Development of an Interleukin-1β Vaccine in Patients with Type 2 Diabetes

Abstract

Interleukin-1β (IL-1β) is a key cytokine involved in inflammatory illnesses including rare hereditary diseases and common chronic inflammatory conditions as gout, rheumatoid arthritis, and type 2 diabetes mellitus, suggesting reduction of IL-1β activity as new treatment strategy. The objective of our study was to assess safety, antibody response, and preliminary efficacy of a novel vaccine against IL-1β. The vaccine hIL1bQb consisting of full-length, recombinant IL-1β coupled to virus-like particles was tested in a preclinical and clinical, randomized, placebo-controlled, double-blind study in patients with type 2 diabetes. The preclinical simian study showed prompt induction of IL-1β-specific antibodies upon vaccination, while neutralizing antibodies appeared with delay. In the clinical study with 48 type 2 diabetic patients, neutralizing IL-1β-specific antibody responses were detectable after six injections with doses of 900 µg. The development of neutralizing antibodies was associated with higher number of study drug injections, lower baseline body mass index, improvement of glycemia, and C-reactive protein (CRP). The vaccine hIL1bQb was safe and well-tolerated with no differences regarding adverse events between patients receiving hIL1bQb compared to placebo. This is the first description of a vaccine against IL-1β and represents a new treatment option for IL-1β-dependent diseases such as type 2 diabetes mellitus (ClinicalTrials.gov NCT00924105).

Canakinumab and cardiovascular outcomes: results of the CANTOS trial

“…These very trials led to additional investigation into exploring the role of canakinumab in suppressing the effects of inflammatory markers. One such trial was the CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcome Study) trial where promising results were seen [9]. During the trial, 10,061 patients with previously diagnosed myocardial infarction were targeted [9].…”

“…One such trial was the CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcome Study) trial where promising results were seen [9]. During the trial, 10,061 patients with previously diagnosed myocardial infarction were targeted [9]. Three doses of canakinumab (50, 150, and 300 mg, administered subcutaneously every 3 months) in addition to a placebo were compared with the primary efficacy point being nonfatal myocardial infarction or cardiovascular death.…”

“…At 4 years, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26, 37, and 41 percentage points greater in the group than in the placebo group that received 50-, 150- and 300-mg, respectively. Furthermore, the incidence rate for primary end point was 4.50 events per 100 person-years in the placebo group as compared to 4.11, 3.86, and 3.90 in the 50-, 150- and the 300-mg group, respectively [9]. The results with the 150-mg dose, but not with the other doses, met the statistical significance for the primary end point.…”

“…The results with the 150-mg dose, but not with the other doses, met the statistical significance for the primary end point. However, no significant difference was noted in all-cause mortality [9]. …”

“…However, there were some adverse side effects of canakinumab in the trial which need to be addressed: patients receiving canakinumab were more prone to having infections due to neutropenia and had significantly more deaths as compared to the placebo group owing to infection or sepsis [9]. However, the all-cause mortality rate was insignificant between the canakinumab and placebo groups [9].…”