| Abstrakt: |
Crohn's disease (CD) is a chronic, complex inflammatory disorder of the gastrointestinal tract that presents significant therapeutic challenges. Despite the availability of a wide range of treatments, many patients experience primary non-response, secondary loss of response, or adverse events, limiting the overall effectiveness of current therapies. Clinical trials often report response rates below 60%, partly due to stringent inclusion criteria. Emerging therapies that target novel pathways offer promise in overcoming these limitations. This review explores the latest investigational drugs in phases I, II, and III clinical trials for treating both luminal and perianal CD. We highlight promising therapies that target known mechanisms, including selective Janus kinase inhibitors, anti-adhesion molecules, tumor necrosis factor inhibitors, and IL-23 selective inhibitors. In addition, we delve into novel therapeutic strategies such as sphingosine-1-phosphate receptor modulators, miR-124 upregulators, anti-fractalkine (CX3CL1), anti-TL1A, peroxisome proliferator-activated receptor gamma agonists, TGFBRI/ALK5 inhibitors, anti-CCR9 agents, and other innovative small molecules, as well as combination therapies. These emerging approaches, by addressing new pathways and mechanisms of action, have the potential to surpass the limitations of existing treatments and significantly improve CD management. However, the path to developing new therapies for inflammatory bowel disease (IBD) is fraught with challenges, including complex trial designs, ethical concerns regarding placebo use, recruitment difficulties, and escalating costs. The landscape of IBD clinical trials is shifting toward greater inclusivity, improved patient diversity, and innovative trial designs, such as adaptive and Bayesian approaches, to address these challenges. By overcoming these obstacles, the drug development pipeline can advance more effective, accessible, and timely treatments for CD. Plain language summary: Crohn's disease: hope on the horizon with new therapies in development Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that affects millions of people worldwide. Many people with CD do not respond well to current treatments, and researchers are looking for new options. Clinical trials are research studies that test new drugs and treatments. They are carefully designed to protect the safety of participants. Several new approaches to treating CD are currently undergoing clinical trials. These include drug candidates in various stages of development, from early research to large-scale phase III trials. Cellular therapies are also being tested, involving the injection of cells locally or intravenously to promote healing. Crohn's disease (CD) is a long-term condition that causes inflammation in the digestive tract. It can be difficult to treat, as current medications don't always work for everyone, and some people experience side effects or stop responding to treatment over time. Even in clinical trials, where new treatments are tested, less than 60% of patients show positive responses. Researchers are working on new treatments that target different pathways involved in Crohn's disease. This review looks at drugs being tested in early to late-stage clinical trials. Some of these drugs target well-known pathways, like JAK inhibitors and IL-23 blockers, while others focus on newer areas, such as specific receptors or molecules involved in inflammation. These emerging therapies aim to provide better, longer-lasting relief for patients. However, developing new treatments isn't easy. Clinical trials for Crohn's disease face many challenges, including complicated trial designs, ethical concerns about using placebos, difficulties in recruiting enough patients, and high costs. To overcome these issues, researchers are exploring more flexible and inclusive trial methods, which could help bring new treatments to patients more quickly and efficiently. [ABSTRACT FROM AUTHOR] |
