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Background Upadacitinib (UPA), a JAK1 selective inhibitor, is being investigated as monotherapy and combination therapy with DMARDs for the treatment of moderate-to-severe RA. To date, no head-to-head trials have compared the effectiveness of UPA with tofacitinib (TOFA). Objectives: To compare the efficacy of UPA 15 mg monotherapy and combination therapy with TOFA 5 mg combination therapy using MAICs. Methods Two MAICs were conducted. MAIC is an indirect comparison technique that utilises individual patient data (IPD) for one treatment and aggregate data for the other treatment to provide comparative evidence after balancing differences in patient characteristics. The first MAIC used IPD from the SELECT-MONOTHERAPY trial of UPA monotherapy vs. methotrexate (MTX) and published data from the Oral Standard trial of TOFA+MTX vs. MTX. The second used IPD from the SELECT-COMPARE trial of UPA+MTX vs. adalimumab (ADA)+MTX and published data from the ORAL Strategy trial of TOFA+MTX vs. ADA+MTX. UPA monotherapy was not compared to TOFA monotherapy based on feasibility analysis and trial selection criteria. Patients in the UPA trials were re-weighted based on age, gender, race, swollen joint count 66/28, tender joint count 68/28, C-reactive protein (CRP), and patient’s global assessment, to match the baseline characteristics in each comparator trial. After matching, ACR20/50/70 and clinical remission (SDAI(CRP)≤3.3, CDAI≤2.8, DAS28-ESR/CRP&amp;lt;2.6) were compared for UPA monotherapy vs. TOFA +MTX relative to MTX at month 3 and UPA+MTX vs. TOFA+MTX relative to ADA+MTX at month 3 and 6 using a Wald test. Results After matching, baseline characteristics were balanced across the trial populations. At month 3, UPA monotherapy patients experienced significantly greater improvement in ACR70 compared to TOFA+MTX with a mean difference in difference (DD) of 9.9% (p &amp;lt; 0.05) while UPA+MTX was associated with a higher ACR50 compared to TOFA+MTX with a DD of 12.9% (p &amp;lt; 0.05). At month 6, UPA+MTX patients experienced significantly larger improvement in SDAI/CDAI/DAS28-ESR clinical remission compared to TOFA+MTX with DDs of 9.1% (p &amp;lt; 0.05), 7.5% (p &amp;lt; 0.05), and 11.3% (p &amp;lt; 0.01), respectively. Conclusion The results from MAICs indicate that treatment with UPA 15 mg when used as monotherapy or in combination with MTX appears to produce improved outcomes at 3/6 months as compared to TOFA 5 mg +MTX (mono: ACR70 and combination: ACR50, SDAI, CDAI and DAS28-ESR remission). Disclosures C. Edwards: Consultancies; Honoraria and research support from Abbvie, BMS, Biogen, Celgene, Fresenius, Janssen, Lilly, Mundipharma, Pfizer, MSD, Novartis, Roche, Samsung, Sanofi, UCB. R. Sawant: Corporate appointments; Employee and Stockholder of Abbvie. E.X. Du: Consultancies; Employee of Analysis Group, Inc., which has received consultancy fees from AbbVie to conduct this study. J. Cammarota: Consultancies; Employee of Analysis Group, Inc., which has received consultancy fees from AbbVie to conduct this study. P. Tang: Consultancies; Employee of Analysis Group, Inc., which has received consultancy fees from AbbVie to conduct this study. V. Garg: Corporate appointments; Employee and Stockholder of Abbvie. A. Friedman: Corporate appointments; Employee and Stockholder of Abbvie. K. Betts: Corporate appointments; Employee of Analysis Group, Inc., which has received consultancy fees from AbbVie to conduct this study.

P224 A matching-adjusted indirect comparison (MAIC) of upadacitinib versus tofacitinib in csDMARD-IR patients with moderate to severe RA