Thioguanine is Effective as Maintenance Therapy for Inflammatory Bowel Disease: A Prospective Multicentre Registry Study

Abstract

SUMMARY Background and aims Thioguanine is a well-tolerated and effective therapy for inflammatory bowel disease (IBD) patients. Prospective, effectiveness data are needed to substantiate the role of thioguanine as a maintenance therapy for IBD. Methods IBD patients, who previously failed azathioprine or mercaptopurine, and initiated thioguanine were prospectively followed for 12 months starting when corticosteroid-free clinical remission was achieved (HBI ≤ 4 or SCCAI ≤ 2). Primary endpoint was corticosteroid-free clinical remission throughout 12 months. Loss of clinical remission was defined as SCCAI > 2 or HBI > 4, need of surgery, escalation of therapy, initiation of corticosteroids or study discontinuation. Additional endpoints were adverse events, drug survival, physician global assessment (PGA) and quality of life (QoL). Results Sustained corticosteroid-free clinical remission at month 3, 6 or 12 months was observed in 75 (69%), 66 (61%) and 49 (45%) of 108 patients, respectively. Thioguanine was continued in 86 patients (80%) for at least 12 months. Loss of response (55%) included escalation to biologicals in 15%, corticosteroids in 10% and surgery in 3%. According to PGA scores, 82% of patients were still in remission after 12 months and QoL scores remained stable. Adverse events leading to discontinuation were reported in 11%, infections in 10%, myelo- and hepatotoxicity each in 6% and portal hypertension in 1% of patients. Conclusion Sustained corticosteroid-free clinical remission over 12 months was achieved in 45% of IBD patients on monotherapy with thioguanine. A drug continuation rate of 80%, together with favourable PGA and QoL scores, underlines the tolerability and effectiveness of thioguanine for IBD.

Drug rediscovery in gastroenterology: from off-label to on-label use of thioguanine in inflammatory bowel disease

“…Two multicentre prospective registry studies were required, evaluating TG use in daily IBD practice (specifically regarding effectiveness and toxicity profile). In these studies, sustained corticosteroid-free clinical remission over 12 months was witnessed in 45% of patients with IBD on monotherapy with TG, with a drug continuation rate of 80% and an acceptable safety profile 68. In February 2022, corroborated by the observed data in these registries, the Dutch regulatory authorities unconditionally registered TG for the treatment of IBD in the Netherlands (figure 4).…”

Letter: Thioguanine, an underutilised option in inflammatory bowel disease?

“…6 AEs including nodular regenerative hyperplasia are extremely rare with the doses used for IBD. [6][7][8][9] Additionally, thioguanine produces more predictable 6-TGN metabolites and may have a quicker onset of action and greater clinical efficacy than conventional thiopurines. 9 An interesting addition to the study would have been a third arm using thioguanine, which would mechanistically achieve similar effects to thiopurine/allopurinol co-therapy and would have been simpler to implement.…”

Letter: Thioguanine, an under‐utilised option in inflammatory bowel disease? Authors' reply

“…2 We agree that the use of first-line thioguanine is an interesting proposition, since it achieves clinical remission in patients who have not responded to, or are intolerant of, conventional thiopurines with or without combination allopurinol. 3,4 In the DECIDER study, we do not think a third arm for thioguanine use would have been feasible since this would have required a larger sample size, and since we had already experienced difficulties in reaching our recruitment targets with only two study arms. We agree that the use of thioguanine as the initial thiopurine therapy requires further research and, potentially, its own randomised trial.…”