Due to its wide variety of conditions, Crohn's disease requires customized long-term treatment depending on the disease type and inflammatory region. When treating patients with Crohn's disease, the location of the disease is challenging because the intestinal tract of the ileum (lower part of the small intestine) is narrow.

Recently, the research results of the K-STAR study, the Real-World Evidence (RWE) study of Stelara, a drug containing the original ingredient ustekinumab, was conducted for the first time in Korean patients, were published in 'IBD (Inflammatory Bowel Diseases) Journal.' The K-STAR study followed the effects and safety of Stelara in Korean patients with Crohn's disease over a year.

This research confirmed clinically and endoscopically improved effects and drug tolerance profile regardless of the disease-affected regions or disease type.다.

On October 14th, Daily Pharm met with the research authors, Dr. Byong Duk Ye, a Professor at Asan Medical Center (Gastroenterology), and Dr. Chang Kyun Lee, a Professor at Kyunghee University (Gastroenterology), and heard about potential changes to the treatment strategy for Crohn's disease after the K-STAR research.

▶ We have heard that the study is the first study to use the Real-World Data collected from Korean patients with Crohn's disease.

Ye: The K-STAR study is a RWE study conducted from April 2018 to April 2022. It enrolled 464 patients with Crohn's disease who have started the Stelara treatment in 44 medical centers. The study evaluated the results of all adverse reactions and the efficacy over the year after the Stelara treatment.

The study was significant because it was the first Stelara RWE to involve Korean patients with Crohn's disease and a multi-agency Post-Marketing Survey (PMS) study where clinical response rate·remission rate, endoscopic remission rate, and improvements to biomarker index were comprehensively evaluated. Furthermore, 60% of the patients enrolled in the study already had complications, including stenosis and fistulas. After the Stelara treatment, these patients had no further advancement in Crohn's disease and remained stable for up to 1 year.

Lee: The study is meaningful because it is an RWE that shows the distribution of disease types and conditions among Koreans undergoing treatments. Unlike previously presented real-world data (RWD)-based studies were retrospective, the K-START study is significant because it collected data over a year, following pre-planned criteria from the beginning of the study.

▶ Stelara monotherapy's clinical remission rate was similar to that of the concomitant use of the drug with immune modulators. What does it entail?

Ye: Patients using immune modulators often report pain during treatment due to a variety of side effects.

Because of this, using the drugs in combination was uneasy. The current research showed that the clinical remission rate of Stelara monotherapy was not significantly different from that of using Stelara in combination with the immune modulator. It lowered the occurrence of side effects due to the immune modulators and provided a medical cost-saving effect

▶ We would like to hear about the report on differences in the treatment outcomes of patients previously treated with a biological agent or not.

Ye: In the research, higher treatment effects were observed in patients with no prior experience with a biological agent than patients with experience of such experience. At 16-20 weeks of treatment, combined effectiveness was 50.3% for patients with no prior experience with a biological agent and 30.7% for patients with prior experience. At 52-66 weeks of treatment, 47.7% and 36.0% of combined effectiveness were observed, respectively. Both follow-up periods showed significant differences. Based on these results, greater effects can be expected when Stelara, a biological agent, is used as the first-line treatment.

In my opinion, the study's importance lies in having Korean patients with Crohn's disease as study participants and in using Stelara monotherapy as the first-line treatment of a biological agent without using the drug in combination with an immune modulator.

Lee: Many patients registered to the previous RWD-based studies already have prior experiences with medication, so they have undergone drug switching. This study is particularly significant because the percentages of patients with prior biological agent treatment (53.4%) and without one (46.6%) are nearly similar.

▶ In the K-STAR study, what treatment effects of Stelara were observed in the regions affected by the disease?

Ye: In this research, the clinical response rate was higher in patients with the disease affecting the ileum (L1) than in patients who have the disease spread to the colon (L2) or ileocolon (L3). Typically, Anti-Tumor Necrosis Factor (TNF) agents, which show strong anti-inflammatory effects, were considered for patients with terminal ileal Crohn's disease. However, this research demonstrated that Stelara could effectively treat terminal ileal Crohn's disease.

▶How would you think the Stelara-treatable patient group would change following this research?

Lee: In Korean patients with Crohn's disease, the ileum is the most affected region. Through this research, Stelara was found to effectively treat terminal ileal Crohn's disease, and the treatable patient group has expanded.

We could expect to achieve treatment effects when providing Stelaral monotherapy at an early stage in patients aged 65 years and older with terminal ileal Crohn's disease who were hesitant about undergoing immune modulators.

Also, Stelara was proven effective in treating patients who initially attempted anti-TNF agents and then experienced diminishing effects. We can now consider various treatment methods in the clinical setting.

Ye: Regardless of disease type, over 50% of all patient groups reached clinical response, clinical remission, and clinical remission without steroids when treated with Stelara.

In other words, patients with Crohn's disease with accompanying complications who were not subject to surgeries had anti-TNF agents as a treatment option. Now, Stelara can be considered depending on clinical conditions.

▶Recently, drug prescription sequence is often discussed when treating IBD, such as Croh's disease. We are curious what drugs are primarily prescribed in treating Crohn's disease.

Ye: Patient-customized prescriptions are important when prescribing drugs. Safety is foremost considered when prescribing to patients who are likely to have a high risk of side effects. Administration methods are important depending on patient lifestyles. We primarily consider treatment effects for patients with poor prognosis and need to modulate inflammation quickly.

Lee: Drug prescription sequence differ depending on patient profiles, so nothing is absolute. Drugs with high safety profiles are primarily used in patients who are prone to having drug-associated side effects, and drugs with superior effects are used for patients who need to treat the inflammation quickly on top of safety. Additionally, the drug prescription order is selected after a comprehensive assessment of cost issues, insurance policies, and lifestyles. In conclusion, we think that the goal of the sequence is to aim for the long-term maintenance of the treatment by considering such treatment decisions.