P658 Comparative Efficacy and Safety of Upadacitinib Versus Tofacitinib as Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: A Matching-Adjusted Indirect Comparison
Reinisch, W.(1)*;Tran, J.(2,3);Patel, K.(4);Borruel, N.(5);Melmed, G.Y.(6);Wegrzyn, L.(3);Levy, G.(3);Ilo, D.(3);Sanchez Gonzalez, Y.(3);Panaccione, R.(7);
(1)Medical University of Vienna, n/a, Wien, Austria;(2)University of Washington, The Comparative Health Outcomes- Policy- and Economics Institute, Seattle, United States;(3)AbbVie Inc., n/a, Chicago, United States;(4)St. George's University Hospital, NHS Foundation Trust, London, United Kingdom;(5)Hospital Vall d'Hebron, Crohn's and Colitis Attention Unit- Digestive System Service, Barcelona, Spain;(6)Cedars-Sinai Medical Center, n/a, Los Angeles, United States;(7)University of Calgary, Department of Gastroenterology and Hepatology, Calgary, Canada;
Background
Upadacitinib (UPA) and tofacitinib (TOFA) are Janus kinase (JAK) inhibitors approved for the treatment of patients (pts) with moderately to severely active ulcerative colitis (UC), but evidence on their comparative efficacy and safety is limited. This study conducted a placebo (PBO)-anchored matching-adjusted indirect comparison (MAIC) of efficacy and safety induction outcomes between UPA and TOFA.
Methods
Pts received oral UPA 45 mg once daily or PBO for 8 weeks in the phase 3 induction studies U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026), and oral TOFA 10 mg twice daily or PBO for 8 weeks in phase 3 OCTAVE 1 and 2 Induction trials (NCT01458951, NCT01465763). MAIC of efficacy outcomes was conducted for bio-naïve and bio-failure pts. These included clinical remission per full Mayo score (FMS; FMS ≤2 with no subscore >1), clinical response per FMS (decrease from baseline in FMS ≥3 points and ≥30%, with a decrease in rectal bleeding score [RBS] of ≥1 or an absolute RBS of 0 or 1), and endoscopic improvement (EI; endoscopic subscore [ES] 0 or 1). The overall population was used to assess endoscopic remission (ER; ES of 0) and safety outcomes including any adverse events (AEs), serious AEs (SAEs) and discontinuation (DC) due to AEs. Baseline characteristics of age, gender, extent and duration of disease, FMS, and corticosteroid use from UPA trials were weighted to match reported OCTAVE pts for primary efficacy outcomes, plus weight, C-reactive protein, and haemoglobin for ER and safety outcomes. Numbers needed to treat/harm (NNT/NNH) were calculated as the inverse of the difference in proportions achieving efficacy/safety outcomes between UPA and TOFA.
Results
The MAIC used data from 961 and 977 UPA pts for primary efficacy and ER/safety outcomes, respectively, and 1,139 TOFA pts. A greater proportion of pts receiving UPA vs TOFA in bio-naïve and bio-failure groups achieved clinical remission, clinical response, and EI (p <0.05, Table 1). PBO-adjusted differences between UPA vs TOFA for clinical remission, clinical response, and EI were 14.6%, 23.0%, and 25.1%, respectively, for bio-naïve pts and 8.5%, 27.7%, and 14.3% for bio-failed pts. ER was also higher in UPA vs TOFA (8.6% difference, p < 0.001). AEs and SAEs were not statistically different between UPA and TOFA pts, but proportion of DC due to AEs were lower in UPA vs TOFA (p < 0.05, Table 2). NNT/NNH analysis showed a favorable benefit-risk profile of UPA vs TOFA.
Conclusion
Pts with moderately to severely active UC achieved greater clinical efficacy and similar safety during induction treatment with UPA compared to TOFA based on MAIC, suggesting a favorable benefit-risk profile of UPA in the JAK class.
