REVIEW - Treatment options in patients with RA failing initial TNF inhibitor therapy

[Guest guest]

Arthritis Research & Therapy 2009, 11(Suppl 1):S1doi:10.1186/ar2666

Published: 6 April 2009

Review

Treatment options in patients with rheumatoid arthritis failing

initial TNF inhibitor therapy: a critical review

Rubbert-Roth1 and Axel Finckh2

1Department of Internal Medicine, University of Cologne,

f-Stelzmann-Strasse, 50924 Cologne, Germany.

2Division of Rheumatology, Department of Internal Medicine, University

Hospital of Geneva, 26 Avenue Beau-Sejour, 1211 Geneva 14,

Switzerland.

Abstract

Conventional disease-modifying antirheumatic drugs such as

methotrexate are the mainstay of treatment for rheumatoid arthritis.

More recently, biologic agents such as etanercept, infliximab and

adalimumab, which act by inhibiting tumour necrosis factor (TNF), have

become available. TNF inhibitors have proved to be very effective in

patients not responding to conventional disease-modifying

antirheumatic drugs. However, about 20% to 40% of patients treated

with a TNF inhibitor fail to achieve a 20% improvement in American

College of Rheumatology criteria, and more lose response over time

(secondary failure or acquired therapeutic resistance) or experience

adverse events following treatment with a TNF inhibitor. In this group

of patients, therapeutic options were limited until recently and an

established treatment approach was to switch from one TNF inhibitor to

another. In recent years, therapeutic options in these patients have

increased with the introduction of biologic agents with novel

mechanisms of action, such as rituximab and abatacept. This review

outlines the current evidence in support of the available treatment

strategies in patients with an inadequate response or intolerance to

an initial TNF inhibitor.

Introduction

Rheumatoid arthritis (RA) is a chronic, progressive, debilitating

autoimmune disease that occurs in approximately 1% of adults [1].

Although the disease may develop at any age, RA occurs most commonly

in people aged 40 to 70 years. Approximately 2.5 times more women than

men are affected [1]. The disease is characterized by chronic

inflammation of the synovium, which over time results in damage to the

joints, leading to pain and disability. RA is associated with

increased mortality, particularly in older women [2,3], and it may

reduce life expectancy by 3 to 18 years [4]. Recent studies have

demonstrated that a substantial proportion of patients continue to

show radiographic progression, even though clinically they are in a

state of low disease activity, suggesting that achieving remission

should be the ultimate goal [5,6].

Disease-modifying antirheumatic drugs (DMARDs) are the mainstay of

treatment for RA. Methotrexate is the most commonly used agent in this

class, and it is effective on standard clinical measures of disease

activity [7], cost-effective and comparatively well tolerated. The

development of biologic agents represented a major advance in the

treatment of RA. The targets of biologic agents are interactions

between the immune effector cells (T lymphocytes, B lymphocytes and

macrophages), which are responsible for inflammation and structural

damage in affected joints, and the signalling molecules involved in

their activation. The first approved biologic agents for the treatment

of RA were inhibitors of tumour necrosis factor (TNF). There are now

three agents available in this treatment class: etanercept, infliximab

and adalimumab. These agents are very effective at improving the signs

and symptoms, and at slowing or preventing structural damage in

patients with RA [8-14]. Newer TNF inhibitors are also in clinical

development for the treatment of RA and include golimumab [15] and

certolizumab pegol [16]. Both of these agents are effective at

improving signs and symptoms of disease, and prevention of structural

damage has been reported for certolizumab pegol [17,18].

***************************************

Read the full article here:

http://arthritis-research.com/content/11/S1/S1

Not an MD