Use of tumor necrosis factor inhibitors in rheumatoid arthritis: a national survey of practicing United States rheumatologists

Abstract

Objectives

To determine the prescribing practices, laboratory monitoring protocols, and perceived barriers of United States rheumatologists in prescribing tumor necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA).

Methods

A survey questionnaire was mailed to 1970 rheumatologists who were randomly selected from a national sample of 3008 rheumatologists. A one-page non-response questionnaire was mailed to approximately 200 randomly selected non-responding rheumatologists to assess non-response bias.

Results

Two mailings yielded a response rate of 22.3% (428 completed, usable surveys out of 1922 deliverable surveys). Rheumatologists reported using all three agents in patients with moderate RA (82–87%), severe RA (94–96%), and in newly diagnosed and mild RA patients (10–18%). In patients with severe RA who inadequately responded to methotrexate, 91% of rheumatologists reported using a TNF inhibitor with one other disease modifying anti-rheumatic drug. Over 94% of rheumatologists reported switching patients from one TNF inhibitor to a different TNF inhibitor due to inadequate response or side effects. Most rheumatologists (96%) ordered the purified protein derivative test for tuberculosis, with almost 82% conducting this test at baseline. Costs to patients and insurance coverage were perceived as major barriers to prescribing these agents although the perception was slightly lower with infliximab than with adalimumab or etanercept.

Conclusions

The use of TNF inhibitors is not restricted to patients with moderate and severe RA. Rheumatologists are fairly similar in their utilization of the three TNF inhibitors although some variation exists in terms of laboratory practices and perceived barriers regarding the use of these agents.

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory, autoimmune disease that affects joints and other tissues. RA affects around 1% of the adult population worldwide [1] and approximately 2–2.5 million people in the United States (US) [2], [3]. The combined direct and indirect costs resulting from RA in the US have been estimated to be approximately $26–$32 billion per year (1998 values) [4].

The treatment options for patients with RA has changed dramatically in the last few years [5], [6]. Tumor necrosis factor (TNF) has become an attractive target for treatment in patients with RA. As a result, three new TNF inhibitors: etanercept, infliximab, and adalimumab, have been approved for use in patients with moderate to severe RA [7]. Clinical trials of these agents have shown that they may be more effective than traditional disease modifying anti-rheumatic drugs (DMARDs) because of their ability to not only attenuate symptoms but also slow disease progression [8]. Despite their clinical effectiveness, these agents are expensive and the annual cost of treatment ranges from $12,000 to $16,000 [9], [10]. A recent study reported the mean direct costs of patients on TNF inhibitors to be almost three times higher ($19,016) than those not receiving these agents ($6164) [11].

While TNF inhibitors have been shown to achieve a marked improvement in outcomes in patients with moderate to severe RA, they have also been associated with certain uncommon but serious adverse events. Since the introduction of these agents, there have been concerns about the potential for adverse events such as injection and infusion-site reactions, infections, malignancies, and neurologic disorders [12]. Thus, there is a need for regular screening and monitoring of patients using these agents [10], [12]. However, there are currently no recommended guidelines available for monitoring patients using TNF inhibitors [5]. Results from a study conducted by Yazici et al. indicate that rheumatologists using TNF inhibitors seem to monitor patients based on their experience with traditional DMARDs, particularly methotrexate (MTX). Also, there seems to be no consensus as to how often the monitoring tests should be performed [5].

Even though etanercept, infliximab, and adalimumab belong to the same class of drugs, they have distinct clinical, pharmacokinetic, and pharmacodynamic properties which can affect physician decision-making regarding the selection of any one of them for therapy [13]. In addition, a number of other factors have been found to affect physician decision-making regarding choice of therapy. These include patient preference, characteristics of the disease itself (for example, disease duration and symptom severity), characteristics of the drug chosen (for example, cost, route of administration, side effect profile), and published evidence documenting the overall experience with each drug [13], [14]. A number of studies have described the practice patterns for traditional DMARDs [15], [16], [17], [18], however, little is known about the prescribing practices, laboratory monitoring protocols, and perceived barriers of US rheumatologists in prescribing TNF inhibitors in RA.

Thus, the objective of the study was to survey a random national sample of rheumatologists to: (i) describe rheumatologists' prescribing patterns for the three TNF inhibitors: etanercept, infliximab, and adalimumab; (ii) describe the laboratory monitoring practices of respondent rheumatologists for patients on TNF inhibitors; and (iii) assess if there are any differences in rheumatologists' perceived barriers (e.g. reimbursement issues, efficacy of TNF inhibitors, patient preference, different modes of administration, safety, and cost) in prescribing TNF inhibitors.