Progression and therapy of inflammatory bowel disease
The inflammatory bowel diseases (IBDs) are progressive, debilitating, and life-limiting diseases of the gastrointestinal tract, which affect people all over the world. IBDs include Crohn’s disease and Ulcerative colitis. People of any age group can be affected by these diseases and can suffer from chronic symptoms, which affect both the gastrointestinal tract and extraintestinal manifestations (Hart and Rubin, 2022). The long-term disease course, progression of disease and outcomes of these diseases can’t be clearly predicted, thereby imposing heavy pressure, impact and uncertainty on clinical treatment, therapy and quality of life. It is difficult to predict which therapy will produce the best response for an individual patient and whether the disease will turn into further complications, such as colorectal cancer (Hart and Rubin, 2022).
Monitoring and assessment of inflammatory bowel disease
Without timely and effective treatment, inflammatory bowel diseases can result in irreversible long-term complications due to progressive nature of Crohn’s disease (CD) and Ulcerative colitis (UC). Previous treatment strategies concentrated on the resolution of symptoms. But nowadays it is evident that there is a clear disconnect between symptoms and active mucosal inflammation in inflammatory bowel disease. Therefore, current treatment strategies focus on treating beyond symptoms to normalization of objective markers of inflammation with the goal of mucosal healing and holistic remission adopting the concept of treat to target (T2T). Besides these, the resolution of inflammation early in the disease course plays a significant role to mitigate the risk of disease progression and improve prognosis.
Some patients suffer from aggressive attack of this disease and adopt different treatment options, while about one-third of the patients have a benign disease course, because inflammatory bowel diseases have highly heterogeneous conditions. Currently, it is difficult to predict treatment response or disease course. Early and effective monitoring, assessment and treatment using a treat-to-target approach can significantly improve patient’s outcomes. Therefore, it is important to conduct proactive monitoring and ensure treatment strategies that can work to fulfil the targets (Plevris and Lees, 2022). Accurate monitoring can help us to determine when to make correct treatment choices and helps us to achieve and maintain remission. Effective monitoring can also indicate whether our treatment choices are not working. Given that clinicians can change treatment strategies in a timely manner to minimize the disease complications.
Therefore, Plevris and Lees (2022) reviewed the currently available tools for disease monitoring with a focus on fecal calprotectin (FC).
Monitoring tools in inflammatory bowel diseases
The following monitoring tools are currently available to diagnose, assess, and monitor the patients with inflammatory bowel diseases (Plevris and Lees, 2022):
- Clinical symptoms and patient-reported outcomes (PROs): For long time, clinical symptoms have been the base or foundation of our monitoring strategies.
- Serum biomarkers:C-Reactive Protein is the main serum biomarker used for monitoring inflammation in inflammatory bowel diseases. It is easy to measure and cheap to perform with a rapid turn-around.
- Stool biomarkers: Fecal calprotectin is the most common and well characterized noninvasive biomarkers in inflammatory bowel diseases.
- Imaging modalities: Cross-sectional imaging is very significant to assess and monitor inflammatory bowel diseases. It can be used to assess for mucosal healing and transmural healing, and to monitor treatment response in patients.
- Ileo-colonoscopy: The criterion standard for assessing and monitoring inflammatory bowel diseases is macroscopic evaluation of the mucosa via ileo-colonoscopy. The ileo-colonoscopy can obtain biopsies allowing for assessment of histologic activity.
Classification of inflammatory bowel disease
Inflammatory bowel disease (IBD) is mainly subdivided into Crohn’s disease and Ulcerative colitis, although it is well-known for its heterogeneous conditions (Verstockt et al., 2022). The current clinical classification tools are suboptimal. Therefore, they should be revised to include the variety of phenotypes encountered in daily clinical practice. Despite revision of these classifications, these will not be sufficient and need more detailed molecular subclassifications. Furthermore, optimized clinical phenotypes can contribute to improved trial designs, future translational research approaches, and better treatment outcomes.
Predicting a patient’s disease course and response to specific treatments
Managing inflammatory bowel disease often encounters difficult situations to make decisions. Gastroenterologists face a lot of questions for treatment of IBDs. They have to think how aggressively they should treat this patient. Do they expect patient to have a mild or aggressive form of disease? Do the patients need a biologic? If so, which one? And when should they start it? The answers to these questions may vary from patient to patient. The growing therapeutic armamentarium will only make these decisions more difficult. However, other specialties have already used the molecular heterogeneity in their diseases to provide some answers. Therefore, Verstockt et al. (2022) reviewed the updates and research progress that can be used to predict the future for any given patient with inflammatory bowel disease, especially course of their disease and response to a particular therapy.
Disease progression in Ulcerative colitis and its prevention
Inflammation to the mucosa causes Ulcerative colitis. Mucosal healing can provide sustained and durable remission. However, despite mucosal healing, we can observe the recurrent phenomenon of persistent clinical disease activity. Therefore, in course of time, Ulcerative colitis can cause an increased risk of progression, adverse transmural effects on the bowel wall, increased risk of neoplasia development, worsening colorectal function; and increased risk of colectomy, hospitalizations, and other extraintestinal comorbidities (Cleveland et al., 2022). In the case of Crohn’s disease, early aggressive intervention or treatment can prevent disease progression and irreversible bowel damage. However, such treatment options to halt disease progression in Ulcerative colitis have been largely overlooked. Therefore, further research has been recommended to advance the treatment options in Ulcerative colitis.
Colorectal cancer screening in inflammatory bowel diseases
Currently available non-invasive methods are not sufficiently optimized for colorectal cancer (CRC) screening for persons with inflammatory bowel diseases. Therefore, patients need to undergo frequent interval screening via colonoscopy (Pratt et al., 2022). Colonoscopy-based screening reduces colorectal cancer incidence in inflammatory bowel disease patients. However, there are still now relatively high rates of interval colorectal cancer. Therefore, the medical researcher must develop more targeted approaches.
Recently, the disease-specific microbiome signatures for both inflammatory bowel diseases and colorectal cancer have been discovered. This innovative approach suggests that stool-based biomarker detection using metagenomics and other culture-independent technologies may help to detect personalized, early, and noninvasive colorectal cancer screening in inflammatory bowel disease patients. Pratt et al. (2022) reported that noninvasive detection of colorectal adenomas and carcinomas from microbial biomarkers provides promising early results.
Short- and long-term goals of management for inflammatory bowel diseases
Short- and long-term treatment targets in inflammatory bowel diseases performed not only symptom control but also endoscopic healing and patient-centered parameters (Le Berre et al., 2022). Treatment options like transmural healing in Crohn’s disease and histologic healing in Ulcerative colitis can provide remission. However, it is not yet clear whether early treatment according to a treat-to-target paradigm affects the natural course of inflammatory bowel diseases. Therefore, further research is needed for prospective disease-modification trials.
Inclusion of pain, fatigue, and emotional wellness into treatment goals
The best practices for the management of inflammatory bowel disease are early diagnosis and the optimal control of inflammation with a continuous cycle of assessment, treatment, monitoring, and adjustment of therapy (Keefer et al., 2022). However, patients get frustrated due to their ongoing challenging symptoms, such as discordant with inflammation, abdominal pain, fatigue, depression, anxiety, and emotional wellness. Healthcare professionals often do not address these problems of patients with inflammatory bowel disease due to lack of time or resources. Therefore, treatment options should include treat-to-target concept, control of inflammation and also emotional wellness.
Prevention to modify inflammatory bowel disease
There are improved therapeutic strategies and therapeutic targets for management of inflammatory bowel disease, however, it is still now a disabling disease with potential to progress and lead to irreversible complications (Torres et al., 2022). There are a lot of evidence that support the concept of a preclinical phase in inflammatory bowel disease, during which immune and inflammatory pathways are already altered. The preclinical phase which precedes the clinical diagnosis is more significant for prevention and management of inflammatory bowel disease. Targeting the early pathogenic events that promote the development of inflammatory bowel disease could prevent or attenuate disease onset and offer a true opportunity for disease modification.
References
Cleveland N.K., Torres J., Rubin D.T., 2022. What does disease progression look like in ulcerative colitis, and how might It be prevented?Gastroenterology 162: 1396-1408.
Hart A.L., Rubin D.T., 2022. Entering the Era of Disease Modification in Inflammatory Bowel Disease. Gastroenterology, Vol. 162 (5), pp. 1367-1369.
Keefer L., Bedell A., Norton C., Hart A.L., 2022. How should pain, fatigue, and emotional wellness be incorporated into treatment goals for optimal management of inflammatory bowel disease?Gastroenterology 162: 1439-1451.
Le Berre C., Ricciuto A., Peyrin-Biroulet L., Turner D., 2022. Evolving short- and long-term goals of management of inflammatory bowel diseases: getting it right, making it last. Gastroenterology 162: 1424-1438.
Plevris N., Lees C.W., 2022. Disease monitoring in inflammatory bowel disease: evolving principles and possibilities. Gastroenterology 162: 1456-1475.
Pratt M., Forbes J.D., Knox N.C., Van Domselaar G., Bernstein C.N., 2022. Colorectal cancer screening in inflammatory bowel diseases—can characterization of GI microbiome signatures enhance neoplasia detection? Gastroenterology 162, 1409-1423.
Torres J., Ungaro R.C., Colombel J.F. Is prevention the best way to modify inflammatory bowel disease? How close are we?Gastroenterology. 2022; 162: 1452-1455.
Verstockt B. Bressler B. Martinez-Lozano H. McGovern D. Silverberg M.S. Time to revisit disease classification in inflammatory bowel disease: is the current classification of inflammatory bowel disease good enough for optimal clinical management?Gastroenterology. 2022; 162: 1370-1382.
Verstockt B., Parkes M., Lee J.C. How do we predict a patient’s disease course and whether they will respond to specific treatments?Gastroenterology 2022; 162: 1383-1395.