The Comparative Safety of Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta-analysis Update of 44 Trials

Tzeyu L. Michaud, Young Hee Rho, Tatyana Shamliyan, Karen M. Kuntz, Hyon K. Choi

Research output: Contribution to journalArticle

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Abstract

Objective The study objective was to evaluate and update the safety data from randomized controlled trials of tumor necrosis factor inhibitors in patients treated for rheumatoid arthritis.

Methods A systematic literature search was conducted from 1990 to May 2013. All studies included were randomized, double-blind, controlled trials of patients with rheumatoid arthritis that evaluated adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab treatment. The serious adverse events and discontinuation rates were abstracted, and risk estimates were calculated by Peto odds ratios (ORs).

Results Forty-four randomized controlled trials involving 11,700 subjects receiving tumor necrosis factor inhibitors and 5901 subjects receiving placebo or traditional disease-modifying antirheumatic drugs were included. Tumor necrosis factor inhibitor treatment as a group was associated with a higher risk of serious infection (OR, 1.42; 95% confidence interval [CI], 1.13-1.78) and treatment discontinuation due to adverse events (OR, 1.23; 95% CI, 1.06-1.43) compared with placebo and traditional disease-modifying antirheumatic drug treatments. Specifically, patients taking adalimumab, certolizumab pegol, and infliximab had an increased risk of serious infection (OR, 1.69, 1.98, and 1.63, respectively) and showed an increased risk of discontinuation due to adverse events (OR, 1.38, 1.67, and 2.04, respectively). In contrast, patients taking etanercept had a decreased risk of discontinuation due to adverse events (OR, 0.72; 95% CI, 0.55-0.93). Although ORs for malignancy varied across the different tumor necrosis factor inhibitors, none reached statistical significance.

Conclusions These meta-analysis updates of the comparative safety of tumor necrosis factor inhibitors suggest a higher risk of serious infection associated with adalimumab, certolizumab pegol, and infliximab, which seems to contribute to higher rates of discontinuation. In contrast, etanercept use showed a lower rate of discontinuation. These data may help guide clinical comparative decision making in the management of rheumatoid arthritis.

Original languageEnglish (US)
Pages (from-to)1208-1232
Number of pages25
JournalAmerican Journal of Medicine
Volume127
Issue number12
DOIs
StatePublished - Dec 1 2014

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Meta-Analysis
Rheumatoid Arthritis
Tumor Necrosis Factor-alpha
Odds Ratio
Safety
Antirheumatic Agents
Confidence Intervals
Randomized Controlled Trials
Infection
Placebos
Therapeutics
Infliximab
Certolizumab Pegol
Adalimumab
Etanercept
Neoplasms

Keywords

  • Adverse events
  • Meta-analysis
  • Rheumatoid arthritis
  • Safety
  • Tumor necrosis factor inhibitors

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The Comparative Safety of Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis : A Meta-analysis Update of 44 Trials. / Michaud, Tzeyu L.; Rho, Young Hee; Shamliyan, Tatyana; Kuntz, Karen M.; Choi, Hyon K.

In: American Journal of Medicine, Vol. 127, No. 12, 01.12.2014, p. 1208-1232.

Research output: Contribution to journalArticle

Michaud, Tzeyu L. ; Rho, Young Hee ; Shamliyan, Tatyana ; Kuntz, Karen M. ; Choi, Hyon K. / The Comparative Safety of Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis : A Meta-analysis Update of 44 Trials. In: American Journal of Medicine. 2014 ; Vol. 127, No. 12. pp. 1208-1232.
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abstract = "Objective The study objective was to evaluate and update the safety data from randomized controlled trials of tumor necrosis factor inhibitors in patients treated for rheumatoid arthritis.Methods A systematic literature search was conducted from 1990 to May 2013. All studies included were randomized, double-blind, controlled trials of patients with rheumatoid arthritis that evaluated adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab treatment. The serious adverse events and discontinuation rates were abstracted, and risk estimates were calculated by Peto odds ratios (ORs).Results Forty-four randomized controlled trials involving 11,700 subjects receiving tumor necrosis factor inhibitors and 5901 subjects receiving placebo or traditional disease-modifying antirheumatic drugs were included. Tumor necrosis factor inhibitor treatment as a group was associated with a higher risk of serious infection (OR, 1.42; 95{\%} confidence interval [CI], 1.13-1.78) and treatment discontinuation due to adverse events (OR, 1.23; 95{\%} CI, 1.06-1.43) compared with placebo and traditional disease-modifying antirheumatic drug treatments. Specifically, patients taking adalimumab, certolizumab pegol, and infliximab had an increased risk of serious infection (OR, 1.69, 1.98, and 1.63, respectively) and showed an increased risk of discontinuation due to adverse events (OR, 1.38, 1.67, and 2.04, respectively). In contrast, patients taking etanercept had a decreased risk of discontinuation due to adverse events (OR, 0.72; 95{\%} CI, 0.55-0.93). Although ORs for malignancy varied across the different tumor necrosis factor inhibitors, none reached statistical significance.Conclusions These meta-analysis updates of the comparative safety of tumor necrosis factor inhibitors suggest a higher risk of serious infection associated with adalimumab, certolizumab pegol, and infliximab, which seems to contribute to higher rates of discontinuation. In contrast, etanercept use showed a lower rate of discontinuation. These data may help guide clinical comparative decision making in the management of rheumatoid arthritis.",
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