The treatment strategy for ulcerative colitis is rapidly evolving with the emergence of new global drugs.

Global guidelines recommend a rapid transition to advanced therapies (ATs) early on if 5-ASA treatment fails. In line with these recommendations, Korea also needs a shift in its treatment paradigm.

However, the early utilization of high-efficacy treatments is limited due to factors such as insurance reimbursement criteria.

In a meeting with DailyPharm, Professor Sang-Bum Kang of Daejeon St. Mary's Hospital (Chairman of the Korean Association for the Study of Intestinal Diseases' Insurance Committee) emphasized the need for re-establishing ulcerative colitis treatment standards and improving the reimbursement system.

Ulcerative Colitis Treatment Paradigm Shifting from 'Sequential Therapy' to 'Treat-to-Target' Approach

Ulcerative colitis is a chronic inflammatory disease of unknown cause that primarily affects the large intestine, potentially spreading inflammation from the rectum upwards.

Notably, uncontrolled ulcerative colitis can be associated with an increased risk of colectomy and hospitalization. Therefore, in moderate and severe cases, strategies involving the early use of treatment options, such as biologics or small-molecule drugs, are being considered to achieve remission.

Professor Kang explained, "Ulcerative colitis symptoms have a vast spectrum, and the course of the disease, including the extent of inflammation and disease activity, can continuously change, making it difficult to determine a patient's condition with fragmented numerical values definitively."

According to Professor Kang, ulcerative colitis treatment usually begins with 5-ASA agents. However, if a patient has high severity at the time of diagnosis and multiple risk factors, it is a principle to use Advanced Therapy (AT) from the early stage.

In this process, Professor Kang emphasizes a personalized treatment strategy tailored to the patient's specific condition.

Previously, a 'step-up' approach was typical, where patients who did not respond to conventional treatments, such as 5-ASA, would progressively move to steroids, immunosuppressants, and then ATs. However, recently, the standard has shifted to 'Treat-to-Target (T2T),' which involves setting clear treatment goals from the beginning and pursuing aggressive treatment accordingly.

Professor Kang explained, "The current ultimate goal of ulcerative colitis treatment is 'mucosal healing,' confirmed endoscopically. Patients who achieve mucosal healing have a lower risk of relapse and can expect a good long-term prognosis. Therefore, rapid achievement of mucosal healing and maintenance of a relapse-free remission state are key indicators of treatment success."

The problem is that conventional drugs alone have limitations in achieving mucosal healing. In contrast, ATs are considered core options in ulcerative colitis treatment due to their higher mucosal healing rates and better response and maintenance effects in mucosal healing.

Indeed, the American Gastroenterological Association (AGA) also, in its latest guideline revision, recommended the early use of proven high-efficacy treatments rather than dose escalation if 5-ASA treatment fails, explicitly naming Zeposia, an S1P modulator, as one of the high-efficacy treatment options.

"Paradigm shift in ulcerative colitis treatment, potential for oral therapy zeposia"

Based on this evidence, Professor Kang emphasized the importance of the initial treatment strategy.

He stated, "Realistically, it's not possible to try every treatment sequentially, and it's meaningless to look back after failing the first treatment and think 'what if I had used something else first'." He stressed, "Above all, it's crucial to make an accurate judgment in initial treatment to select the optimal drug and achieve maximum effect."

Some reports indicate that 70-80% of all ulcerative colitis patients can achieve symptom control with first-line treatment alone, suggesting the need for a strategy that deploys the best "weapon" tailored to the patient's characteristics.

During the treatment paradigm shift, the once-daily oral new drug Zeposia (ozanimod) is also gaining attention as a new alternative for ulcerative colitis treatment.

Zeposia is a sphingosine 1-phosphate (S1P) receptor modulator, featuring an innovative mechanism that inhibits inflammation by blocking the migration pathways of inflammatory immune cells.

Professor Kang stated, "Zeposia is expected to be effective when used as a first-line treatment for moderate ulcerative colitis patients who have failed conventional therapies like 5-ASA agents." He added, "This efficacy was proven in Zeposia's Phase 3 clinical trials, and consistent results have been confirmed in long-term follow-up and real-world data."

Professor Kang also shared an experience where a patient who had previously used biologics but showed insufficient efficacy was switched to Zeposia, and their prognosis significantly improved within 8 weeks.

He also said, "Among various AT options, Zeposia is evaluated as a less burdensome drug that can be used long-term. When considering treatment effects, patients who are typically young and actively engaged in socioeconomic activities are suitable for Zeposia treatment."

"Diversified ulcerative colitis treatment options require reimbursement system support"

While the emergence of new drugs like Zeposia has further diversified treatment options for ulcerative colitis, there's a growing call for the insurance reimbursement environment to support their practical utilization.

Regarding this, Professor Kang pointed out, "In Korea, reimbursement is only approved for ATs if patients have tried steroids or immunosuppressants and shown no effect or experienced side effects," and added, "The currently applied reimbursement criteria were established 20 years ago, creating a significant disparity from both the latest treatment trends and clinical reality."

Currently, domestic reimbursement criteria stipulate that patients must score 6 points or more out of 12 on the Mayo Scoring System for Assessment of Ulcerative Colitis Activity.

However, experts evaluate that some assessment indicators, such as stool frequency and the presence of bloody stools, rely heavily on patient statements and exhibit significant variations in physician assessment, resulting in a lack of objectivity.

Professor Kang emphasized, "Ulcerative colitis, an unpredictable, intractable disease, requires flexible treatment access. However, due to rigid reimbursement conditions, the latest treatments cannot be utilized appropriately." He stressed, "While it's impossible to accommodate all demands with limited finances, reimbursement criteria must be adjusted to match current clinical standard so that severe patients can receive high-efficacy treatment on time."

In line with these demands, the Korean Association for the Study of Intestinal Diseases is working on a revision of its ulcerative colitis treatment guidelines to reflect the evolving treatment landscape.

Professor Kang stated, "We have formed a TF team within the association and are working on new guidelines." He added, "We plan to prepare more practical treatment guidelines by differentiating recommendation grades and evidence levels, similar to the AGA."

He explained that they are particularly considering factors like the national health insurance reimbursement system to tailor the recommendations to the Korean context.

Professor Kang said, "It has already been 5 years since the ulcerative colitis guidelines were released, and during that time, various new drugs have emerged, significantly changing the treatment environment. I believe now is the opportune time to re-establish treatment standards and push for improvements in the reimbursement system."

Finally, Professor Kang said, "In the future, research on personalized treatment should be strengthened, selecting the optimal treatment for each patient based on biomarkers such as intestinal microbes or genetic information." He concluded, "We plan to strive not only for the introduction of the latest treatments but also for the advancement of precision medicine and the training of next-generation specialized personnel."