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21-04-2013 | Metabolism | Article

Monoclonal antibody single therapy not effective in Type 1 diabetes


Free abstract

medwireNews: The monoclonal antibodies canakinumab and anakinra, inhibitors of the innate immune mediator interleukin-1β, do not seem to be effective at slowing the decline of β-cell function in individuals with recent-onset Type 1 diabetes, report researchers.

The results of two randomised, placebo-controlled trials show that neither of the monotherapies had a significant effect on stimulated C-peptide concentrations or glycated hemoglobin (HbA1c) levels among such patients, report Jay Skyler (University of Miami Miller School of Medicine, USA) and colleagues.

However, "interleukin-1 blockade might be more effective in combination with treatments that target adaptive immunity in organ-specific autoimmune disorders," says the team.

As reported in The Lancet, all of the individuals included in the trials had a diagnosis of recent-onset Type 1 diabetes and a mixed-meal tolerance-test (MMTT)- stimulated C-peptide of at least 0.2 nmol/L.

"Persistent endogenous insulin secretion, defined as stimulated C-peptide concentration greater than 0.2 nmol/L during MMTT, is associated with reduced occurrence of hypoglycemia and microvascular complications," explain Skyler et al. "Thus, interventions that stop or delay decline of β-cell function are desirable."

Receiver-operating characteristic analysis showed that of 69 individuals randomly allocated to receive monthly injections of canakinumab 2 mg/kg or placebo for 12 months, the mean 2-hr area under the curves (AUCs) for MMTT-stimulated C-peptide were similar between the two groups at the end of treatment, at 0.41 nmol/L and 0.40 nmol/L, respectively, after adjustment for age, gender, and baseline C-peptide.

In addition, time to stimulated peak C-peptide of less than 0.2 nmol/L and HbA1c level were not significantly different between the groups at the end of treatment.

Similarly, of 69 individuals randomly allocated to daily 100 mg anakinra or placebo, the mean 2-hr AUCs for stimulated C-peptide did not significantly differ between the groups, at 0.53 nmol/L and 0.51 nmol/L at the end of treatment, and no between-group differences were observed for time to peak C-peptide of less than 0.2 nmol/L or HbA1c levels.

Although neither of the anti-interleukin-1β monotherapies were effective in these trials, the approach may still be beneficial in combination therapy, say the researchers, who note that previous studies found that the combination of interleukin-1β blockade and anti-CD3 monoclonal antibody was more effective at achieving remission of diabetes than the use of anti-CD3 monoclonal antibody alone.

"Interleukin-1β blockade might be more suitable for combination therapy protocols in new-onset type 1 diabetes or in prevention trials in individuals with pre-type diabetes," they conclude.

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

By Sally Robertson, medwireNews Reporter

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