Actieve thiopurinemetabolieten bij pediatrische patiënten met inflammatoire darmziekten in remissie: Azathioprine monotherapie versus combinatietherapie met TNF-α-blokkers

To compare the concentration of the active metabolites of azathioprine (AZA), 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine ribonucleotides (6-MMPR), in paediatric patients with quiescent inflammatory bowel disease (IBD) on AZA monotherapy and AZA in combination with anti-tumour necrosis factor (TNF) therapy (i.e. infliximab [IFX] or adalimumab [ADAD. Design and methods In this exploratory retrospective observational study we extracted the medical records of paediatric IBD patients treated with AZA, IFX or ADA between January 1st 2009 and December 31st 2019 in Zuyderland Medical Centre, Heerlen/Sittard-Geleen, the Netherlands. 6-TGN levels were compared between patients on AZA monotherapy and combination therapy. In the combination therapy group, the correlation between 6-TGN levels and anti-TNF-α trough levels was evaluated. Results Thirty-six paediatric patients with IBD were included (12 patients on combination therapy and 24 patients on AZA monotherapy). The mean 6-TGN level was 298 pmol/8*108 red blood cells (RBC) in the combination therapy group and 360 pmol/8*108 RBC in the AZA monotherapy group (P = 0.122). From the 12 patients on combination therapy, 9 IFX trough levels were available. There was no correlation between 6-TGN level and IFX trough level. In 5 out of 9 patients (55%) an IFX trough level of < 3 mg/L was found (mean 3.3 mg/L; standard deviation 1.6). Conclusion In this study, the 6-TGN and 6-MMPR levels in paediatric IBD patients treated with AZA in combination with IFX or ADA were comparable with those of patients on AZA monotherapy. Further (prospective) research in a larger paediatric patient population is needed to evaluate whether relatively low 6-TGN levels could be sufficient to maintain long term clinical remission in patients on azathioprine and anti-TNF combination therapy.