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. 2022 Sep 1;158(9):997-1004.
doi: 10.1001/jamadermatol.2022.2360.

Absolute and Relative Risk of New-Onset Psoriasis Associated With Tumor Necrosis Factor-α Inhibitor Treatment in Patients With Immune-Mediated Inflammatory Diseases: A Danish Nationwide Cohort Study

David Thein  1   2   3 , Alexander Egeberg  1 , Lone Skov  2   3 , Nikolai Loft  2   3
Affiliations

Absolute and Relative Risk of New-Onset Psoriasis Associated With Tumor Necrosis Factor-α Inhibitor Treatment in Patients With Immune-Mediated Inflammatory Diseases: A Danish Nationwide Cohort Study

David Thein et al. JAMA Dermatol. .

Abstract

Importance: Tumor 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.

Objective: To investigate the associated risk between new-onset psoriasis and TNFi treatment compared with nonbiologic conventional treatment.

Design, setting, and participants: Using 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.

Exposures: For 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 measures: The 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.

Results: The 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 relevance: In 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Mr Thein reported receiving research grants from Herlev and Gentofte Hospital, Mogens Wedell-Wedellsborgs Fond, and Ebba Celinders Legat during the conduct of the study. Dr Egeberg reported having received research funding from Pfizer, Eli Lilly, Novartis, Bristol Myers Squibb, AbbVie, Janssen Pharmaceuticals, the Danish National Psoriasis Foundation, the Simon Spies Foundation, and the Kgl Hofbundtmager Aage Bang Foundation, and honoraria as consultant and/or speaker from AbbVie, Almirall, LEO Pharma, Zuellig Pharma Ltd, Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co, Ltd, Pfizer, Eli Lilly, Novartis, Union Therapeutics, Galderma, Dermavant, UCB, Mylan, Bristol Myers Squibb, and Janssen Pharmaceuticals outside the submitted work. Prof Skov reported personal fees (speaker) from AbbVie, Eli Lilly, Novartis, Pfizer, and LEO Pharma; personal fees (advisory board) from AbbVie, Janssen-Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, Bristol Myers Squibb, Boehringer Ingelheim, and Sanofi; investigator feed to the hospital from AbbVie, Sanofi, Janssen-Cilag, Boehringer Ingelheim, AstraZeneca, Eli Lilly, Novartis, and Regeneron; and grants to the hospital from Novartis, Sanofi, Bristol Myers Squibb, Janssen-Cilag, UCB, and LEO Pharma outside the submitted work. Dr Loft reported personal fees from Janssen-Cilag and Eli Lilly outside the submitted work.

Figures

Figure 1.
Figure 1.. Flow Diagram for the Inclusion and Exclusion of Patients
The patients relevant for the sensitivity analysis are marked with dashed lines. IBD indicates inflammatory bowel disease; IMID, immune-mediated inflammatory disease; RA, rheumatoid arthritis; TNFi, tumor necrosis factor-α inhibitor.
Figure 2.
Figure 2.. Cumulative Incidence Plot of All Types of Psoriasis, Nonpustular Types of Psoriasis, and Pustular Types of Psoriasis
Conventional therapy indicates nonbiologic therapy relevant to inflammatory bowel disease or rheumatoid arthritis. TNFi indicates tumor necrosis factor-α inhibitor.
Figure 3.
Figure 3.. Forest Plot Over the Risk of Developing Psoriasis
TNFi indicates tumor necrosis factor-α inhibitor.
See this image and copyright information in PMC

Comment in

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