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
Author(s): ,
J Gold
Affiliations:
Neuroscience and Trauma, Blizard Institute, Queen Mary University London, Barts and the London School of Medicine and Dentistry, London, United Kingdom;The Albion Centre, Prince of Wales Hospital, Sydney, NSW, Australia
,
M Calado Marta
Affiliations:
Neuroscience and Trauma, Blizard Institute, Queen Mary University London, Barts and the London School of Medicine and Dentistry, London, United Kingdom
,
U.C Meier
Affiliations:
Neuroscience and Trauma, Blizard Institute, Queen Mary University London, Barts and the London School of Medicine and Dentistry, London, United Kingdom
,
T Christensen
Affiliations:
Department of Biomedicine, Aarhus University, Aarhus, Denmark
,
D Miller
Affiliations:
Institute of Neurology, University College Hospital
,
D Altmann
Affiliations:
Medical Statistics Department, London School of Hygiene and Tropical Medicine, London, United Kingdom
,
D Holden
Affiliations:
Neuroscience and Trauma, Blizard Institute, Queen Mary University London, Barts and the London School of Medicine and Dentistry, London, United Kingdom
,
L Bianchi
Affiliations:
Neuroscience and Trauma, Blizard Institute, Queen Mary University London, Barts and the London School of Medicine and Dentistry, London, United Kingdom
,
R Adiutori
Affiliations:
Neuroscience and Trauma, Blizard Institute, Queen Mary University London, Barts and the London School of Medicine and Dentistry, London, United Kingdom
,
D MacManus
Affiliations:
Institute of Neurology, University College Hospital
,
T Yousry
Affiliations:
Institute of Neurology, University College Hospital
,
K Schmierer
Affiliations:
Neuroscience and Trauma, Blizard Institute, Queen Mary University London, Barts and the London School of Medicine and Dentistry, London, United Kingdom
,
B Turner
Affiliations:
Neuroscience and Trauma, Blizard Institute, Queen Mary University London, Barts and the London School of Medicine and Dentistry, London, United Kingdom
G Giovannoni
Affiliations:
Neuroscience and Trauma, Blizard Institute, Queen Mary University London, Barts and the London School of Medicine and Dentistry, London, United Kingdom
ECTRIMS Online Library. Gold J. Sep 15, 2016; 146288; P448
Julian Gold
Julian Gold
Contributions
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Abstract

Abstract: P448

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - MS and infections

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 and 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 or Multiple Sclerosis Related Virus (MSRV) 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.

Disclosure:

M. Calado Marta Nothing to disclose

D. MacManus Nothing to disclose

T.Yousry Nothing to disclose

D. Miller Nothing to disclose

D. R. Altmann Nothing to disclose

U. C. Meier Nothing to disclose

T. Christensen Nothing to disclose

D. H.Maruszak Nothing to disclose

D. Holden Nothing to disclose

L. Bianchi Nothing to disclose

R. Adiutori Nothing to disclose

K. Schmierer Nothing to disclose

B.Turner Nothing to disclose

G. Giovannoni Nothing to disclose

J. Gold Nothing to disclose

This study was funded by Merck Sharpe and Dohme

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