About 10% of patients with autoimmune hepatitis are nonresponsive or intolerant to thiopurine therapy.
A skewed metabolism, leading to the preferential generation of toxic thiopurine metabolites instead of the metabolic active 6-tioguanine nucleotides, may explain this unfavorable outcome.
Dr de Boer and colleages examined co-administration of allopurinol to low-dose thiopurine therapy may effectively revert this deviant metabolism, as has been shown in inflammatory bowel disease.
The team described the effect of adding allopurinol to low-dose thiopurine therapy in patients with AIH with intolerance or nonresponse to normal thiopurine dosages due to a skewed metabolism.
The researchers examined the clinical efficacy and tolerability of allopurinol–thiopurine combination therapy with allopurinol 100 mg and low-dose thiopurine in eight AIH patients with a skewed thiopurine metabolism.
Patients were switched because of dose-limiting intolerance, nonresponse or loss of response to conventional thiopurine treatment.
|All 8 patients showed biochemical improvement with a reduction|
|Alimentary Pharmacology & Therapeutics|
The research team reported that all 8 patients showed biochemical improvement with a reduction in median alanine aminotransferase levels of 62 U/L at start to 35 U/L at 1 month.
This clinical benefit was sustained in 7 patients.
The doctors found that allopurinol–thiopurine combination therapy effectively bypassed thiopurine side effects in 4 of 5 patients.
Median 6-tioguanine nucleotides levels increased from 100 to 200 pmol/8 × 108 red blood cells at 3 months.
The researchers observed that median 6-MMP levels decreased in all patients from 6090 to 175 pmol/8 × 108 RBC.
Dr de Boer's team concluded, "Allopurinol safely and effectively optimises thiopurine therapy in patients with autoimmune hepatitis with intolerance and/or nonresponse due to an unfavorable thiopurine metabolism."