A 2025 systematic review and network meta-analysis of 36 phase III randomized controlled trials (RCTs), involving 14,270 patients with moderate-to-severe ulcerative colitis (UC), assessed the comparative efficacy of biologics and small molecules in achieving clinical remission, endoscopic improvement, and histological outcomes. Medications evaluated included advanced therapies such as upadacitinib, risankizumab, guselkumab, and other agents targeting interleukin pathways, Janus kinase (JAK) inhibition, and integrin interaction. Endoscopic improvement was the primary outcome, defined as a Mayo Endoscopic Score (MES) ≤1 during the induction phase (week 6–14) and maintenance phase (week ≥30). Results demonstrated that upadacitinib consistently ranked highest across most efficacy parameters, including clinical remission, endoscopic improvement, and histological outcomes, particularly in biologic-experienced patients. In the induction of endoscopic improvement, upadacitinib achieved a SUCRA score of 99.2%, followed by risankizumab (91.4%) and tofacitinib (81.9%). Therefore, the initiation of upadacitinib seems to be the most beneficial for inpatient management, but not all data may strictly reflect the inpatient setting or assessed Crohn's Disease (CD). [1]
A 2024 systematic review and meta-analysis evaluated the efficacy and safety of upadacitinib in patients with moderate-to-severe CD and UC. The primary outcomes assessed included clinical remission, clinical response, endoscopic remission, endoscopic response, and corticosteroid-free remission. Secondary outcomes comprised adverse events, serious adverse events, and treatment discontinuation due to safety concerns. The meta-analysis demonstrated that upadacitinib was effective in both CD and UC, with clinical remission rates of 45.8% and 25.4%, respectively. Clinical response rates were higher, reaching 53.6% in CD and 72.6% in UC. Endoscopic remission was observed in 25.3% of patients with CD and 14.9% of those with UC, while endoscopic response rates were 40.2% and 36.3%, respectively. The corticosteroid-free remission rate was 43.2% in CD and 75.7% in UC. Safety analyses indicated that upadacitinib was well tolerated, with a pooled serious adverse event rate of 6.0% and no significant differences in overall adverse events compared to placebo. However, herpes zoster infections occurred more frequently in the upadacitinib group. No significant differences were observed in venous thromboembolism, malignancies, gastrointestinal perforations, or major cardiovascular events. These findings support the utility of upadacitinib in patients with moderate-to-severe IBD, particularly those unresponsive to conventional therapies, while highlighting the need for ongoing safety monitoring. [2]
A 2024 systematic review and meta-analysis evaluated the therapeutic efficacy and safety of upadacitinib in patients with inflammatory bowel disease (IBD). The primary endpoint focused on clinical remission rates, while secondary outcomes assessed clinical response, endoscopic response, endoscopic remission, and the incidence of adverse events (AEs). A pooled meta-analysis of clinical remission rates demonstrated an overall response of 38% (95% CI; 32–45%), with RCTs reporting a remission rate of 36%, real-world studies 25%, retrospective studies 40%, and cohort studies 55%. Endoscopic outcomes showed remission rates of 19% in RCTs and 29% in cohort studies, while endoscopic response rates reached 41% and 57%, respectively. Adverse events occurred in 69% of IBD patients, with a slightly lower rate in those with ulcerative colitis (65%) and a higher rate in Crohn’s disease (75%). Infections, abdominal pain, and nasopharyngitis were among the most frequently reported AEs, though serious AEs were infrequent. Despite some variability between controlled trials and real-world data, findings reinforced the efficacy of upadacitinib in both induction and maintenance therapy for IBD. [3]
A 2025 meta-analysis systematically evaluated the safety profile of upadacitinib in adult patients with IBD, including UC and CD. Data from six RCTs encompassing 2,611 patients demonstrated no significant increase in serious adverse events (SAEs) between upadacitinib (6.1%) and placebo (7%; risk ratio [RR], 0.77; 95% CI: 0.50 to 1.20; p= 0.25), with moderate heterogeneity (I² = 39%). Secondary findings indicated a higher incidence of neutropenia (RR, 5.63; 95% CI: 1.90 to 16.65; p= 0.0002) and CK elevation (RR, 2.34; 95% CI: 1.22 to 4.47; p= 0.01) in the upadacitinib group. However, anemia (RR, 0.36; 95% CI: 0.27 to 0.48; p<0.00001) and arthralgia (RR, 0.47; 95% CI: 0.30 to 0.75; p= 0.001) were significantly reduced. Subgroup analysis revealed that upadacitinib was associated with a significant reduction in SAEs for UC (RR, 0.49; 95% CI: 0.28 to 0.83; p= 0.009) but not for CD. No significant differences emerged for serious infections, hepatic disorders, or herpes zoster. While major cardiovascular events, venous thromboembolism, and malignancies were monitored, their low incidence precluded meaningful statistical analysis. These findings suggest that upadacitinib maintains a favorable safety profile relative to placebo in this patient population, though continued pharmacovigilance is warranted to clarify long-term risks. [4]
A 2023 systematic review evaluated the efficacy and safety of upadacitinib in the treatment of CD through a comprehensive synthesis of randomized controlled trials and prospective cohort studies. Two randomized controlled trials and one prospective cohort study were included, assessing clinical remission, endoscopic response, and adverse event profiles. A 2020 randomized controlled trial involving 220 patients demonstrated that upadacitinib at a twice-daily 24 mg dose significantly improved clinical and endoscopic remission rates compared to placebo, with adjusted risk differences of 11.2% (95% CI −6.1 to 28.5) and 21.0% (95% CI 6.8 to 35.2), respectively. A 2022 randomized controlled trial with 107 patients maintained clinical remission rates of 61% at 30 months with upadacitinib 15 mg once daily, while endoscopic response remained stable at 68% at 24 months. Additionally, an 8-week prospective cohort study conducted in 2023 on 40 patients reported that 80% of those without small intestinal involvement achieved clinical remission. Across all studies, adverse events such as herpes zoster, intestinal perforations, non-melanoma skin cancer, anemia, and adjudicated cardiovascular events were observed, underscoring the necessity of vigilant safety monitoring. These findings position upadacitinib as a promising therapeutic option for CD, though careful patient selection and long-term safety evaluations remain critical. [5]
A 2023 case series described the use of upadacitinib as salvage therapy for acute severe ulcerative colitis (ASUC) in infliximab-experienced patients who failed to respond to intravenous corticosteroids. Six patients from two Australian tertiary inflammatory bowel disease centers were treated with upadacitinib 45 mg once daily following corticosteroid failure. All patients had prior exposure to infliximab, with three experiencing primary non-response, two developing secondary loss of response, and one discontinuing due to intolerance. Patients were given the option of cyclosporin as a bridge to alternative biologic therapy, proceeding to colectomy, or off-label use of upadacitinib. Patients transitioned from intravenous corticosteroids to a prednisone taper over five weeks, and prior advanced therapies and immunomodulators were discontinued. All six patients demonstrated a clinical response to upadacitinib during hospitalization, with five achieving response by day 5 and the sixth by day 7. By week 8, four patients were in corticosteroid-free clinical remission, with three demonstrating biochemical remission (fecal calprotectin <150 μg/mL, CRP<5 mg/L) and four achieving transmural healing on intestinal ultrasound. One patient required colectomy at week 15 due to refractory disease, while five remained colectomy-free at week 16. Endoscopic assessments in three patients showed a median Mayo endoscopic subscore of 1, and intestinal ultrasound confirmed a reduction in bowel wall thickness. Among adverse events, two patients developed acne, while no severe infections, venous thromboembolism, malignancies, or major cardiovascular events were reported. The report suggested that upadacitinib may be a viable salvage therapy option for steroid-refractory ASUC in infliximab-experienced patients, though prospective studies are necessary to confirm safety and efficacy before routine use can be recommended. [6]