Initiating Anti-TNF Therapy in a Patient With RA
Initiating Anti-TNF Therapy in a Patient With RA
When should treatment with tumor necrosis factor (TNF) blockers in a patient with rheumatoid arthritis (RA) be initiated?
Dr. Samar
Stanley B. Cohen, MD
Clinical Professor, University of Texas Southwestern Medical Center at Dallas
The primary reason for initiating biologic therapy in RA is the presence of continued disease activity despite treatment with conventional therapy. Although biologics can be used as initial disease-modifying therapy, their cost and concerns over safety have relegated their use after initial treatment with disease-modifying antirheumatic drug (DMARD) therapy. The American College of Rheumatology Guidelines for the management of RA, although somewhat outdated, recommend combination therapy with currently approved agents for patients with active disease despite adequate doses of methotrexate treatment of 3-6 months' duration. A report from the BeSt trial demonstrated that institution of sequential DMARDs or combination DMARDs after methotrexate failure was not as effective as adding infliximab to methotrexate. Additionally, 3 separate databases have demonstrated a greater likelihood to induce remission with combination TNF inhibitor/methotrexate than either methotrexate or TNF inhibitor alone.
Defining what constitutes an incomplete response is currently controversial. On the basis of the tight control for rheumatoid arthritis (TICORA) and the BeSt studies, both of which targeted a Disease Activity Score (DAS) indicative of low disease activity, many rheumatologists are now targeting a DAS 28 score of 2.4 or less in individual patients, altering treatment in an attempt to achieve this target. Unfortunately the DAS requires knowledge of the erythrocyte sedimentation rate or C-reactive protein at the time of the patient visit as well as a calculator, which might limit its applicability in daily practice. Other measures of disease activities, such as the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI), are being evaluated in the clinic setting; preliminary data suggest that they might be useful indices to monitor disease activity.
The more traditional rheumatologists believe that presence of synovitis is indicative of active disease and that the goal for treatment should be a total absence of synovitis. Progression of structural damage is unlikely in the absence of synovitis, although recent studies using magnetic resonance imaging or ultrasound have demonstrated occult joint inflammation in patients with no clinical synovitis. Long-term patient outcome data are not yet available.
Recent concerns over the safety of biologics have modified our zeal for disease remission in patients with comorbidities such as diabetes mellitus and COPD, as well as among the elderly. We might be willing to accept more disease activity in a patient with adequate physical function and quality of life in this situation. This is the "art of medicine," and a decision to start TNF inhibitors requires a thorough analysis of the individual benefits and risks and informed discussion with the patient.
Question
When should treatment with tumor necrosis factor (TNF) blockers in a patient with rheumatoid arthritis (RA) be initiated?
Dr. Samar
Response From the Expert
Stanley B. Cohen, MD
Clinical Professor, University of Texas Southwestern Medical Center at Dallas
The primary reason for initiating biologic therapy in RA is the presence of continued disease activity despite treatment with conventional therapy. Although biologics can be used as initial disease-modifying therapy, their cost and concerns over safety have relegated their use after initial treatment with disease-modifying antirheumatic drug (DMARD) therapy. The American College of Rheumatology Guidelines for the management of RA, although somewhat outdated, recommend combination therapy with currently approved agents for patients with active disease despite adequate doses of methotrexate treatment of 3-6 months' duration. A report from the BeSt trial demonstrated that institution of sequential DMARDs or combination DMARDs after methotrexate failure was not as effective as adding infliximab to methotrexate. Additionally, 3 separate databases have demonstrated a greater likelihood to induce remission with combination TNF inhibitor/methotrexate than either methotrexate or TNF inhibitor alone.
Defining what constitutes an incomplete response is currently controversial. On the basis of the tight control for rheumatoid arthritis (TICORA) and the BeSt studies, both of which targeted a Disease Activity Score (DAS) indicative of low disease activity, many rheumatologists are now targeting a DAS 28 score of 2.4 or less in individual patients, altering treatment in an attempt to achieve this target. Unfortunately the DAS requires knowledge of the erythrocyte sedimentation rate or C-reactive protein at the time of the patient visit as well as a calculator, which might limit its applicability in daily practice. Other measures of disease activities, such as the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI), are being evaluated in the clinic setting; preliminary data suggest that they might be useful indices to monitor disease activity.
The more traditional rheumatologists believe that presence of synovitis is indicative of active disease and that the goal for treatment should be a total absence of synovitis. Progression of structural damage is unlikely in the absence of synovitis, although recent studies using magnetic resonance imaging or ultrasound have demonstrated occult joint inflammation in patients with no clinical synovitis. Long-term patient outcome data are not yet available.
Recent concerns over the safety of biologics have modified our zeal for disease remission in patients with comorbidities such as diabetes mellitus and COPD, as well as among the elderly. We might be willing to accept more disease activity in a patient with adequate physical function and quality of life in this situation. This is the "art of medicine," and a decision to start TNF inhibitors requires a thorough analysis of the individual benefits and risks and informed discussion with the patient.
