Successful treatment with very low-dose etanercept in a patient with etanercept-induced liver dysfunction

Abstract

Etanercept is a fusion protein that composes the soluble TNF receptor p75 and Fc region of immunoglobulin G1. Etanercept is usually administered subcutaneously at a dose of 10 or 25 mg twice a week in Japanese patients with rheumatoid arthritis (RA). There are a few reports of etanercept-induced liver dysfunction [1, 2]. A 37-year-old Japanese woman suffered from Raynaud’s phenomenon in 1996. She received a diagnosis of RA in 1998. Although she had high titre of antinuclear antibodies (1:10,240), she had no specific antibodies such as anti-ds DNA antibodies, anti-Scl-70 antibodies and antiSS-A antibodies. The serology for hepatitis B and C was negative. The medication programme for RA included sulfasalazine, bucillamine, methotrexate, mizoribine and actarit, which induced nausea, epigastric pain, persistent coughing, and a sensation of fatigue and numbness, respectively. Auranofin, penicillamine, aurothiomalate and tacrolimus each had no desirable effect. Mizoribine, bucillamine and actarit are used for RA only in Japan. Etanercept was initiated at a dose of 25 mg weekly to the female patient in January 2007. Her DAS28 score using CRP decreased from the level of high disease activity to the level of low disease activity 16 weeks after administration. However, her liver function tests such as ALT had deteriorated progressively since 12 weeks after etanerceptintroduction (Fig. 1). At the 20th week, etanercept was discontinued because of liver dysfunction, while the other medications maintained same. Because her liver function tests improved to a normal range at the 28th week, etanercept was resumed at a dose of 12.5 mg weekly at this point. Unfortunately, her liver function tests again showed abnormal 4 weeks after resumption, and etanercept was discontinued again. At the 36th week, etanercept was tried again at a dose of 12.5 mg every 10 days. Thereafter, her liver function tests remained within normal values, and her DAS28 score remained stable within good response by the EULAR criteria for 90 weeks (Fig. 1). Her hand X-ray did not deteriorate for 2 years (data not shown). She received etanercept at total doses of 37.5 mg monthly because of etanercept-induced and dose-dependent liver dysfunction. Her RA activity stabilised in good conditions with etanercept, which was used at even lower dose than the usual. Leak and Rincon-Aznar reported a similar patient with psoriatic arthritis, who experienced dose-related etanercept-induced liver toxicity [1]. It might