Review of Routine Laboratory Monitoring for Patients with Rheumatoid Arthritis Receiving Biologic or Nonbiologic DMARDs

Table 3

Proportions of patients who experienced increases in liver enzymes during RA .

% of	≤6 months	>6 months	Clinical sequelae
	ALT or AST > 3 × ULN	ALT or AST > 3 × ULN
Conventional synthetic DMARDs
Methotrexate	3.6% [60]	>2 × ULN: 12.9% [57]; 25% [56]	3.7% of patients discontinued due to liver toxicity [57]; 4.2% discontinued by 2 years due to liver toxicity [56]
Leflunomide	>5 × ULN: 3.0% [82]	1.5%–6.4% [30, 56]	Due to grade 2 hepatotoxicity, 1 patient (1%) was withdrawn from LEF treatment and 1 patient (1%) continued LEF at a reduced dose [82].; 1.6% of patients discontinued by 2 years [56]
LEF + MTX	6.8% [83]	3.8% for LEF + MTX; (0.8% for MTX + placebo) [30]; 17% [83]	Four patients (4.5%) were withdrawn from treatment due to persistent elevation of plasma liver enzyme level
Sulfasalazine	4% [84]	N/A	N/A
Biologic
Adalimumab	3.5% [85]; <1% (w/MTX) [62]	<1% (w/MTX) [62]	N/A
Infliximab	>5 × ULN: <1%	≥3 × ULN: 5%	N/A
Etanercept	Grades 2–4: 0% [86]	Grades 2–4: 0% [86]	N/A
Golimumab	Any ALT or AST elevation: 0% (monotherapy); 4.4%–6.3% (w/MTX) [58]	N/A	N/A
Tocilizumab	3.4%–6.5% [31, 87]	11% (TCZ + MTX); 2%-3% (MTX → TCZ) [88]; 10.8% [27]	There were no serious liver function disorders during TCZ treatment [89].; Seven patients (1.1%) prematurely discontinued due to elevated liver aminotransferases (with concomitant MTX) [87]
Anakinra	N/A	Patients with elevated liver enzymes: <1% [90]	N/A
Targeted small-molecule DMARD
Tofacitinib	1.1%–1.6% (w/MTX) [91]; ≤1.0% [92]	<1% [91]; 3.2% (w/MTX) [62]	N/A

ALT, alanine aminotransferase; AST, aspartate aminotransferase; DMARD, disease-modifying antirheumatic drug; LEF, leflunomide; MTX, methotrexate; N/A, not available; RA, rheumatoid arthritis; TCZ, tocilizumab; ULN, upper limit of normal. ALT and AST levels, grade 3 was >5 to 10 × ULN and grade 4 was >10 × ULN. are the proportions of patients with ALT or AST ≥ 3 × ULN except where noted. data were available for rituximab, certolizumab, or abatacept. of these patients were also taking methotrexate or nonsteroidal anti-inflammatory drugs. medical letter (personal communication), data on file.