Real-World Data on Short-Term and Long-Term Treatment Results of Ustekinumab in Patients with Steroid-Resistant/Dependent Ulcerative Colitis.

Introduction: Ustekinumab is an IgG1 kappa monoclonal antibody directed against the common p40 subunit of interleukin-12 and interleukin-23, which activate Th1- and Th17-mediated immune responses, respectively. It has proven efficacy for the treatment of moderate to severe ulcerative colitis (UC) in the UNIFI phase III clinical trial; however, data on its efficacy in the real world are limited. In this study, we aimed to assess the real-world efficacy of ustekinumab. Methods: This observational study included 30 patients with UC who received ustekinumab from April 2020 to April 2022. We examined demographic information, disease type and activity (Mayo score, partial Mayo score [PMS]), use of biologics, concomitant use of predonisolone (PSL), 8-week ustekinumab clinical response rate, remission induction rate, 44- and 152-week remission maintenance rate, continuation rate, and 44-week steroid-free remission rate. The primary outcomes were the short- and long-term efficacy of ustekinumab. Results: Included patients (53% women; mean age: 41.2 years [16-80 years]) had an average disease duration of 86 weeks. The Mayo score (median) was 7.4 and the PMS was 5.4. Two (7%), 24 (80%), and four (13%) patients had a Mayo endoscopic subscore (MES) of MES1, MES2, and MES3, respectively. The median serum CRP was 1.0 mg/dL. Five patients had no history of biotherapy (naive), while eight and 17 had a history of one and two or more biologic agents, respectively. Eight patients were PSL-resistant and 22 were PSL-dependent. The 8-week clinical response rate was 73% and the clinical remission induction rate was 70%. The remission maintenance rates at 44 and 152 weeks were 67% and 63%, respectively. The ustekinumab retention rate was 67% (86-week mean follow-up period). Regarding biologic failure cases, the clinical response rate in the failure group with up to one biologic agent (including naive cases) was 84.6%, which was higher than the 58.0% rate in the failure group with two or more biologic agents (p = 0.06). Steroid-free remission rates at 44 and 152 weeks were 63% each. In the logistic regression analysis parameters for discontinuation of ustekinumab, only PMS remained significant after multivariate analysis (p = 0.018). Conclusion: Our study showed short-term and long-term ustekinumab effectiveness, especially with comparative low disease activity.

Serum leucine-rich alpha-2 glycoprotein in monitoring disease activity and intestinal mucosal healing for biotherapy-naïve cases with ulcerative colitis.

Background and Aim: Serum leucine-rich alpha-2 glycoprotein level has been reported to be a useful biomarker in assessing mucosal healing in patients undergoing biotherapy, where mucosal lesions caused by ulcerative colitis are difficult to assess endoscopically. However, no such reports have been reported in biotherapy-naïve cases. Methods: Sixty-eight patients with ulcerative colitis (UC) who were biotherapy-naïve at Kindai University Hospital between October 2021 and October 2022 were enrolled. We prospectively examined the correlation between leucine-rich alpha-2 glycoprotein (LRG), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and Geboes scores with clinical endoscopic activity using the Mayo endoscopic subscore (MES). Results: Mucosal healing was achieved in 39 (57%) patients. Univariate analysis revealed that the factors associated with mucosal healing were LRG (P = 0.0024), CRP (P = 0.1078), ESR (P = 0.0372), and Geboes scores (P = 0.0075). Logistic regression analysis identified LRG and Geboes scores as independent factors associated with mucosal healing assessed using MES (P = 0.0431 for LRG and P = 0.0166 for Geboes scores). Conclusion: LRG was found to be the easiest marker to monitor disease activity and mucosal inflammation in UC patients with biotherapy-naïve cases, with a performance equivalent to that of Geboes scores.

Ulcerative Colitis-associated Spondyloarthritis Successfully Treated with Infliximab in the Absence of Enhanced TNF-α Responses.

Although concurrent occurrence of spondyloarthritis (SpA) and ulcerative colitis (UC) is sometimes seen, the profiles of cytokines have been poorly understood in UC-associated SpA. We herein report a case of UC-associated SpA successfully treated with infliximab (IFX). Profiles of cytokines in the serum and colonic mucosa were characterized by an enhanced expression of IL-6 but not tumor necrosis factor (TNF)-α. Successful induction of remission by IFX was associated with the downregulation of IL-6 expression but no significant alteration in TNF-α expression. These findings suggest that some cases of UC-associated SpA might be driven by IL-6, and IFX might be effective in cases lacking enhanced TNF-α responses.