Disease-modifying antirheumatic drugs prove most cost-effective in very early RA

Key Points

Therapeutic strategies involving early conventional disease-modifying antirheumatic drugs (DMARD) or early biologics are preferred in treating very early rheumatoid arthritis (RA), but the additional costs of early biologics may not be justified for all patients, according to a recent study reported in the Annals of Internal Medicine.

The researchers analyzed the cost-effectiveness of very early intervention in RA using a model that examined radiologic progression with both reversible and irreversible dysfunction. Emerging research suggests that if RA is diagnosed and treated very early, long-term remission may be possible without the need for continuing treatment. Further, they note early treatment of RA with biologics may yield superior results when compared to treatment with conventional DMARDs in terms of hard outcomes, such as radiographic structural joint damage, but not necessarily in terms of disease activity.

The present analysis considered adults with very early RA, which was operationally defined as symptoms lasting less than 3 months in duration. An individual sampling model tracked the course of disease over time, with changes in important variables (principally radiographic joint damage and functional disability) at selected time points at which events (toxicities, treatment initiation, treatment discontinuation, or death) occurred. For US patients, an estimated lifetime costs and benefits was calculated and expressed as quality-adjusted life-years (QALYs) from both a healthcare provider and societal perspective.

Three models were chosen for analysis and hypothetical patient cohorts were tracked through them. The models were as follows:

1. The pyramid strategy in which initial nonsteroidal anti-inflammatory drugs, patient education, joint protection and therapeutic exercise, pain management, and low-dose corticosteroids are administered as needed, followed by DMARDs at 1 year for nonresponders.

2. The early DMARD strategy in which conventional DMARDs (such as leflunomide, sulfasalazine, hydroxychloroquine, or methotrexate) are given within 12 weeks of symptom onset.

3. The early biologic strategy in which very early use of biologics, defined as 3 sequential necrosis factor inhibitors, in combination with methotrexate, is employed.

In the pyramid and early DMARD strategies, patients initially receive conventional DMARDs; patients receive agents from the early biologic strategy if they did not respond to therapy with 3 conventional DMARDs, alone or in combination. It was assumed that the patients would follow 1 of 3 courses: drug-free remission, a mild course with slow disease progression, or rapid disease progression. Each patient's response to treatment was characterized as excellent (low residual disease activity), good, moderate, or none.

Treatment effects on radiographic progression were determined, and estimates of the QALYs for various health states were determined by using the mean health utility of each health state. Estimates were obtained for all medical and social care costs, including joint replacements, and unit costs for medications as well as outpatient and inpatient care.

Upon analysis, both the early DMARD strategy and the early biologic strategy increased quality-adjusted life more than the pyramid strategy. When the cost of very early intervention is factored in, the cost-effectiveness ratio of the early DMARD strategy is $4,849 per QALY (95% CI, $0 to $16,354 per QALY) compared with the pyramid strategy. The benefits of the early biologic strategy come at a substantial incremental cost although it offers the most benefit during the first 10 years. The model assumes that after this period, patients for whom the 3 biologics have failed would revert to conventional DMARDs, which are less effective in severe, established RA. Therefore, patients who followed this strategy had less benefit over time than patients following other strategies who began receiving biologics later in their disease course.

The researchers note that their results should be interpreted carefully. They point out that a limitation of modeling cost-effectiveness in RA is that extrapolations of long-term benefits are often made with little or no long-term data. They also assumed that a patient's disease cannot be predicted at outset and add that if treatments could be targeted to patients with severe progressive disease or those likely to respond, more benefit would be realized.

In conclusion, the researchers found early intervention with a DMARD may be an attractive economic option, given the future costs that would probably be saved (eg, through reduced long-term joint damage and subsequent surgery). Therefore, prompt initiation of conventional DMARD therapy for patients with very early RA is the most rational use of resources.

SOURCE

Finckh A, Bansback N, Marra CA, et al. Treatment of very early rheumatoid arthritis with symptomatic therapy, disease-modifying antirheumatic drugs, or biologic agents: a cost-effectiveness analysis. Ann Intern Med. 2009;151:612-621.