Combined therapy with CD4+CD25highCD127− T regulatory cells and anti-CD20 antibody in recent-onset type 1 diabetes is superior to monotherapy: Randomized phase I/II trial
Maciej Zieliński, Magdalena Żalińska contributed equally to this work.
Funding information: H2020 Innovation In SMEs, Grant/Award Number: 830559 - TREG; National Centre for Research and Development, Poland, Grant/Award Number: STRATEGMED1/233368/1/NCBR/2014
Abstract
Aims
Monotherapy with autologous expanded CD4+CD25highCD127− T regulatory cells (Tregs) or rituximab has been documented to slow disease progression in patients with recent-onset type 1 diabetes mellitus (T1DM). Whether a combined therapy including both drugs would further benefit this patient population is unknown.
Materials and Methods
We conducted a three-arms clinical trial to explore the efficacy and safety of the combined treatment with Tregs and rituximab in paediatric patients with T1DM. The patients were allocated to three groups: Tregs only (n = 13), Tregs + rituximab (n = 12) and control (n = 11). The key primary efficacy analyses were C-peptide levels (mixed meal tolerance test) and the proportion of patients in remission at 12 and 24 months.
Results
At month 24, as compared with the control, both treatment groups remained superior in the area under the curve of C-peptide mixed meal tolerance test, whereas in the analysis of all visits only the combined therapy improved area under the curve at 12 and 24 months. The proportion of patients in remission was significantly higher in the combined group than in the control group at 3, 6, 9 and 21 months but not at 18 and 24 months. There was no significant difference between the Tregs only group and control group. Adverse events occurred in 80% patients, mostly in the combined group and Tregs only group. No adverse events led to the withdrawal of the intervention or death. All comparisons were performed with alpha level of 5%.
Conclusions
Over 2 years, combined therapy with Tregs and rituximab was consistently superior to monotherapy in delaying T1DM progression in terms of C-peptide levels and the maintenance of remission.
CONFLICT OF INTEREST
NMT, MM and PT are co-inventors of patents related to presented content and stakeholders of POLTREG venture. Medical University of Gdańsk received payment for the license to presented content. The other authors declare that they have no competing interests.
Open Research
PEER REVIEW
The peer review history for this article is available at https://publons.com/publon/10.1111/dom.14723.
DATA AVAILABILITY STATEMENT
The full report and supplementary materials to this article will be attached to the study web registration page: https://www.isrctn.com/search?q=ISRCTN37116985.
