Meds & Biologics
When your gastroenterologist recommends an immunosuppressant for ulcerative colitis, the name alone can feel alarming. Medications like azathioprine, 6-mercaptopurine (6-MP), methotrexate, and cyclosporine belong to a class of drugs that reduce immune system activity, and hearing that your treatment plan involves "suppressing your immune system" understandably raises concerns. But these medications occupy a specific and well-defined role in UC management. They are not a first resort, and they are not used without careful monitoring. Understanding when and why your doctor has chosen one of these drugs, what the timeline looks like, and what to expect from the monitoring process can turn a source of anxiety into something you can prepare for.
Thiopurines: Azathioprine and 6-Mercaptopurine
Azathioprine (often sold as Imuran) and its active metabolite 6-mercaptopurine (6-MP, sold as Purinethol) are the most commonly prescribed immunosuppressants for ulcerative colitis. These thiopurines work by interfering with DNA synthesis in rapidly dividing immune cells, gradually reducing the overactive immune response that drives colonic inflammation.
The primary role of azathioprine for ulcerative colitis is as a steroid-sparing maintenance agent. If you have achieved remission with corticosteroids but flare every time your doctor tapers the dose, a thiopurine may allow you to get off steroids for good. A 2025 Cochrane systematic review of five placebo-controlled studies found that 45% of patients in the thiopurine group failed to maintain remission compared to 67% on placebo, confirming a meaningful maintenance benefit.
Thiopurines also serve a second strategic role: combination therapy with biologic medications. The 2025 ACG guidelines recommend adding a thiopurine when infliximab is used for moderate-to-severe UC because the combination reduces the body's tendency to form antibodies against the biologic, improving both drug levels and long-term effectiveness.
One of the most important things to know about thiopurines is that they are slow. Most patients need 8 to 12 weeks, sometimes longer, before seeing a clinical benefit. They are not rescue drugs. They are long-game medications designed to hold remission once you get there.
Testing and Monitoring Before You Start
Before prescribing azathioprine or 6-MP, your gastroenterologist will order a TPMT (thiopurine methyltransferase) enzyme test and often a NUDT15 genotype test. These genetic tests determine how your body metabolizes thiopurines. About 10% of the population has intermediate TPMT activity, meaning they need a lower dose, and roughly 1 in 300 people have very low or absent activity, making thiopurines potentially dangerous at standard doses due to the risk of severe bone marrow suppression.
Once you begin therapy, expect regular blood work. Most gastroenterologists check complete blood counts and liver function tests every one to two weeks initially, then monthly for the first several months, and every two to three months thereafter. This monitoring catches problems early, including:
Leukopenia (low white blood cell count), the most clinically significant risk
Elevated liver enzymes, which can signal hepatotoxicity
Pancreatitis, which occurs in roughly 3-5% of patients and typically appears within the first few weeks
The dose of azathioprine needs to be reduced or the therapy discontinued entirely in 9-28% of patients because of side effects. If you develop nausea, fatigue, or unexplained fevers, report them promptly rather than waiting for your next scheduled appointment.
Methotrexate: A Different Role in UC
Methotrexate has strong evidence supporting its use in Crohn's disease, but its role in ulcerative colitis is more limited and specific. The METEOR and MERIT-UC trials showed that methotrexate monotherapy was not superior to placebo for inducing or maintaining remission in UC. That finding has shaped how gastroenterologists use it today.
Where methotrexate does appear in UC treatment is as a combination partner with biologic therapies, particularly anti-TNF agents like infliximab and adalimumab. The AGA's pharmacological management guidelines note that methotrexate can be paired with biologics to reduce immunogenicity, similar to how thiopurines are used. In practice, methotrexate is often chosen over azathioprine for patients who have had thiopurine side effects like pancreatitis, since methotrexate works through a completely different mechanism.
Methotrexate is given as a weekly injection or oral dose, typically 15-25 mg, always with folic acid supplementation to reduce side effects. A small retrospective cohort of 50 UC patients on oral methotrexate with steroid-dependent disease showed steroid-free remission rates of 42%, suggesting it may still have a steroid-sparing role for selected patients even if the large trials were disappointing.
Cyclosporine: The Emergency Option
Cyclosporine occupies a completely different position from the other immunosuppressants discussed here. It is not a maintenance medication. It is a rescue therapy for acute severe ulcerative colitis (ASUC) that has not responded to intravenous corticosteroids, and its purpose is to prevent emergency colectomy.
When a patient is hospitalized with ASUC and IV steroids are failing after three to five days, the decision narrows to two options: intravenous cyclosporine or infliximab. Cyclosporine works fast, often within days, and is effective in 50-80% of patients in the short term. It is given intravenously at a dose of 2 mg/kg/day under close monitoring, including blood level checks and kidney function tests.
The important context about cyclosporine is what happens after the acute crisis passes. It is a bridge, not a destination. Patients who respond to IV cyclosporine are typically transitioned to an oral thiopurine or a biologic for long-term maintenance. Studies show that while short-term colectomy avoidance rates are strong, nearly 70% of patients eventually require colectomy over one to seven years without effective maintenance therapy afterward.
Living With Immunosuppressant Therapy
The practical realities of taking immunosuppressants extend beyond the pills and blood draws. The Crohn's and Colitis Foundation notes that you should avoid live vaccines while on these medications, stay current on inactivated vaccines including annual flu shots, and practice common-sense infection precautions. The risk of serious infections is real but modest, and for most patients it is far outweighed by the risk of uncontrolled disease activity.
You should also know that very rare cases of lymphoma have been reported with long-term thiopurine use, particularly in younger male patients. Your gastroenterologist will weigh this risk against the severity of your disease and the available alternatives. For many patients with steroid-dependent or steroid-refractory UC, immunosuppressants remain among the most effective tools available.
Immunosuppressants take months to work, and the waiting period between starting therapy and seeing results can feel uncertain. Track your symptoms consistently with Aidy so you and your GI can evaluate effectiveness with real data, not guesswork.