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

Abstract

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.

• Authors: Roy M Fleischmann, Ricardo Blanco, Stephen Hall, Glen T D Thomson, Filip E Van den Bosch, Cristiano Zerbini, Louis Bessette, Jeffrey Enejosa, Yihan Li, Yanna Song, Ryan DeMasi, In-Ho Song
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 80 Issue 4 Pg. 432-439 (04 2021) ISSN: 1468-2060 [Electronic] England
• PMID: 33148701 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

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

Topics

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