Most Effective UC Medication for Clinical Remission
For biologic-naïve patients with moderate-to-severe ulcerative colitis, upadacitinib is the single most effective medication for inducing clinical remission, achieving remission in approximately 49% of patients—substantially higher than any other advanced therapy. 1
Evidence Hierarchy and Treatment Selection
First-Line Therapy in Jurisdictions Allowing JAK Inhibitors
Upadacitinib demonstrates superior efficacy with moderate-to-high certainty evidence showing clinically important benefit over infliximab, adalimumab, vedolizumab, etrasimod, ustekinumab, mirikizumab, tofacitinib, and filgotinib for inducing clinical remission. 1 The absolute remission rate of 49% with upadacitinib far exceeds all comparators, with the next closest being risankizumab at 35% and ozanimod at 35%. 1
- Upadacitinib ranked highest (P score 0.96) in network meta-analysis including all advanced therapies for biologic-naïve patients. 1
- The magnitude of benefit meets the pre-specified minimal clinically important difference of 5% absolute risk difference compared to other active treatments. 1
First-Line Therapy Where JAK Inhibitors Are Restricted (U.S.)
In the United States, where FDA restricts JAK inhibitors to second-line use, risankizumab and ozanimod are the most effective first-line options, both achieving approximately 35% clinical remission rates. 1
The ranking by P-scores for biologic-naïve patients excluding JAK inhibitors: 1
- Risankizumab: P score 0.83,35% remission rate
- Ozanimod: P score 0.81,35% remission rate
- Guselkumab: P score 0.66,27% remission rate
- Infliximab: P score 0.64,26% remission rate
- Golimumab: P score 0.62,26% remission rate
Risankizumab demonstrates likely important benefit over adalimumab, ustekinumab, mirikizumab, tofacitinib, and filgotinib with moderate certainty evidence. 1
Biologic-Exposed Patients
For patients with prior biologic exposure, upadacitinib remains superior, with moderate certainty evidence showing clinically important benefit over adalimumab, vedolizumab, ozanimod, etrasimod, mirikizumab, risankizumab, guselkumab, and filgotinib. 1
- Tofacitinib also demonstrates moderate certainty evidence of clinically important benefit in biologic-exposed patients, though with lower absolute efficacy than upadacitinib. 1
- IL-23 antagonists (risankizumab, mirikizumab, guselkumab) show moderate certainty evidence of benefit over placebo in biologic-exposed populations. 1
Critical Implementation Considerations
Combination Therapy Requirement
TNF antagonists must be combined with thiopurines or methotrexate rather than used as monotherapy. 2 In the UC SUCCESS trial, infliximab plus azathioprine achieved 39.7% corticosteroid-free remission at 16 weeks versus 22.1% with infliximab monotherapy (p=0.017). 3
FDA Restrictions on JAK Inhibitors
JAK inhibitors (tofacitinib, upadacitinib, filgotinib) carry FDA restrictions limiting use to patients who have failed or are intolerant to TNF antagonists due to safety concerns including thrombosis, malignancy, and serious infections. 2 This regulatory constraint explains the divergence between efficacy data and real-world prescribing patterns in the United States.
Infliximab as Historical Standard
While infliximab demonstrates lower efficacy than newer agents in network meta-analysis, it remains FDA-approved for moderate-to-severe UC with a recommended dose of 5 mg/kg at weeks 0,2,6, then every 8 weeks. 4 Infliximab shows possibly important benefit over adalimumab, mirikizumab, tofacitinib, and filgotinib with low certainty evidence. 1
Endoscopic Outcomes
The hierarchy for endoscopic improvement parallels clinical remission outcomes, with upadacitinib demonstrating superior mucosal healing rates compared to all other advanced therapies in biologic-naïve patients. 1 This alignment between symptomatic and objective outcomes strengthens the recommendation for upadacitinib as the most effective agent when available.