Dataset Information

The risk of infection and malignancy with tumor necrosis factor antagonists in adults with psoriatic disease: a systematic review and meta-analysis of randomized controlled trials.

ABSTRACT:

Background

There is a need to better understand the safety of tumor necrosis factor (TNF) inhibitors in patients with psoriatic disease in whom TNF inhibitors are frequently used as monotherapy.

Objective

We sought to examine the risks of infection and malignancy with the use of TNF antagonists in adult patients with psoriatic disease.

Methods

We conducted a systematic search for trials of TNF antagonists for adults with plaque psoriasis and psoriatic arthritis. We included randomized, placebo-controlled trials of etanercept, infliximab, adalimumab, golimumab, and certolizumab for the treatment of plaque psoriasis and psoriatic arthritis. Twenty of 820 identified studies with a total of 6810 patients were included. Results were calculated using fixed effects models and reported as pooled odds ratios.

Results

Odds ratios for overall infection and serious infection over a mean of 17.8 weeks were 1.18 (95% confidence interval [CI] 1.05-1.33) and 0.70 (95% CI 0.40-1.21), respectively. When adjusting for patient-years, the incidence rate ratio for overall infection was 1.01 (95% CI 0.92-1.11). The odds ratio for malignancy was 1.48 (95% CI 0.71-3.09) and 1.26 (95% CI 0.39-4.15) when nonmelanoma skin cancer was excluded.

Limitations

Short duration of follow-up and rarity of malignancies and serious infections are limitations.

Conclusions

There is a small increased risk of overall infection with the short-term use of TNF antagonists for psoriasis that may be attributable to differences in follow-up time between treatment and placebo groups. There was no evidence of an increased risk of serious infection and a statistically significant increased risk in cancer was not observed with short-term use of TNF inhibitors.

SUBMITTER: Dommasch ED

PROVIDER: S-EPMC3095673 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Publications

The risk of infection and malignancy with tumor necrosis factor antagonists in adults with psoriatic disease: a systematic review and meta-analysis of randomized controlled trials.

Dommasch Erica D ED Abuabara Katrina K Shin Daniel B DB Nguyen Josephine J Troxel Andrea B AB Gelfand Joel M JM

Journal of the American Academy of Dermatology 20110218 6

<h4>Background</h4>There is a need to better understand the safety of tumor necrosis factor (TNF) inhibitors in patients with psoriatic disease in whom TNF inhibitors are frequently used as monotherapy.<h4>Objective</h4>We sought to examine the risks of infection and malignancy with the use of TNF antagonists in adult patients with psoriatic disease.<h4>Methods</h4>We conducted a systematic search for trials of TNF antagonists for adults with plaque psoriasis and psoriatic arthritis. We included ...[more]

PMID: 21315483

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Project description:Background & aimsTumor necrosis factor (TNF)-α antagonists have been associated with drug-induced liver injury (DILI). We reviewed cases of DILI in the United States to identify those associated with use of TNF-α antagonists.MethodsWe searched the U.S. DILI Network (DILIN) database, from 2003 to 2011, for cases associated with TNF-α antagonists. Mean Roussel-Uclaf Causality Assessment Method scores were calculated. A DILIN severity score was assigned according to a previously published scale, and we identified 6 subjects likely to have DILI associated with use of TNF-α antagonists. We also searched PubMed for articles that reported hepatotoxicity from TNF-α antagonists, identifying 28 additional cases suitable for analysis.ResultsThe drugs presumed to have caused DILI were infliximab (n = 26), etanercept (n = 4), and adalimumab (n = 4). The anti-TNF-α agent was the probable cause of 12 cases of DILI (35%), a very likely cause for 21 (62%), and a definite cause for 1 (3%). Median latency was 13 weeks (range, 2-104); however, 7 cases (20%) had latency periods longer than 24 weeks. Twenty-two of 33 subjects who underwent serologic analysis (67%) tested positive for anti-nuclear and/or smooth muscle antibodies. Of these 22, 17 underwent liver biopsy; 15 subjects had clear features of autoimmunity. The 22 subjects with autoimmune features had longer median latency (16 vs 10 weeks) and higher peak levels of alanine aminotransferase (784 vs 528 U/L) than the 12 without such features. There was 1 case of severe cholestasis. All but one subject improved after discontinuation of the implicated drug; 12 subjects received corticosteroid therapy. No deaths were attributed to liver injury, although one patient with preexistent cirrhosis required liver transplantation.ConclusionsAcute liver injury caused by TNF-α antagonists may be a class effect because multiple agents in this category have been implicated. The most common presentation is an autoimmune phenotype with marked hepatocellular injury, but a mixed non-autoimmune pattern or predominant cholestasis also occurs. The prognosis is usually good after drug discontinuation, although some patients may benefit from a course of corticosteroids. ClinicalTrials.gov: Number, NCT00345930.

Dataset Information

The risk of infection and malignancy with tumor necrosis factor antagonists in adults with psoriatic disease: a systematic review and meta-analysis of randomized controlled trials.

Background

Objective

Methods

Results

Limitations

Conclusions

Publications

The risk of infection and malignancy with tumor necrosis factor antagonists in adults with psoriatic disease: a systematic review and meta-analysis of randomized controlled trials.

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