IBD Journal Scan
Key articles from high impact journals in last month
Editorial Recommendations
December-2024
Acute severe Ulcerative Colitis
Recent advances and review of literature
Comparing Infliximab Dosing Strategies in Steroid-Refractory Acute Severe Ulcerative Colitis
The optimal dosing of infliximab for steroid-refractory acute severe ulcerative colitis (ASUC) remains uncertain. This multicenter, open-label randomized controlled trial assessed the efficacy of intensified (10 mg/kg) and standard (5 mg/kg) infliximab dosing in achieving clinical response by day 7, alongside long-term outcomes. Conducted across 13 Australian hospitals, 138 patients were randomly assigned to three induction regimens. By day 7, clinical response rates were similar between 10 mg/kg (65%) and 5 mg/kg (61%, p=0.62). Outcomes, including remission, steroid-free remission, and colectomy rates by month 3, showed no significant differences among the induction strategies. Adverse events were comparable across groups. These findings affirm infliximab as an effective therapy in ASUC without evidence supporting higher initial dosing.
Tofacitinib in Acute Severe Ulcerative Colitis: A Promising Option
Tofacitinib shows potential as a treatment for acute severe ulcerative colitis (ASUC). This systematic review analyzed 21 studies, including 148 cases, to evaluate its efficacy and safety. Tofacitinib was primarily used after steroid and infliximab or cyclosporine failure, with patients aged 17–34 years and disease durations of 0.7–10 years. Colectomy-free survival rates were 85% at 30 days, 86% at 90 days, and 69% at 180 days. Clinical remission ranged from 35–69%, with endoscopic remission at 55%. Adverse events, mainly infections, occurred in 22 patients, leading to treatment discontinuation in seven cases. While tofacitinib demonstrates promising outcomes for refractory ASUC patients, large-scale, high-quality studies are needed to confirm its place in treatment algorithms.
Evaluating Upadacitinib for Acute Severe Ulcerative Colitis
Acute severe ulcerative colitis (ASUC) poses significant clinical challenges with a high risk of colectomy. Upadacitinib (UPA), a selective Janus kinase (JAK)-1 inhibitor approved for moderate-to-severe ulcerative colitis, has shown promise in ASUC. This systematic review analyzed 11 studies involving 55 patients treated with UPA, often off-label. The findings indicate rapid and sustained clinical improvement, with a 90-day colectomy rate of 16.3%. Among non-colectomy patients, 80% achieved steroid-free remission at follow-up. Adverse events were infrequent, with two cases of venous thromboembolism reported. UPA appears to be a safe and effective option for ASUC, although further large-scale studies are needed to confirm its efficacy and establish its role in treatment guidelines.
Advanced Therapies for Steroid-Refractory ASUC: A Network Meta-Analysis
Steroid-refractory acute severe ulcerative colitis (SR ASUC) often requires colectomy in approximately 40% of cases. Advanced therapies may lower these rates, but comparative effectiveness studies are limited. This network meta-analysis evaluated rescue therapies for SR ASUC using data from six randomized controlled trials and 15 cohort studies involving 2,004 patients. Treatments included tofacitinib, infliximab (standard and accelerated regimens), tacrolimus, cyclosporine, ustekinumab, and adalimumab. Compared to placebo, tofacitinib (OR: 0.09), accelerated infliximab (OR: 0.16), standard infliximab (OR: 0.2), and tacrolimus (OR: 0.24) significantly reduced short-term colectomy rates. Cyclosporine and high-dose infliximab showed potential benefits, while ustekinumab and adalimumab did not. Advanced therapies are effective rescue options for SR ASUC and should be integrated into treatment strategies.
Predicting Response to Rescue Therapy in ASUC: Insights and Future Directions
Acute severe ulcerative colitis (ASUC) is a critical condition requiring colectomy in patients unresponsive to rescue therapy. While predicting outcomes to corticosteroids has been extensively studied, understanding factors influencing rescue therapy response remains essential for improving care. This systematic review analyzed 101 eligible studies from 3,509 screened records, identifying 42 clinical, hematological, biochemical, endoscopic, or pharmacological factors linked to therapy outcomes. Older age (≥50), thiopurine exposure, cytomegalovirus or Clostridioides difficile infection, high C-reactive protein (CRP ≥30 mg/L), hypoalbuminemia, and severe endoscopic findings were associated with poor response. The roles of fecal calprotectin and infliximab levels remain unclear. Incorporating these predictors into clinical models can guide therapeutic decisions and enhance outcomes for ASUC patients.
Advances and Challenges in ASUC Therapy: A Systematic Review of RCTs
Acute severe ulcerative colitis (ASUC), marked by bloody diarrhea and systemic inflammation, poses a high risk of colectomy and mortality. Since the landmark 1955 cortisone trial, which established corticosteroids as first-line therapy and introduced disease severity criteria, progress in drug development for ASUC has been limited. In the 1990s and early 2000s, infliximab and ciclosporin demonstrated efficacy, but little advancement has been made for this high-risk population. This systematic review evaluates all interventional randomized controlled trials (RCTs) conducted in hospitalized severe UC patients, examining treatment efficacy, evolving trial designs, eligibility criteria, and study populations. Additionally, it highlights ongoing trials, explores challenges in ASUC drug development, and offers insights into future clinical trial strategies to advance therapeutic options.