Pro‐inflammatory cytokine‐based treatments have proven to be safe and effective for treatment of various autoimmune diseases. Thus, inhibition of expression of those molecules can induce important changes in pancreatic β‐cells induce important changes in pancreatic β‐cells [51].
The aim of using the Anti‐Interleukin‐1 in newly diagnosed T1D subjects is to test the feasibility, safety/tolerability and potential efficacy of anti‐IL‐1 therapy in maintaining or enhancing β‐cell function in people with new onset T1D. Anti‐IL‐1 administration for rheumatoid arthritis has been proven to be well tolerated in patients [52, 53]. IL‐1 is also involved in T1D progression by activating T‐helper cells and improving the number of circulating memory T‐cells [54]. The active substance is interleukin‐1 receptor antagonist, a blocker of an immune‐signal molecule named interleukin‐1. Two randomized placebo‐controlled trials aimed to assess whether canakinumab, a human monoclonal anti‐interleukin‐1 antibody, or anakinra, a human interleukin‐1 receptor antagonist, improved β‐cell function in recent‐onset T1D, but their effectiveness was not demonstrated [54, 55].
More recently, the ongoing clinical trial EXTEND (Clinical trial NCT02293837; www.clinicaltrials.gov) is currently examining whether the blockade of IL‐6 signaling through tocilizumab, an anti‐IL‐6 receptor antibody, can induce a protection of β‐cell function in T1D patients (ages 6 to 17 years) (Table 2.3).
Interleukin‐8 appears to be another important mediator in the progression of T1D. Circulating levels of IL‐8 are elevated in children with T1D compared to non‐diabetic controls. Furthermore, levels of IL‐8 correlate with glycemic control, higher level being associated to poorer glucose control. As a result, the modulation or inhibition of IL8 activity may be a valid target for the development of novel treatments aimed to control the progression of T1D.
A multicenter, randomized, double‐blind, placebo‐controlled phase 2 trial of CXCR1/2 IL‐8 inhibitor (Ladarixin) has just presented its results at the American Diabetes Association's (ADA) 80th Scientific Sessions (Clinical trial NCT02814838; www.clinicaltrials.gov). The trial involved 76 patients with new‐onset T1D, randomly (2:1) assigned to receive either Ladarixin treatment (400 mg b.i.d. for 3 cycles of 14 days on/14 days off – treatment group) or placebo (control group). Although results indicated no statistically significant differences in stimulated C‐peptide at weeks 13 and 26, investigators noted 76.6% of patients receiving Ladarixin had an HbA1c below 7% and a daily insulin requirement of less than 0.50 IU/kg compared to just 45.8% of patients receiving placebo. Furthermore, in a prespecified subgroup analysis of patients with fasting C‐peptide below the median value of the trial population at baseline, MMTT AUC of C‐peptide trended at week 13 and reached statistical significance at week 26.
Incretin‐based Therapies
Recent knowledge regarding the heterogeneity in the extent of the β‐cell impairment and pancreatic lesions