Impact of a risk-sharing agreement in rheumatoid arthritis in Spain
Introduction
Access to new drugs faces different challenges that must be taken into account: a combination of high prices of new patented medicines and the uncertainty related to their clinical effectiveness and use in real life imply a dilemma for decision-makers [1]. Indeed, on the one hand, the real effectiveness of a new drug is unknown, as it may differ from the efficacy shown in clinical trials, especially when it comes to specific patient sub-populations. On the other hand, the health expenditure associated with the introduction of the new drug in the market is also uncertain, because expenditure will depend on prescription patterns, the dimension of the target population, patients’ demand, and available treatment alternatives.
An increasingly common way of dealing with these uncertainties is through the adoption of alternative financing schemes for pharmaceutical innovations, such as Risk Sharing Agreements (RSAs) [2]. RSAs are among the most commonly used financial tools in this context, and their main objective is to replace traditional payment models based on a fixed price per drug container, for alternative models where payment is linked to clinical results [3]. RSAs have been implemented for years in many high-income countries, especially when it comes to new drugs such as biological agents and other cancer-related drug therapies, drugs targeting infectious diseases (e.g. hepatitis C), rare diseases, and autoimmune diseases like rheumatoid arthritis (RA) [4,5].
RA is a chronic autoimmune disease that entails a significant human and economic burden [6]. Worldwide, its prevalence rates vary between 0.3 % and 1% [7]. In Spain, the estimated prevalence of RA is 0.8 % [8]. In addition, RA has no cure, and approximately 30 % of patients do not respond to traditional disease-modifying antirheumatic drugs (DMARDs) and become candidates for biologic treatments such as tumor necrosis factor inhibitors (TNFi) [9]. In recent years, the availability of TNFi has enabled a better control of the disease, which in turn has allowed for improvements in patients’ functional capacity and quality of life. For this reason, TNFi are recommended by clinical guidelines [10].
The first RSA on the treatment of RA in Spain was developed in 2013, between the University Hospital of Bellvitge (Catalonia) and the certolizumab pegol (CZP) manufacturing laboratory (UCB Pharma). CZP is a biologic TNF alpha blocker for the treatment of adult RA patients whose response to DMARDs has been inadequate. CZP was authorized by the EMA in October 2009 [11], and has been commercialized in Spain since December 2009 [12]. Efficacy data from three pivotal trials (RAPID-1, RAPID-2, and FAST4WARD) showed that most patients treated with CZP were good responders at 12 weeks of treatment [[13], [14], [15], [16]]. Furthermore, fast improvements in physical function and in symptom reduction were able to predict satisfactory results in the long run [[17], [18], [19]]. Hence, as the decision to continue treatment with CZP depends on the results at week 12, the RSA stated that the laboratory would refund all CZP doses provided to patients who did not reach an optimal or satisfactory clinical response at that time. This agreement has already been implemented in several hospitals across 9 Autonomous Communities in Spain [20].
In 2016, the expected economic impact of this RSA was assessed in a cohort of 81 patients [21]. However, nowadays, there are real effectiveness data regarding the CZP treatment in a larger population of patients. Therefore, the objective of this study was to assess the real economic impact associated with the implementation of the current RSA in a sample of RA patients treated with CZP in Spain, and to assess the potential impact of an alternative RSA.
Section snippets
Patients
We used data from a cross-sectional study carried out in 2017 on a sample of 138 patients distributed across 19 Spanish hospitals where the original RSA had been implemented on adult patients diagnosed with moderate to severe RA. All patients were treated with CZP after an inadequate response to DMARDs, including methotrexate.
Clinical effectiveness criteria
The clinical effectiveness measure was the Disease Activity Score (DAS), which is a continuous measure of RA disease activity that combines information from swollen
Structure of the model
The structure of the study is shown in Fig. 2. Of the 138 patients who participated in the cross-sectional study, data was incomplete in 41 patients. Therefore, the data from 97 adult patients (distributed across 18 hospitals in Spain) were considered for this research. After 12 weeks of treatment, 72 patients showed an adequate response, whereas the remaining patients showed an inadequate response, either in terms of DAS28 (n = 28) or because they prematurely discontinued treatment due to
Discussion
RSAs are an increasingly used innovative financial tool whose purpose is to control the uncertainty associated with the effectiveness and/or real safety of new healthcare interventions, especially in early stages of adoption. Under an RSA, different healthcare stakeholders become jointly responsible for the success and risks associated with a new treatment, which may favor access to innovation, savings generation, rationalization of public expenditure on health, and efficiency in the healthcare
Conclusions
This study sheds light on the savings that have been generated within the hospital's pharmacy service under the current RSA for the treatment of RA patients with CZP in Spain. Beyond isolated pilot experiences, the implementation of performance-based financial schemes is a way of introducing continuous evaluation in healthcare management. Adequately designed and evaluated RSAs may be relevant instruments for reaching efficiency in the healthcare system.
Declaration of Competing Interest
The authors declare that there is not conflict of interest that could be perceived as prejudicing the impartiality of the research reported and there is not any competing financial interest in relation to the work described in this article.
Acknowledgments
The participating investigators of the Study Group Ariesgo collected data. Theywere Rosa Garcia Portales, José Manuel Fernandez Ovies, Antonio Fernández Nebro, Isabel Muñoz, Jose María Salazar, José Luis Álvarez, Juan Francisco Rangel, Manuel Romero, Florentina Horno, Juan Povedano, Javier Bautista, Juan Povedano, Gabriel Ramírez, Enrique Raya, Sara Marsall, Julio Martínez Cutillas, RaimónSanmartí, Ramón Casabona, Inés Gozalo, José Miguel Ruiz, Tomás Casasin, Nuria San Juan, Azucena Hernández,
References (41)
- et al.
Dealing with uncertainty and high prices of new medicines: a comparative analysis of the use of managed entry agreements in Belgium, England, the Netherlands and Sweden
Soc Sci Med
(2015) - et al.
Rheumatoid arthritis — Anti-TNF
Int Immunopharmacol
(2015) - et al.
Performance-based risk-sharing arrangements—good practices for design, implementation, and evaluation: report of the ISPOR good practices for performance-based risk-sharing arrangements task force
Value Health
(2013) - et al.
Effect of risk-share agreements on budget impact: a case study of CZP in the treatment of rheumatoid arthritis. PSY13
Value Health
(2012) - et al.
Risk-sharing agreements in the EU: a systematic review of major trends
Pharm Open Access
(2018) - et al.
Aplicación de los contratos de riesgo compartido a la financiación de nuevos medicamentos
Gestión Clínica y Sanitaria
(2005) - et al.
The implementation of managed entry agreements in central and Eastern Europe: findings and implications
Pharmacoeconomics
(2017) - et al.
Performance-based risk-sharing arrangements for pharmaceutical products in the United States: a systematic review
J Manag Care Spec Pharm
(2017) - et al.
The global burden of rheumatoid arthritis: estimates from the Global Burden of Disease 2010 study
Clin Epidemiol Res
(2014) - WHO. Chronic rheumatic conditions. WHO n.d. http://www.who.int/chp/topics/rheumatic/en/ (accessed July 29,...
Proyecto SROI-AR Impacto clínico, asistencial, económico y social del abordaje ideal de la artritis reumatoide en comparación con el abordaje actual
Madrid: Fundación Weber
Spanish Rheumatology Society and Hospital Pharmacy Society Consensus on recommendations for biologics optimization in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis
Rheumatology
Certolizumab pegol in the treatment of rheumatoid arthritis: a comprehensive review of its clinical efficacy and safety
Rheumatology (Oxford)
Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study
Arthritis Rheum
Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial
Ann Rheum Dis
Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study
Ann Rheum Dis
Rapid improvement in the signs and symptoms of rheumatoid arthritis following certolizumab pegol treatment predicts better long-term outcomes: post-hoc analysis of a randomized controlled trial
J Rheumatol
Clinical, ultrasound, and predictability outcomes following certolizumab pegol treatment (with methotrexate) in patients with moderate-to-Severe rheumatoid arthritis: 52-Week results from the CZP-SPEED study
Adv Ther
Cited by (4)
Should Canada adopt managed access agreements in Canada for expensive drugs?
2023, Journal of Law and the BiosciencesThe Challenges of Outcomes-Based Contract Implementation for Medicines in Europe
2022, PharmacoEconomics