The prevalence of comorbidities in patients with multiple sclerosis: population-based registry data.

BACKGROUND: Comorbidities occur frequently in persons with multiple sclerosis (MS). The aim of the present study was to determine the prevalence of the most common comorbidities in the population of MS patients in Belgrade, Serbia. MATERIAL AND METHODS: Data on diagnosed and fully documented comorbidities were taken from the Belgrade MS population registry. The list of explored comorbidities included cardiovascular, malignant, and autoimmune diseases; psychiatric disorders; epilepsy; and type 2 diabetes. In the data analysis, crude, age- and gender-specific, and age-adjusted prevalence was calculated. Additionally, comorbidities were analyzed in patients with various MS phenotypes. RESULTS: The most prevalent group of comorbidities were psychiatric (prevalence (Prev) = 20.59%, 95% CI 19.10-22.17) and cardiovascular comorbidities (Prev = 15.23%, 95% CI 13.93-16.63). The most prevalent single comorbidities were depression (Prev = 11.82%, 95% CI 10.64-13.11) and hypertension (Prev = 11.41%, 95% CI 10.25-12.68). Type 2 diabetes was significantly more prevalent in patients with primary progressive MS compared with the patients with relapsing-remitting and secondary progressive MS (p < 0.001). We found statistically significant positive correlation between number of comorbidities and progression index (p < 0.001). Patients treated with disease-modifying therapies (DMTs) had significantly higher risk of developing comorbidity, after treatment initiation, compared with those who were untreated (p = 0.001). CONCLUSIONS: Our study demonstrated high prevalence of comorbidities in persons with MS, with psychiatric and cardiovascular diseases being the most common. Furthermore, our findings confirmed the association of comorbidities with progression of disability and emphasized their role in treatment decision-making in MS.

Validation of the Serbian Version of Multiple Sclerosis Spasticity Scale 88 (MSSS-88).

OBJECTIVE: Multiple Sclerosis Spasticity Scale (MSSS)-88 has been developed for self-assessment of spasticity symptoms in patients with multiple sclerosis (MS). The objective of this study was to validate MSSS-88 and evaluate the psychometric properties in patients with MS in Serbia. METHODS: The study comprised 65 MS patients with spasticity. MSSS-88 consists of 88 items grouped in eight sections. Internal consistency of the MSSS-88SR subscales was determined using Cronbach's alpha coefficient. Test/retest reliability with an intra-class correlation coefficient (ICC) for each MSSS-88SR subscale was performed. Clinical validity of MSSS-88SR was determined by correlations with the Numeric Rating Scale (NRS) and the Modified Ashworth Scale (MAS). RESULTS: The range of Cronbach's alpha for all scales and ICC was 0.91-0.96 and 0.84-0.91, respectively. All ICCs were statistically significant (p<0.05). All evaluated subscales of MSSS-88 were significantly correlated with the NRS scale. The highest correlation coefficients were registered between the WL subscale and the EDSS and MAS, while the strongest relationship was observed between the MSS subscale and the NRS. CONCLUSION: The Serbian translated version of this instrument may be useful as a clinical measure for spasticity and functionality in patients with MS.

Pharmacogenomic study in patients with multiple sclerosis: Responders and nonresponders to IFN-ß.

OBJECTIVES: We aimed to investigate the association between polymorphisms located in type I interferon (IFN)-induced genes, genes belonging to the toll-like receptor (TLR) pathway, and genes encoding neurotransmitter receptors and the response to IFN-ß treatment in patients with multiple sclerosis (MS). METHODS: In a first or screening phase of the study, 384 polymorphisms were genotyped in 830 patients with MS classified into IFN-ß responders (n = 416) and nonresponders (n = 414) according to clinical criteria. In a second or validation phase, the most significant polymorphisms associated with IFN-ß response were genotyped in an independent validation cohort of 555 patients with MS (281 IFN-ß responders and 274 nonresponders). RESULTS: Seven single nucleotide polymorphisms (SNPs) were selected from the screening phase for further validation: rs832032 (GABRR3; p = 0.0006), rs6597 (STUB1; p = 0.019), rs3747517 (IFIH1; p = 0.010), rs2277302 (PELI3; p = 0.017), rs10958713 (IKBKB; p = 0.003), rs2834202 (IFNAR1; p = 0.030), and rs4422395 (CXCL1; p = 0.017). None of these SNPs were significantly associated with IFN-ß response when genotyped in an independent cohort of patients. Combined analysis of these SNPs in all patients with MS (N = 1,385) revealed 2 polymorphisms associated with IFN-ß response: rs2277302 (PELI3; p = 0.008) and rs832032 (GABRR3; p = 0.006). CONCLUSIONS: These findings do not support an association between polymorphisms located in genes related to the type I IFN or TLR pathways or genes encoding neurotransmitter receptors and the clinical response to IFN-ß. Nevertheless, additional genetic and functional studies of PELI3 and GABRR3 are warranted.

Efficacy and safety of subcutaneous interferon ß-1a in relapsing-remitting multiple sclerosis: further outcomes from the IMPROVE study.

BACKGROUND: The IMPROVE study demonstrated that the fetal bovine serum (FBS)- and human serum albumin (HSA)-free formulation of subcutaneous (sc) interferon (IFN) beta-1a had beneficial effects on the numbers of combined unique active magnetic resonance imaging (MRI) lesions in relapsing-remitting multiple sclerosis (RRMS). Here we report additional MRI endpoints (including post hoc analyses), and clinical efficacy, safety, and immunogenicity outcomes. METHODS: Patients with active RRMS were randomized (2:1) to IFN beta-1a, 44 mcg sc three times weekly (tiw) (n=120), or placebo (n=60), for 16 weeks (double-blind phase). All patients then received IFN beta-1a, 44 mcg sc tiw, for 24 weeks (rater-blind phase). Patients underwent MRI brain scans every 4 weeks. RESULTS: Compared with placebo, there was a 68% reduction in the mean cumulative number of new gadolinium-enhancing lesions with IFN beta-1a as early as week 4 (p<0.001), and a 53% reduction in the mean cumulative number of new T2 lesions as early as week 8 (p=0.025; post hoc analyses). During the 16-week double-blind phase, the relapse rate was 0.14 (95% confidence interval [CI] 0.09-0.23) with IFN beta-1a and 0.33 (95% CI 0.22-0.52) with placebo (p=0.010). Safety outcomes were consistent with those expected with IFN-beta treatment. CONCLUSIONS: The FBS/HSA-free formulation of sc IFN beta-1a has a beneficial impact on MRI and efficacy outcomes as early as 4 weeks after treatment initiation in patients with RRMS and has a safety profile consistent with previous trials of sc IFN beta-1a.