The Effect of Tildrakizumab on Cardiometabolic Risk Factors in Psoriasis by Metabolic Syndrome Status: Post Hoc Analysis of Two Phase 3 Trials (ReSURFACE 1 and ReSURFACE 2)

Mean percent changes from baseline (95% CI) at week 64/52 for patients with MetS relative to patients without MetS were –1.9 (–4.0, 0.2) vs 0.2 (−1.0, 1.4) for SBP, –0.8 (–3.6, 2.0) vs 0.9 (–0.5, 2.3) for DBP, and 12.6 (0.8, 24.4) vs 2.9 (–0.3, 6.1) for FG. The increased mean change in FG was due to 3 outlier values; median percent change in FG was 0.7% vs 1.0% in patients with vs without MetS, respectively.

Median FG values at baseline and week 64/52 for patients receiving tildrakizumab 100 mg with (109.0 and 103.0 mg/dL) and without MetS (91.0 and 93.0 mg/dL) were comparable; values for tildrakizumab 200 mg with (both 101.0 mg/dL) and without MetS (94.0 and 93.0 mg/dL) were also similar (Figure 2A). Percentages of patients with glucose values shifts from baseline are shown in Figure 2B.

This is the first study to examine the impact of IL-23 inhibition alone on cardiometabolic risk factors in patients with moderate to severe psoriasis with and without MetS. In this exploratory analysis, changes in cardiometabolic disease risk factors following treatment with tildrakizumab were limited and generally similar regardless of tildrakizumab dose or MetS status. In patients with MetS receiving tildrakizumab 100 mg, mean changes in FG, TG, and SBP were numerically decreased relative to patients without MetS; patients with MetS receiving tildrakizumab 200 mg had numerical decreases in mean changes in SBP and DBP relative to patients without MetS. Patients without MetS did not show increases in risk factors for MetS during the study. Targeted, prospective studies may provide further understanding of these findings.

The limited changes in cardiometabolic risk factors in patients with psoriasis following tildrakizumab treatment are consistent with a recent post hoc clinical study reporting no increased short-term risk of increased CV events or worsening diabetic complications by MetS status.¹⁹ These results support the safety of tildrakizumab on cardiometabolic risk factors for psoriasis patients regardless of MetS status. Since the odds of having cardiometabolic risk factors of MetS increase with the severity of psoriasis,²³ further analyses on patient subgroups by disease severity are needed to evaluate differential impact of tildrakizumab on these factors. In addition, there were no dose-related effects of tildrakizumab treatment. Importantly, unlike with other biologics,^12,17 patients without MetS did not develop new MetS risk factors following tildrakizumab treatment.

While recent studies demonstrate an association between MetS and psoriasis, and recently published guidelines address management of comorbidities—including MetS—in psoriasis patients, there are limited data on the effect of biologic treatments on CV risk factors of MetS.^19,24 In a recent study in patients with psoriatic arthritis, etanercept and adalimumab significantly improved the MetS components of waist circumference, TG, HDL-C, and glucose compared with methotrexate.²⁵ Treatment of psoriasis with secukinumab did not alter adipocytokine lev-