TY - JOUR
T1 - Rheumatoid arthritis
T2 - Strategies in the management of patients showing an inadequate response to TNFα antagonists
AU - Lutt, Joseph R.
AU - Deodhar, Atul
PY - 2008
Y1 - 2008
N2 - 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)-α - 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 TNFα 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 TNFα antagonist dose may lead to improved responses, as demonstrated in some dose escalation studies. Switching to another TNFα 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 TNFα antagonists. Genotypic studies have identified TNF and TNF receptor polymorphisms that appear to predict independently whether a patient will respond to a TNFα 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 TNFα 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 TNFα antagonists.
AB - 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)-α - 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 TNFα 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 TNFα antagonist dose may lead to improved responses, as demonstrated in some dose escalation studies. Switching to another TNFα 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 TNFα antagonists. Genotypic studies have identified TNF and TNF receptor polymorphisms that appear to predict independently whether a patient will respond to a TNFα 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 TNFα 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 TNFα antagonists.
KW - Abatacept, therapeutic use
KW - Rheumatoid arthritis, treatment
KW - Rituximab, therapeutic use
KW - Tumour necrosis factor alpha inhibitors, therapeutic use
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U2 - 10.2165/00003495-200868050-00003
DO - 10.2165/00003495-200868050-00003
M3 - Review article
C2 - 18370440
AN - SCOPUS:41349113569
SN - 0012-6667
VL - 68
SP - 591
EP - 606
JO - Drugs
JF - Drugs
IS - 5
ER -