TDM offers benefits in thiopurine-treated children with leukaemia, IBD

Therapeutic drug monitoring (TDM) helps identify children treated by thiopurine for acute lymphoblastic leukaemia (ALL) and inflammatory bowel disease (IBD) who have not reached their target levels or are over treated, reports a recent study.

“Including TDM in follow-up may help physicians to adjust dosage with the aim of reducing adverse effects and improve treatment outcome,” the investigators said.

This study analysed the first paediatric TDM samples obtained in 2021, regardless of indication and thiopurine drug. Target concentration ranges stood at 200‒500, <6,000 pmol/8 × 10⁸ red blood cells (RBC) for active 6-thioguanine (6TGN) and 6-methylmercaptopurine nucleotides (6MMPN).

A total of 492 children were evaluated, of whom 64.8 percent had IBD, 22.6 percent had ALL, and 12.6 percent had another autoimmune disease (mean ages at TDM: 7.5 years in ALL and 13.7 years in IBD; p<0.0001). ALL patients received 6-mercaptopurine (mean dose 1.7 mg/kg/d with methotrexate), and those with IBD received azathioprine (1.9 mg/kg/d with anti-inflammatory drugs and/or monoclonal antibodies).

Median concentrations were 213.7 and 1,144.6 pmol/8 × 10⁸ RBC for 6TGN and 6MMPN, respectively. Of the children, only 38.8 percent reached the recommended therapeutic range for both compounds. Fifty-seven out of 260 patients had “abnormal” aminotransferases and blood tests, of which 8.1 percent had high alanine aminotransaminase and 3.4 percent had abnormal blood count.

Age at TDM and thiopurine methyltransferase genotype in ALL and azathioprine dose in IBD significantly correlated with increased 6TGN. “The impact of associated treatment in IBD patients was also significant,” according to the investigators.

“Azathioprine and 6-mercaptopurine are prescribed in ALL and IBD,” they noted.