medwireNews: Higher BETA-2 scores and the use of anakinra in combination with etanercept are associated with sustained graft survival among people with type 1 diabetes who undergo allogeneic islet transplantation, Canadian research shows.
James Shapiro and colleagues from the University of Alberta in Edmonton analyzed data for 255 people (58% women, 85% White) who received at least one islet infusion (median age 49 years at first transplant) between 1999 and 2019.
Of these, 88% of patients received two or more infusions, 37% received three or more, 13% received four or more, and 2% received five infusions.
During a median 7.4 years of follow-up, 10% of patients died, giving a mortality rate of 11.6 deaths per 1000 patient–years. The estimated 20-year patient survival probability was 74%.
Shapiro et al note that the mortality rate was higher than those observed in cohorts from Lille and Miami (both approximately 3 per 1000 patient–years) but say that the current population was older, with 11% aged over 60 years at baseline and 25% of deaths occurring in this age group.
Just over a third (36%) of patients experienced graft failure, and median graft survival, defined as a maintaining a fasting plasma C-peptide level above 0.1 nmol/L throughout follow-up, was 5.9 years.
Sustained graft survival, defined as graft survival for at least 90% of follow-up time, was achieved in 70% of participants.
These individuals were significantly older than those without sustained graft survival (median 49.4 vs 44.2 years) and had a significantly longer median type 1 diabetes duration (33.5 vs 26.2 years) and significantly lower median baseline insulin requirements (0.53 vs 0.59 units/kg per day).
In addition, the proportion of patients who received at least three infusions was significantly higher among recipients with versus without sustained graft survival, at 42% of 178 versus 25% of 77 patients. Conversely, median glycated hemoglobin concentrations were similar between the two groups (8.2 vs 8.5%; 66.1 vs 69.4 mmol/mol).
In multivariate analyses, combined use of anakinra plus etanercept and better graft function (BETA-2 score of ≥15) during the first year of transplantation were each significantly associated with sustained graft survival, at adjusted odds ratios of 7.5 and 4.1, respectively. Conversely, there was no association between graft survival and total islet mass.
Shapiro and co-authors report in The Lancet Diabetes & Endocrinology that the majority (79%) of participants achieved insulin independence at some point during follow-up, with a median duration of 2.3 years, but they note that “typically two or more islet infusions were required” before participants could stop insulin use.
In terms of safety, rates of end-stage renal disease and severe infection were similar between the groups with and without sustained graft survival, but procedural complications were significantly less common (5% of 443 infusions vs 10% of 167) and cancer was significantly more common (16% of 178 participants vs 5% of 77) in the former than in the latter group.
Shapiro et al conclude: “Although some limitations with our study remain, such as the retrospective component, a relatively small sample size, and the absence of non-transplant controls, we found that the combined use of anakinra plus etanercept and the BETA-2 score were associated with improved outcomes, and therefore these factors could inform clinical practice.”
In an accompanying comment Rainer Gruessner (SUNY Downstate Health Sciences University, New York City, USA) describes the research as a “landmark study” and suggests that it “might help to gain more widespread application of islet transplantation.”
However, he also points out “some unresolved key issues,” including the high rate of multiple transplants typically needed for sustained transplant survival, which “must be seen a [as] major hindrance” to increased adoption of the procedure.
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Lancet Diabetes Endocrinol 2022; doi:10.1016/S2213-8587(22)00114-0
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