Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that primarily affects the joints of the body. Characterized by acute and chronic inflammation of the synovium, or soft tissue surrounding the joints, patients are subject to severe pain, stiffness, and fatigue, all of which can affect a patient’s ability to perform activities of daily living and overall health-related quality of life (HRQoL). Prolonged inflammation may lead to damage and destruction of the joints through erosion of the cartilage and bone and, consequently, disability and premature mortality. Other areas of the body may be affected as well, including the eyes, lungs, heart, or skin. It is estimated that about 1% of Canadians have the disease.

Upadacitinib is a Janus kinase (JAK) inhibitor. JAK mediates the effects of cytokines and their production, thus JAK inhibitors may have more of a global effect on various cytokine production than do biologics, which tend to target specific cytokines. Upadacitinib is the third JAK inhibitor approved in Canada, the first being tofacitinib, followed by baricitinib, both of which were previously reviewed and issued recommendations by the CADTH Canadian Drug Expert Committee.

The systematic review protocol for the current review was established before the granting of Notice of Compliance from Health Canada for upadacitinib. The objective is to perform a systematic review of the beneficial and harmful effects of upadacitinib 15 mg extended-release tablets for once daily administration for the treatment of moderate to severe RA in adult patients who have responded inadequately to, or who are intolerant to, one or more disease-modifying antirheumatic drugs (DMARDs). Upadacitinib may be used as monotherapy or in combination with methotrexate or other conventional synthetic DMARDs (csDMARDs).

Contents

• Abbreviations
• Executive Summary
  • Introduction
  • Stakeholder Engagement
  • Clinical Evidence
  • Conclusions
• Introduction
  • Disease Background
  • Standards of Therapy
  • Drug
• Stakeholder Engagement
  • Patient Group Input
  • Clinician Input
• Clinical Evidence
  • Systematic Review (Pivotal and Protocol-Selected Studies)
  • Findings From the Literature
  • Results
  • Indirect Evidence
  • Other Relevant Studies
• Discussion
  • Summary of Available Evidence
  • Interpretation of Results
• Conclusions
• Appendix 1. Literature Search Strategy
• Appendix 2. Excluded Studies
• Appendix 3. Detailed Outcome Data
• Appendix 4. Description and Appraisal of Outcome Measures
• References

Version: Final (with redactions)

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