Effective use of TNF antagonists

Abstract

Tumor necrosis factor (TNF) antagonists are biologic response modifiers that have significantly improved functional outcomes in patients with rheumatoid arthritis (RA). RA is a progressive disease in which structural joint damage can continue to develop even in the face of symptomatic relief. Before the introduction of biologic agents, the management of RA involved the use of disease-modifying antirheumatic drugs (DMARDs) early in the course of disease. This focus on early treatment, combined with the availability of the anti-TNF agents, has contributed to a shift in treatment paradigms favoring the early and timely use of DMARDs with biologic therapies. Improvement in symptom control does not always equate to a reduction in disease progression or disability. With the emergence of structure-related outcome measures as the primary means for assessing the effectiveness of antirheumatic agents, the regular use of X-rays is recommended for the continued monitoring and evaluation of patients. In addition to the control of symptoms and improvement in physical function, a reduction in erosions and joint-space narrowing should be considered among the goals of therapy, leading to a better quality of life. Adherence to therapy is an important element in optimizing outcomes. Durability of therapy with anti-TNF agents as reported from clinical trials can also be achieved in the clinical setting. Concomitant methotrexate therapy might be important in maintaining TNF antagonist therapy in the long term. Overall, the TNF antagonists have led to improvements in clinical and radiographic outcomes in patients with RA, especially those who have failed to show a complete response to methotrexate.

Figure 1

Study of delayed and early treatment on disease outcome in patients with recent-onset rheumatoid arthritis (RA). *P < 0.05 compared with the delayed-treatment group. Adapted, with permission, from Excerpta Medica [2].

Figure 2

Change in Sharp scores, joint-space narrowing (JSN), and joint erosion (JE) scores showing that rheumatoid arthritis progresses at a constant, linear rate. Adapted, with permission, from John Wiley & Sons, Inc. [8].

Figure 3

Potential pathogenic pathway for rheumatoid arthritis, supporting a relationship between structural damage and clinical symptoms. Adapted, with permission, from Excerpta Medica [9].

Figure 4

Data from the ATTRACT (Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis With Concomitant Therapy) study showing the superiority of infliximab plus methotrexate (MTX) over methotrexate alone, as determined by the median change in the modified Sharp score. Data from [12].

Figure 5

Data from the ERA (Early Rheumatoid Arthritis) trial showing the superiority of etanercept over methotrexate, as determined by improvements in erosion and Sharp scores, but not joint-space narrowing score at 2 years. Adapted, with permission, from John Wiley & Sons, Inc. [15].

Figure 6

Preliminary radiographic data from the ATTRACT (Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis With Concomitant Therapy) study, indicating the superiority of infliximab plus methotrexate over methotrexate alone in patients who did and did not achieve an ACR20 (that is, ACR20 responders and non-responders). ACR20 is a more than 20% improvement in tender and swollen joint counts and at least three of the following disease activity variables: the patient's assessment of pain, the patient's global assessment of disease activity, the physician's global assessment of disease activity, the patient's assessment of physical function, and the erythrocyte sedimentation rate or C-reactive protein level. *P < 0.05 versus placebo. Data on file, Centocor, Inc., Malvern, PA, USA.