Background Anti-TNFα therapy is routinely used in several rheumatic diseases in last fifteen years. However, these drugs have also raised new problems, particularly the increased risk of reactivation of latent tuberculosis (LTBI). Most cases of LTBI develop soon after initiation of anti TNF-α therapy. The risk of TB is higher for patients receiving monoclonal antibody than soluble receptor. The knowledge about this risk leads to a need of screening for active and latent tuberculosis in patients before biological therapy is started. Although the incidence of TB in Czech Republic is decreasing in the last years with the lowest number of reported TB cases in 2010, The Czech Rheumatology Society released very strict recommendations for LTBI screening. In case of proved LTBI the therapy with isoniazid (INH) for six months is obligatory and the treatment with TNF-α inhibitor can be initiated after one month to discriminate side effects of both drugs.
Objectives To evaluate the toxicity of INH in LTBI treatment and the influence of co-medication to hepatotoxicity in different rheumatologic diagnoses.
Methods 87 patients treated with INH due to LTBI were assessed. LTBI was diagnosed by the positivity of PPD test or QFT. We analyzed the occurrence of side effects of INH, mainly the hepatotoxicity. Severe hepatitis was considered when the serum alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), gamma glutamyl transpeptidase (GGT) and/or alkaline phosphatase (ALP) levels were at least three fold increased of the upper limit of normal (ULN).
Results Out of 87 patients treated with INH, 51 (58.6%) were male and 36 (41.4%) female; the mean age in the studied group was 43.4 years (SD ± 13.2), median 40. The number of AS patients was 47 (54%), RA 29 (33.3%) and PsA 11 (12.6%). LTBI was diagnosed and treated before starting TNF-α therapy in 41 cases (47.1%). The other 46 cases (52.9%) had LTBI diagnosed during biological therapy. In this group the mean time of treatment with biologics was 22.7 months (± 20.0), median of 14 months; most of the patients were treated with infliximab (24; 52.2%), adalimumab (17; 37%) and only 5 patients (10.9%) with etanercept.
Out of 87 patients 84 were treated for LTBI with INH in monotherapy and 4 for active TB. One of the patients with active TB was previously treated with INH in recommended doses before starting TNF-α. When evaluating the INH side effects the most frequent was hepatotoxicity and the most often situation was the elevation of liver function tests (LFTs) from normal range to twofold or threefold of ULN (n=30). Nine patients were treated with INH in monotherapy, 21 had other concomitant medication.
Conclusions According to our results the risk of serious hepatotoxicity is only slightly increased. In the studied group of 87 patients a withdrawal of INH due to hepatotoxicity characterized by threefold elevation of ULN was indicated only in four patients (4.6%) and two of them were concomitantly treated with methotrexate. The influence of concomitant medication on LFTs elevation was easily reduced by lowering of doses or withdrawing the drug or in some cases hepatoprotective agents could help. The other side effects were rare in our group; we had just one case of allergy and one uncommon case of optic neuritis.
This work was supported by the grant number 000 000 23728, Ministry of Health of Czech Republic.
Disclosure of Interest K. Hviscova Grant/Research support from: Ministry of Health of Czech Republic, Grant Number 000 000 23728, L. Sedova: None Declared, K. Pavelka: None Declared
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