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6-thioguanine shows favorable response for autoimmune hepatitis

Recently published data showed that treatment with 6-thioguanine demonstrated similar success rates and favorable tolerance compared with mycophenolate mofetil for autoimmune hepatitis, or AIH.

“Studies in inflammatory bowel disease are increasingly considering the use of 6-mercaptopurine (6-MP) or 6-thioguanine (6-TG), which both exhibit a more direct metabolism to the active metabolite of azathioprine: 6-TG nucleotides,” Clémence Legué, MD, from the Centre Hospitalier Universitaire de Rennes, France, and colleagues wrote. “Our results show that 6-TG could be considered as a relevant option for second-line therapy for AIH in azathioprine-intolerant patients.”

Legué and colleagues retrospectively reviewed hospital data of 17 patients with AIH who received treatment with 6-thioguanine (6-TG) as second or third-line therapy.

Mean patient age was 54 years (range, 46-68 years) and autoimmune scores ranged from 6 to 7. Patients previously discontinued treatment with azathioprine after an average of 2 months (range, 1.3-4.2 months) due to digestive (n = 11), cutaneous (n = 3), hematologic (n = 2) or nonresponse-related intolerance (n = 1).

Eleven patients received 6-TG as second-line therapy and six patients received it as third-line therapy after intolerance to mycophenolate mofetil following azathioprine.

Side effects from azathioprine therapy regressed after initiation of 6-TG in all patients, including normalization of transaminases within 3 months for 16 patients.

Eleven patients maintained biologic response, one patient was lost to follow-up, and one patient ceased 6-TG therapy after 13 months due to anemia. Four patients relapsed including a patient with previous azathioprine intolerance.

Of the nonresponders, one patient had corticosteroids reintroduced and displayed normalized transaminases. Three patients switched to tacrolimus or mycophenolate mofetil.

Two patients experienced dry-eye syndrome and anemia. One patient with cirrhosis had cytopenia that regressed after 6-TG was decreased from 20 mg per day to 10 mg per day.

Eight patients who had liver biopsies after an average of 35 months (range, 20-52 months) of treatment. One patient who had sinusoidal fibrosis and thickening of the hepatic vein wall at baseline showed signs of nodular regenerative hyperplasia after 10 months without clinical portal hypertension.

Of the two patients with liver biopsies whose fibrosis worsened, one ceased 6-TG treatment after 1 month and 1 relapsed. – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.