Oral contraceptives and MS disease activity in a contemporary real-world cohort.

BACKGROUND: There is uncertainty regarding the effect of oral hormonal contraceptives (OC) on multiple sclerosis (MS) course. OBJECTIVE: To evaluate the hypothesis that OC use is associated with decreased risk of relapses in an observational study of women of childbearing age with new-onset MS starting a first-line injectable disease-modifying therapy (DMT). METHODS: From our CLIMB longitudinal observational study, we identified 162 women with MS or CIS with known OC use who initiated injectable DMT within two years of symptom onset, and categorized OC use at DMT onset as past, ever or never. Our primary analysis was comparison of annualized relapse rate from baseline DMT start across the three OC use categories using a negative binomial regression model. RESULTS: In this cohort of 162 women, 81 were treated with interferon therapy and 81 with glatiramer acetate. Mean ages for current-, past-, and never-OC users were 31.4 ( n = 46), 40.3 ( n = 66), and 37.9 ( n = 50) years, respectively ( p < 0.05); mean disease duration (1.0 years) and median baseline EDSS (1.0) did not differ between groups. Prior OC users had significantly lower relapse rates than never-users ( p = 0.031); the lower annualized relapse rate in current-users relative to never-users was not significant ( p = 0.91). Annualized relapse rate was not significantly different across the OC groups ( p = 0.057, three-group comparison). RESULTS: These observations provide reassurance for women newly diagnosed that OC use, past or current, does not appear to be associated with greater risk of relapses.

Depression and fatigue in patients with multiple sclerosis.

BACKGROUND: Previous research has examined the components of depression and fatigue in multiple sclerosis (MS), but the findings have been inconsistent. The aim of this study was to explore the associations between overall and subscale scores of the Center for Epidemiologic Studies-Depression Scale (CES-D) and the Modified Fatigue Impact Scale (MFIS) as well as the longitudinal changes in scores in a large cohort of MS patients. METHODS: MS subjects who completed a battery of patient reported outcome (PRO) measures including the CES-D and MFIS (N=435) were included in our analysis. At the first available MFIS measurement, Pearson's correlation coefficient was used to estimate the association between the CES-D and MFIS in terms of both total scores and subscale scores. In addition, the longitudinal change in each total score and subscale score was estimated using a linear mixed model, and the association between the measures in terms of longitudinal change was estimated using Pearson's correlation coefficient and linear mixed models. RESULTS: At baseline, 15% of subjects were classified as high on both depression and fatigue scales, 16% were classified as high on the fatigue scale only, and 9% were classified as high on the depression scale only. There was a high correlation between CES-D and MFIS total scores (r=0.62). High correlations were also observed between the somatic and retarded activity subscales of the CES-D and each of the MFIS subscales (r≥0.60). In terms of longitudinal change, the change over the first year between the CES-D and MFIS total scores showed a moderate correlation (r=0.49). Subjects with high fatigue scores but low depression scores at baseline were more likely than subjects with low baseline fatigue and depression scores to develop high depression scores at follow-up. CONCLUSIONS: Our study demonstrated that depression and fatigue in MS share several features and have a similar longitudinal course. But using cut-off scores to define depression and fatigue, our study also found that non-depressed subjects with high fatigue may be at a greater risk for developing depression.

Risk attitudes and risk perceptions in individuals with multiple sclerosis.

BACKGROUND: Little is known about risk attitudes and risk perceptions in multiple sclerosis (MS). OBJECTIVES: The objectives of this paper are to investigate the range of risk attitudes and risk perceptions and examine associations between risk attitudes and risk perceptions and demographic and clinical features of the disease. METHODS: A total of 223 individuals completed a risk questionnaire. Risk attitude was measured using two rating scales and a standard gamble scenario. Risk perception was measured by asking participants to estimate the likelihood of disease progression and the likelihood of minor and serious side effects associated with common MS therapies. RESULTS: Participants were risk neutral overall and risk averse on issues related to health and safety. There was a significant association between disease duration and risk attitude, with patients with longer disease duration showing greater tolerance for risk. On the standard gamble scenario, males were significantly more likely to take treatments with a likelihood of death of 1:10,000 or 1:100,000 than females. Individuals with higher disability or a progressive disease course were significantly more likely to expect progression at two, five and 10 years. CONCLUSION: Individuals with MS demonstrate low tolerance for risk. Risk attitudes and perceptions are influenced by some demographic and clinical features of the disease.

Patient-reported outcomes in multiple sclerosis: Relationships among existing scales and the development of a brief measure.

Several patient-reported outcome (PRO) measures are commonly used in multiple sclerosis (MS) research, but the relationship among items across measures is uncertain. We proposed to evaluate the associations between items from a standard battery of PRO measures used in MS research and to develop a brief, reliable and valid instrument measure by combining these items into a single measure. Subjects (N = 537) enrolled in CLIMB complete a PRO battery that includes the Center for Epidemiologic Studies Depression Scale, Medical Outcomes Study Modified Social Support Survey, Modified Fatigue Impact Scale and Multiple Sclerosis Quality of Life-54. Subjects were randomly divided into two samples: calibration (n = 269) and validation (n = 268). In the calibration sample, an Exploratory Factor Analysis (EFA) was used to identify latent constructs within the battery. The model constructed based on the EFA was evaluated in the validation sample using Confirmatory Factor Analysis (CFA), and reliability and validity were assessed for the final measure. The EFA in the calibration sample revealed an eight factor solution, and a final model with one second-order factor along with the eight first-order factors provided the best fit. The model combined items from each of the four parent measures, showing important relationships among the parent measures. When the model was fit using the validation sample, the results confirmed the validity and reliability of the model. A brief PRO for MS (BPRO-MS) that combines MS-related psychosocial and quality of life domains can be used to assess overall functioning in mildly disabled MS patients.

The 2D:4D ratio, a proxy for prenatal androgen levels, differs in men with and without MS.

OBJECTIVE: To determine whether the 2D:4D ratio (ratio of the second and fourth digit lengths), a proxy for lower prenatal androgen to estrogen ratio, differs in men with and without multiple sclerosis (MS) using a case-control study design. METHODS: We obtained 2 digital scans of the right hand for men with MS presenting to a scheduled clinic visit at a large MS referral center, and for men without autoimmune or endocrine diseases. All individuals were aged 18 to 65 years, right-handed, and reported no prior digit trauma. We calculated a mean 2D:4D ratio using digital calipers. In participants with MS, we assessed age at first MS symptoms, MS type, and the MS Severity Score; 51 had provided a testosterone level within 10 years of symptom onset. Our primary analysis was a cross-sectional comparison of the 2D:4D ratio between men with and without MS, using a 2-sample t test for independent samples assuming unequal variance. RESULTS: In total, we scanned 137 men with MS and 145 men without MS. A statistically significant association between 2D:4D ratio and MS status was observed in the univariate logistic regression model (p<0.05). These differences were not associated with age or race, which differed between the 2 groups. In participants with MS, the 2D:4D ratio was not correlated with MS type, age at first symptoms, or MS Severity Score (p>0.15 for each), and it was not correlated with adult testosterone levels (r=0.06, p=0.68, n=51). CONCLUSIONS: During the prenatal period, low androgens could represent a risk factor for MS.

Evaluation of an online platform for multiple sclerosis research: patient description, validation of severity scale, and exploration of BMI effects on disease course.

OBJECTIVES: To assess the potential of an online platform, PatientsLikeMe.com (PLM), for research in multiple sclerosis (MS). An investigation of the role of body mass index (BMI) on MS disease course was conducted to illustrate the utility of the platform. METHODS: First, we compared the demographic characteristics of subjects from PLM and from a regional MS center. Second, we validated PLM's patient-reported outcome measure (MS Rating Scale, MSRS) against standard physician-rated tools. Finally, we analyzed the relation of BMI to the MSRS measure. RESULTS: Compared with 4,039 MS Center patients, the 10,255 PLM members were younger, more educated, and less often male and white. Disease course was more often relapsing remitting, with younger symptom onset and shorter disease duration. Differences were significant because of large sample sizes but small in absolute terms. MSRS scores for 121 MS Center patients revealed acceptable agreement between patient-derived and physician-derived composite scores (weighted kappa = 0.46). The Walking domain showed the highest weighted kappa (0.73) and correlation (rs = 0.86) between patient and physician scores. Additionally, there were good correlations between the patient-reported MSRS composite and walking scores and physician-derived measures: Expanded Disability Status Scale (composite rs = 0.61, walking rs = 0.74), Timed 25 Foot Walk (composite rs = 0.70, walking rs = 0.69), and Ambulation Index (composite rs = 0.81, walking rs = 0.84). Finally, using PLM data, we found a modest correlation between BMI and cross-sectional MSRS (rho = 0.17) and no association between BMI and disease course. CONCLUSIONS: The PLM population is comparable to a clinic population, and its patient-reported MSRS is correlated with existing clinical instruments. Thus, this online platform may provide a venue for MS investigations with unique strengths (frequent data collection, large sample sizes). To illustrate its applicability, we assessed the role of BMI in MS disease course but did not find a clinically meaningful role for BMI in this setting.