Early thiopurine use avoids need for surgery in UC

Early thiopurine maintenance therapy – within the first five years of an ulcerative colitis diagnosis and maintained for at least six months – is associated with a 9-fold relative risk reduction in colectomy (HR 0.10) and 4-fold risk reduction in disease extent progression (HR 0.26).

A study of 982 patients from the Sydney IBD Cohort compared outcomes in patients diagnosed from 1970 to 2009.

It found thiopurine use increased and early thiopurine maintenance increased over time with decade of diagnosis from 0.7% in 1970-1979 to 2.4% in 1980-1989, 7.7% in 1990-1999 and 18.3% in 2000-2009 (p<0.0001).

The median duration of thiopurine exposure in the early thiopurine maintenance group was four years.

“On multivariate Cox regression analysis, early thiopurines maintenance therapy significantly decreased the need for surgery (hazard ratio, 0.13; 95% CI, 0.03–0.55; P=0.006),” the study said.

Similarly, when analysed with propensity score matching, early thiopurine maintenance was still associated with significantly reduced probability of colectomy (HR 0.10; 95% CI, 0.03–0.43; P=0.002).

Early thiopurine maintenance therapy was associated with reduced risk of proximal progression of disease extent (HR 0.29; 95% CI, 0.10–0.78; p=0.015).

These findings were independent of decade of diagnosis.

The study, published in the European Journal of Gastroenterology and Hepatology, said surgery was an objective marker of more severe and complex ulcerative colitis.

“In this cohort study, 12% of our subjects underwent colectomy during follow-up, consistent with prior studies. Colectomy rates decreased over time and paralleled the increased use of thiopurines.”

“The number of patients on early thiopurine maintenance therapy needed to prevent one colectomy was 18 patients at 5 years and 12 patients at 10 years after ulcerative colitis diagnosis.”

They concluded early maintenance thiopurine treatment might be an effective strategy to control inflammation and prevent cumulative intestinal damage.

Senior investigator on the study Professor Rupert Leong from Concord Hospital told the limbic that a lot of people undersell the efficacy of thiopurines.

“A lot of people focus on the biologics but if you actually go back to the pivotal RCTs, it actually does show thiopurines are effective in ulcerative colitis. A lot of people have forgotten those data,” he said.

“In order to get biologics, patients need to fail thiopurines first so it’s not a substitute, it’s a pathway. Patients need to have gone onto this at least 3 months before they can access biologics anyway.

“Patients might be expecting to go onto biologics but find themselves not needing to go on them.”

He said thiopurines are obviously less costly than biologics but also reduce the access requirements such as infusions and the need for subcutaneous injections.

“We are recommending early use of thiopurines and good use of thiopurines and this might actually rescue patients from needing biologics in the first place which can reduce costs for patients,” he said.

He said the magnitude of the benefit in the study was quite surprising.

“In fact we think the benefit might be even higher if this study was conducted in the modern times because we are using thiopurines better now than in the past because we have access to therapeutic drug monitoring.”

“We are able to optimise treatment to ensure patients have the best thiopurine level in the blood whereas this was not previously available. So in fact the benefits are probably even more than we showed.”

“There is a role for thiopurines if given appropriately which is early – within 5 years of disease – and given for at least 6 months, and in the modern paradigm which is to use 6-TGN levels. When you have all three, it does reduce the need for surgery and proximal progression of the disease.”

Professor Leong recognised the contributions of international fellow Dr Fadi Mourad, now in Lebanon, and fellow and first author Dr Viraj Kariyawasam.

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