31.5 ± 8 for the biosimilar medication and the reference arm respectively. One-year follow-up revealed a mean difference of 0.084 in EDSS (95% CI: 0.069-0.237) between the two groups in favor of the biosimilar medication. This value did not exceed the predefined non-inferiority margin of 0.1. There were no statistically significant differences in relapse rate and systemic and local adverse events of the two groups. The results show that the biosimilar interferon 1-a is non-inferior to the reference product in terms of efficacy while it demonstrates comparable safety. In conclusion the biosimilar interferon 1-a can be considered as an effective and safe alternative to the reference product due to lower cost and more availability.

LACTRIMS 2018

Background: In CARE-MS II (NCT00548405), alemtuzumab (two courses; 12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved outcomes versus subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis (RRMS) patients with inadequate response to prior therapy. In a 4-year extension (NCT00930553), patients could receive additional alemtuzumab courses (12 mg/day on 3 days; at least 12 months apart) as needed for disease activity or receive another disease-modifying therapy (DMT; investigator discretion); efficacy was maintained with 50% receiving no additional alemtuzumab or DMT through Year 6. Following this extension, patients could continue in TOPAZ (NCT02255656), an additional 5-year extension. Objectives: Evaluate alemtuzumab efficacy/safety through Year 8 in CARE-MS II patients. Methods: In TOPAZ, patients can receive as-needed alemtuzumab (at least 12 months apart) or receive another DMT. Results: 300/435 (69%) patients completed TOPAZ Year 2 (Year 8 post-alemtuzumab); 44% received neither additional alemtuzumab nor another DMT. In Year 8, annualized relapse rate was 0.18; 85% were relapse-free. From baseline through Year 8, 70% had stable/improved EDSS, mean change in EDSS was +0.17, 64% were free from 6-month confirmed disability worsening, and 47% achieved 6-month confirmed disability improvement. In Year 8, 70% were free of magnetic resonance imaging (MRI) disease activity; 58% achieved no evidence of disease activity. Median percent cumulative brain volume loss from baseline through Year 8 was −1.06%. Safety remained consistent through Year 8. Conclusion: Alemtuzumab efficacy and safety were maintained through Year 8 in the absence of continuous treatment, with 69% of patients completing Year 8 post-alemtuzumab and 44% receiving no additional treatment after the initial two courses.

Atrophied Brain Lesion Volume: A New Imaging Biomarker in Multiple Sclerosis.

Lesion accrual in multiple sclerosis (MS) is an important and clinically relevant measure, used extensively as an imaging trial endpoint. However, lesions may also shrink or disappear entirely due to atrophy. Although generally ignored or treated as a nuisance, this phenomenon may actually be an important stand-alone imaging biomarker. Therefore, we investigated the rate of brain lesion loss due to atrophy (atrophied lesion volume) in MS subtypes compared to baseline lesion volume and to new and enlarging lesion volumes, and evaluated the independent predictive value of this phenomenon for clinical disability. A total of 192 patients (18 clinically isolated syndrome, 126 relapsing-remitting MS, and 48 progressive) received 3T magnetic resonance imaging at baseline and 5 years. Lesions were quantified at baseline, and new/enlarging lesion volumes were calculated over the study interval. Atrophied lesion volume was calculated by combining baseline lesion masks with follow-up SIENAX-derived cerebrospinal fluid partial volume maps. Measures were compared between disease subgroups, and correlations with disability change (Expanded Disability Status Scale [EDSS]) were evaluated. Hierarchical regression was employed to determine the unique additive value of atrophied lesion volume. Atrophied lesion volume was different between MS subtypes (P = .02), and exceeded new lesion volume accumulation in progressive MS (298.1 vs. 75.5 mm3 ). Atrophied lesion volume was the only significant correlate of EDSS change (r = .192 relapsing, r = .317 progressive, P < .05), and explained significant additional variance when controlling for brain atrophy and new/enlarging lesion volume (R2 .092 vs. .045, P = .003). Atrophied lesion volume is a unique and clinically relevant imaging marker in MS, with particular promise in progressive MS.

Cognitive dysfunction and the progression of neurodegenerative process in patients with multiple sclerosis

Neurodegeneration (ND) is the basis of the gradual increase in neurological deficit and cognitive impairment in patients with multiple sclerosis (MS). Morphometry of the brain is the method for monitoring of ND. The possibility of using neuropsychological tests for this purpose is being actively discussed. To examine the effect of treatment with interferon beta-1b (IFNb-1b) on the development of the neurodegenerative process according to morphometry and cognitive testing. Twenty-three patients with relapsing-remitting MS were examined. The control group included 10 healthy people. All patients received IFNb-1b in a dose of 9.6 million IU. EDSS, MSFC, depression and anxiety Beck test, Wechsler test, magnetic resonance imaging (MRI) of the brain, voxel morphometry with FreeSurfer 5.3 were used. The EDSS score was 4.0 before treatment. In MS patients, MSFC and Wechsler scores were worse in comparison with similar indicators of the control group. Deterioration of neurological status, motor function test and PASAT during exacerbation was identified in 7 patients. Morphometry revealed the increase in hypointense white matter lesions (HWML) (p<0.05) in patients with MS. There was a downward trend in the cortical and subcortical gray matter volume and the increase in ventricular volume. A direct correlation between the amount of HWML and the degree of disability on EDSS scale (p=0.018), the inverse correlation between HWML and Wechsler test, PASAT (p<0.05) were identified. After a year of therapy, there were no statistically significant changes in motor and cognitive functions and no signs of 'pseudoatrophy'. Morphometric data in MS were changed compared to healthy controls. There were correlations between morphometry results, disability and cognitive dysfunction. After a year of IFNb-1b therapy, there were no significant changes in cognitive function and EDSS.

Global loss of myelin water over 5 years in multiple sclerosis normal-appearing white matter

Background: Reduced myelin water fraction (MWF, a marker for myelin), increased geometric mean T2 (ieGMT2, reflecting intra/extracellular water properties), and increased T1 (related to total water content) have been observed in cross-sectional studies of multiple sclerosis (MS) normal-appearing white matter (NAWM). Objective: To assess longitudinal changes of magnetic resonance (MR) measures in relapsing-remitting MS (RRMS) brain NAWM. Methods: A total of 11 subjects with RRMS and 4 controls were scanned on a 3T MRI at baseline and long-term follow-up (LTFU; 3.2–5.8 years) with a 32-echo T2 relaxation and an inversion recovery T1 sequence. For every voxel, MWF, ieGMT2, and T1 were obtained. Mean, peak height, and peak location from NAWM mask-based histograms were determined. Results: In MS subjects, NAWM MWF mean decreased by 8% (p = 0.0016). No longitudinal changes were measured in T1 or ieGMT2. There was no relationship between change in any MR metric and change in EDSS. Control white matter showed no differences over time in any metric. Conclusion: The decreases we observed in MWF suggest that changes in myelin integrity and loss of myelin may be occurring diffusely and over long time periods in the MS brain. The timescale of these changes indicates that chronic, progressive myelin damage is an evolving process occurring over many years.

Sodium intake and multiple sclerosis activity and progression in BENEFIT.

To assess whether a high-salt diet, as measured by urinary sodium concentration, is associated with faster conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and MS activity and disability. BENEFIT was a randomized clinical trial comparing early versus delayed interferon beta-1b treatment in 465 patients with a CIS. Each patient provided a median of 14 (interquartile range = 13-16) spot urine samples throughout the 5-year follow-up. We estimated 24-hour urine sodium excretion level at each time point using the Tanaka equations, and assessed whether sodium levels estimated from the cumulative average of the repeated measures were associated with clinical (conversion to MS, Expanded Disability Status Scale [EDSS]) and magnetic resonance imaging (MRI) outcomes. Average 24-hour urine sodium levels were not associated with conversion to clinically definite MS over the 5-year follow-up (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.67-1.24 per 1g increase in estimated daily sodium intake), nor were they associated with clinical or MRI outcomes (new active lesions after 6 months: HR = 1.05, 95% CI = 0.97-1.13; relative change in T2 lesion volume: -0.11, 95% CI = -0.25 to 0.04; change in EDSS: -0.01, 95% CI = -0.09 to 0.08; relapse rate: HR = 0.78, 95% CI = 0.56-1.07). Results were similar in categorical analyses using quintiles. Our results, based on multiple assessments of urine sodium excretion over 5 years and standardized clinical and MRI follow-up, suggest that salt intake does not influence MS disease course or activity. Ann Neurol 2017;82:20-29.

Cerebellar volume as imaging outcome in progressive multiple sclerosis.

Background and purposeTo assess whether cerebellar volumes changes could represent a sensitive outcome measure in primary-progressive MS.Material and methodsChanges in cerebellar volumes over one-year follow-up, estimated in 26 primary-progressive MS patients and 20 controls with Freesurfer longitudinal pipeline, were assessed using Wilcoxon test and tested for their correlation with disability worsening by a logistic regression. Clinical worsening was defined as EDSS score increase or change of >20% for 25-foot walk test or 9-hole peg test scores at follow-up. Sample sizes for given treatment effects and power were calculated. The findings were validated in an independent cohort of 20 primary-progressive MS patients.ResultsSignificant changes were detected in brain T1 lesion volume (p<0.01), cerebellar T2 and T1 lesion volume (p<0.01 and p<0.05), cerebellar volume, cerebellar cortex volume, and cerebellar WM volume (p<0.001). Only cerebellar volume and cerebellar cortex volume percentage change were significantly reduced in clinically progressed patients when compared to patients who did not progress (p<0.01; respectively AUC of 0.91 and 0.96). Cerebellar volume percentage changes were consistent in the exploration and validation cohorts (cerebellar volume -1.90±1.11% vs -1.47±2.30%; cerebellar cortex volume -1.68±1.41% vs -1.56±2.23%). Based on our results the numbers of patients required to detect a 30% effect are 81 per arm for cerebellar volume and 162 per arm for cerebellar cortex volume (90% power, type 1 error alpha = 0.05).ConclusionsOur results suggest a role for cerebellar cortex volume and cerebellar volume as potential short-term imaging metrics to monitor treatment effect in primary-progressive MS clinical trials.

Serum neurofilament is associated with progression of brain atrophy and disability in early MS.

To investigate a potential effect of riluzole on serum neurofilaments (Nf) compared to placebo and the relationship between longitudinal clinical and MRI outcomes and serum Nf levels. Serum samples were obtained from participants enrolled in a randomized double-blind trial of neuroprotection with riluzole vs placebo as an add-on to weekly interferon-β (IFN-β)-1a IM initiated 3 months after randomization. Nf measurements were performed by ELISA and electrochemiluminescence immunoassay. Longitudinal serum samples were available from 22 riluzole and 20 placebo participants over 24 months. There was no observed treatment effect with riluzole. Nf light chain (NfL) levels decreased over time (p = 0.007 at 24 months), whereas the Nf heavy chain was unchanged (p = 0.997). Changes in NfL were correlated with EDSS change (p = 0.009) and neuropsychological outcomes. Brain volume decreased more rapidly in patients with high baseline NfL (p = 0.05 at 12 months and p = 0.008 at 24 months) and this relationship became stronger at 24 months (p = 0.024 for interaction). Higher and increasing NfL predicted higher number of gadolinium-enhancing lesions (p < 0.001 for both). Our findings support the potential value of serum NfL as a marker of neuroaxonal injury in early multiple sclerosis. Its reduction over time could represent regression to the mean, or a possible treatment effect of IFN-β-1a. The association with whole brain atrophy and the formation of acute white matter lesions has relevant implications to use serum NfL as a noninvasive biomarker of the overall consequences of brain damage and ongoing disease activity. NCT00501943.

Decreased interferon-β induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis.

Interferon-β (IFN-β) is used in the treatment of multiple sclerosis (MS). IFN-β activation of signal transduction and activation of transcription (STAT)-4 is linked to its immunomodulatory effects. Previous studies suggest a type I IFN deficit in immune cells of patients MS, but data on interferon-α/β receptor (IFNAR) expression and the relationship with treatment response are conflicting. Here, we compare IFN-β-mediated STAT4 activation in immune cells of untreated patients with MS and controls. Peripheral blood mononuclear cells from 27 untreated patients with relapsing MS, obtained before the initiation of IFN-β treatment, and 12 matched controls were treated in vitro with IFN-β. Total and phosphorylated STAT4 (pSTAT4) and IFNAR were measured by flow cytometry and quantitative PCR. The patients were followed up for 5years. pSTAT4 induction by IFN-β was lower in patients with MS than in controls, as was expression of IFNAR. pSTAT4 expression did not correlate with the clinical outcome at 5years, measured by EDSS change. There was a negative correlation between the baseline IFNAR1 mRNA levels and relapse rate. The results suggest decreased IFN-β responsiveness in patients with MS, associated with reduced STAT4 activation and reduced IFNAR expression. This reduced responsiveness does not appear to affect the long-term clinical outcome of IFN-β treatment.

ANALYSIS OF THE COURSE OF PREGNANCY, DELIVERY AND POSTPARTUM PERIOD IN WOMEN WITH MULTIPLE SCLEROSIS

Актуальность. В связи с высокой распространенностью рассеянного склероза среди женщин репродуктивного возраста вопросам ведения беременности у таких пациенток уделяется особое внимание.

Specific clinical phenotypes in relapsing multiple sclerosis: The impact of relapses on long-term outcomes

ObjectiveThe impact of relapses on the disease course of relapsing MS remains to be determined. This study aims to identify and characterize clinical phenotypes of relapse onset MS in a longitudinally studied cohort. MethodsWe recorded the clinical course of MS during the first decade of disease, using five-year epochs. Patients were stratified as: no worsening due to relapse or secondary progression (type A), relapse with worsening seen without secondary progression (type B), secondary progression with no worsening due to relapse (type C), worsening due to relapses mixed with secondary progression (type D). ResultsOf 176 patients followed from diagnosis for 12.62±4.18 years, 93.2% (164/176) had increased disability in their first 5-year epoch of MS and 52.2% (72/138) in the next. The phenotypes significantly differed by EDSS change during each epoch (p<0.001), final confirmed MSSS (p≤0.002) and relapse rate (p<0.001). Type D fared worse than others by change in EDSS and MSSS. ConclusionWe identified multiple specific phenotypes of MS and temporal shifts between phenotypes according to relapse type and progression.

Disease phenotype analyses of relapsing-remitting multiple sclerosis in Canada and Saudi Arabia

Background: Multiple sclerosis (MS) exhibits a spectrum of clinical findings, especially in relapsing-remitting MS (RR-MS). To assess the effects of geographic location and ethnicity on RR-MS phenotype, we investigated RR-MS patients in Canada and Saudi Arabia. Methods: A retrospective cross-sectional analysis of patients receiving active care in MS Clinics was performed in Medina, Saudi Arabia and Edmonton, Alberta. Demographic and clinical data was collected for each patient. Results: 98 patients with treated RR-MS were recruited (n=51, Medina; n=47, Edmonton); 40 patients were Caucasian (Edmonton) while 46 patients were Bedouin (Medina). Although the disease duration was longer in the Edmonton (5.7+2.3 yr) compared to the Medina group (4.4+1.4 yr) (p&lt;0.05), the mean age of RR-MS onset, relapse rate and EDSS change were similar. The female:male ratio was comparable in Edmonton (35:12) and Medina (32:19), as was the risk of optic neuritis. The likelihood of an infratentorial lesion-associated presentation differed (Edmonton, n=23; Medina; n=13) among groups (p&lt;0.05). Spinal cord lesions on MRI were more frequent in Edmonton (n=18) compared to Medina (n=1) patients (p&lt;0.05). Conclusions: Despite differences in location, ethnicity, and a predominance of infratentorial lesion burden the Edmonton group, the RR-MS phenotype displayed similar disease severity and trajectory in these cohorts.

RESPONSIVENESS OF MSMSS IN PROGRESSIVE MULTIPLE SCLEROSIS

<h3>Background</h3> The search for treatments of progressive multiple sclerosis (PMS) necessitates meaningful markers of disease progression for clinical trials. <h3>Aim</h3> We investigated the responsiveness of the MS Muscle Strength scale (MSMSS), a recently developed physician-based instrument, to determine its value as outcome measure in PMS. <h3>Methods</h3> 54 pwPMS (SPMS=45/PPMS=9) were examined using the MSMSS and again &gt;12 months. Group-level and individual-level indices of change were calculated using Rasch-derived estimates. Change in EDSS was used as external criterion of disability progression. <h3>Results</h3> Between examinations, the sample lost strength (mean change in Rasch-derived estimate −0.88 logits; SD 1.08) and became more disabled (mean increase in EDSS 0.20 points; SD 0.56). Group-level indices of change were greater for the MSMSS than the EDSS (ES 0.59 vs 0.17; SRM 0.81 vs 0.36). Paired t-tests were significant for both MSMSS (p&lt;0.001) and EDSS (p=0.013). Guyatt9s responsiveness index for the MSMSS was moderate (0.73). Individual-level loss of strength reached statistical significance in 46% of the group. <h3>Conclusions</h3> The MSMSS was more sensitive to changes occurring within this sample than the EDSS. This finding supports use of the MSMSS as marker for disease severity in clinical trials and epidemiological studies in PMS.

Does Lipoic Acid Consumption Affect the Cytokine Profile in Multiple Sclerosis Patients: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Background: A limited amount of data exists regarding the effect of lipoic acid (LA), an oral antioxidant supplement, on cytokine profiles among multiple sclerosis (MS) patients. Objective: We aimed to assess the effect of daily consumption of LA on the cytokine profiles in MS patients. Methods: In this double-blind, placebo-controlled, randomized clinical trial, 52 relapsing-remitting MS patients with an age range of 18-50 years were recruited into 2 groups: LA consumption (1,200 mg/day) or placebo. Patients followed their prescribed supplements for 12 weeks. Fasting blood samples for cytokine profile measurement were collected at baseline and after the intervention. Anthropometric parameters were measured based on the standard guidelines. Results: INF-γ, ICAM-1, TGF-β and IL-4 were significantly reduced in the LA group compared to the placebo group [(INF-γ: 0.82 ± 0.2 vs. 0.2 ± 0.2 pg/ml, p < 0.0001), (ICAM-1: 20.2 ± 9.4 vs. 8 ± 10 ng/ml, p = 0.0001), (TGF-β: 103.1 ± 20.2 vs. 54.9 ± 26 ng/ml, p < 0.0001) and (IL-4: 0.1 ± 0.1 vs. 1.02 ± 1.7 ng/ml, p = 0.0112)]. No significant changes in TNF-α, IL-6, EDSS and MMP-9 were found between the LA and placebo groups (p = 0.6, p = 0.8, p = 0.09 and p = 0.8, respectively). Conclusion: The results suggested that consumption of 1,200 mg LA per day beneficially affects several inflammatory cytokines including INF-γ, ICAM-1 TGF-β and IL-4. Further investigations are needed to verify the beneficial role of LA on other cytokine profiles among MS patients.

Validating predictors of disease progression in a large cohort of primary-progressive multiple sclerosis based on a systematic literature review.

BackgroundNew agents with neuroprotective or neuroregenerative potential might be explored in primary-progressive Multiple Sclerosis (PPMS) - the MS disease course with leading neurodegenerative pathology. Identification of patients with a high short-term risk for progression may minimize study duration and sample size. Cohort studies reported several variables as predictors of EDSS disability progression but findings were partially contradictory.ObjectiveTo analyse the impact of published predictors on EDSS disease progression in a large cohort of PPMS patients.MethodsA systematic literature research was performed to identify predictors for disease progression in PPMS. Individual case data from the Sylvia Lawry Centre (SLC) and the Hamburg MS patient database (HAPIMS) was pooled for a retrospective validation of these predictors on the annualized EDSS change.ResultsThe systematic literature analysis revealed heterogeneous data from 3 prospective and 5 retrospective natural history cohort studies. Age at onset, gender, type of first symptoms and early EDSS changes were available for validation. Our pooled cohort of 597 PPMS patients (54% female) had a mean follow-up of 4.4 years and mean change of EDSS of 0.35 per year based on 2503 EDSS assessments. There was no significant association between the investigated variables and the EDSS-change.ConclusionNone of the analysed variables were predictive for the disease progression measured by the annualized EDSS change. Whether PPMS is still unpredictable or our results may be due to limitations of cohort assessments or selection of predictors cannot be answered. Large systematic prospective studies with new endpoints are needed.

Use of fingolimod in patients with relapsing remitting multiple sclerosis in Kuwait

BackgroundPost-marketing studies are important to confirm what was established in clinical trials, and to assess the intermediate and long-term efficacy and safety. ObjectiveTo assess efficacy and safety of fingolimod in multiple sclerosis (MS) in Kuwait. MethodsWe retrospectively evaluated MS patients using the MS registries in 3 MS clinics. Relapsing remitting MS patients according to revised 2010 McDonald criteria who had been treated with fingolimod for at least 12 months were included. Primary endpoint was proportion of relapse-free patients at last follow-up. Secondary endpoints were mean change in EDSS and proportion of patients with MRI activity (gadolinium-enhancing or new/enlarging T2 lesions). Results76 patients met the inclusion criteria. Mean age and mean disease duration were 34.43 and 7.82 years respectively. Mean duration of exposure to fingolimod was 18.50 months. Proportion of relapse-free patients was 77.6% at last follow-up. Mean EDSS score significantly improved (2.93 versus 1.95; p<0.0001) while 17.1% of patients continued to have MRI activity versus 77.6% at baseline (p<0.0001). Four patients stopped fingolimod due to disease breakthrough (n=3) and lymphadenitis (n=1). ConclusionFingolimod is safe and effective in reducing clinical and radiological disease activity in relapsing remitting MS patients. Our results are comparable to reported results of phase III studies.

Clinical course in multiple sclerosis patients presenting with a history of progressive disease

ObjectivesDetermine the likelihood of worsening clinical status in the near-term course of progressive MS and evaluate the predictive validity of our diagnostic impression of progressive forms of MS. MethodsRetrospective review of charts from 175 patients seen between 2000 and 2007 who were diagnosed with either primary or secondary progressive multiple sclerosis. Data extracted included demographic factors, neurological examination findings to determine EDSS, timed 25 foot walk (T25FW) when available, duration of symptoms, clinical course as documented on initial visit, and history of disease-modifying agent (DMA) use. Significant change in EDSS was defined as a change of one point or more from initial to final clinical evaluation. Significant change in T25FW was defined as a ±20% difference from baseline. ResultsOf the 175 charts reviewed, 35 patients met criteria and had sufficient documentation to allow for EDSS abstraction. Twenty-four patients (68.6%) showed no significant change in EDSS from baseline while eleven patients (31.4%) worsened and none improved. For those patients that had T25FW data available, 6 out of 20 (30%) patients worsened while 11 (55%) showed no change. Three patients (15%) improved. ConclusionIn this observational study at a tertiary care MS center, patients classified as progressive MS did not progress as often, or as rapidly, as previous studies have suggested. Greater than two-thirds of patients in this cohort, did not increase 1 step on the EDSS.

Predictive value of health-related quality of life in progression of disability and depression in persons with multiple sclerosis: a 3-year study

In our study, we examined whether health-related quality of life (HRQoL) could predict changes in disability, depression, and fatigue in patients with multiple sclerosis (MS) over a 3-year follow-up period. A group of 109 consecutive MS patients (McDonald's criteria) referring to the Institute of Neurology, Belgrade were enrolled in the study. At two time points during the study (baseline, and after a 3-year period) an HRQoL (measured by MSQoL-54), EDSS, Hamilton Rating Scale for Depression (HDRS) and Fatigue Severity Scale (FSS) were assessed. At the end of a 3-year follow-up, 12 out of 109 patients (11%) had dropped out. Multiple linear regression analysis showed that Physical Health scale of MSQoL-54 is significant independent predictor of change in EDSS after 3 years (p = 0.035). Mental health composite score of MSQoL-54 was predictor of change in HDRS score (p = 0.049). In separate regression analysis, only social function was independent predictor of the development of depression (p = 0.041). None of the HRQoL domains had predictive effect on the change of FSS. Our study suggests that baseline HRQoL scores, measured by MSQoL-54, could be applied as a prognostic marker for progression of both, disability, and severity of depressive symptoms in MS.