Introduction

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease affecting approximately 1% of the population; RA is characterised by joint damage, functional disability, reduced quality of life and premature mortality . Due to the progressive nature of RA and associated long-term disability, there exists considerable economic burden to patients and society. Individuals with RA have been shown to incur disproportionately high resource use, and indirect costs including lost productivity, compared to other major chronic illnesses .

Earlier and more aggressive treatment with traditional disease-modifying anti-rheumatic drugs (tDMARDs) have become the mainstay of RA therapeutic management in North America and other areas of the world . In North America, the most commonly prescribed tDMARDs include methotrexate (MTX), sulphasalazine (SSZ), hydroxychloroquine (HCQ) and leflunomide (LEF) . Within the past 15 years, a number of biologic response modifiers (BRMs) have emerged. Currently approved BRMs for use in Canada include tumour necrosis factor (TNF) alpha inhibitors as a class, which consists of etanercept (ETA) (ENBREL; Immunex Corporation, Thousand Oaks, California, USA), infliximab (INF) (REMICADE ^® ; Janssen Biotech Inc., Horsham, Pennsylvania, USA), adalimumab (ADA) (Abbott Laboratories Ltd.; North Chicago, Illinois, USA), golimumab (GOL) (Janssen Biotech Inc., Horsham, Pennsylvania, USA) and certolizumab pegol (CTZ) (CIMZIA ^® ; UCB Inc., Brussels, Belgium); BRMs with mechanisms of action other than inhibiting TNF include abatacept (ABA) (ORENCIA ^® ; Bristol-Myers Squibb, New York City, New York, USA) – a T-cell co-stimulatory inhibitor; rituximab (RTX) (RITUXAN ^® ; Hoffman-La Roche Ltd., Basel, Switzerland) – a B-lymphocyte depleting agent; tocilizumab (TCZ) (ACTEMRA; Hoffman-La Roche Ltd., Basel, Switzerland) – an interleukin-6 antagonist; and anakinra (AKR) (Kineret ^® ; Swedish Orphan Biovitrum AB, Stockholm, Sweden) – an interleukin-1 antagonist . These BRMs have transformed the RA treatment paradigm with their superior ability to slow disease progression, reduce joint damage and functional disability when added to tDMARDs . However, BRMs are considerably more expensive than tDMARDs, they may cost from $10,000–$20,000 or more annually compared to between $500 and $1000 annually for tDMARDs . Beyond BRMs, the most recent development has been a novel class of small molecule DMARDs that can be administered orally, such as the Janus kinase (JAK) inhibitor, tofacitinib from Pfizer Inc., currently in phase III clinical trials for RA .

Due to the relatively high cost of BRMs, myriad economic evaluations have emerged in the past decade in attempts to inform policy makers on decisions regarding the allocation of resources to BRMs in the RA treatment armamentarium . Economic evaluations such as cost-effectiveness analyses (CEAs) and cost-utility analyses (CUAs) compare the costs and consequences (outcomes) of two or more possible courses of action, to aid in the decision making of which course of action provides best value for money . A ratio of costs and outcomes does not itself provide information about whether or not a treatment is cost effective, since a treatment strategy can only be judged to be cost effective in relation to status quo or other viable courses of action . Guidelines specify that new treatments – here the BRMs – should therefore be compared to conventional care. Thus, the comparators chosen in the analysis become of paramount importance as results generated in the form of incremental cost-effectiveness ratios (ICERs) are relative to the costs and outcomes of the reference comparator. However, over the years that BRMs have been available, what constitutes conventional care has changed. Consequently, the relevance of previous CEAs are drawn into question.

This article reviews the key areas where changes to the RA treatment paradigm challenges findings of existing economic evaluations. The first key area is the first-line consideration of BRMs in individuals with RA who have not been treated with a tDMARD (DMARD naïve). The second key area is the consideration of BRMs for individuals with RA who have had an inadequate response to one or more previous traditional DMARDs (DMARD-IR). Lastly, since TNF alpha inhibitors have become the standard second-line therapy after tDMARDs in many jurisdictions, it is not clear which is the most cost-effective BRM to try after TNF alpha inhibitor failure.