Adiutori, R

Altmann, D

Bianchi, L

Christensen, T

Giovannoni, G

Gold, J

Holden, D

MacManus, D

Marta, MC

Meier, UC

Miller, D

Schmierer, K

Turner, B

Yousry, T

Multiple Sclerosis Journal

Queen Mary Research Online

Title: Phase 2 baseline versus treatment clinical trial of the HIV drug raltegravir in patients with active relapsing remitting multiple sclerosis: the INSPIRE study biomarker outcome resultsAuthor(s): J. Gold1,5, M. Calado Marta1, U. C. Meier1, T. Christensen4 , D. Miller2, D. Altmann3, D. Holden1, L. Bianchi1, R. Adiutori1 , D. MacManus2, T. Yousry2, K. Schmierer1, B. Turner1, G. Giovannoni1 Institute(s): 1Neuroscience and Trauma, Queen Mary University of London, Blizard Institute, Barts and the London School of Medicine and Dentistry, 2Institute of Neurology. University College London, 3Medical Statistics Department, London School of Hygiene and Tropical Medicine, London, United Kingdom, 4Department of Biomedicine, Aarhus University, Aarhus, Denmark, 5The Albion Centre, Prince of Wales Hospital, Sydney, NSW, Australia.Background: INSPIRE was a Phase 2b clinical trial, 3 month baseline followed by 3 months treatment, to investigate the effect of the HIV integrase inhibitor, raltegravir 400mg twice a day, on the number of gadolinium (Gd)-enhanced MRI lesions in people with active RRMS. The primary outcome was negative.Objectives & Methods: The 20 participants enrolled were monitored monthly with saliva collection for EBV shedding, blood collection for safety monitoring, virology, including Human Endogenous RetroViral expression (HERVs); measurement of immunological and inflammatory markers, as well as Gd-enhanced MRI and clinical measurements, throughout duration of the trial. Results: Statistically significant positive correlation was detected between HERV-W (Multiple Sclerosis Related Virus) Gag Flix B cells and the number of Gd-enhanced lesions (r = -0.54; p = 0.012), which was independent of any potential influence of the trial drug administration. Regarding EBV shedding, there was no significant correlation between the amount of EBV shedding and the number of lesions, but there was a borderline significant association between EBV shedding and the number of total lesions (OR 0.79 per lesion; p = 0.08), which may be due to the development of new lesions or inflammatory activity.  No change was detected in inflammatory markers (IL-8, IL-1β, IL-6, IL-10, TNF, IL-12p70 and HCRP), which were all within normal limits both before and after the intervention. Serum CD163 expression was also unchanged by Raltegravir. Conclusion: Borderline significance for the association between EBV shedding and the total number of lesions, probably driven by new lesion development, may indicate EBV shedding as a marker of inflammatory disease activity. In conclusion, interesting correlations between HERV-W markers, EBV shedding and new MRI lesions, independent from treatment effects, were found. 

Phase 2 baseline versus treatment clinical trial of the HIV drug raltegravir in patients with active relapsing remitting multiple sclerosis: the INSPIRE study biomarker outcome results

Phase 2 baseline versus treatment clinical trial of the HIV drug raltegravir in patients with active relapsing remitting multiple sclerosis: the INSPIRE study biomarker outcome results

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