Immunological and short-term brain volume changes in relapsing forms of multiple sclerosis treated with interferon beta-1a subcutaneously three times weekly: an open-label two-arm trial.

Michael G Dwyer,Xin Zhang,Bianca Weinstock-Guttman,Cheryl Kennedy,Niels Bergsland,Robert Zivadinov,Silva Markovic-Plese,Jackie Durfee,Fernando Dangond,David Hojnacki,Brooke Hayward,Yazhong Tao,Deepa P Ramasamy

doi:10.1186/s12883-015-0488-9

Abstract

BackgroundBrain volume atrophy is observed in relapsing–remitting multiple sclerosis (RRMS).MethodsBrain volume changes were evaluated in 23 patients with RRMS treated with interferon β-1a 44 μg given subcutaneously (SC) three times a week (tiw) and 15 healthy controls. Percentages of whole brain and tissue-specific volume change were measured from baseline (0 months) to 3 months, from 3 to 6 months, and from baseline to 6 months using SIENAX Multi Time Point (SX-MTP) algorithms. Immunological status of patients was also determined and correlations between subsets of T cells and changes in brain volume were assessed.ResultsInterferon β-1a 44 μg SC tiw in 23 patients with RRMS resulted in significant reductions in whole brain and gray matter tissue volume early in the treatment course (baseline to 3 months; mean change; –0.95 %; P = 0.030, –1.52 %; P = 0.004, respectively), suggesting a short-term treatment-induced pseudoatrophy effect. From baseline to 6 months, there were significant correlations observed between decreased T- cell expression of IL-17 F and decreased whole brain and brain tissue-specific volume.ConclusionsThese findings are consistent with the interpretation of the pseudoatrophy effect as resolution of inflammation following treatment initiation with interferon β-1a 44 μg SC tiw, rather than disease-related tissue loss.Trial registrationClinicalTrials.gov; NCT01085318

Highlights

Brain volume atrophy is observed in relapsing–remitting multiple sclerosis (RRMS)
All 15 Healthy control (HC) and 21/23 patients completed the study; one patient was lost to follow-up and one patient discontinued owing to the investigator’s decision
In whole brain and gray matter (GM), the effect of IFN β-1a SC treatment was associated with a reduction in brain tissue volume; in both cases the majority of the reduction occurred shortly following treatment initiation, in comparison with the 3–6-month period, a result that is highly consistent with an acute pseudoatrophy effect

Summary

Introduction

Brain volume atrophy is observed in relapsing–remitting multiple sclerosis (RRMS). Methods: Brain volume changes were evaluated in 23 patients with RRMS treated with interferon β-1a 44 μg given subcutaneously (SC) three times a week (tiw) and 15 healthy controls. Dwyer et al BMC Neurology (2015) 15:232 resolution of inflammation, edema, and cellular infiltration rather than the loss of actual brain tissue [19, 20] Because both destructive tissue atrophy and these beneficial/benign pseudoatrophy changes may result in similar observations of brain volume reduction and confound efficacy measurements [21], it is critical to disentangle the two to understand the true impact of DMDs. Some initial work was done by looking at atrophy rates over different study time periods [9], and showed that the effect was predominantly driven by loss in whitematter (WM) volume; this loss was greater with higher initial inflammatory activity as measured by gadoliniumenhancing lesions. One important complementary approach might be to evaluate brain volume changes in combination with key immunological markers

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