Which has more data on Ulcerative Colitis, Tofacitinib (Xeljanz) or Upadacitinib (Rinvoq)?

Which JAK Inhibitor Has More Data in Ulcerative Colitis?

Tofacitinib has substantially more clinical trial data and longer-term safety follow-up in ulcerative colitis compared to upadacitinib, with up to 7.8 years of exposure data versus upadacitinib's more limited trial experience. 1

Volume and Duration of Clinical Trial Data

Tofacitinib's Extensive Evidence Base

• Tofacitinib has been studied in 1,220 patients across phase 2 and 3 induction trials, with 1,613 patient-years of exposure in the overall clinical program 2

• Long-term safety data extends up to 7.8 years, with 1,157 patients receiving at least one dose of tofacitinib in the global clinical program 1

• The tofacitinib program includes multiple completed phase 3 trials (OCTAVE Induction 1 and 2, OCTAVE Sustain) plus an open-label long-term extension study (OCTAVE Open) 3, 2

• 412 patients (35.6%) received tofacitinib for more than 4 years, providing robust long-term efficacy and safety data 1

Upadacitinib's More Limited Dataset

• Upadacitinib's UC program consists of two induction studies (U-ACHIEVE Induction and U-ACCOMPLISH) and one maintenance study (U-ACHIEVE Maintenance), with 474 patients in the U-ACHIEVE induction trial 3

• The upadacitinib trials are more recent, with less accumulated long-term follow-up data compared to tofacitinib's nearly 8-year experience 3

Comparative Trial Design and Patient Populations

Tofacitinib Trial Characteristics

• The OCTAVE program included 53-58% of patients with prior anti-TNF exposure, providing extensive data in biologic-experienced populations 3

• Tofacitinib has specific data on extended induction (16 weeks) showing 52.2% of initial non-responders achieved clinical response with extended treatment 4

• Dedicated analyses exist for tofacitinib efficacy stratified by prior TNF inhibitor failure status across 1,139 induction patients and 593 maintenance patients 5

Upadacitinib Trial Characteristics

• Upadacitinib trials included 30-35% of patients with prior exposure to 2 biologics, representing a more treatment-refractory population 3

• The upadacitinib induction trials demonstrated clinical remission rates of 33% and 26% with placebo rates of only 4% and 5% 3

Real-World Evidence and Post-Marketing Data

Tofacitinib's Mature Safety Profile

• Comprehensive safety data from rheumatoid arthritis populations informed UC prescribing, including the ORAL Surveillance study that identified cardiovascular and malignancy risks 3

• Post-hoc analyses of tofacitinib UC trials and observational studies did not identify clear increases in venous thromboembolism or major adverse cardiovascular events in UC populations 3

• Multiple real-world cohort studies have compared tofacitinib to vedolizumab and other biologics in UC, including propensity-matched analyses and registry-based studies 3

Upadacitinib's Emerging Evidence

• Multiple real-world cohorts have supported the high remission and response rates observed in upadacitinib trials, though with shorter follow-up 3

• Real-world studies comparing upadacitinib to tofacitinib are emerging, with meta-analyses showing upadacitinib effectiveness in patients with prior tofacitinib exposure (127 patients across 5 studies) 6

Network Meta-Analysis Inclusion

Both agents are included in the 2024 American Gastroenterological Association network meta-analysis, but tofacitinib's longer market presence means more comparative effectiveness data exists 3

• In biologic-exposed patients, tofacitinib showed a relative risk of 10.45 (95% CI 2.09-52.22) for clinical remission versus placebo, with a P-score of 0.87 3

• Upadacitinib demonstrated superior efficacy with a relative risk of 14.05 (95% CI 4.94-43.94) and P-score of 0.93, though based on fewer patient-years of data 3

Safety Data Maturity

Tofacitinib Safety Database

• Incidence rates for key adverse events are well-established: serious infections 1.69 per 100 patient-years, herpes zoster 3.30 per 100 patient-years, malignancies 0.84 per 100 patient-years, and MACE 0.29 per 100 patient-years 1

• Dose-dependent herpes zoster risk is clearly documented, with maintenance trial showing IR of 6.6 (95% CI 3.2-12.2) for tofacitinib 10 mg twice daily versus 1.0 for placebo 2

• Five cases of pulmonary embolism were reported in patients taking tofacitinib 10 mg twice daily, including one fatality 7

Upadacitinib Safety Profile

• Safety concerns from the JAK inhibitor class apply to upadacitinib, but UC-specific long-term safety data remains more limited compared to tofacitinib 3

• The FDA boxed warning requiring prior TNF antagonist failure applies to all JAK inhibitors, informed primarily by tofacitinib rheumatoid arthritis data 3

Clinical Implications

Despite having more extensive data, tofacitinib demonstrates lower efficacy than upadacitinib in network meta-analyses, with upadacitinib classified as higher efficacy and tofacitinib as intermediate efficacy by the AGA 8

• The greater volume of tofacitinib data provides more confidence in long-term safety estimates, particularly for rare adverse events requiring extended follow-up 1

• Upadacitinib's superior efficacy (clinical remission 29.1% vs 18.9% for tofacitinib) must be weighed against less mature long-term safety data 8