Isoniazid for Latent Tuberculosis Well Tolerated in Patients Taking Methotrexate

August 30, 2007 — The use of isoniazid for latent tuberculosis (LTB) was well tolerated in patients with rheumatoid arthritis (RA) who were already receiving treatment with methotrexate, according to a retrospective chart review reported in the August 20 Online First issue of the Annals of the Rheumatic Diseases.
"Reactivation of Mycobacterium tuberculosis (TB) is a significant problem with all available tumor necrosis factor (TNF) antagonists when used to treat rheumatoid arthritis (RA), psoriatic arthritis, psoriasis and other inflammatory diseases," write Adam Mor, PhD, from New York University School of Medicine in New York, and colleagues. "Concerns have been raised regarding the appropriate management of patients with latent TB (LTB) exposure (or active TB infection) before initiating TNF antagonists since the safety data of combined therapy 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 therapy in RA patients before initiating TNF antagonists."
The study authors retrospectively reviewed the medical records of 44 patients seen at the Bellevue Hospital Arthritis Clinic, New York, NY, between 2002 and 2006, and who were treated simultaneously with methotrexate and isoniazid. The main endpoint was increase in liver function tests (LFTs).
Although 11% of patients had transient increases in LFTs, this in no case exceeded twice the upper limit of normal values, and all resolved spontaneously without intervention. When isoniazid and methotrexate were given together, the incidence of abnormal findings on LFTs was no higher than that seen with either drug given alone.
"The use of INH for LTB was well tolerated in RA patients on a background regimen of MTX," the investigators write. "While the risks and benefits of all therapy must always be considered, in our experience the additive risk of INH to MTX in terms of hepatotoxicity was low. Nonetheless it is prudent to follow LFT closely on patients taking this combination."
None of the patients developed evidence of reactivation of TB reactivation.
Limitations of the study include a small sample, possible selection bias, exclusion of patients with abnormal findings on LFTs at baseline, folic acid treatment used in combination with methotrexate in all patients, and the inability to identify any subset of patients with an increased risk of developing abnormal findings on LFTs during treatment with both drugs.
This study has received no external funding, and the authors have disclosed no relevant financial relationships.
Ann Rheum Dis. Published online August 20, 2007.