A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with Moderate-to-Severe Rheumatoid Arthritis

Abstract

Introduction: Upadacitinib and tofacitinib are Janus kinase inhibitors approved for moderateto-severe rheumatoid arthritis (RA). In the absence of head-to-head trials comparing their effectiveness, this study assessed the efficacy of upadacitinib 15 mg once-daily monotherapy/combination therapy against tofacitinib 5 mg twice-daily combination therapy among patients with RA using matching-adjusted indirect comparisons (MAICs). Methods: The first of two MAICs used individual patient data (IPD) from the 14-week SELECT-MONOTHERAPY trial (upadacitinib [n = 217] vs. methotrexate [n = 216]) and published data from the ORAL Standard trial (tofacitinib ? methotrexate [n = 204] vs. methotrexate [n = 108]). The second MAIC used

The JAK/STAT signaling pathway: from bench to clinic

“…417 Compared to the first approved JAK inhibitor, tofacitinib combined with methotrexate, upadacitinib displays better outcomes as both a monotherapy and a combination therapy at 3 and 6 months. 418 In addition to its use as an RA treatment, researchers are exploring other indications of upadacitinib, such as Crohn's disease, ulcerative colitis, atopic dermatitis, psoriatic arthritis, and ankylosing spondylitis. [419][420][421][422][423] The most common adverse events are infections and increases in lipid parameters, creatine phosphokinase, and hepatic aminotransferase, followed by a reduction in neutrophil and lymphocyte counts.…”

Clinical Efficacy of Sarilumab Versus Upadacitinib Over 12 weeks: An Indirect Treatment Comparison

“…Recently, two studies compared RA therapies using a MAIC: one assessed the effects of upadacitinib against In the MAIC, the effective sample size of TARGET was reduced to 46% (166/365) of the initial population (sarilumab, n = 92; placebo, n = 74). In the STC, by design, baseline characteristics were adjusted via a regression equation instead of a propensity score matching approach those of another JAK inhibitor, tofacitinib [17], and the other compared the JAK inhibitor baricitinib with tofacitinib, the TNFa inhibitor adalimumab, and the IL-6 receptor inhibitor tocilizumab [12]. Both studies used approaches similar to ours, with some differences in the adjustment factors.…”

“…Both studies used approaches similar to ours, with some differences in the adjustment factors. The comparison of upadacitinib and tofacitinib was conducted by weighing data from the upadacitinib trial SELECT-MONOTHERAPY based on age, sex, race, and the baseline values of SJC66/28, TJC68/28, CRP, and patients' global assessment [17]; the study concluded that upadacitinib was associated with improved outcomes versus tofacitinib. The four-treatment comparison was conducted by adjusting data from the baricitinib trial RA-BEGIN based on age, sex, and the baseline scores of DAS28-ESR, pain VAS, and HAQ-DI [12]; in this study, greater pain reduction and improved physical function were found for baricitinib with adalimumab and tocilizumab, but not for baricitinib versus tofacitinib.…”

2023 Management Recommendations of Bangladesh Rheumatology Society on Pharmacological Treatment of Rheumatoid Arthritis With Synthetic and Biologic Disease-Modifying Drugs

“…Baricitinib-MTX combination decreased joint damage more than MTX monotherapy [ 84 ]. Upadacitinib-MTX combination had higher remission than the tofacitinib-MTX combination [ 85 ].…”