Azathioprine dose reduction in inflammatory bowel disease patients on combination therapy: an open‐label, prospective and randomised clinical trial

Roblin, Xavier; Boschetti, Gilles; Williet, Nicolas; Nancey, Stéphane; Marotte, Hubert; Berger, Anne‐Emmanuelle; Phélip, Jean-Marc; Peyrin–Biroulet, Laurent; Colombel, Jean Fréd́eric; Tedesco, Émilie Del; Paul, Stéphane; Flourié, Bernard

doi:10.1111/apt.14106

Cited by 109 publications

(99 citation statements)

References 32 publications

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“…In a randomized control trial, 1–1.25 mg/kg/day azathioprine was as effective as full‐dose azathionprine in terms of preventing clinical relapse after 1 year in IBD patients on remission on combination therapy. Thus, a low‐dose immunosuppressant for short duration (6–12 months) is an effective strategy for combination therapy Statement 4: Episodic treatment should be avoided to prevent sensitization.…”

Section: Resultsmentioning

confidence: 99%

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Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

Ooi

Hilmi

Banerjee

et al. 2019

J of Gastro and Hepatol

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The Asia–Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia–Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all‐encompassing, and future revisions are likely as new data continue to emerge.

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Section: Resultsmentioning

confidence: 99%

“…Thus, a low-dose immunosuppressant for short duration (6-12 months) is an effective strategy for combination therapy. [41][42][43]…”

Section: Statementmentioning

confidence: 99%

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

Ooi

Hilmi

Banerjee

et al. 2019

J of Gastro and Hepatol

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“…Conversely, high trough levels have been associated with clinical and biochemical remission, C‐reactive protein and faecal calprotectin normalisation, mucosal healing and even fistula healing . Consequently, different strategies have been developed to tackle low trough levels, such as adding azathioprine to infliximab during the most vulnerable period of 6‐12 months after its initiation, a strategy known as combination treatment . By improving pharmacokinetics, azathioprine co‐treatment increases infliximab trough levels .…”

Section: Introductionmentioning

confidence: 99%

Optimised infliximab monotherapy is as effective as optimised combination therapy, but is associated with higher drug consumption in inflammatory bowel disease

Drobne

Kurent

Golob

et al. 2019

Aliment Pharmacol Ther

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Background: Combination treatment with azathioprine for 6-12 months is the preferred strategy for starting infliximab due to improved pharmacokinetics. However, optimised infliximab monotherapy with proactive dose escalations in case of low trough levels is a potentially safer but under-studied alternative.Aim: To compare the clinical success and infliximab consumption of combination vs optimised monotherapy strategies.Methods: We studied the clinical success and infliximab consumption with both strategies in 149 patients (94 Crohn's disease; 55 ulcerative colitis) starting infliximab and undergoing intensive drug monitoring assisted treatment optimisation.Results: The drug retention rates were similar for optimised monotherapy and combination treatment after induction (96% vs 97%, P = 0.73), after the first year (90% vs 83%, P = 0.23) and at the end of follow-up (74% vs 75%, P = 0.968). Similarly, no significant differences were observed for steroid use at year 1 (5% vs 14%, P = 0.08) or mucosal healing at the end of follow-up (64% vs 67%, P = 0.8). Higher infliximab consumption (7.6 mg/kg q8 weeks [interquartile range (IQR): 5.9-10.3] vs 6.4 mg/kg q8 weeks [IQR: 5.2-8.0], P = 0.019) combined with lower trough levels (1.7 µg/mL [IQR: 0.3-6.6] vs 5.0 µg/mL [2.5-8.7], P = 0.012) resulted in almost 3-fold higher drug-to-trough ratio (3.9 vs 1.5) in monotherapy compared to combination strategy at year 1. At the end of follow-up, when azathioprine had been discontinued for a median of 14 [IQR: 3-33] months, these differences disappeared. Conclusions:In this study, optimised infliximab monotherapy was as clinically effective as combination therapy, but was associated with significantly higher infliximab consumption. The infliximab-sparing effect disappeared after azathioprine withdrawal.

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“…Future prospective studies are needed to evaluate the optimal 6‐TGN concentration in CD patients with NUDT15 wild type. Last but not the least, the present study excluded cases with concomitant biologics given that prior studies reported that a lower level of 6‐TGN is adequate to achieve therapeutic levels of infliximab, which in turn are associated with clinical outcomes such as mucosal healing . To avoid the cofounding factor from concomitant biologics in maintaining clinical remission, we excluded those cases in our study.…”

Section: Discussionmentioning

confidence: 99%

Low 6‐thioguanine nucleotide level: Effective in maintaining remission in Chinese patients with Crohn's disease

Feng

Guo

Zhang

et al. 2018

J of Gastro and Hepatol

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Azathioprine dose reduction in inflammatory bowel disease patients on combination therapy: an open‐label, prospective and randomised clinical trial

Abstract: Under combination therapy, AZA dose reduction, but not withdrawal, appears to be as effective as continuation of AZA at full dose.

Cited by 109 publications

References 32 publications

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

Optimised infliximab monotherapy is as effective as optimised combination therapy, but is associated with higher drug consumption in inflammatory bowel disease

Low 6‐thioguanine nucleotide level: Effective in maintaining remission in Chinese patients with Crohn's disease

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