Impact of psoriasis disease activity and other risk factors on serum urate levels in patients with psoriasis and psoriatic arthritis-a post-hoc analysis of pooled data from three phase 3 trials with secukinumab

Abstract

Objectives: Our aims were to determine if the Psoriasis Area Severity Index (PASI) score and serum urate (SU) levels were associated at baseline and whether the change in PASI score during 12 weeks of treatment resulted in a significant change in SU, adjusted for relevant confounders.

Methods: Data from patients with psoriasis/PsA (n = 1042/204) in three phase 3 randomized control trials treated with secukinumab (dose 300 mg, n = 628) or placebo (n = 414) were pooled. At baseline, values for SU, PASI and the following covariates were assessed: age, sex, BMI, estimated glomerular filtration rate, and medication with diuretics. To assess the changes in PASI (ΔPASI) and SU (Δurate), the differences (week 12 minus baseline) in patients receiving the active drug were used. Multivariable linear regression, adjusting for covariates, was used to assess the association between PASI and SU at baseline with all patients pooled and to assess the association between Δurate and ΔPASI over 12 weeks of treatment with secukinumab.

Results: The degree of skin involvement of psoriasis showed a statistically significant, albeit modest, association with SU (R 2 = 0.014, P < 0.0001 univariately), whereas known risk factors for hyperuricaemia had a much larger impact cross-sectionally at baseline (R 2 = 0.33, P < 0.0001). Furthermore, a substantial improvement in PASI score resulted in only a modest decrease of SU over 12 weeks of treatment with secukinumab (R 2 = 0.014, P < 0.0001 univariately).

Conclusions: There is a statistically significant, albeit modest, association with both extent and change in PASI score and SU in patients with psoriasis, compatible with a potential pathophysiological relationship between urate and psoriasis.

Trial registration: ERASURE: clinicaltrials.gov, https://ichgcp.net/clinical-trials-registry/NCT01365455" title="See in ClinicalTrials.gov">NCT01365455; FIXTURE: clinicaltrials.gov, https://ichgcp.net/clinical-trials-registry/NCT01358578" title="See in ClinicalTrials.gov">NCT01358578; SCULPTURE: clinicaltrials.gov, https://ichgcp.net/clinical-trials-registry/NCT01406938" title="See in ClinicalTrials.gov">NCT01406938.

Keywords: gout; hyperuricaemia; psoriasis; risk factors; urate.

© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig. 1

Urate and Psoriasis Area Severity Index score at weeks 0 and 12 for placebo and to week 52 for secukinumab-treated patients (A) Serum urate at weeks 0 and 12 for the placebo group and at intervals between baseline and week 52 for the secukinumab-treated group with 95% CIs. Means of urate (in micromoles per litre) are given in the table below. (B) PASI score at weeks 0 and 12 for the placebo group and at intervals between baseline and week 52 for the secukinumab-treated group with 95% CIs. Means of PASI score are given in the table below. PASI: Psoriasis Area Severity Index.

Fig. 2

Multivariable linear regression models, with urate at baseline as the dependent variable, in secukinumab and placebo groups n = 1042. All continuous variables were standardized, with the exception of the dependent variable, urate. eGFR: estimated glomerular filtration rate; NS, not significant.