TY - JOUR
T1 - Efficacy and Safety of Tofacitinib, Baricitinib, and Upadacitinib for Rheumatoid Arthritis
T2 - A Systematic Review and Meta-Analysis
AU - Wang, Faping
AU - Sun, Ling
AU - Wang, Shaohua
AU - Davis, John M.
AU - Matteson, Eric L.
AU - Murad, M. Hassan
AU - Luo, Fengming
AU - Vassallo, Robert
N1 - Publisher Copyright:
© 2020 Mayo Foundation for Medical Education and Research
PY - 2020/7
Y1 - 2020/7
N2 - Objective: To assess the efficacy and safety profiles of different dosing regimens of tofacitinib, baricitinib, and upadacitinib, novel selective oral Janus activated kinase inhibitors, in rheumatoid arthritis (RA). Methods: Randomized controlled trials of tofacitinib (5 and 10 mg twice daily) baricitinib (2 and 4 mg daily), and upadacitinib (15 and 30 mg daily) in RA were identified from MEDLINE, EMBASE, and Cochrane databases through December 11, 2019. Random-effects models were used to estimate pooled mean differences and relative risks (RRs). American College of Rheumatology 20%, Health Assessment Questionnaire–Disability Index, adverse events, risk for infection, venous thromboembolic events, and malignancy were calculated. Results: Twenty trials with an overall low risk of bias involving 8982 patients were identified. Tofacitinib, baricitinib, and upadacitinib improved RA control as determined by American College of Rheumatology 20% (RR, 2.03; 95% CI, 1.87 to 2.20) and Health Assessment Questionnaire–Disability Index scores (mean differences, −0.31; 95% CI, −0.34 to −0.28) compared with placebo. Adverse events were more frequent with upadacitinib, 30 mg, daily (RR, 1.15; 95% CI, 1.02 to 1.30); upadacitinib, 15 mg, daily (RR, 1.14; 95% CI, 1.02 to 1.27); and baricitinib, 4 mg, daily (RR, 1.13; 95% CI, 1.02 to 1.24). The risk for infection was highest with tofacitinib, 10 mg, twice daily (RR, 2.75; 95% CI, 1.72 to 4.41), followed by upadacitinib, 15 mg, daily (RR, 1.35; 95% CI, 1.14 to 1.60) and baricitinib, 4 mg, daily (RR, 1.28; 95% CI, 1.12 to 1.45). Data for venous thromboembolic events were not available for tofacitinib or baricitinib, but there was no increase in risk with upadacitinib (15 mg daily: RR, 2.34; 95% CI, 0.34 to 15.92). Conclusion: Tofacitinib, baricitinib, and upadacitinib significantly improve RA control. Head-to-head Janus activated kinase inhibitor clinical trials are needed to further inform decision making.
AB - Objective: To assess the efficacy and safety profiles of different dosing regimens of tofacitinib, baricitinib, and upadacitinib, novel selective oral Janus activated kinase inhibitors, in rheumatoid arthritis (RA). Methods: Randomized controlled trials of tofacitinib (5 and 10 mg twice daily) baricitinib (2 and 4 mg daily), and upadacitinib (15 and 30 mg daily) in RA were identified from MEDLINE, EMBASE, and Cochrane databases through December 11, 2019. Random-effects models were used to estimate pooled mean differences and relative risks (RRs). American College of Rheumatology 20%, Health Assessment Questionnaire–Disability Index, adverse events, risk for infection, venous thromboembolic events, and malignancy were calculated. Results: Twenty trials with an overall low risk of bias involving 8982 patients were identified. Tofacitinib, baricitinib, and upadacitinib improved RA control as determined by American College of Rheumatology 20% (RR, 2.03; 95% CI, 1.87 to 2.20) and Health Assessment Questionnaire–Disability Index scores (mean differences, −0.31; 95% CI, −0.34 to −0.28) compared with placebo. Adverse events were more frequent with upadacitinib, 30 mg, daily (RR, 1.15; 95% CI, 1.02 to 1.30); upadacitinib, 15 mg, daily (RR, 1.14; 95% CI, 1.02 to 1.27); and baricitinib, 4 mg, daily (RR, 1.13; 95% CI, 1.02 to 1.24). The risk for infection was highest with tofacitinib, 10 mg, twice daily (RR, 2.75; 95% CI, 1.72 to 4.41), followed by upadacitinib, 15 mg, daily (RR, 1.35; 95% CI, 1.14 to 1.60) and baricitinib, 4 mg, daily (RR, 1.28; 95% CI, 1.12 to 1.45). Data for venous thromboembolic events were not available for tofacitinib or baricitinib, but there was no increase in risk with upadacitinib (15 mg daily: RR, 2.34; 95% CI, 0.34 to 15.92). Conclusion: Tofacitinib, baricitinib, and upadacitinib significantly improve RA control. Head-to-head Janus activated kinase inhibitor clinical trials are needed to further inform decision making.
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U2 - 10.1016/j.mayocp.2020.01.039
DO - 10.1016/j.mayocp.2020.01.039
M3 - Article
C2 - 32499126
AN - SCOPUS:85085637469
SN - 0025-6196
VL - 95
SP - 1404
EP - 1419
JO - Mayo Clinic proceedings
JF - Mayo Clinic proceedings
IS - 7
ER -