RESEARCH - Risk of elevated liver enzymes associated with anti-TNF biologics

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Ann Rheum Dis. 2010 May 6. [Epub ahead of print]

Risk of elevated liver enzymes associated with TNF inhibitor

utilisation in patients with rheumatoid arthritis.

Sokolove J, Strand V, Greenberg JD, Curtis JR, Kavanaugh A, Kremer JM,

Anofrei A, G, Calabrese L, Hooper M, Baumgartner S, Furst DE; on

behalf of the CORRONA Investigators.

1Stanford University, Palo Alto, California, USA.

Abstract

OBJECTIVE: Liver function test (LFT) elevations are reported with the

use of tumour necrosis factor inhibitors (TNF-Is). The aim of this

study was to compare LFT elevations in patients with rheumatoid

arthritis receiving adalimumab (ADA), etanercept (ETN) or infliximab

(INF) enrolled in the Consortium of Rheumatology Researchers of North

America from October 2001 to March 2007.

METHODS: Alanine aminotransferase (ALT) and/or aspartate

aminotransferase (AST) levels >1x upper limit of normal (ULN) were

considered elevations and ALT/AST levels >2x ULN were considered

abnormalities. Treatments included TNF-Is, methotrexate (MTX),

leflunomide and other disease-modifying antirheumatic agents (DMARDs).

Patients were censored after their first LFT elevation. Three

analytical models were evaluated: (1) individual TNF-I vs

non-biological DMARDs (primary model); (2) individual TNF-I plus MTX

vs MTX monotherapy; and (3) limited to new users of individual TNF-I

vs non-biological DMARDs. ORs for LFT elevations were estimated using

generalised estimating equation logistic regression.

RESULTS: 6861 patients (ADA: 849; ETN: 1383; INF: 1449) with 22 522

determinations were analysed. LFT elevations >1x ULN with TNF-I use

were seen in 5.9% of AST/ALT determinations and abnormalities >2x ULN

in 0.77%. In the primary model the adjusted ORs for LFT elevations >1x

ULN were ADA 1.35 (95% CI 1.09 to 1.66), ETN 1.00 (95% CI 0.83 to

1.21) and INF 1.58 (95% CI 1.35 to 1.86). For 2x ULN, adjusted ORs

were ADA 1.72 (95% CI 0.99 to 3.01), ETN 1.10 (95% CI 0.64 to 1.88)

and INF 2.40 (95% CI 1.53 to 3.76). Similar results were obtained in

other models.

CONCLUSION: The overall incidence of LFT elevations >1x ULN with TNF-I

use was uncommon and abnormalities >2x ULN were rarely observed.

Significant differences were most consistently observed with INF, less

commonly with ADA and were not observed with ETN compared with

comparator DMARDs.

PMID: 20448284

http://www.ncbi.nlm.nih.gov/pubmed/20448284

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