Acute haemorrhagic ulcerative colitis Treatment

Rescue Therapies When Steroids Are Not Enough

When patients do not respond adequately to intravenous steroids by day three, medical teams must act quickly to implement rescue therapy. Two main options exist: cyclosporin and infliximab. Both are powerful immunosuppressive treatments that work differently from steroids and can prevent the need for emergency surgery.34

Cyclosporin is an immunosuppressant medicine that reduces the activity of the immune system, thereby decreasing inflammation. It is given slowly through an intravenous drip at a dose of 2 milligrams per kilogram of body weight per day. Treatment typically continues for around seven days. Research shows that approximately 75 percent of patients have short-term response to cyclosporin, meaning their symptoms improve enough to avoid immediate surgery. About 50 percent maintain long-term response, particularly when they begin taking thiopurine medicines (such as azathioprine) around day seven to help maintain the improvement.35

Side effects of intravenous cyclosporin can include uncontrollable shaking or trembling of body parts, excessive hair growth, extreme tiredness, swollen gums, nausea, vomiting, and diarrhea. More serious complications can include high blood pressure and reduced kidney and liver function, so patients are monitored regularly with blood tests during treatment to check for these problems.5

Infliximab is a type of medicine called a biologic that works by targeting and blocking a protein called tumor necrosis factor. This protein plays a key role in causing inflammation in ulcerative colitis. Infliximab is given as a single intravenous infusion at a dose of 5 milligrams per kilogram of body weight. Like cyclosporin, it has a response rate of approximately 70 percent in the short term and 50 percent for long-term control.35

Recent clinical trials have shown that cyclosporin and infliximab are equally effective as rescue therapies for acute severe ulcerative colitis. The choice between them often depends on the patient's previous treatment history, any existing conditions, and the doctor's experience with each medicine. Patients who do not respond to either cyclosporin or infliximab within seven days should be considered for surgical treatment because further delay increases the risk of life-threatening complications.37

When Surgery Becomes Necessary

Surgery is sometimes the best treatment option for acute severe ulcerative colitis, either as an emergency procedure for immediate life-threatening complications or as a planned intervention when medical therapies have failed. The most common surgical procedure involves removing the diseased colon through an operation called a colectomy.48

Immediate surgery is required for patients with intestinal perforation (a hole in the colon), uncontrollable bleeding that causes severe blood loss, or toxic megacolon (a condition where inflammation spreads deep into the intestinal wall and the colon stops working and becomes dangerously dilated). These are life-threatening emergencies that cannot wait for medical treatment to work.46

For patients who do not have immediate life-threatening complications but fail to respond to both corticosteroids and rescue therapy, planned surgery offers a chance to remove the diseased tissue and restore health. While surgery is a major decision with significant recovery time, it can ultimately improve quality of life for patients with severe disease that does not respond to medical management.85

JAK Inhibitors: A New Class of Medicines

JAK inhibitors represent an innovative class of medicines that work by blocking specific enzymes called Janus kinases inside immune cells. These enzymes play a crucial role in transmitting signals that cause inflammation. By blocking them, JAK inhibitors can reduce inflammation throughout the colon without requiring intravenous infusions like biologic medicines.5

The advantage of JAK inhibitors is that they are taken as oral tablets, making them more convenient than infusion therapies. Clinical trials have studied these medicines in moderate to severe ulcerative colitis, including some patients with acute episodes. The trials typically progress through three phases: Phase I studies test safety in small groups of volunteers, Phase II trials assess whether the medicine works effectively in patients with the disease, and Phase III trials compare the new treatment to current standard therapies in larger patient groups.5

Biologic Medicines: Targeting Specific Inflammatory Pathways

Beyond infliximab, which is already used in acute severe cases, researchers are testing additional biologic medicines that target different proteins involved in the inflammatory process. These medicines work by blocking receptors or proteins that the immune system uses to trigger inflammation in the intestinal lining. By preventing these signals from being sent or received, biologic medicines can reduce damage to the colon.5

Alpha 4 integrin inhibitors are one type of biologic being studied. These medicines prevent certain white blood cells from traveling to the intestines by blocking proteins on their surface that allow them to stick to blood vessel walls. This keeps inflammatory cells out of the colon, reducing inflammation.5

Interleukin inhibitors are another category of biologic medicines in clinical trials. Interleukins are chemical messengers that immune cells use to communicate and coordinate inflammatory responses. By blocking specific interleukins involved in ulcerative colitis, these medicines can disrupt the inflammatory cascade before it damages the colon lining.5

Clinical trials for biologic medicines typically involve administering the treatment as an intravenous infusion every four to twelve weeks or as an injection every one to two weeks. Researchers measure how many patients achieve remission (no symptoms), how quickly symptoms improve, and whether the colon lining heals. They also carefully monitor for side effects and complications.5

Sphingosine 1-Phosphate Receptor Modulators

Sphingosine 1-phosphate receptor modulators are oral medications that work by a different mechanism. They prevent certain types of immune cells called lymphocytes from leaving lymph nodes and traveling to sites of inflammation in the body, including the colon. By keeping these inflammatory cells trapped in lymph nodes, the medicines reduce the immune attack on the intestinal lining.5

This class of medicine has shown promise in clinical trials for moderate to severe ulcerative colitis. The advantage is that patients take the medication by mouth rather than requiring injections or infusions. Trials are studying the optimal dosing, timing of treatment, and which patients are most likely to benefit from this approach.

Trial Locations and Patient Eligibility

Clinical trials for ulcerative colitis treatments are conducted worldwide, including locations in the United States, Europe, and other regions. Patients interested in participating in trials typically need to meet specific criteria, such as having moderate to severe disease that has not responded adequately to standard treatments, being within certain age ranges, and not having specific health conditions that would make trial participation unsafe.

Trial eligibility often excludes patients with certain complications, active infections, or those taking medications that might interfere with the study treatment. Doctors conducting trials carefully screen potential participants to ensure they can safely receive the experimental therapy and provide meaningful data to answer research questions.

Preliminary results from many of these trials have shown encouraging signs, including improvements in clinical symptoms, reductions in inflammatory markers in the blood, and healing of the colon lining visible on colonoscopy. However, these treatments are still being studied, and their safety and effectiveness compared to existing therapies need to be fully established before they become widely available.