Thiopurines for maintenance therapy of ulcerative colitis in adults

For patients with severe initial disease or frequent relapses despite maintenance therapy with 5-aminosalicylates, prolonged remission may be achieved with a thiopurine.

For the steps that should be undertaken before starting thiopurine therapy, see Considerations before starting immunomodulatory therapy in the Rheumatology guidelines—the considerations are the same as for rheumatological diseases. Thiopurine methyltransferase (TPMT) genotype (or phenotype) testing should be performed before starting therapy (see Specific considerations for use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs))—TPMT genotype (or phenotype) testing is the same as for rheumatological diseases.

If a thiopurine is required for maintenance therapy of ulcerative colitis, add:

For factors to consider when reviewing the patient after thiopurine therapy has started, see Considerations during immunomodulatory therapy in the Rheumatology guidelines—the considerations are the same as for rheumatological diseases.

Thiopurines are associated with potentially significant adverse effects (eg hepatitis, lymphopenia, pancytopenia, pancreatitis). Monitor carefully for complications, especially during the first 3 months of therapy, with blood tests every 2 to 4 weeks. For details, see Specific considerations for use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)—the monitoring requirements are the same as for rheumatological diseases. The European Crohn’s and Colitis organisation website also includes information about monitoring required throughout thiopurine therapy.

Adverse effects of thiopurines can limit tolerability and adherence. This can be due to shunting, where thiopurines are preferentially metabolised to 6-methyl-mercaptopurine (6-MMP) in preference to 6-tioguanine nucleotides (6-TGN), resulting in adverse effects (eg hepatitis, nausea) and decreased efficacy. This can be confirmed by measuring thiopurine metabolites.

Shunting can be reversed by co-administration of allopurinol; reduce the dose of azathioprine or mercaptopurine to one-third of the patient’s current dose and addThe Gastroenterological Society of Australia (GESA), Updated 2018:

An alternative therapy for patients who cannot tolerate azathioprine or mercaptopurine is tioguanine. UseMeijer, 2016:

The factors to consider when reviewing the patient after tioguanine therapy has started are the same as for azathioprine and mercaptopurine, see Considerations during immunomodulatory therapy in the Rheumatology guidelines—the considerations are the same as for rheumatological diseases.