Azathioprine and 6-MP for Ulcerative Colitis: A 2025 Cochrane Review on Long-Term Remission

For many people living with ulcerative colitis (UC), getting through a flare is only half the challenge. Keeping the disease quiet over the months and years that follow is where azathioprine and its metabolic sibling, 6-mercaptopurine (6-MP), come in. These thiopurine immunomodulators have been prescribed in UC for more than five decades, yet questions about how well they work, what the monitoring involves, and what the risks really are remain common in our community. A February 2025 Cochrane systematic review by Hasskamp, Meinhardt, Patton, and Timmer addresses exactly this, synthesising the available randomised controlled trial evidence on azathioprine and 6-MP for maintaining remission in UC and providing the most current gold-standard assessment of these medications (Hasskamp et al., 2025).

What Are Azathioprine and 6-MP, and Why Are They Used in UC?

Azathioprine and 6-mercaptopurine belong to a class of drugs called thiopurines. Azathioprine is a prodrug: once absorbed, the body converts it into 6-MP and then into active metabolites that interfere with the production of purines, the building blocks cells need to replicate DNA. This effect falls particularly hard on rapidly dividing immune cells, including the T-lymphocytes that drive the inflammatory response responsible for UC symptoms.

The goal in ulcerative colitis is not just to bring a flare under control (induction of remission) but to keep the disease from returning once it has quietened (maintenance of remission). Aminosalicylates such as mesalazine are usually tried first for maintenance, but for people with moderate to severe UC or those who relapse on aminosalicylates, thiopurines become an important option.

The NHS is clear about this role: azathioprine is used to treat moderate to severe UC and works by suppressing the immune system to reduce inflammation, and it can take up to three months to take effect (NHS: ulcerative colitis treatment).

What Does the 2025 Cochrane Review Assess?

Cochrane systematic reviews are considered the gold standard in evidence synthesis. They apply strict, pre-specified criteria to identify and pool all available randomised controlled trials on a specific clinical question, then assess both the size and the certainty of the evidence. They are not based on one study or one team's clinical experience, and they use a standardised rating system (GRADE) to communicate how confident we should be in each finding.

The 2025 review by Hasskamp and colleagues focuses specifically on the maintenance question: in adults with ulcerative colitis who have achieved remission, do azathioprine or 6-MP reduce the risk of relapse compared with placebo or other agents? (Hasskamp et al., 2025). It represents an update of earlier Cochrane work in this area and incorporates the most recent trial evidence.

This is a different, and arguably more practical, question than whether these drugs can bring an active flare under control. Many people who end up on long-term thiopurine therapy are not in crisis; they are managing well and want to stay that way.

Before Starting: The TPMT Test

One of the most important points that anyone approaching thiopurine therapy should know is that a simple blood test should be done first. The enzyme thiopurine methyltransferase (TPMT) governs how the body breaks down 6-MP metabolites. Around one in every 300 people has very low or absent TPMT activity. If azathioprine or 6-MP is given to someone in this group at a standard dose, the metabolites can accumulate to levels that cause severe, potentially life-threatening suppression of the bone marrow.

The NHS recommends TPMT testing before starting azathioprine, because people with low or absent TPMT activity are at higher risk of serious bone marrow suppression and may need a lower dose or a different medication (NHS: ulcerative colitis treatment). People with intermediate TPMT activity (roughly one in ten) may also need a dose adjustment. This is a straightforward, standard pre-treatment check, not an unusual precaution.

Ongoing Monitoring: What to Expect

Thiopurines are not a medication you start and then set aside. Because they suppress immune function, they require regular blood test monitoring throughout the time you take them. The NHS monitoring protocol typically includes:

• Full blood count (FBC): to detect bone marrow suppression, which can lower white cell counts, red cell counts, and platelets
• Liver function tests (LFTs): because thiopurines can cause elevated liver enzymes in some people

Monitoring is typically more frequent in the first few months and then settles into a routine schedule agreed with your IBD team. The risk of problems tends to be highest early in treatment or after a dose change.

The Side Effect Picture

Thiopurines carry a well-characterised side effect profile that patients should understand before starting:

Common and usually manageable: Nausea and general gastrointestinal discomfort are the most frequently reported side effects, particularly in the first few weeks. Taking the medication with food and splitting the daily dose can help. Some people switch from azathioprine to 6-MP if nausea is persistent, as they have different pharmacological profiles even though they share active metabolites.

Serious but dose-managed: Bone marrow suppression (myelosuppression) is dose-related and is why the TPMT test and regular FBC monitoring matter. It can manifest as low white blood cell count (leukopenia), which increases infection risk. If white cell counts fall below a threshold, the gastroenterology team will adjust the dose or pause the medication.

Rare but important to know: There is a small increased risk of certain infections, particularly opportunistic infections, because of the immune-suppressing effect. There is also a small absolute increase in the risk of lymphoma with long-term thiopurine use. This risk is real but, in absolute terms, remains low for most adults on standard doses; the clinical decision about whether to use thiopurines weighs this risk against the harm from uncontrolled UC. People who are concerned about this should discuss it directly with their gastroenterologist, who can help contextualise the risk for their specific situation.

What This Means for People on Thiopurines

The existence of a 2025 Cochrane systematic review on azathioprine and 6-MP for UC maintenance is meaningful for several reasons. First, it means this question is being kept under active review at the highest level of evidence synthesis. Second, Cochrane reviews are publicly accessible and transparent about what the evidence shows and where uncertainty remains.

For people already taking thiopurines: being on a medication that has a Cochrane evidence base is a form of reassurance. It does not mean there is nothing to monitor or no side effects to watch for; it means the decision to use these drugs is grounded in synthesised trial data, not anecdote.

For people who have been advised to start thiopurines: understanding that there is a Cochrane systematic review behind this treatment recommendation may help put the conversation with your gastroenterologist in context. The TPMT test, the monitoring schedule, and the side effect discussion are all part of a treatment framework that the evidence supports.

For people who stopped thiopurines and are wondering whether to reconsider: that conversation belongs with your IBD team, who can weigh your specific disease course, current options, and the current evidence base together.

This article is an AI-assisted curation of published research and NHS guidance. It is not medical advice. If you are taking or considering azathioprine or 6-MP for ulcerative colitis, always consult your specialist or care team before making any changes to your treatment.