Navigating treatment resistance: Janus kinase inhibitors for ulcerative colitis

Abstract

The management of refractory ulcerative colitis (UC) and acute severe UC (ASUC) is challenging due to the lack of standardized approaches in cases resistant to multiple treatments. In this editorial, I investigate the efficacy and safety of Janus kinase inhibitors, particularly upadacitinib and tofacitinib, in controlling severe and refractory disease. I highlight a notable case report by Xu et al, which explores the case of a patient with primary nonresponse to two classes of biologics and two fecal microbiota transplants who exhibited a remarkable response to upadacitinib. Furthermore, I discuss the use of tofacitinib in refractory UC and ASUC, either as monotherapy or in combination with biologics, which has shown promising response rates. Additionally, emerging evidence of upadacitinib efficacy in ASUC is presented. Overall, these cases emphasize the complex nature of managing refractory ASUC and the potential of small-molecule therapies to achieve remission. Further research is needed to refine treatment strategies for patients with treatment-resistant UC.

Keywords: Inflammatory bowel disease; Infliximab; Janus kinase inhibitor; Tofacitinib; Ulcerative colitis; Upadacitinib.

Figure 1

Colonoscopy. Pre-biologic. Ulcerative colitis with friability and ulcers, Mayo endoscopic score 2. A: Transition zone in the transverse colon; B: Sigmoid colon.

Figure 2

Colonoscopy. Pre-Tofacitinib. Improvement, but still presenting ulcerative colitis with patchy areas of friability and ulcers, Mayo endoscopic score 2. A: Transition zone in the transverse colon; B: Sigmoid colon.

Figure 3

Colonoscopy. Maintenance therapy with infliximab, three years after tofacitinib was withdrawn. Scarred mucosa, Mayo endoscopic score 0. A: Transition zone in the transverse colon; B: Sigmoid colon.