Psoriasis Medication May Slow Type 1 Diabetes Onset

TOPLINE:

The monoclonal antibody ustekinumab, approved for treating psoriasis, psoriatic arthritis, and inflammatory bowel disease, appears to safely protect pancreatic beta-cell function in children with new-onset type 1 diabetes (T1D), by targeting the interleukin (IL)-12/IL-23 pathway. 

METHODOLOGY:

• A double-blind, randomised controlled phase 2 trial of ustekinumab in 72 adolescents aged 12-18 years with recent-onset (≤ 100 days) T1D, randomised 2:1 to ustekinumab or placebo, of whom 62 (41 ustekinumab and 21 placebo) were included in the primary outcome analysis at 52 weeks.
• C-peptide area under the curve (AUC) in a 2-hour mixed meal tolerance test was compared between the two groups at weeks 28 and 52, and adjusted for sex, baseline age, C-peptide AUC, A1c, and exogenous insulin dose.

TAKEAWAY:

• Ustekinumab was associated with a 49% higher C-peptide AUC at week 52 (ustekinumab vs placebo: 0.45 nmol/L/min vs 0.30 nmol/L/min; geometric ratio, 1.49; P = .02).
• A1c levels rose across both groups from 50 mmol/mol at baseline to 56 mmol/mol at week 52, not a significant difference (P = .15).
• Exogenous insulin use increased from baseline to week 52 in both groups (0.42 to 0.63 units/kg in the control group vs 0.51 to 0.63 units/kg in the ustekinumab group) with no difference between the groups after adjustment for baseline factors (P = .38).
• There were no serious adverse events considered to be treatment related.
• Frequency and type of side effects were comparable between the ustekinumab and placebo groups.

IN PRACTICE:

“Our exploratory data suggest a role for a subset of T_H17 cells in T1D that can be modulated at low risk by IL-12/IL-23 inhibition, with benefits on β-cell preservation. This represents a significant advance in treatment precision,” the authors wrote.

SOURCE:

Conducted by Danijela Tatovic, of the Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK, and colleagues. This study was published online July 30, 2024, in Nature Medicine.

LIMITATIONS:

T-cell assays were exploratory rather than primary endpoints. No adjustment made for multiple testing. Underpowered to detect changes in metabolic parameters.

DISCLOSURES:

Funded by the Efficacy and Mechanism Evaluation Programme, a partnership between the National Institute for Health and Care Research and the Medical Research Council, as well as Breakthrough T1D and Diabetes UK. Danijela Tatovic has no further disclosures.