Treatment Options for Rheumatoid Arthritis Beyond TNF-α Inhibitors

Yusuf Yazici; Ismail Simsek


Expert Rev Clin Pharmacol. 2010;3(5):663-666. 

In This Article

Abstract and Introduction


The treatment of rheumatoid arthritis has changed over the last 15 years. Early and aggressive treatment, use of methotrexate as the anchor drug and combination treatment, with older disease-modifying drugs or biologics, have become the norm. TNF inhibitors were the first biologic agents available to rheumatologists and are still currently used as first-line biologics, in addition to other newer biologic agents. Abatacept, rituximab and tocilizumab are available biologics that use a different mode of action to TNF inhibitors, and can be used after a TNF inhibitor is tried. Abatacept is also currently used as a first-line biologic and others can also be used once data are available.


Rheumatoid arthritis (RA) treatment has changed dramatically over the last 15 years. Not only has the number of options available to clinicians increased, the approach to treatment has evolved too.[1] The recognition that RA is associated with significant comorbidities and early mortality[2] has led rheumatologists to start treating RA early and aggressively, which has yielded better short- and long-term results over the last 10 years and, therefore, better outcomes.[3] Methotrexate (MTX) was recognized as the anchor drug for the treatment of RA,[4] with possibly the best long-term drug survival among disease-modifying antirheumatic drugs (DMARDs).[5] This was followed by the realization that part of an aggressive treatment strategy needs to include a target of low disease activity or remission measured by one of the objective disease activity indices. Studies such as TICORA,[6] BeSt[7] and Fin RaCo[8] have shown that once targeting a disease activity level and tailoring treatment to reach that goal is implemented, it is possible to achieve low disease activity and control of symptoms for the majority of patients, using many different treatment regimens.

Our current approach to RA treatment can be summarized as follows: starting MTX early in disease, and aggressively increasing the dose to the maximum tolerated by the patient, by up to 25 mg a week. Studies have shown that this (with or without low-dose prednisone) will lead to remission-like responses in up to 50% of RA patients.[4] Another 20% of patients have good responses and the last 30% have either no or an inadequate response to MTX. Then clinicians need to add another DMARD to the regimen, for example, sulfasalazine, hydroxychloroquine with sulfasalazine, or a biologic agent, which until recently, included one of the three TNF inhibitors – etanercept, infliximab or adalimumab. There are data to suggest that for severe patients (i.e., those with more than 20 swollen and tender joints), a MTX plus TNF inhibitor combination may achieve good disease control.[9] Recent data suggest that adding a biologic agent rather than going for triple therapy with sulfasalazine and hydroxychloroquine may have better outcomes,[10] and this may be the optimal regimen for many of our patients.

The choice of TNF inhibitor or biologic to use is generally dependent on patient and physician preference, as clinical efficacy and safety profiles of these agents are similar with very few adverse event profile differences.[11] Studies have suggested that the chances of responding to a second TNF inhibitor are improved if the reason for discontinuing the first TNF inhibitor was an adverse event or secondary failure, in contrast to primary failure, where the patient does not have a response to the TNF inhibitor from the start, rather than losing the initial good response over time (i.e., secondary failure).[12] Many rheumatologists will use another TNF inhibitor once a first TNF inhibitor has lost its efficacy, but new options with different modes of action (MOA) are now available, and some of these may be considered as first-line biologic agents and have been used in this setting with increasing frequency, at least in the USA.

Currently, we have three different MOA biologics: abatacept, rituximab and tocilizumab.


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