Article Text

Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme
  1. Stanley B Cohen1,
  2. Ronald F van Vollenhoven2,
  3. Kevin L Winthrop3,
  4. Cristiano A F Zerbini4,
  5. Yoshiya Tanaka5,
  6. Louis Bessette6,
  7. Ying Zhang7,
  8. Nasser Khan7,
  9. Barbara Hendrickson7,
  10. Jeffrey V Enejosa7,
  11. Gerd R Burmester8
  1. 1 Metroplex Clinical Research Center, Dallas, Texas, USA
  2. 2 Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands
  3. 3 Oregon Health and Science University, Portland, Oregon, USA
  4. 4 Centro Universitario Central Paulista, São Paulo, Brazil
  5. 5 University of Occupational and Environmental Health Japan, Kitakyushu, Fukuoka, Japan
  6. 6 Laval University, Quebec City, Quebec, Canada
  7. 7 AbbVie Inc, North Chicago, Illinois, USA
  8. 8 Charité Universitätsmedizin Berlin, Berlin, Germany
  1. Correspondence to Professor Stanley B Cohen, Metroplex Clinical Research Center, Dallas, Texas, USA; arthdoc{at}


Objectives This integrated analysis presents the safety profile of upadacitinib, a Janus kinase inhibitor, at 15 mg and 30 mg once daily in patients with moderately to severely active rheumatoid arthritis (RA).

Methods Treatment-emergent adverse events (TEAEs) and laboratory data from five randomised, placebo- or active-controlled phase III trials of upadacitinib for patients with RA were analysed and summarised. Exposure-adjusted event rates are shown for placebo (three trials; 12/14 weeks), methotrexate (two trials; mean exposure: 36 weeks), adalimumab (one trial; mean exposure: 42 weeks), upadacitinib 15 mg (five trials; mean exposure: 53 weeks) and upadacitinib 30 mg (four trials; mean exposure: 59 weeks).

Results 3834 patients received one or more doses of upadacitinib 15 mg (n=2630) or 30 mg (n=1204), for a total of 4020.1 patient-years of exposure. Upper respiratory tract infection, nasopharyngitis and urinary tract infection were the most commonly reported TEAEs with upadacitinib. Rates of serious infection were similar between upadacitinib 15 mg and adalimumab but higher compared with methotrexate. Rates of herpes zoster and creatine phosphokinase (CPK) elevations were higher in both upadacitinib groups versus methotrexate and adalimumab, and rates of gastrointestinal perforations were higher with upadacitinib 30 mg. Rates of deaths, malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs) were similar across treatment groups.

Conclusion In the phase III clinical programme for RA, patients receiving upadacitinib had an increased risk of herpes zoster and CPK elevation versus adalimumab. Rates of malignancies, MACEs and VTEs were similar among patients receiving upadacitinib, methotrexate or adalimumab.

Trial registration numbers SELECT-EARLY: NCT02706873; SELECT-NEXT: NCT02675426; SELECT-COMPARE: NCT02629159; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847.

  • arthritis
  • rheumatoid
  • adalimumab
  • methotrexate

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  • Handling editor Josef S Smolen

  • Presented at Some data in this paper have been presented previously at European League Against Rheumatism 2019 (Cohen SB, et al. Ann Rheum Dis 2019;78:357: Abstract THU0167) and ACR 2019.

  • Contributors SBC, LB, GRB and CAFZ were involved in the acquisition of data. All authors were involved in the analysis and interpretation of the data, drafting the article and revising it for critically important intellectual content, and reviewing and approving the final version of the manuscript.

  • Funding AbbVie funded the study and had a role in the study design, data collection, data analysis, data interpretation and writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

  • Competing interests SBC received grants and consultation fees from Amgen, AbbVie, Boehringer Ingelheim, Gilead, Pfizer, Roche and Sandoz. RFvV received grants from AbbVie, Arthrogen, BMS, GSK, Lilly, Pfizer and UCB and personal fees from AbbVie, AstraZeneca, Biotest, BMS, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche and UCB. KLW received consulting fees and research grants from AbbVie, BMS, Lilly, Pfizer, Roche and UCB. CAFZ received research grants from Amgen, GSK, Lilly, Merck, Novartis, Pfizer, Sanofi-Aventis, Servier and Roche, participated on advisory boards and speaker’s bureau for Merck, Pfizer, and Sanofi-Aventis and served as a consultant for Pfizer. YT received speaking fees and/or honoraria from AbbVie, Asahi-Kasei, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Gilead, GSK, Janssen, Lilly, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi and YL Biologics and received research grants from Asahi-Kasei, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Takeda and UCB. LB received speaking fees, consulting fees and research grants from AbbVie, Amgen, BMS, Celgene, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi and UCB. YZ, NK, BH and JVE are full-time employees of AbbVie and may hold AbbVie stock or stock options. GRB received speaking or consulting fees from AbbVie, Gilead, Janssen, Lilly, MSD, Pfizer, Roche and UCB.

  • Patient consent for publication Not required.

  • Ethics approval Studies were conducted in compliance with the Declaration of Helsinki, International Conference on Harmonisation of Technical Regulations for Pharmaceuticals for Human Use guidelines, and applicable local country regulations. All study-related documents were approved by independent ethics committees and institutional review boards. All patients provided written, informed consent.

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

  • Data availability statement Data are available on reasonable request. AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymised, individual and trial­-level data (analysis datasets), as well as other information (eg, protocols and Clinical Study Reports), provided the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a Data Sharing Agreement. Data requests can be submitted at any time, and the data will be accessible for 12 months, with possible extensions considered. For more information on the process or to submit a request, visit­science/clinical­trials/clinical­trialsdata­and­information­sharing/data­and­information­sharing­withqualified­researchers.html.

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