Etanercept

Summary

Abstract

Etanercept (Enbrel®), which inhibits the activity of tumour necrosis factor-α, is indicated in the treatment of patients with active rheumatoid arthritis (RA). A lifetime cost-utility analysis in patients with severe disease-modifying antirheumatic drug (DMARD)-resistant RA in the UK suggested that etanercept is associated with acceptable cost-utility ratios relative to traditional nonbiological DMARDs. In a 12-month cost-utility study in Spain, etanercept was predicted to be dominant over infliximab plus methotrexate in patients with active, refractory RA with regards to the cost per QALY gained and cost per American College of Rheumatology (ACR) 20 response achieved. In short-term cost-effectiveness analyses conducted in the US, the cost effectiveness of etanercept relative to other treatments in patients with methotrexate-naive or -resistant RA depends on whether predicted incremental cost-effectiveness ratios of at least $US41 900 per ACR 20 response or $US34 800 per ACR 70 weighted response over a 6-month period are considered acceptable (1999 values).

The relative efficacy and cost effectiveness of etanercept and other biological DMARDs will be clarified when appropriate data from directly comparative clinical and/or long-term pharmacoeconomic studies become available. Etanercept may prevent or delay disability, which may produce reductions in nondrug costs that could help offset its acquisition cost.

Rheumatoid Arthritis

RA, a chronic autoimmune disease, is characterised by symmetrical joint swelling and tenderness, progressive joint damage, pain, loss of function, disability and premature mortality. Substantial direct, indirect and intangible costs, which increase as the severity of the disease increases, are associated with RA. Early aggressive treatment of RA with DMARDs may prevent or delay disease progression.

Clinical Profile

In well designed clinical trials and their extension phases, subcutaneous etanercept 25mg twice weekly produced rapid, sustainable clinical responses in methotrexate-naive or DMARD-resistant patients with RA. Etanercept was generally associated with significantly higher ACR 20, 50 and 70 response rates during the first 6 months of treatment, slower radiographic progression and more rapid improvement in measures of health-related quality of life (HR-QOL) than methotrexate in a 1-year trial in methotrexate-naive patients with early RA. In 6-month trials in DMARD-resistant patients, a significantly greater proportion of patients achieved ACR 20, 50 and 70 responses at 3 and 6 months with etanercept monotherapy or etanercept plus methotrexate than with placebo or methotrexate plus placebo. Other measures of disease activity also improved to a significantly greater extent with etanercept than with the comparators.

Most adverse events associated with etanercept in clinical trials were of mild-to-moderate severity. Approximately one-third of patients experienced mild-to-moderate injection site reactions. Infections, which occurred at a similar frequency with etanercept and placebo, were the most common serious adverse event.

Pharmacoeconomic Analyses

In patients with DMARD-resistant RA, a lifetime cost-utility model from the perspective of a healthcare payer in the UK predicted that third-line etanercept is cost effective compared with current care (a sequence of intramuscular gold, leflunomide and ciclosporin plus methotrexate as third-, fourth and fifth-line therapy). The incremental cost per QALY gained of etanercept followed by current care relative to current care alone was £16 330 (year 2000 values). The etanercept sequence was associated with higher drug and monitoring costs, but lower costs for other healthcare interventions, and greater effectiveness and QALYs gained. When loss-of-productivity and long-term care costs were included in sensitivity analysis, the incremental cost per QALY gained decreased to <£8000.

From the perspective of society, etanercept was predicted to be dominant over infliximab plus methotrexate with regards to cost per QALYs gained and cost per ACR 20 response achieved in a modelled 12-month cost-utility analysis in patients with active, refractory RA in Spain.

US cost-effectiveness analyses have modelled events during the first 6 months of various treatments in patients with RA and have predicted incremental cost-effectiveness ratios (ICERs) as the additional cost per ACR 20 response or ACR 70 weighted (70W) response relative to the next-best nondominated option. When total costs (direct plus loss-of-productivity costs) were considered in methotrex ate-naive patients, etanercept was more effective, but also more costly, than leflunomide, methotrexate.15 mg/week, sulfasalazine or no treatment; predicted ICERs of etanercept relative to other treatments were $US41 900 per ACR 20 response and $US40 800 per ACR 70W response over 6 months (1999 values). In methotrexate-resistant patients, etanercept plus methotrexate was more effective, but was also more costly than etanercept monotherapy, ciclosporin plus methotrexate, triple therapy (hydroxychloroquine, sulfasalazine and methotrexate), continuation of methotrexate therapy or no second-line treatment when total costs were considered. Predicted ICERs of etanercept relative to other treatments were $US42 600 per ACR 20 response and $US34 800 per ACR 70W response over 6 months. Etanercept monotherapy was both more effective and more costly than triple therapy for both ACR outcomes. When only direct costs were considered, the ICERs of etanercept were slightly higher.

In cost-minimisation analyses from a healthcare payer or societal perspective in The Netherlands or the US, the total per-patient annual costs associated with etanercept were estimated to be less than those associated with infliximab.