Upadacitinib is a Janus kinase (JAK) inhibitor (also referred to as a targeted synthetic disease-modifying antirheumatic drug [tsDMARD] in practice), indicated for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate. The recommended dose of upadacitinib is 15 mg daily as monotherapy or combination therapy. At the sponsor-submitted price of $48.68 per 15 mg tablet, the annual treatment cost is $17,770.
The sponsor submitted a cost-utility analysis that considered upadacitinib as initial treatment for moderate-to-severe RA after an inadequate response or are intolerant to either a conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR population) or a biologic disease-modifying antirheumatic drug (bDMARD-IR population). The sponsor’s analysis was conducted from the perspective of a Canadian publicly funded health care payer over a five-year time horizon. Comparators included csDMARDs, bDMARDs, and other tsDMARDs. The pharmacoeconomic submission was based on a Markov model, where treatment response was evaluated using the American College of Rheumatology (ACR) response criteria. The model was composed of four main health states after the evaluation of initial treatment: 20% improvement in ACR criteria (ACR20); 50% improvement in ACR criteria (ACR50); 70% improvement in ACR criteria (ACR70); and lack of adequate treatment response (i.e., did not achieve minimum of ACR20). Patients who had an inadequate response or discontinued treatment owing to a serious adverse event (SAE) could receive a subsequent treatment and transition to any of the previously mentioned health states. If an adequate response was not achieved on subsequent treatment, patients received best supportive care (BSC), the prior therapy (bDMARD or tsDMARD) which patients achieved the best treatment effect. A sponsor-commissioned network meta-analysis (NMA) was submitted and informed the comparative ACR response at weeks 12 and 24. SAEs were incorporated on the basis of an NMA previously conducted by CADTH4 and updated to include upadacitinib and other missing comparators. Long-term discontinuation was included in the model owing to a loss of treatment effect over time. Health state utility values for ACR response and nonresponse were based on Health Assessment Questionnaire (HAQ) scores mapped to the Health Utility Index 3 (HUI-3) tool.
In the sponsor’s base case, upadacitinib + csDMARD was associated with both higher total costs and quality-adjusted life-years (QALYs) when compared to csDMARD monotherapy in both target populations. In the csDMARD-IR population, the preferred option is csDMARD monotherapy if the decision-maker’s willingness to pay (WTP) is below $74,979 per QALY, infliximab 3 mg/kg + csDMARD if the decision-maker’s WTP is between $74,979 and $80,897 per QALY, etanercept 50 mg + csDMARD if the decision-maker’s WTP is between $80,897 and $107,659 per QALY, and upadacitinib + csDMARD if the decision-maker’s WTP is more than $107,659 per QALY. In the bDMARD-IR population, the preferred option is a csDMARD if the decision-maker’s WTP is below $104,193 per QALY, upadacitinib + csDMARD if the decision-maker’s WTP is between $104,193 and $303,516 per QALY, and tocilizumab 8 mg/kg + csDMARD if the decision-maker’s WTP is more than $303,516 per QALY. Other treatments were dominated or extendedly dominated.
Funding: CADTH receives funding from Canada’s federal, provincial, and territorial governments, with the exception of Quebec.
Disclaimer: The information in this document 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. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services.
While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document. The views and opinions of third parties published in this document do not necessarily state or reflect those of CADTH.
CADTH is not responsible for any errors, omissions, 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 contents of this document or any of the source materials.
This document may contain links to third-party websites. CADTH does not have control over the content of such sites. Use of third-party sites is governed by the third-party website owners’ own terms and conditions set out for such sites. CADTH does not make any guarantee with respect to any information contained on such third-party sites and CADTH is not responsible for any injury, loss, or damage suffered as a result of using such third-party sites. CADTH has no responsibility for the collection, use, and disclosure of personal information by third-party sites.
Subject to the aforementioned limitations, the views expressed herein are those of CADTH and do not necessarily represent the views of Canada’s federal, provincial, or territorial governments or any third party supplier of information.
This document is prepared and intended for use in the context of the Canadian health care system. The use of this document outside of Canada is done so at the user’s own 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.
