Infliximab Is Associated With an Increased Risk of Serious Infection in Patients With Psoriasis in the U.K. and Republic of Ireland

Results From the British Association of Dermatologists Biologic Interventions Register (BADBIR)

Z.Z.N. Yiu; ; D.M. Ashcroft; I. Evans; K. McElhone; M. Lunt; C.H. Smith; S. Walton; R. Murphy; N.J. Reynolds; A.D. Ormerod; C.E.M. Griffiths; R.B. Warren; BADBIR Study Group

Disclosures

The British Journal of Dermatology. 2019;180(2):329-337. 

In This Article

Abstract and Introduction

Abstract

Background: Patients with psoriasis and clinicians are concerned that infliximab may be associated with a risk of serious infections.

Objectives: To compare the risk of serious infections associated with infliximab in patients with chronic plaque psoriasis against a cohort on nonbiologic systemic therapies.

Methods: A prospective cohort study was performed using data from the British Association of Dermatologists Biologic Interventions Register (BADBIR). Infliximab was compared with nonbiologic systemic therapies, inclusive of any exposure to methotrexate, ciclosporin, acitretin, fumaric acid esters, psoralen-ultraviolet A or hydroxycarbamide. Serious infections were those associated with hospitalization, the use of intravenous antimicrobial therapy and/or those that led to death. Propensity score inverse probability treatment weights were used to adjust for potential confounding from a priori identified covariates. Cox proportional hazards models were calculated to obtain hazard ratios (HRs).

Results: In total, 3843 participants were included for analysis up to October 2016. The incidence rates were significantly higher in the infliximab cohort (47·8 per 1000 person-years) [95% confidence interval (CI) 35·7–64·0], compared with 14·2 per 1000 person-years (95% CI 11·5–17·4) in the nonbiologic systemic cohort. Infliximab was associated with an overall increase in the risk of serious infection compared with nonbiologics [adjusted HR (adjHR) 1·95, 95% CI 1·01–3·75] and methotrexate only (adjHR 2·96, 95% CI 1·58–5·57) and a higher risk of serious infection in the first 6 months of therapy (adjHR 3·49, 95% CI 1·14–10·70).

Conclusions: Infliximab is associated with an increased risk of serious infections compared with nonbiologic systemic therapies in patients with psoriasis in the U.K. and the Republic of Ireland.

Introduction

Infliximab, a chimeric monoclonal antibody against tumour necrosis factor-α, is highly efficacious for the treatment of psoriasis.[1] In the U.K., infliximab use for psoriasis is reserved for patients with very severe disease, i.e. with a Psoriasis Area and Severity Index (PASI) ≥ 20 and Dermatology Life Quality Index (DLQI) > 18, compared with other biologic therapies where the disease severity criteria are lower, i.e. PASI ≥ 10, DLQI > 10. The British Association of Dermatologists guidelines for biologic therapies in psoriasis specifically recommend that infliximab is reserved for people with very severe disease or where other available biologic agents have failed or cannot be used.[2] By indication, patients treated with infliximab are therefore substantially different to those treated with other biologic therapies.

One of the main adverse events leading to discontinuation of biologic therapies is infection.[3] Serious infections, which are defined as those associated with significant morbidity or mortality, are therefore a legitimate concern for clinicians and patients. Most of the evidence for the quantification of the risk of serious infection in patients with psoriasis on infliximab is drawn from data in randomized clinical trials (RCTs) with important limitations including poor external validity,[4] low event rates and unclear reporting of outcome.[5] A systematic review of RCTs found that infliximab was associated with a nonstatistically significant increase in the risk of serious infection compared with placebo at weeks 20–30 [Peto odds ratio 3·53, 95% confidence interval (CI) 0·31–40·37].[5] Two prospective observational cohort studies have reported on the risk of serious infection with infliximab in patients with psoriasis; one study with 184 patients (264·2 person-years) on infliximab showed nonstatistically significant increased risk with infliximab compared with methotrexate,[6] while another study showed statistically significant increased risk compared with retinoids/phototherapy in a prevalent cohort (1151 patients, 2253 person-years) but not in an incident cohort (246 patients, 324 person-years).[7] Both observational studies were limited by a small incident cohort of patients on infliximab.

Our objective is to determine whether infliximab elevates the risk of serious infection above that of nonbiologic systemic therapies in patients with psoriasis, using a large, national, prospective psoriasis registry – the British Association of Dermatologists Biologic Interventions Register (BADBIR).

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