Effects of secukinumab on metabolic and liver parameters in plaque psoriasis patients

Abstract

Background Psoriasis is associated with metabolic, liver and cardiovascular comorbidity. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin‐17A, has shown significant and sustained efficacy in the treatment of moderate to severe psoriasis. Objectives This was an exploratory post hoc analysis of pooled data from three phase 3 studies in plaque psoriasis patient populations. The objective was to show the course of metabolic and liver parameters under secukinumab, etanercept or placebo treatment over time. A further objective was to assess the impact of selected comorbidities and metabolic characteristics on high‐sensitivity C‐reactive protein (hs‐CRP), as a surrogate marker of systemic inflammation. Methods Data from the phase 3 randomized controlled trials [FIXTURE (NCT01358578), ERASURE (NCT01365455) and SCULPTURE (NCT01406938); n = 3010] were included in this analysis. Patients were treated with secukinumab 150 mg or 300 mg, placebo or etanercept 50 mg (FIXTURE only) as active comparator. A set of metabolic and liver parameters was longitudinally assessed over 52 weeks. Multivariate regression analyses assessed the impact of selected comorbidities and metabolic characteristics on hs‐CRP levels at baseline and under treatment. Results Secukinumab treatment reduced hs‐CRP levels. Body weight and uric acid levels tended to decrease over 52 weeks with secukinumab. Secukinumab showed a neutral effect on fasting plasma glucose, lipid parameters and liver enzymes. Psoriatic arthritis, metabolic syndrome, obesity, impaired glucose metabolism, and hyperuricemia were each associated with increased hs‐CRP levels at baseline. Concomitant obesity attenuated the decline in hs‐CRP under treatment. Conclusions These analyses suggest neutral to favourable long‐term trends in metabolic and liver parameters under secukinumab treatment. Metabolic comorbidities were associated with increased hs‐CRP levels, reflecting the role of systemic inflammatory processes in their pathophysiology.

Methotrexate vs secukinumab safety in psoriasis patients with metabolic syndrome

“…16,17 In contrast, IL-17A inhibitor secukinumab had a neutral effect on the metabolic parameters as already described in a previous subanalysis assessing fasting plasma glucose, lipid parameters (triglycerides, cholesterol, HDL, and LDL) and liver enzymes, from the phase 3 randomized controlled trials (ie, FIXTURE, ERASURE, and SCULP-TURE). 18 The greater efficacy of secukinumab over methotrexate in terms of PASI 75 and PASI 90 reduction was consistent with the results a network meta-analysis on systemic pharmacological treatments for chronic plaque psoriasis, 19 although our finding should be taken with caution because it was not blinded.…”

Psoriatic Arthritis and Diabetes Mellitus: A Narrative Review

“…To the best of our knowledge, only a clinical study on the effects of anti-IL-17 on DM and insulin sensitivity has been conducted. A study by Egeberg et al on patients treated with ixekizumab and another one by Gerdes et al on patients treated with secukinumab (both anti-IL-17A agent) found no significant differences in FBG with the placebo [96,97].…”

Changes in metabolic parameters in psoriatic patients treated with secukinumab

“… 28 Gerdes et al demonstrated that secukinumab had a neutral effect on lipid parameters. 20 In the VIP-S study, 29 slight increases in total cholesterol and LDL were observed following secukinumab treatment, but no changes in inflammatory markers or TG levels were seen. Consistent with Gerdes’ study, LDL, HDL, and total cholesterol levels remained unchanged in our study; however, the TG level increased significantly in PASI-90–, who had higher baseline hs-CRP levels than PASI-90+.…”