HLA type, islet cell antibodies, and glucose intolerance in cystic fibrosis.

Abstract

<h3>Objective:</h3> To compare cerebral gray matter (GM) atrophy over two years in patients with relapsing forms of multiple sclerosis (MS) starting fingolimod vs. those untreated. <h3>Background:</h3> GM atrophy has clinical relevance in MS. Fingolimod has known clinical and conventional MRI therapeutic efficacy; the effect on GM is unknown. <h3>Design/Methods:</h3> Patients starting fingolimod [n=24, age (mean±SD) 41.2±11.6 years, Expanded Disability Status Scale (EDSS) score 1.1±1.4; 58% women] were compared to untreated patients [n=29, age 45.7±8.4 years, EDSS 1.0±1.2; 93% women]. Baseline, 1 and 2 year MRI was applied to an SPM12 pipeline to assess brain parenchymal fraction (BPF) and cortical gray matter fraction (cGMF). T2 lesion volume (T2LV) and gadolinium-enhancing (Gd+) lesions were assessed. Change was modeled using a mixed effects linear regression with a random slope and fixed effects for time, group and the time by group interaction. The group difference in slope was assessed using the interaction term. <h3>Results:</h3> cGMF remained stable in fingolimod (p&gt;0.05), but decreased in the untreated group (p&lt;0.001) over two years (group difference p&lt;0.001). BPF change did not differ between groups (all timepoints p&gt;0.05). T2LV increased over two years in the untreated (p&lt;0.001) but not fingolimod group (p&gt;0.45) (group difference p&lt;0.001). cGMF results were similar after adjusting for sex and baseline Gd+ lesions in year 1, and in year 2 when age-adjusted (all p&lt;0.1). EDSS decreased over 2 years in the untreated (p&lt;0.05) but not fingolimod group (p&gt;0.05) (group difference p&lt;0.05). T25FW decreased in year 1 in fingolimod (p&lt;0.02) but not the untreated group (p&gt;0.05) (group difference p&lt;0.05). <h3>Conclusions:</h3> These results suggest a treatment effect of fingolimod on GM atrophy two years after starting therapy. GM atrophy is more sensitive to treatment effects than whole brain atrophy. However, due to the non-randomized, retrospective design, and small sample size, these results require confirmation in future studies. Study Supported by: Novartis, Inc. <b>Disclosure:</b> Dr. Dupuy has nothing to disclose. Dr. Yousuf has nothing to disclose. Dr. Tauhid has nothing to disclose. Dr. Chu has nothing to disclose. Dr. Kim has nothing to disclose. Dr. Tummala has nothing to disclose. Dr. Chitnis received personal compensation for activities with Roche-Genentech and Sanofi-Genzyme. Dr. Chitnis received research support from EMD Serono, Biogen, Novartis and Verily. Dr. Healy has received personal compensation for activities with Biogen Idec Worldwide Medical Biostatistics MS Advisory Board. Dr. Healy has received research support from Merck Serono SA, Verily Life Sciences, Genentech, and Novartis. Dr. Bakshi has received personal compensation for activities with AbbVie, EMD-Serono, Genentech Inc., and Novartis as a consultant. Dr. Bakshi has received research support from Biogen, EMD-Serono, Novartis, and Sanofi/Genzyme.