IL-1 Inhibition as Targeted Treatment for Rheumatoid Arthritis, Type 2 Diabetes

Interleukin (IL)-1 inhibition is a potential targeted treatment for patients with both rheumatoid arthritis (RA) and type 2 diabetes (T2D), according to study results published in PLoS Medicine.

Researchers conducted a multicenter, open-label, randomized controlled study (Treatment of Rheumatoid Arthritis and Comorbidities with Kineret [TRACK]; ClinicalTrials.gov Identifier: NCT02236481) to assess whether IL-1 reduction improved glycemic and inflammatory parameters.

Patients were randomly assigned to 1 of 2 study arms, receiving either anakinra, a human IL-1 receptor antagonist, or a tumor necrosis factor inhibitor (TNFi). Baseline antidiabetic and RA therapies were continued throughout the study.

A total of 41 patients were enrolled, and 39 met the inclusion criteria for the current study; 70.2% had seropositive RA. Active disease was indicated in all patients, and they were treated with methotrexate: 10.3% of patients received methotrexate-hydroxychloroquine combination therapy, and 7.7% received methotrexate-sulfasalazine combination therapy. Type 2 diabetes (percentage of glycated hemoglobin [HbA1c%], 7.77±0.70) was also indicated in all patients. A total of 22 patients were assigned to the anakinra group and 17 to the TNFi group; both groups had similar baseline characteristics.

Investigators noted a “progressive reduction” of HbA1c% in patients in the anakinra group compared with those in the TNFi group. At baseline, no difference was observed; at 3 months, HbA1c% in the anakinra group was 6.95%±0.61 and 7.63%±0.68 in the TNFi group (P =.0038). Additional significant HbA1c% reductions were noted in the anakinra group after 6 months of treatment. Further analysis was conducted using linear mixed models, which confirmed the significant effects of anakinra in the treatment groups.

Fasting plasma glucose was also progressively reduced in the anakinra group compared with the TNFi group at 3 months (109.78±30.58 mg/dL vs 133.06±27.72 mg/dL) and 6 months (100.81±11.11 mg/dL vs 140.93±39.45 mg/dL) of treatment.

In terms of RA disease activity, both groups demonstrated high disease activity at baseline. Throughout the study period, the Disease Activity Score (DAS) in 28 Joints was reduced in both groups and persisted for 6 months. Patients were also analyzed for European League Against Rheumatism (EULAR) response; a significant percentage of patients in the anakinra group reached a good EULAR clinical response compared with those in the TNFi group (95.0% vs 62.5%; P =.030).

Finally, investigators examined the safety profile of the study drugs. No severe adverse events or deaths were reported. The most common adverse event in the anakinra group was urticarial lesions at the injection site. Nonsevere infections, including influenza, nasopharyngitis, upper respiratory tract infection, urinary tract infection, and diarrhea were noted in both groups.

Study limitations included the open-label study design and a “previously unplanned ad interim analysis,” which the researchers noted was more prone to biases, as well as potential complications from the real-life study design and the ongoing use of other drugs such as methotrexate.

“Our results suggest that IL-1 inhibition may be considered as a target treatment for [patients] with both RA and T2D,” the researchers concluded. “Based on our pilot study, future studies are needed to further assess the use of IL-1-inhibiting agents in patients with both RA and T2D and to assess long-term outcomes on [cardiovascular disease].”

Reference

Ruscitti P, Masedu F, Alvaro S, et al. Anti-interleukin-1 treatment in patients with rheumatoid arthritis and type 2 diabetes (TRACK): a multicenter, open-label randomised controlled trial [published online September 12, 2019]. PLoS Med. doi:10.1371/journal.pmed.1002901