REVIEW - RA: strategies in the management of patients showing an inadequate respone to TNF-alpha antagonists

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Drugs. 2008;68(5):591-606.

Rheumatoid arthritis: strategies in the management of patients showing

an inadequate response to TNFalpha antagonists.

Lutt JR, Deodhar A.

Division of Arthritis and Rheumatic Diseases (OP09), Oregon Health and

Science University, Portland, OR 97239, USA.

The introduction of medications that target specific proinflammatory

cytokines has revolutionized the management of patients with

rheumatoid arthritis. The agents that antagonize the effects of tumour

necrosis factor (TNF)-alpha -- infliximab, etanercept and adalimumab

-- have consistently shown very good efficacy for controlling the

clinical and radiographic manifestations of the disease. However, it

has become apparent that some patients will receive no clinical

benefit, gradually lose the effect over time or experience adverse

effects with the TNFalpha antagonists. The management of these

patients is challenging and there are no clear guidelines. The

concomitant administration of a disease-modifying antirheumatic drug,

such as methotrexate, has been shown to improve outcomes. Optimization

of the methotrexate or TNFalpha antagonist dose may lead to improved

responses, as demonstrated in some dose escalation studies. Switching

to another TNFalpha antagonist is a step that is supported by small,

mostly uncontrolled studies. Finally, the T-cell co-stimulation

antagonist abatacept, as well as the B-cell depleting agent rituximab,

are also available for use in patients who have had an inadequate

response or intolerance to the TNFalpha antagonists.Genotypic studies

have identified TNF and TNF receptor polymorphisms that appear to

predict independently whether a patient will respond to a TNFalpha

antagonist, but genotyping is not available for routine use in

clinical practice. Until such tools for predicting response are widely

available, the management of patients with poor responses to TNFalpha

antagonists will have to depend upon the wishes of the patient

regarding medication dosage schedules and adverse effect profiles, as

well as how comfortable the treating physician is with the available

biological medications. In this article, we review the current data

and construct an algorithm to help guide clinicians in the management

of patients with inadequate responses to the TNFalpha antagonists.

PMID: 18370440

http://www.ncbi.nlm.nih.gov/pubmed/18370440

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