Absolute and Relative Risk of New-Onset Psoriasis Associated With Tumor Necrosis Factor-α Inhibitor Treatment in Patients With Immune-Mediated Inflammatory Diseases

Abstract

ImportanceTumor necrosis factor-α inhibitor (TNFi)–associated psoriasis is a rare adverse event following TNFi treatment. Data on the risk of developing TNFi-associated psoriasis when treated with TNFi are sparse.ObjectiveTo investigate the associated risk between new-onset psoriasis and TNFi treatment compared with nonbiologic conventional treatment.Design, Setting, and ParticipantsUsing Danish national registries (1995-2018), this cohort study included patients with inflammatory bowel disease (IBD) and/or rheumatoid arthritis (RA) who received either conventional therapy or TNFi treatment. Patients may not have been diagnosed with psoriasis prior to initiation of treatment. Patients were followed up for up to 5 years. Cox regression models with robust variance were used to compare the risk of developing any type of psoriasis, nonpustular psoriasis, and pustular psoriasis. Patients receiving conventional therapy were used as reference. Data analysis was performed from January 1995 to December 2018.ExposuresFor the present study, the term conventional therapy was used for the nonbiological therapy. For biological therapy, a distinction was made between TNFi treatment and non-TNFi biological therapy.Main Outcomes and MeasuresThe outcome of psoriasis was defined as a registered International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code of psoriasis and/or having 2 consecutive prescriptions of topical vitamin D analogues.ResultsThe study included 109 085 patients, of which 62% were female. Median (IQR) age was 50 (34-64) years. Of the included patients, 108 024 received conventional therapy and 20 910 received TNFi treatment. During follow-up, 1471 (1.4%) patients developed any type of psoriasis, of which 1332 developed nonpustular psoriasis, 127 patients developed palmoplantar pustulosis, and 12 patients developed generalized pustulosis. The incidence rates for developing any type of psoriasis per 1000 patient-years were 3.0 (95% CI, 2.9-3.2) for conventional therapy and 7.8 (95% CI, 7.5-8.9) for TNFi. During treatment with TNFi, the hazard ratio was 2.12 (95% CI, 1.87-2.40; P < .001) for developing nonpustular psoriasis and 6.50 (95% CI, 4.60-9.23; P < .001) for pustular psoriasis compared with conventional treatment. Exposure needed for 1 additional patient to be harmed was 241 patient-years for any type of TNFi-associated psoriasis, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis.Conclusions and RelevanceIn a Danish nationwide cohort of patients with immune-mediated inflammatory diseases treated with TFNi or conventional treatment and no history of psoriasis, in TFNi-treated patients, nonpustular types of psoriasis constituted the most events, whereas pustular types of psoriasis had the highest relative risk. Although the risk of new-onset psoriasis increased for both nonpustular and pustular types of psoriasis in TFNi-treated patients, the absolute risk remained modest at 241 patient-years of exposure need for 1 additional event and an estimated absolute risk difference around 5 per 1000 patient-years, indicating that the approach to treatment of patients in need of TNFi treatment should not change.

Palmoplantar Pustulosis: A Systematic Review of Risk Factors and Therapies

“… 19 , 20 TNF-α-induced non-pustular psoriasis had a higher risk of occurring than PPP, but PPP had a higher relative risk (HR 6.5, p<0.001). 22 In contrast to PPP occurring independently of TNF-α inhibitors, TNF-α-induced PPP was more common in men (HR 19.682) and younger patients (HR 14.318). 21 …”

“…Increased risk predominant in younger patients (HR 14.318, 95% CI 2.915–70.315). Infliximab but not adalimumab showed significant associations with risk of PPP: HR 9.504, 95% CI 2.767–32.648 High Thein D, 2022 22 Cohort study 3 TNF-α inhibitor 109,085 108,024 patients received conventional therapy and 20,910 received TNF-α inhibitor, 62% female, median age 50 (34–64) years with TNF-α inhibitor for IBD or RA 0.12% development of new PPP. TNF-α inhibitor-associated Pso: Non-pustular Pso is more prevalent but pustular Pso has the highest relative risk (HR of developing a pustular type of psoriasis 6.50 (95% CI, 4.60–9.23; P < 0.001)) High Kim M, 2021 23 Retrospective cohort study 3 Nail involvement 116 116 patients with PPP from Seoul University Hospital, 59.9% female, 14.7% had concomitant Pso and 8.6% had concomitant PsA, 66.3% had Involvement NAPSI is correlated with PPPASI (p=0.01) and involvement area (p=0.04); Crumbling was associated with higher PPPASI (p = 0.01) and onycholysis was associated with lower PPPASI (P = 0.03).…”

Tumor necrosis factor‐α inhibitor‐associated psoriasis: Facts and hypotheses

“…Notably, biologics reduced the severity of symptoms in some patients and affected RA activity; however, determining which biologics resulted in less severe disease was difficult. Recently, Thein et al 15 reported hazard ratios (HRs) of 2.12 (95% CI: 1.87–2.40; P < 0.001) and 6.50 (95% CI: 4.60–9.23; P < 0.001) for developing non‐pustular and pustular psoriasis, respectively, compared with conventional treatment.…”

Algorithmic identification of treatment-emergent adverse events from clinical notes using large language models: a pilot study in inflammatory bowel disease

“…Existing approaches for AE surveillance may involve prospective registry studies, spontaneous postmarketing reporting (e.g., the Food and Drug Administration’s AE Reporting System [FAERS]) 1 , literature searches, and/or analyses of the structured data from claims and electronic health records databases 2,3 . These approaches have provided important data on the postmarket safety of medications but are limited by expense, small numbers, under/over-reporting 4,5 , missing data, limitations in inferring causality, and suboptimal sensitivity and specificity.…”