Juvenile idiopathic arthritis (JIA) is a relatively common, chronic childhood disorder, with clinical manifestations mainly related to joint inflammation and including joint effusion, joint line tenderness and warmth, restricted range of movement, and limitation of movement secondary to pain. Systemic onset JIA (sJIA) is a subtype of the disease accounting for approximately 4% to 15% of patients, and is defined as arthritis in one or more joints for at least 6 weeks in a child younger than 16 years with or preceded by fever of at least 2 weeks that is documented to be daily for at least 3 days and accompanied by one or more of the following: evanescent erythematous rash, generalized lymphadenopathy, hepatomegaly or splenomegaly, and serositis. Patients with sJIA experience an intense inflammatory state leading to a particularly refractory course and persistent disease. As a result, these patients are at high risk for serious complications such as joint damage and growth impairment, as well as macrophage activation syndrome (MAS), a life-threatening complication developing in 10% to 15% of children with sJIA and associated with a mortality rate that may reach 20%.

Canakinumab is a fully human monoclonal antibody that selectively binds and neutralizes interleukin-1 beta, which plays a key role in the inflammatory process of sJIA. Canakinumab has a Health Canada indication for the management of active sJIA in patients 2 years and older. The manufacturer has requested that canakinumab be evaluated for reimbursement for the management of active sJIA in patients 2 years and older who are contraindicated to, or have discontinued, any biologic therapy for lack of efficacy or intolerance. The objective of this report was to perform a systematic review of the beneficial and harmful effects of canakinumab subcutaneous injection for the management of active sJIA in patients aged ≥ 2 years.

Contents

• Clinical Review Report
  • ABBREVIATIONS
  • EXECUTIVE SUMMARY
    • Introduction
    • Results and Interpretation
    • Conclusions
  • 1. INTRODUCTION
    • 1.1. Disease Prevalence and Incidence
    • 1.2. Standards of Therapy
    • 1.3. Drug
  • 2. OBJECTIVES AND METHODS
    • 2.1. Objectives
    • 2.2. Methods
  • 3. RESULTS
    • 3.1. Findings from the Literature
    • 3.2. Included Studies
    • 3.3. Patient Disposition
    • 3.4. Exposure to Study Treatments
    • 3.5. Critical Appraisal
    • 3.6. Efficacy
    • 3.7. Harms
  • 4. DISCUSSION
    • 4.1. Summary of Available Evidence
    • 4.2. Interpretation of Results
    • 4.3. Potential Place in Therapy
  • 5. CONCLUSIONS
  • APPENDIX 1. PATIENT INPUT SUMMARY
    • 1. Brief Description of Patient Groups Supplying Input
    • 2. Condition Related Information
    • 3. Current Therapy Related Information
    • 4. Expectations About the Drug Being Reviewed
  • APPENDIX 2. LITERATURE SEARCH STRATEGY
  • APPENDIX 3. EXCLUDED STUDIES
  • APPENDIX 4. DETAILED OUTCOME DATA
    • 1. Efficacy — Adapted ACR Pedi Response
    • 2. Efficacy — Disease Activity
    • 3. Efficacy — Health-Related Quality of Life and Functional Outcomes
    • 4. Harms Outcomes
  • APPENDIX 5. VALIDITY OF OUTCOME MEASURES
    • Aim
    • Findings
  • APPENDIX 6. SUMMARY OF LONG-TERM DATA
  • APPENDIX 7. SUMMARY OF INDIRECT TREATMENT COMPARISONS
    • 1. Introduction
    • 2. Description of ITCs identified
    • 3. Conclusion
  • REFERENCES
• Pharmacoeconomic Review Report
  • ABBREVIATIONS
  • EXECUTIVE SUMMARY
    • Background
    • Summary of Identified Limitations
    • Results and Conclusions
  • 1. SUMMARY OF THE MANUFACTURER’S PHARMACOECONOMIC SUBMISSION
  • 2. MANUFACTURER’S BASE CASE
  • 3. SUMMARY OF MANUFACTURER’S SENSITIVITY ANALYSES
  • 4. LIMITATIONS OF MANUFACTURER’S SUBMISSION
  • 5. CADTH COMMON DRUG REVIEW REANALYSES
  • 6. ISSUES FOR CONSIDERATION
  • 7. PATIENT INPUT
  • 8. CONCLUSIONS
  • APPENDIX 1. COST COMPARISON
  • APPENDIX 2. SUMMARY OF KEY OUTCOMES
  • APPENDIX 3. ADDITIONAL INFORMATION
  • APPENDIX 4. SUMMARY OF OTHER HEALTH TECHNOLOGY ASSESSMENT REVIEWS OF CANAKINUMAB
  • APPENDIX 5. REVIEWER WORKSHEETS
    • Manufacturer’s Model Structure
    • Manufacturer’s Sensitivity Analyses
    • Manufacturer’s Results
    • Manufacturer’s Sensitivity Analyses
    • CADTH Common Drug Review Reanalyses
  • REFERENCES
• CADTH CANADIAN DRUG EXPERT COMMITTEE FINAL RECOMMENDATION
  • Recommendation
  • Criteria
  • Conditions
  • Reasons for the Recommendation
  • Of Note
  • Background
  • Research Gaps

This review report was prepared by the Canadian Agency for Drugs and Technologies in Health (CADTH). In addition to CADTH staff, the review team included two clinical experts in rheumatology and pediatric rheumatology who provided input on the conduct of the review and the interpretation of findings.

Through the CADTH Common Drug Review (CDR) process, CADTH undertakes reviews of drug submissions, resubmissions, and requests for advice, and provides formulary listing recommendations to all Canadian publicly funded federal, provincial, and territorial drug plans, with the exception of Quebec.

The report contains an evidence-based clinical and/or pharmacoeconomic drug review, based on published and unpublished material, including manufacturer submissions; studies identified through independent, systematic literature searches; and patient-group submissions. In accordance with CDR Update – Issue 87, manufacturers may request that confidential information be redacted from the CDR Clinical and Pharmacoeconomic Review Reports.

The information in this report is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. The information in this report should not be used as a substitute for the application of clinical judgment with respect to the care of a particular patient or other professional judgment in any decision-making process, nor is it intended to replace professional medical advice. While CADTH has taken care in the preparation of this document to ensure that its contents are accurate, complete, and up-to-date as of the date of publication, CADTH does not make any guarantee to that effect. CADTH is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in the source documentation. CADTH is not responsible for any errors or omissions or injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the information in this document or in any of the source documentation.

This document is intended for use in the context of the Canadian health care system. Other health care systems are different; the issues and information related to the subject matter of this document may be different in other jurisdictions and, if used outside of Canada, it is at the user’s risk. This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada.

CADTH takes sole responsibility for the final form and content of this document, subject to the limitations noted above. The statements and conclusions in this document are those of CADTH and not of its advisory committees and reviewers. The statements, conclusions, and views expressed herein do not necessarily represent the views of Health Canada or any Canadian provincial or territorial government. Production of this document is made possible by financial contributions from Health Canada and the governments of Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Northwest Territories, Nova Scotia, Nunavut, Ontario, Prince Edward Island, Saskatchewan, and Yukon.