Methotrexate combined with isoniazid treatment for latent tuberculosis is well tolerated in patients with rheumatoid arthritis: experience from an urban arthritis clinic.
OBJECTIVE
Reactivation of Mycobacterium tuberculosis (TB) is a significant problem with all available tumour necrosis factor (TNF) antagonists when used to treat rheumatoid arthritis (RA), psoriatic arthritis, psoriasis and other inflammatory diseases. Concerns have been raised regarding the appropriate management of patients with latent TB (LTB) exposure (or active TB infection) before initiating TNF antagonists as the safety data of combined treatment with two potentially hepatotoxic medications, methotrexate (MTX) and isoniazid (INH), is lacking. The goal of this study was to investigate the toxicity of MTX and INH treatment in patients with RA before initiating TNF antagonists.


METHODS
To investigate the toxicity of MTX and INH treatment in patients with RA we performed a retrospective chart review of patients seen at the Bellevue Hospital Arthritis Clinic in New York City between 2002 and 2006. Forty-four patients who were concomitantly treated with both drugs were included. The primary outcome investigated was increase in liver function tests (LFT).


RESULTS
Transient increases in LFT were seen in 11% of patients, but in no case was this more than twice the upper limit of normal values. All abnormal LFT resolved spontaneously without intervention. In addition, no patient has developed signs or symptoms of TB reactivation.


CONCLUSIONS
The use of INH for LTB was well tolerated in patients with RA on a background regimen of MTX. While the risks and benefits of all treatment must always be considered, in our experience the additive risk of INH to MTX in terms of hepatotoxicity was low. None the less it is prudent to follow LFT closely on patients taking this combination.
Mor
A
A
Division of Rheumatology, Department of Medicine, New York University School of Medicine, Hospital for Joint Diseases, 301 East 17th Street, New York, NY 10003, USA. mora01@med.nyu.edu
Bingham
C O
CO
Kishimoto
M
M
Izmirly
P M
PM
Greenberg
J D
JD
Reddy
S
S
Rosenthal
P B
PB
D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007538:Isoniazid / Q000009:adverse effects*; D008111:Liver Function Tests; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D055502:Secondary Prevention; D014376:Tuberculosis / Q000150:complications / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014504:Urban Health
D018501:Antirheumatic Agents; D000995:Antitubercular Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D007538:Isoniazid; D008727:Methotrexate