Successful and Risk-Minimizing Treatment of Ulcerative Colitis by Positive Switch from JAK Inhibitors to Ustekinumab

Background: Janus kinase (JAK) inhibitors are highly effective at inducing remission in moderate-to-severe ulcerative colitis (UC). Because JAK inhibitors are small molecules, they can be administered orally, are rapidly absorbed, and have a rapid onset of action. However, potential adverse events, such as serious infections, opportunistic infections, herpes zoster infections, venous thrombosis, and cardiovascular events have been identified. To avoid the side effects associated with the long-term administration of JAK inhibitors, switching to biologics may be considered, even if remission is maintained with JAK inhibitors (positive switch). Case Report: Case 1: A 53-year-old man with steroid-dependent UC achieved rapid symptomatic improvement and complete mucosal healing on upadacitinib. Due to recurrent common colds and concerns regarding long-term adverse events, he underwent a positive switch to ustekinumab. Clinical and endoscopic remission have been maintained for one year. Case 2: A 36-year-old woman with refractory UC achieved clinical remission and mucosal healing with filgotinib following inadequate response to vedolizumab and corticosteroids. Given her desire for pregnancy and the potential risks of long-term JAK inhibitor use, she was switched to ustekinumab, which is considered safe during pregnancy. Remission has been maintained for one year. Conclusion: In two UC patients who achieved mucosal healing with a JAK inhibitor, remission was successfully maintained after switching to ustekinumab. These cases suggest that a positive switch may be a reasonable option for patients who respond to JAK inhibitors but have concerns about long-term safety. Additional cases are required to better define the clinical role of this strategy.