October 29, 2024
A real-world study comparing second-line biologic therapies showed that Janus kinase (JAK) inhibitors can achieve symptom control with comparable rates of complications and mortality to those of monoclonal antibodies when used to treat moderate to severe ulcerative colitis (UC). Lead author Emily Shu-Yen Chan, MD, MSc, presented the findings in a poster session at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania.
Patients with moderate to severe UC often require second-line biologic therapies for effective symptom control. JAK inhibitors have emerged as a viable second-line therapy for individuals with UC who do not achieve complete clinical response after first-line biologic therapies. Nevertheless, concerns surrounding the risk for adverse events, first signaled in studies of JAK inhibitors for the treatment of rheumatoid arthritis (Martinez-Molina C et al. Medicina Clínica; English Edition 2024;163:391-396), persist in the clinical community and among individuals living with UC.
A population-based, longitudinal cohort study conducted at the Weiss Memorial Hospital, in Chicago, Illinois, was designed to compare the real-world efficacy and safety of JAK inhibitors, specifically tofacitinib, upadacitinib, and filgotinib, to those of anti-integrin and interleukin (IL) antibodies vedolizumab, ustekinumab, and mirikizumab in the treatment of moderate to severe UC. The study included people diagnosed with moderate to severe UC between January 2018 and January 2024 whose electronic health records were extracted from the TriNetX network. More than 2,500 individuals treated with JAK inhibitors were propensity-score matched with anti-integrin and anti-IL monoclonal antibody users diagnosed with moderate to severe UC, who had similar demographic characteristics, comorbidities, concomitant medications, and laboratory results.
Patients treated with JAK inhibitors had lower rates of complications, including megacolon, diarrhea, fatigue, abdominal pain, and anemia, compared with those treated with vedolizumab, ustekinumab, and mirikizumab during an average follow-up period of 3 years. More importantly, the risk of presenting to the emergency department was significantly reduced for patients with UC who used JAK inhibitors compared to those treated with monoclonal antibodies. No significant differences were observed in all-cause mortality, use of systemic steroids, severe sepsis, colon cancer, or colectomy between the two groups. However, JAK inhibitor users had higher risks for rectal bleeding and hospitalization.
“In this real-world study comparing second-line biologics, JAK inhibitors appear to be non-inferior to anti-integrin and anti-IL monoclonal antibodies in terms of symptom control and incident mortality for patients with moderate to severe UC,” Chan concluded. The authors stressed that additional clinical trials are necessary to investigate whether these findings are reproducible in larger populations. Additional research could also clarify the safety profile of JAK inhibitors in the treatment of refractory UC.