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)

Abstract

Background: Metabolic syndrome (MetS) is the most prevalent comorbidity in psoriasis and increases the risk of cardiovascular disease, diabetes, and mortality. Assessment of impacts of biologic therapies on cardiometabolic risk factors are relatively limited. This study evaluated the effect of tildrakizumab on cardiometabolic risk factors in patients with moderate to severe plaque psoriasis and stratified by MetS status. Methods: In this post hoc analysis of reSURFACE 1/2, tildrakizumab 100 and 200 mg were continuously administered to patients with moderate to severe plaque psoriasis at weeks 0 and 4, and every 12 weeks thereafter. Mean and mean percent changes from baseline were assessed for fasting serum glucose, low/high-density lipoprotein-cholesterol, total cholesterol, triglyceride levels, body weight, and blood pressure at week 64/52 for reSURFACE 1 and 2, respectively, in patients with and without MetS. Results: A total of 369 patients in reSURFACE 1 and 2 received continuous tildrakizumab 100 mg and 330 received tildrakizumab 200 mg; 21.4% and 20.3% in reSURFACE 1 and 2, respectively, had MetS. At week 64/52, mean changes in cardiometabolic risk factors from baseline did not significantly differ regardless of MetS status. Numerically larger mean decreases in fasting glucose, triglycerides, and systolic blood pressure following tildrakizumab 100 mg and in systolic and diastolic blood pressure following tildrakizumab 200 mg were observed in patients with MetS relative to those without MetS. Conclusions: Changes in cardiometabolic disease risk factors following tildrakizumab treatment were limited. Risk factors were not increased in patients with MetS vs without MetS.

Five‐year efficacy and safety of tildrakizumab in patients with moderate‐to‐severe psoriasis who respond at week 28: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2)*

“…Safety data were generally comparable with the 3‐year analysis and results from treatment for up to 4 years with guselkumab and 2 years with risankizumab, supporting overall safety of IL‐23p19 inhibitors 11–13 . TIL safety findings in patients with elevated risk for AE‐SI, such as patients with metabolic syndrome 14,15 and elderly patients, 16 do not differ significantly from data presented here; long‐term analyses are ongoing. Safety concerns with anti‐IL‐17 agents include candidiasis, inflammatory bowel disease and suicidal ideation (brodalumab only) 17 .…”

Clinical Efficacy and Safety of Psoriasis Treatments in Patients with Concomitant Metabolic Syndrome: A Narrative Review

“…In one retrospective study, treatment with adalimumab, etanercept, and ustekinumab was associated with a 9% increase in serum triglyceride levels in 139 patients diagnosed with psoriasis [ 72 ]. Safety analyses of the secukinumab and ixekizumab clinical trials revealed no clinically relevant effects on lipid profiles [ 73 , 74 ], and analysis of serum lipid profiles in patients with or without MetS treated with tildrakizumab showed very limited changes from baseline [ 75 ].…”

“…Clinical trial data assessing cardiometabolic laboratory parameters following secukinumab and ixekizumab treatment showed no significant changes from baseline fasting glucose levels or insulin sensitivity [ 63 , 73 , 74 ]. Tildrakizumab use was not associated with consistent changes from baseline glucose levels, and favorable trends were observed in some patients [ 75 ]. Comparable data are not yet available for risankizumab and guselkumab.…”

Psoriatic Arthritis and Metabolic Syndrome: Is There a Role for Disease Modifying Anti-Rheumatic Drugs?

“…Moreover, it has been hypothesized that IL-23 inhibition may be more effective in patients with comorbidities in PsO patients (83). However, a recent post-hoc analysis of two clinical trials revealed no differences between PsO patients with and without MetS (84). Nevertheless, no evidence on its impact on MetS components in PsA is available.…”