Multiple sclerosis in Morocco: Epidemiological, clinical, and therapeutic profile.

OBJECTIVE: This study aims to describe the clinical, therapeutic, and epidemiological profiles of MS patients in Morocco. METHODS: This descriptive study involved 170 patients representing four Morocco regions. We collected the data using an electronic survey. RESULTS: The results show female dominance in patients with MS. Besides, most patients present with relapsing-remitting MS (RRMS). The main clinical symptoms reported by patients are fatigue, cognitive issues, spasticity, bowel or bladder complaints, and visual issues. Furthermore, the findings show that almost half of the patients use Interferon bêta-1a and azathioprine as disease-modifying therapies; 60.5 % use traditional and complementary medicine, of which 30.6 % use cupping, 30 % recite the Holy Quran, and 28.2 % use apitherapy. The findings show that there is a statistically significant relationship between specific MS factors such as professional activity (p = 0.0071), degree of satisfaction with treatment (p = 0.005), stress (p = 0.014), and the frequency of relapses. CONCLUSIONS: In addition to DMT, patients also use traditional and complementary medicine. There is also a relationship between some epidemiological characteristics and the frequency of relapses in patients with MS.

Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: A prospective multicohort study of the ABIRISK consortium.

BACKGROUND: Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited. METHODS AND FINDINGS: The European consortium ABIRISK (Anti-Biopharmaceutical Immunization: prediction and analysis of clinical relevance to minimize the RISK) conducted a clinical and genomic multicohort prospective study of 560 patients with multiple sclerosis (MS, n = 147), rheumatoid arthritis (RA, n = 229), Crohn's disease (n = 148), or ulcerative colitis (n = 36) treated with 8 different biopharmaceuticals (etanercept, n = 84; infliximab, n = 101; adalimumab, n = 153; interferon [IFN]-beta-1a intramuscularly [IM], n = 38; IFN-beta-1a subcutaneously [SC], n = 68; IFN-beta-1b SC, n = 41; rituximab, n = 31; tocilizumab, n = 44) and followed during the first 12 months of therapy for time to ADA development. From the bioclinical data collected, we explored the relationships between patient-related factors and the occurrence of ADAs. Both baseline and time-dependent factors such as concomitant medications were analyzed using Cox proportional hazard regression models. Mean age and disease duration were 35.1 and 0.85 years, respectively, for MS; 54.2 and 3.17 years for RA; and 36.9 and 3.69 years for inflammatory bowel diseases (IBDs). In a multivariate Cox regression model including each of the clinical and genetic factors mentioned hereafter, among the clinical factors, immunosuppressants (adjusted hazard ratio [aHR] = 0.408 [95% confidence interval (CI) 0.253-0.657], p < 0.001) and antibiotics (aHR = 0.121 [0.0437-0.333], p < 0.0001) were independently negatively associated with time to ADA development, whereas infections during the study (aHR = 2.757 [1.616-4.704], p < 0.001) and tobacco smoking (aHR = 2.150 [1.319-3.503], p < 0.01) were positively associated. 351,824 Single-Nucleotide Polymorphisms (SNPs) and 38 imputed Human Leukocyte Antigen (HLA) alleles were analyzed through a genome-wide association study. We found that the HLA-DQA1*05 allele significantly increased the rate of immunogenicity (aHR = 3.9 [1.923-5.976], p < 0.0001 for the homozygotes). Among the 6 genetic variants selected at a 20% false discovery rate (FDR) threshold, the minor allele of rs10508884, which is situated in an intron of the CXCL12 gene, increased the rate of immunogenicity (aHR = 3.804 [2.139-6.764], p < 1 × 10-5 for patients homozygous for the minor allele) and was chosen for validation through a CXCL12 protein enzyme-linked immunosorbent assay (ELISA) on patient serum at baseline before therapy start. CXCL12 protein levels were higher for patients homozygous for the minor allele carrying higher ADA risk (mean: 2,693 pg/ml) than for the other genotypes (mean: 2,317 pg/ml; p = 0.014), and patients with CXCL12 levels above the median in serum were more prone to develop ADAs (aHR = 2.329 [1.106-4.90], p = 0.026). A limitation of the study is the lack of replication; therefore, other studies are required to confirm our findings. CONCLUSION: In our study, we found that immunosuppressants and antibiotics were associated with decreased risk of ADA development, whereas tobacco smoking and infections during the study were associated with increased risk. We found that the HLA-DQA1*05 allele was associated with an increased rate of immunogenicity. Moreover, our results suggest a relationship between CXCL12 production and ADA development independent of the disease, which is consistent with its known function in affinity maturation of antibodies and plasma cell survival. Our findings may help physicians in the management of patients receiving biotherapies.

Informe diário de evidências COVID-19: busca realizada em 22 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 22, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 20 artigos e 10 protocolos.

Informe diário de evidências COVID-19: busca realizada em 17 de junho de 2020 / COVID-19 daily evidence report: search conducted on June 17, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 15 artigos.

Pharmacological treatment other than corticosteroids, intravenous immunoglobulin and plasma exchange for Guillain-Barré syndrome.

BACKGROUND: Plasma exchange and intravenous immunoglobulin, but not corticosteroids, are beneficial in Guillain-Barré syndrome (GBS). The efficacy of other pharmacological agents is unknown. This review was first published in 2011 and previously updated in 2013, and 2016. OBJECTIVES: To assess the effects of pharmacological agents other than plasma exchange, intravenous immunoglobulin and corticosteroids for GBS. SEARCH METHODS: On 28 October 2019, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase for treatments for GBS. We also searched clinical trials registries. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) or quasi-RCTs of acute GBS (within four weeks from onset) of all types and degrees of severity, and in individuals of all ages. We discarded trials that investigated only corticosteroids, intravenous immunoglobulin or plasma exchange. We included other pharmacological treatments or combinations of treatments compared with no treatment, placebo or another treatment. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. MAIN RESULTS: We found six trials of five different interventions eligible for inclusion in this review. The trials were conducted in hospitals in Canada, China, Germany, Japan and the UK, and included 151 participants in total. All trials randomised participants aged 16 years and older (mean or median age in the trials ranged from 36 to 57 years in the intervention groups and 34 to 60 years in the control groups) with severe GBS, defined by the inability to walk unaided. One trial also randomised patients with mild GBS who were still able to walk unaided. We identified two new trials at this update.The primary outcome measure for this review was improvement in disability grade four weeks after randomisation. Four of six trials had a high risk of bias in at least one respect. We assessed all evidence for the outcome mean improvement in disability grade as very low certainty, which means that we were unable to draw any conclusions from the data. One RCT with 19 participants compared interferon beta-1a (IFNb-1a) and placebo. It is uncertain whether IFNb-1a improves disability after four weeks (mean difference (MD) -0.1; 95% CI -1.58 to 1.38; very low-certainty evidence). A trial with 10 participants compared brain-derived neurotrophic factor (BNDF) and placebo. It is uncertain whether BDNF improves disability after four weeks (MD 0.75; 95% CI -1.14 to 2.64; very low-certainty evidence). A trial with 37 participants compared cerebrospinal fluid (CSF) filtration and plasma exchange. It is uncertain whether CSF filtration improves disability after four weeks (MD 0.02; 95% CI -0.62 to 0.66; very low-certainty evidence). One trial that compared the Chinese herbal medicine tripterygium polyglycoside with corticosteroids with 43 participants did not report the risk ratio (RR) for an improvement by one or more disability grade after four weeks, but did report improvement after eight weeks. It is uncertain whether tripterygium polyglycoside improves disability after eight weeks (RR 1.47; 95% CI 1.02 to 2.11; very low-certainty evidence). We performed a meta-analysis of two trials comparing eculizumab and placebo with 41 participants. It is uncertain whether eculizumab improves disability after four weeks (MD -0.23; 95% CI -1.79 to 1.34; very low-certainty evidence). Serious adverse events were uncommon in each of the trials and evidence was graded as either low or very low. It is uncertain whether serious adverse events were more common with IFNb-1a versus placebo (RR 0.92, 95% CI 0.23 to 3.72; 19 participants), BNDF versus placebo (RR 1.00, 95% CI 0.28 to 3.54; 10 participants) or CSF filtration versus plasma exchange (RR 0.13, 95% CI 0.01 to 2.25; 37 participants). The trial of tripterygium polyglycoside did not report serious adverse events. There may be no clear difference in the number of serious adverse events after eculizumab compared to placebo (RR 1.90, 0.34 to 10.50; 41 participants). We found no clinically important differences in any of the outcome measures selected for this review in any of the six trials. However, sample sizes were small and therefore clinically important benefit or harm cannot be excluded. AUTHORS' CONCLUSIONS: All six RCTs were too small to exclude clinically important benefit or harm from the assessed interventions. The certainty of the evidence was low or very low for all interventions and outcomes.

Vitamin D3 supplementation and neurofilament light chain in multiple sclerosis.

OBJECTIVES: Low circulating vitamin D levels are associated with an increased risk of active MRI lesions and relapses in several cohorts with relapsing remitting multiple sclerosis (RRMS). Randomized controlled supplementation trials are, however, negative on their primary endpoints, while secondary MRI endpoints suggest anti-inflammatory effects. Circulating levels of neurofilament light chain (NfL) are a biomarker of disease activity in RRMS. We explored whether 48-week high-dose vitamin D3 supplements were associated with lower circulating NfL levels. MATERIALS & METHODS: Of N = 40 Dutch interferon beta-treated participants with RRMS of the SOLAR trial, plasma samples at baseline and 48-week follow-up were available. Of these participants, N = 24 were supplemented with 14 000 IU/d vitamin D3 and N = 16 with placebo. Twenty-five hydroxyvitamin D3 (25(OH)D3 ) levels were measured with LC-MS/MS, and NfL levels were measured in duplicate with Simoa. RESULTS: Serum 25(OH)D3 levels at 48 weeks were increased in the vitamin D3 when compared to placebo group (median level 281 [IQR 205-330] vs 72 [39-88] nmol/L; P < .01). NfL levels at 48 weeks did not differ between the treatment groups (median level 25.4 [IQR 19.6-32.2] vs 25.3 [17.9-30.1] pg/mL; P = .74). Higher week 48 NfL level showed a trend toward association with a higher risk of combined unique active lesions on the week 48 MRI scan (OR 2.39 [95% CI 0.93-6.12] for each 10 pg/mL increase; P = .07). CONCLUSIONS: Supplementation of high-dose vitamin D3 for 48 weeks was not associated with lower NfL levels. This study does not support an effect of vitamin D3 on this biomarker of neuro-axonal injury.

Randomized trial of daily high-dose vitamin D3 in patients with RRMS receiving subcutaneous interferon ß-1a.

OBJECTIVE: In the phase II, randomized, double-blind, placebo-controlled Supplementation of Vigantol Oil versus Placebo Add-on in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Receiving Rebif Treatment (SOLAR) study (NCT01285401), we assessed the efficacy and safety of add-on vitamin D3 in patients with RRMS. METHODS: Eligible patients with RRMS treated with SC interferon-ß-1a (IFN-ß-1a) 44 µg 3 times weekly and serum 25(OH)D levels <150 nmol/L were included. From February 15, 2011, to May 11, 2015, 229 patients were included and randomized 1:1 to receive SC IFN-ß-1a plus placebo (n = 116) or SC IFN-ß-1a plus oral high-dose vitamin D3 14,007 IU/d (n = 113). The revised primary outcome was the proportion of patients with no evidence of disease activity (NEDA-3) at week 48. RESULTS: At 48 weeks, 36.3% of patients who received high-dose vitamin D3 had NEDA-3, without a statistically significant difference in NEDA-3 status between groups (placebo 35.3%; odds ratio 0.93; 95% confidence interval [CI] 0.53-1.63; p = 0.80). Compared with placebo, the high-dose vitamin D3 group had better MRI outcomes for combined unique active lesions (incidence rate ratio 0.68; 95% CI 0.52-0.89; p = 0.0045) and change from baseline in total volume of T2 lesions (difference in mean ranks: -0.074; p = 0.035). CONCLUSIONS: SOLAR did not establish a benefit for high-dose vitamin D3 as add-on to IFN-ß-1a, based on the primary outcome of NEDA-3, but findings from exploratory outcomes suggest protective effects on development of new MRI lesions in patients with RRMS. CLINICALTRIALSGOV IDENTIFIER: NCT01285401. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS treated with SC IFN-ß-1a, 48 weeks of cholecalciferol supplementation did not promote NEDA-3 status.

Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE).

OBJECTIVE: To evaluate the safety and efficacy of cholecalciferol in patients with relapsing-remitting MS (RRMS). METHODS: In this double-blind, placebo-controlled parallel-group, 2-year study, 181 patients with RRMS were randomized 1:1. Key inclusion criteria were a low serum 25-hydroxy vitamin D (25OHD) concentration (<75 nmol/L), a treatment with interferon beta-1a 44 µg (SC 3 times per week) 4 months ± 2 months before randomization, and at least one documented relapse during the previous 2 years. Patients received high-dose oral cholecalciferol 100,000 IU or placebo every other week for 96 weeks. Primary outcome measure was the change in the annualized relapse rate (ARR) at 96 weeks. Secondary objectives included safety and tolerability of cholecalciferol and efficacy assessments (ARR, MRI parameters, and Expanded Disability Status Scale [EDSS]). RESULTS: The primary end point was not met. In patients who completed the 2-year follow-up (45 with cholecalciferol and 45 with placebo), all efficacy parameters favored cholecalciferol with an ARR reduction (p = 0.012), less new hypointense T1-weighted lesions (p = 0.025), a lower volume of hypointense T1-weighted lesions (p = 0.031), and a lower progression of EDSS (p = 0.026). The overall rate of adverse events was well balanced between groups. CONCLUSIONS: Although the primary end point was not met, these data suggest a potential treatment effect of cholecalciferol in patients with RRMS already treated with interferon beta-1a and low serum 25OHD concentration. Together with the good safety profile, these data support the exploration of cholecalciferol treatment in such patients with RRMS. CLINICALTRIALSGOV IDENTIFIER: NCT01198132. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS and low serum 25OHD, cholecalciferol did not significantly affect ARRs.

Combination therapy with interferon beta-1a and sesame oil in multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Several effector mechanisms are involved in the immunopathology of MS and a variety of medications such as beta interferons are applied to treat the disease. This study was conducted to evaluate the anti-inflammatory and immunomodulatory effects of sesame oil in combination with interferon beta-1a in MS treatment. METHODS: Ninety-three MS patients were enrolled in the study. The patients were randomly divided into two groups. The control group (n = 39) received 30 µg/week of interferon beta-1a intra-muscularly. The sesame oil-treated group (n = 54) received interferon beta-1a the same as the control group with the addition of 0.5 ml/kg/day of oral sesame oil for 6 months. RESULTS: After the 6-month study period, the interleukin (IL)-10 concentration in the sesame oil-treated group was significantly greater than that of the control group (p = 0.04). The concentrations of interferon-γ (IFN-γ), nitric oxide (NO), and tumor necrosis factor-α (TNF-α) in the sesame oil group after treatment were significantly less than those of the control group (p = 0.029, p = 0.0001, and p = 0.01, respectively). Lymphocyte proliferation in the sesame oil-treated group was significantly lower at the end of the study than at the beginning (p = 0.001). CONCLUSION: Sesame oil, through a decrease in IFN-γ secretion and anti-inflammatory and anti-oxidant activities, may have beneficial effects for MS patients.

The Assessment for Disinvestment of Intramuscular Interferon Beta for Relapsing-Remitting Multiple Sclerosis in Brazil.

In Brazil, inclusion and exclusion of health technologies within the Unified Health System (SUS) is the responsibility of the National Committee for Health Technology Incorporation (CONITEC). A recent Cochrane systematic review demonstrated that intramuscular interferon beta 1a (IFN-ß-1a-IM) was inferior to the other beta interferons (IFN-ßs) for multiple sclerosis (MS). As a result, CONITEC commissioned an analysis to review possible disinvestment within SUS. The objective of this paper is to describe the disinvestment process for IFN-ß-1a-IM in Brazil. The first assessment comprised a literature review and mixed treatment comparison meta-analysis. The outcome of interest was the proportion of relapse-free patients in 2 years. This analysis confirmed the inferiority of IFN-ß-1a-IM. Following this, CONITEC recommended disinvestment, with the decision sent for public consultation. More than 3000 contributions were made on CONITEC's webpage, most of them against the preliminary decision. As a result, CONITEC commissioned a study to assess the effectiveness of IFN-ß-1a-IM among Brazilian patients in routine clinical care. The second assessment involved an 11-year follow-up of a non-concurrent cohort of 12,154 MS patients developed by deterministic-probabilistic linkage of SUS administrative databases. The real-world assessment further demonstrated that IFN-ß-1a-IM users had a statistically higher risk of treatment failure, defined as treatment switching or relapse treatment or death, with the assessment showing that IFN-ß-1a-IM was inferior to the other IFN-ßs and to glatiramer acetate in both direct and indirect analysis. In the drug ranking with 40,000 simulations, IFN-ß-1a-IM was the worst option, with a success rate of only 152/40,000. Following this, CONITEC decided to exclude the intramuscular presentation of IFN-ß from the current MS treatment guidelines, giving patients who are currently on this treatment the option of continuing until treatment failure. In conclusion, we believe this is the first example of this new disinvestment process in action, providing an exemplar for other treatments in Brazil as well as other countries.

Pharmacological treatment other than corticosteroids, intravenous immunoglobulin and plasma exchange for Guillain-Barré syndrome.

BACKGROUND: Plasma exchange and intravenous immunoglobulin, but not corticosteroids, are beneficial in Guillain-Barré syndrome (GBS). The efficacy of other pharmacological agents is unknown. This review was first published in 2011 and updated in 2013 and 2016. OBJECTIVES: To assess the effects of pharmacological agents other than plasma exchange, intravenous immunoglobulin and corticosteroids for GBS. SEARCH METHODS: On 18 January 2016, we searched the Cochrane Neuromuscular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for treatments for GBS. We also searched clinical trials registries. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) or quasi-RCTs of acute GBS (within four weeks from onset) of all types and degrees of severity, and in individuals of all ages. We discarded trials that investigated only corticosteroids, intravenous immunoglobulin or plasma exchange. We included other pharmacological treatments or combinations of treatments compared with no treatment, placebo or another treatment. We also identified a number of non-randomised studies during the search, the results of which we considered in the Discussion. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. MAIN RESULTS: We identified no new trials during this update of the review. In previous versions of this review we identified only very low quality evidence for four different interventions published in four studies. Each study had a high risk of bias in at least one respect. One RCT with 19 participants comparing interferon beta-1a and placebo showed no clinically important difference in any outcome between groups. Another with 10 participants comparing brain-derived neurotrophic factor and placebo showed no clinically important difference in any outcome between groups. A third with 37 participants comparing cerebrospinal fluid filtration and plasma exchange also showed no clinically important difference in any outcome between groups. In a fourth with 43 participants, the risk ratio for an improvement by one or more disability grade after eight weeks was greater with the Chinese herbal medicine tripterygium polyglycoside than with corticosteroids (risk ratio 1.47; 95% confidence interval 1.02 to 2.11); other outcomes in this trial showed no difference. Serious adverse events were uncommon with each of these treatments and in the control groups. AUTHORS' CONCLUSIONS: The quality of the evidence was very low. Three small RCTs, comparing interferon beta-1a or brain-derived neurotrophic factor with placebo, and cerebrospinal fluid filtration with plasma exchange, showed no significant benefit or harm for any of the interventions. A fourth small trial showed that the Chinese herbal medicine, tripterygium polyglycoside, hastened recovery in people with GBS to a greater extent than corticosteroids, but this result needs confirmation. We were unable to draw any useful conclusions from the few observational studies we identified.

Multiple sclerosis influences on the augmentation of serum Klotho concentration.

We have already shown that the concentration of secreted form of Klotho decreases in the cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis (RRMS). The current study aimed at assessing possible changes in the serum Klotho concentration of MS patients. Participants involved 15 new cases of RRMS patients in the relapse phase, 15 RRMS patients who had been suffering from the disease for more than three years and were under regular treatments (interferon beta-1a) and, finally, 15 non-MS patients who constituted the control group. Beside thorough neurological examinations, demographic and clinical data (e.g. gender, age, duration of disease and expanded disability status scale) were obtained. Serum Klotho concentration was measured using ELISA method. The results showed no statistically meaningful difference between new cases of RRMS (585.56pg/ml±153.99) and control group (556.81pg/ml±120.36; P=0.859). The serum Klotho level, however, was significantly higher in patients with prolonged disease duration (696.94pg/ml±170.52; P=0.037) in comparison with the subjects in the control group. In conclusion, this study showed that serum Klotho concentration tends to be higher in MS patients when compared to control group. This finding might be attributed to treatment of MS patients with immunomodulatory drugs or a compensatory response to enhance CNS regeneration and/or vitamin D biosynthesis. Further studies are required to elucidate the role of Klotho in MS pathophysiology.

The Effect of Vitamin A Supplementation on FoxP3 and TGF-ß Gene Expression in Avonex-Treated Multiple Sclerosis Patients.

Multiple sclerosis (MS) is an autoinflammatory condition of the central nervous system with impaired T helper (Th)17 and regulatory T cell (Treg) balance that is involved in disease immunopathogenesis. The vitamin A active metabolite, retinoic acid, can re-establish this imbalance through the modulation of gene expression of specific nuclear receptors including Forkhead box P3 (FoxP3). At present, few data exist on the impact of vitamin A supplementation on T cell balance. This study reports the results of a clinical trial, over a 6-month period, of 36 relapsing-remitting MS (RRMS) patients that received vitamin A (25,000 IU retinyl palmitate) or placebo (one capsule of placebo per day). Peripheral blood mononuclear cells were isolated from patients, and the expression of FoxP3 and transforming growth factor (TGF)-ß gene expression was measured using real-time PCR at the beginning and end of the study. The results of this study showed that vitamin A upregulated TGF-ß and FoxP3 gene expression. Therefore, vitamin A supplementation can be considered as a new approach in MS prevention and treatment.