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Targeting CXCR1/2 does not improve insulin secretion after pancreatic islet transplantation: A phase 3, double-blind, randomized, placebo-controlled trial in type 1 diabetes

Lookup NU author(s): Professor James Shaw, Dr Aaron Liew

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Diabetes Association Inc., 2020.

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Abstract

© 2020 by the American Diabetes Association.OBJECTIVE Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients. RESEARCH DESIGN AND METHODS A phase 3, multicenter, randomized, double-blind, parallel-assignment study (NCT01817959) was conducted in recipients of islet allotransplants randomized (2:1) to reparixin or placebo in addition to immunosuppression. Primary outcome was the area under the curve (AUC) for C-peptide during the mixed-meal tolerance test at day 75 6 5 after the first and day 365 6 14 after the last transplant. Secondary end points included insulin independence and standard measures of glycemic control. RESULTS The intention-to-treat analysis did not show a significant difference in C-peptide AUC at both day 75 (27 on reparixin vs. 18 on placebo, P 5 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P 5 0.71). There was no statistically significant difference between treatment groups at any time point for any secondary variable. Analysis of patient subsets showed a trend for a higher percentage of subjects retaining insulin independence for 1 year after a single islet infusion in patients receiving reparixin as compared with patients receiving placebo (26.7% vs. 0%, P 5 0.09) when antithymocyte globulin was used as induction immunosuppression. CONCLUSIONS In this first double-blind randomized trial, islet transplantation data obtained with reparixin do not support a role of CXCR1/2 inhibition in preventing islet inflammation-mediated damage.


Publication metadata

Author(s): Maffi P, Lundgren T, Tufveson G, Rafael E, Shaw JAM, Liew A, Saudek F, Witkowski P, Golab K, Bertuzzi F, Gustafsson B, Daffonchio L, Ruffini PA, Piemonti L, Nano R, Mercalli A, Lampasona V, Magistretti P, Sordi V, Antonio S, Antonioli B, Galuzzi M, Tosca MC, De Carlis L, Colussi G, Korsgren O, Pollard H

Publication type: Article

Publication status: Published

Journal: Diabetes Care

Year: 2020

Volume: 43

Issue: 4

Pages: 710-718

Print publication date: 20/03/2020

Online publication date: 04/02/2020

Acceptance date: 11/12/2019

Date deposited: 30/04/2020

ISSN (print): 0149-5992

ISSN (electronic): 1935-5548

Publisher: American Diabetes Association Inc.

URL: https://doi.org/10.2337/dc19-1480

DOI: 10.2337/dc19-1480

PubMed id: 32019854


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