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Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response
  1. Roy M Fleischmann1,
  2. Mark C Genovese2,
  3. Jeffrey V Enejosa3,
  4. Eduardo Mysler4,
  5. Louis Bessette5,6,
  6. Charles Peterfy7,
  7. Patrick Durez8,
  8. Andrew Ostor9,
  9. Yihan Li10,
  10. In-Ho Song3
  1. 1 Medicine, University of Texas Southwestern, Dallas, Texas, USA
  2. 2 Rheumatology, Stanford University, Palo Alto, California, USA
  3. 3 Immunology Clinical Development, Abbvie Inc, North Chicago, Illinois, USA
  4. 4 Organización Medica de Investigación, Buenos Aires, Argentina
  5. 5 Universite Laval Faculte de medecine, Quebec City, Quebec, Canada
  6. 6 Centre de recherche du CHU de Québec, Université Laval, Quebec City, Québec, Canada
  7. 7 Spire Sciences Inc, Boca Raton, Florida, USA
  8. 8 Pôle de Recherche en Rhumatologie, Institut de Recherche Experimentale et Clinique, Universitde Louvain, UCL, Brussels, Belgium
  9. 9 Cabrini Medical Center, Malvern, Victoria, Australia
  10. 10 Data and Statistical Sciences, AbbVie Inc, North Chicago, Illinois, USA
  1. Correspondence to Dr Roy M Fleischmann, Medicine, University of Texas Southwestern, Dallas, TX 75390, USA; rfleischmann{at}arthdocs.com

Abstract

Background In SELECT-COMPARE, a randomised double-blind study, upadacitinib 15 mg once daily was superior to placebo or adalimumab on background methotrexate (MTX) for treating rheumatoid arthritis signs and symptoms and inhibited radiographical progression versus placebo at 26 weeks. Here we report 48-week safety and efficacy in patients who continued their original medication or were rescued to the alternative medication for insufficient response.

Methods Patients on MTX received upadacitinib 15 mg, placebo or adalimumab for 48 weeks. Rescue without washout, from placebo or adalimumab to upadacitinib or upadacitinib to adalimumab occurred if patients had <20% improvement in tender joint count (TJC) or swollen joint count (SJC) (weeks 14/18/22) or Clinical Disease Activity Index (CDAI) >10 (week 26); remaining placebo patients were switched to upadacitinib at week 26. Efficacy was analysed by randomised group (non-responder imputation), as well as separately for rescued patients (as observed). Treatment-emergent adverse events per 100 patient-years were summarised.

Results Consistent with responses through week 26, from weeks 26 to 48, responses by randomised group including low disease activity, clinical remission and improvements in pain and function remained superior for upadacitinib versus adalimumab; radiographical progression remained lower for upadacitinib versus placebo (linear extrapolation). Although both switch groups responded, a higher proportion of patients rescued to upadacitinib from adalimumab achieved CDAI ≤10 at 6 months postswitch versus patients rescued from upadacitinib to adalimumab. Safety at week 48 was comparable to week 26.

Conclusion Upadacitinib+MTX demonstrated superior clinical and functional responses versus adalimumab+MTX and maintained inhibition of structural damage versus placebo+MTX through week 48. Patients with an insufficient response to adalimumab or upadacitinib safely achieved clinically meaningful responses after switching to the alternative medication without washout.

  • rheumatoid arthritis
  • methotrexate
  • dmards (biologic)
  • dmards (synthetic)

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors RMF, MG, CP, YL and I-HS participated in the design of the study. RF, EM, LB, CP, PD and AO participated in the acquisition and interpretation of data. MG participated in the interpretation of data. JVE,YL and I-HS participated in the analysis and interpretation of data. CP participated in the analysis of data. RF, YL and I-HS contributed to the drafting of the manuscript. All authors contributed to the critical revision of the manuscript for important intellectual content.

  • Funding This study (NCT02629159) was funded by AbbVie, Inc.

  • Competing interests RF has received research grants and consulting fees from AbbVie, Eli Lilly, and Pfizer. MG has served as a consultant for, and has received grants from, AbbVie, Eli Lilly, Pfizer, Galapagos, and Gilead. EM has received research grants and consulting fees from AbbVie, Eli Lilly, Pfizer, Roche, BMS, and Sandoz. LB has served as a speaker on behalf of, and received consulting fees and research grants from, Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Eli Lilly and Novartis. CP is an employee and shareholder of Spire Sciences, has served as a speaker on behalf of Amgen, Bristol-Myers Squibb and has served as a consultant for Centrexion, Crescendo Bioscience, Daiichi Sankyo, EMD Serono, Five Prime, Flexion Therapeutics, Genentech, Gilead, GlaxoSmithKline, Pfizer, Plexikkon, Regeneron, Roche and SetPoint. PD has received speaker fees from BMS, Sanofi, Eli Lilly, and Celltrion. AO has served as a speaker on behalf of, and has received consulting fees and/or research grants from BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Eli Lilly and Novartis. JVE, YL, and I-HS are employees of AbbVie and may own stock or stock options.

  • Patient consent for publication Not required.

  • Ethics approval The study was conducted per the International Conference on Harmonisation guidelines, applicable regulations, and the Declaration of Helsinki. Study-related documents were approved by the United States Central Institutional Review Board (Quorum #31009) and other local institutional ethics committees and review boards.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

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