Rheumatoid Arthritis (RA) is a long-term inflammatory auto-immune disease that mainly affects the lining of synovial joints. It can cause irreversible joint damage, economic challenges, and early death [1]. The global prevalence of RA is estimated to be 0.46% in population-based studies [2]. However, the cause of RA is still not well understood, and there is no known cure despite recent advances in treatment [1, 3]. Early and proactively taking disease-modifying antirheumatic drugs (DMARDs) is the best way to treat RA today [4]. DMARDs are a type of RA drug that modulates a person’s immune system. Different types of DMARDs can be divided into conventional and newer biological therapy [4]. Methotrexate is an example of a conventional cheap treatment and considered a first-line strategy [4]. In cases of non-response, biological therapy such as Adalimumab is regarded as an effective treatment but expensive option [4].
Currently, the standard clinical practice is to use methotrexate, corticosteroids, and/or biological drugs to prevent joint damage and functional disability and improve quality of life [5, 6]. The Australian Government provides medical care through Medicare and Pharmaceutical Benefits Schemes (PBS) in Australia. The PBS has subsidised biological DMARDs therapy for RA since 2003, if there is a favourable cost-effectiveness recommendation. The Australian Government spent A$2.29 billion on biological medicines through the PBS in 2015-16, representing 21.1% of the total PBS expenditure of A$10.84 billion [7]. Among the top 10 most common biologics, Adalimumab is the most common and expensive brand name medication used for RA [8], costing A$121.2 million from 2014 to 2015 [9], with an average of A$23,000 per patient annually.
Regarding the effectiveness of biological therapy compared with conventional treatment, researchers from the United States and Canada conducted a three-year clinical study with 353 people with RA [10]. One group was administered biological medication (etanercept) and methotrexate; the other group received methotrexate and two conventional DMARDs [10]. Both groups had comparable outcomes after six months; 73% of both groups had improved mobility and reduced pain and stiffness [10]. While patients who did not progress with one treatment switched to another, and both improved [10]. The study showed no need for expensive biologics if methotrexate is ineffective and conventional medications for RA are equally effective and less costly [10]. Accordingly, the savings can be used to expand access to biologics to more patients without incurring additional costs.
In Australia, there is limited information about the effectiveness of biological treatment in RA over time compared to conventional DMARDs due to limited data resources [11]. However, admission to hospitals is an available method for assessing medications’ effectiveness and safety in people with RA. In addition, they allow us to determine whether fewer healthcare visits balance the higher biological therapy costs. The long-term effects of biological therapy on RA hospital admissions will help doctors and policymakers decide if this expensive treatment is worth it compared with conventional DMARDs.
The putting of this question is significant to determine the value of expensive biological therapy for RA. For example, in Western Australia, UWA researchers, with support from the Arthritis Foundation, found that both conventional and biological DMARDs have a role in reducing RA hospitalisations.
The annual mean cost of RA admissions in pre biological DMARDs period was higher (AUD$ 13.5 million) compared with the post biological DMARDs period (AUD$ 4.3 million). However, the annual mean cost of biological DMARDs utilisation was AUD$ 22.5 million in 2003–2014, which is higher than the annual mean cost of conventional DMARDs (AUD$ 4.8 million) and RA hospital admission cost savings (AUD$ 9.2 million) over the same period (Table 1).
Table 1: The annual mean cost with biological disease-modifying anti-rheumatic drugs utilisation in Rheumatoid Arthritis at Western Australia (1995–2014).
| Direct health care costs | 1995–2002 | 2003–2014 | Mean difference |
| Mean annual cost of RA hospital admissions | AUD$ 13.5 million/year | AUD$ 4.3 million/year | AUD$ −9.2 million/year |
| Mean annual cost of conventional DMARDs utilisation | AUD$ 2.2 million/year | AUD$ 4.8 million /year | AUD$ +2.6 million/year |
| Mean annual costs of bDMARDs utilisation | – | AUD$ 22.5 million/year | AUD$ +22.5 million/year |
| Total mean annual costs | AUD$ 15.7 million/year | AUD$ 31.6 million/year | AUD$ +15.9 million/year |
AUD$= Australian dollar, (−), cost savings; (+), excess costs; bDMARDs, biological disease-modifying anti-rheumatic drugs; RA, rheumatoid arthritis; WA, Western Australia.
Restricting access to biological therapy because of the cost may reduce total treatment costs but may result in suboptimal management of RA, especially for patients who have not responded adequately to methotrexate and leflunomide. Consequently, hospital admissions and direct and indirect costs may increase; this scenario was evident before the escalation of biological therapy and its introduction in 2003.
A second question was the impact of biological therapy on quality of life and absence from work that adds to the cost. Still, there is no evidence that biological therapy will reduce hospital admissions further, especially with gradual increases in RA patients’ utilisation due to restricted access and limited data regarding the number of patients on monotherapy and the level of treatment adherence. However, according to our previous study results regarding the trend of mortality for people with RA compared with the general population in Western Australia [13], we found a significant reduction in RA deaths after 2003, suggesting biological DMARDs may provide some benefit over time compared to conventional DMARDs alone [13]. However, in terms of averted RA hospitalisations, our study found that not all biological therapy has shown equivalent effects based on Principal Component Analysis. For example, Infliximab was the least effective among biological therapy at reducing RA hospitalisations.
The innovation of this research was to use Principal Component Analysis to determine the relationship between conventional DMARDs and biological therapy use and hospital admission rates. An essential feature of this statistical approach is that it reduces many intercorrelated variables to a few dimensions that collectively capture a critical portion of their variability. For example, in Western Australia, increased use of conventional DMARDs therapy has led to a significant decline in hospital admissions for patients with RA, followed by a more modest decline following the introduction of biological therapy. This information will assist local and national policymakers in making informed decisions about the use of biological therapy and resource allocation for RA patients.
About the author:
By Dr Khalid Almutairi BS Pharm, MClinPharm, M.H.A, PhD W.Aust. Dr Khalid Almutairi is a Clinical Researcher and Clinical Pharmacy Specialist in Intensive Care Units with Expertise in Infectious Diseases, Autoimmune Diseases, and Pharmaceutical Utilisation and Related Costs Using Linked Big Data from the Health Department of Western Australia and Hospital-based Electronic Recording Systems.
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