‘No correct answer for IBD drugs, but quick treatment needed’

AbbVie's JAK inhibitor Rinvoq (upadacitinib) has expanded its prescribing reach with health insurance coverage for inflammatory bowel disease (IBD). Industry insiders pay attention to Rinvoq's prescribing performance, which will be driven by its clinical efficacy and oral convenience.

AbbVie Korea held a news press conference at the Sofitel Ambassador Seoul Hotel in Songpa-gu, Seoul, on Friday to celebrate the reimbursement of Rinvoq, a selective JAK1 inhibitor, for adult patients with moderate to severe active ulcerative colitis and Crohn's disease.

Under an administrative notice issued by the Ministry of Health and Welfare on April 1, Rinvoq got reimbursement for patients with moderate-to-severe active ulcerative colitis and Crohn's disease who have not had an adequate response to or are intolerant of universal therapies such as corticosteroids, 6-mercaptopurine or azathioprine, or for whom these agents are contraindicated; corticosteroids or immunosuppressive agents) and patients with moderate to severe ulcerative colitis who do not respond to or are intolerant of universal therapy (two or more agents: corticosteroids or immunosuppressive agents); or patients with moderate to severely active Crohn's disease (CDAI of 220 or higher) for whom such therapy is contraindicated.

Professor Ye Byong-duk of the Department of Gastroenterology at Asan Medical Center explained IBD's characteristics and treatment strategies and presented data from Rinvoq’s key clinical trials. Inflammatory bowel disease (IBD) is a group of diseases of unknown cause that cause chronic, recurrent inflammation of the intestines, including ulcerative colitis and Crohn's disease. It is incurable and characterized by periods of remission followed by flare-ups.

In the past, it was rarely seen among Asians, but the number of Korean patients has been increasing for various reasons, including Westernized dietary habits. Over the past 10 years, from 2010 to 2019, the number of Crohn's disease patients increased 2.37 times, and the number of ulcerative colitis patients increased 2.32 times, with 37,439 ulcerative colitis patients and 18,463 Crohn's disease patients as of 2019.

“Inflammatory bowel disease, especially Crohn's disease, is a progressive disease, and its course is difficult to predict, requiring constant monitoring and management,” Professor Ye said. “Prolonged inflammation can damage the intestine through strictures, fistulas/perforations, and intra-abdominal abscesses. So, early treatment is necessary to prevent intestinal damage.”

In two induction studies (UC1, UC 2) and one 52-week maintenance and extension study (UC 3) in adults with moderately to severely active ulcerative colitis, clinical remission rates at week 52 in the maintenance study were 42 percent in the Rinvoq 15 mg arm and 52 percent in the Rinvoq 30 mg arm (compared to 12 percent in the placebo arm, P<0.0001).

Additionally, at Week 52, the endoscopic improvement rate was 49 percent in the Rinvoq 15 mg arm and 62 percent in the Rinvoq 30 mg arm (14 percent in the placebo arm, P<0.0001). Endoscopic remission rates were 24 percent in the Rinvoq 15 mg arm and 26 percent in the Rinvoq 30 mg arm (6 percent in the placebo arm, P<0.0001). In the two induction studies, 14 percent and 18 percent of patients in the Rinvoq 45 mg arm achieved endoscopic remission at Week 8 (compared to 1 percent and 2 percent in the placebo arm, respectively, P<0.0001).

Rinvoq also improved clinical response from week 2 of treatment, with more patients achieving steroid-free clinical remission at week 52 compared to placebo.

In addition, in two induction studies (CD 1 and CD 2) followed by one 52-week maintenance and one long-term extension study (CD 3) in adult patients with moderate-to-severe active Crohn's disease, the clinical remission rate at Week 52 in the maintenance studies was 36 percent in the Rinvoq 15 mg arm and 46 percent in the Rinvoq 30 mg arm (compared to 14 percent in the placebo arm, P<0.001).

At Week 52, endoscopic response rates were 28 percent in the Rinvoq 15 mg arm and 40 percent in the Rinvoq 30 mg arm (7 percent in the placebo arm, P<0.001). Endoscopic response rates were 19 percent in the Rinvoq 15 mg arm and 29 percent in the Rinvoq 30 mg arm (6 percent in the placebo arm, P<0.001).

In the two induction studies, 19 percent and 29 percent of patients in the Rinvoq 45 mg arm achieved endoscopic remission at Week 12 (compared to 2 percent and 7 percent in the placebo arm, respectively, P<0.001). Rinvoq showed rapid symptom improvement from week 2 of treatment, with more patients achieving steroid-free clinical remission at weeks 12 and 52 compared to placebo.

“In Korean patients with inflammatory bowel disease, perianal disease is a common complication, and Rinvoq has been shown to reduce not only intestinal inflammation but also anal complications meaningfully,” Professor Ye said.

Asked about the criteria for selecting a drug to treat inflammatory bowel disease, which has recently increased treatment options with the advent of various drugs, Professor Lee said, “There is no right answer. The decision of which drug to use first depends on the patient's disease status, socioeconomic status, and oral/injectable preference.”

Regarding the tendency to delay prescribing the newest drug, Rinvoq, Professor Ye said, “The strategy of using other drugs first and Rinvoq later is not necessarily a good one. It is less effective in patients with advanced inflammation and less effective in patients with other biologics. It's important to get the mucosal therapy going quickly. Because it's taken orally once a day, it may be used first in patients who prefer it.