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"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provides continual resources and support, as the caregiver team navigates the course of a disease.

Great strides have been made in ulcerative colitis (UC) treatment since the first agents became available in the 1950s. Nevertheless, drug developers and the academic research community continue to seek more effective and safer ways to control and potentially even cure UC. The ClinicalTrials.gov database lists some two dozen ongoing phase II/III trials of novel agents, some in the "me-too" class but also many with mechanisms of action unlike those of existing drugs. Dozens of others involve existing drugs for which UC would be a new indication or could be approved for a new population. Here is a rundown.

New UC Indications for Existing Drugs

Pharmaceutical companies are always trying to find new uses for products they already market. UC's pathology is similar to those involved in a number of other autoimmune conditions, such as rheumatoid arthritis and plaque psoriasis; companies are now taking their approved drugs for those diseases and conducting trials in UC patients in hopes of gaining formal approvals. Among them are:

• Risankizumab (Skyrizi), now approved for psoriasis, psoriatic arthritis, and Crohn's disease

• Guselkumab (Tremfya), now approved for psoriasis

• Deucravacitinib (Sotyktu), now approved for psoriasis

• Spesolimab (Spevigo), now approved for pustular psoriasis

As well, pediatric studies are underway for a number of medications already approved for UC in adults.

Novel Targets/New Ways of Hitting Old Targets

Research into UC's underlying pathology in recent years has revealed a plethora of potential points of intervention to limit or shut down the disease process.

The first biologic drugs approved for UC block TNF activity, and anti-TNF drugs remain a popular choice for step-up therapy when first-line medications such as mesalamine are not sufficient. These agents generally target TNF directly, binding to it or its receptors to thwart downstream signaling.

Whenever a novel medication achieves (or seems likely to achieve) blockbuster status, a race begins to develop similar products to grab market share -- that is, "me too" drugs. That is now the case for a number of agents approved for UC. In the coming years, patients and clinicians are likely to see competitors for the following:

• Ozanimod (Zeposia), a sphingosine-1-phosphatase modulator; ClinicalTrials.gov lists four agents in phase II/III testing with similar mechanisms

• Tofacitinib (Xeljanz), a Janus-activated kinase (JAK) inhibitor; two other JAK inhibitors are also listed

• Ustekinumab (Stelara), an IL-12/23 inhibitor; two other anti-IL-23 products (guselkumab and risankizumab) are already approved for UC, and the trials database lists three others in advanced clinical development

• Vedolizumab (Entyvio), an integrin inhibitor; three anti-integrin agents are listed, including

It's Not Just About Drugs

One of the most exciting recent developments in all of medicine is the realization that the intestinal microbiome is vital to proper health (and affects the whole body, not just the intestine). Many studies have shown that UC patients' microbiome differs from that of "normal" people. Whether the microbiome contributes to UC symptoms, however, is not clear. A number of trials are now in progress that may answer the question.

Some of these are exploring whether direct manipulation of the microbiome, through fecal microbiota transplantation (FMT), are effective as UC treatments. (FMT is already available to patients who want it, despite a lack of clear evidence that it's effective; the commercial FMT product that won FDA approval in late November only carries an indication for recurrent Clostridioides difficile infection.) Another approach involves dietary supplements to make the UC patient's to beneficial microbiota. And are still being tested as well.

Read previous installments in this Medical Journeys series:

Part 1: UC: Understanding the Epidemiology and Pathophysiology

Part 2: UC: Symptoms, Exams, Diagnosis

Part 3: UC: How and Why Does It Arise?

Part 4: Case Study: Why Is This Teen's Ulcerative Colitis So Severe, So Resistant?

Part 5: UC: Initial Treatments and Response Monitoring

Part 6: UC: Dietary and Lifestyle Interventions

Part 7: Ulcerative Colitis: Second-Line Treatments

Part 8: Case Study: Painful Distended Abdomen and Weight Loss -- What Is the Cause?

Part 9: Ulcerative Colitis: Helping Patients Live With Chronic Disease

Part 10: When Surgery Must Be Considered

Part 11: Understanding and Identifying the Long-Term Complications