It has been suggested that people in racial/ethnic minority groups are healthier when they live in areas with a higher concentration of people from their own ethnic group, a so-called ethnic density effect. Ethnic density effects are still contested, and the pathways by which ethnic density operates are poorly understood. The aim of this study was to systematically review the literature examining the ethnic density effect on physical health, mortality, and health behaviors. Most studies report a null association between ethnic density and health. Protective ethnic density effects are more common than adverse associations, particularly for health behaviors and among Hispanic people. Limitations of the literature include inadequate adjustment for area deprivation and limited statistical power across ethnic density measures and study samples.

Objective:To understand the efficacy of cladribine (CLAD) treatment in MS through analysis of lymphocyte subsets collected, but not reported, in the pivotal phase III trials of cladribine and alemtuzumab induction therapies.Methods:The regulatory submissions of the CLAD Tablets Treating Multiple Sclerosis Orally (CLARITY) (NCT00213135) cladribine and Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, study one (CARE-MS I) (NCT00530348) alemtuzumab trials were obtained from the European Medicine Agency through Freedom of Information requests. Data were extracted and statistically analyzed.Results:Either dose of cladribine (3.5 mg/kg; 5.25 mg/kg) tested in CLARITY reduced the annualized relapse rate to 0.16–0.18 over 96 weeks, and both doses were similarly effective in reducing the risk of MRI lesions and disability. Surprisingly, however, T-cell depletion was rather modest. Cladribine 3.5 mg/kg depleted CD4+ cells by 40%–45% and CD8+ cells by 15%–30%, whereas alemtuzumab suppressed CD4+ cells by 70%–95% and CD8+ cells by 47%–55%. However, either dose of cladribine induced 70%–90% CD19+ B-cell depletion, similar to alemtuzumab (90%). CD19+ cells slowly repopulated to 15%–25% of baseline before cladribine redosing. However, alemtuzumab induced hyperrepopulation of CD19+ B cells 6–12 months after infusion, which probably forms the substrate for B-cell autoimmunities associated with alemtuzumab.Conclusions:Cladribine induced only modest depletion of T cells, which may not be consistent with a marked influence on MS, based on previous CD4+ T-cell depletion studies. The therapeutic drug-response relationship with cladribine is more consistent with lasting B-cell depletion and, coupled with the success seen with monoclonal CD20+ depletion, suggests that B-cell suppression could be the major direct mechanism of action.

The most consistent associations with ethnic density are found for psychoses. Ethnic density may also protect against other mental disorders, but presently, as most studies of ethnic density have limited statistical power, and given the heterogeneity of their study designs, our conclusions can only be tentative.

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Background:A number of elements of the pivotal ‘cladribine tablets treating multiple sclerosis orally’ (CLARITY) trial have remained unpublished.Objective:To report the impact of cladribine on health-related quality of life (QoL) in people with relapsing multiple sclerosis (pwRMS).Methods:QoL data from the phase III trial of two different doses (3.5 and 5.25 mg/kg) of oral cladribine in pwRMS were acquired from the European Medicines Agency through Freedom of Information. Spearman’s rank correlation was used to analyse the relationship between baseline QoL scores and baseline Expanded Disability Status Scale (EDSS) scores. Responses of the Euro Quality of Life 5 Dimensions (EQ-5D) and Multiple Sclerosis Quality of Life-54 (MSQOL-54) questionnaires were compared between treatment and control groups using univariate analyses of covariance.Results:In total, n = 5148 EQ-5D responses and n = 894 MSQOL-54 physical, mental health and dimension scores were extracted. Baseline EQ-5D indices correlated with EDSS scores. After 2 years, pwRMS taking 3.5 (p = .001) and 5.25 mg/kg (p = .022) reported significantly improved EQ-5D index scores compared with placebo. Positive, yet non-significant, differences were detected in MSQOL-54 scores between cladribine and placebo.Conclusion:Analysis of the CLARITY dataset suggests that, over and above its established clinical efficacy, cladribine leads to improved QoL over 96 weeks. ClinicalTrials.gov identifier: NCT00213135.