Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis

Ann Rheum Dis. 2021 Apr;80(4):432-439. doi: 10.1136/annrheumdis-2020-218412. Epub 2020 Nov 4.


Objectives: To evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy.

Methods: SELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts ('non-responders') and at week 26 based on Clinical Disease Activity Index (CDAI) >10 ('incomplete-responders') without washout.

Results: A total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups.

Conclusions: These observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout.

Trial registration: ClinicalTrials.gov NCT02629159.

Keywords: adalimumab; arthritis; health care; outcome assessment; rheumatoid; therapeutics; tumor necrosis factor inhibitors.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / therapeutic use
  • Antirheumatic Agents*
  • Arthritis, Rheumatoid* / chemically induced
  • Arthritis, Rheumatoid* / drug therapy
  • Double-Blind Method
  • Heterocyclic Compounds, 3-Ring / adverse effects
  • Humans
  • Janus Kinase Inhibitors*
  • Methotrexate / therapeutic use
  • Treatment Outcome


  • Antirheumatic Agents
  • Heterocyclic Compounds, 3-Ring
  • Janus Kinase Inhibitors
  • upadacitinib
  • Adalimumab
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT02629159