Intensive Treatment With Tumor Necrosis Factor Inhibitors for Achieving Remission
Recent progress in the treatment of RA has changed diagnosis of RA, treatment goal and treatment strategies; 2010 Rheumatoid Arthritis Classification Criteria by an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) collaborative initiative, ACR/UELAR provisional definition of remission in RA for clinical trial and recommendation of treating RA to target by an international task force have been published based on accumulated background information in terms of management of RA. Thus, clinical remission has recently become an achievable goal in many patients in clinical trials and clinical practice, and rapid and appropriate induction of remission is a prerequisite to halt joint damage and functional disabilities, which revealed improved outcomes with strategic therapeutic approaches.
Intensive Treatment by Tumor Necrosis Factor Inhibitors
Global evidence of the efficacy and safety of TNF inhibitors including infliximab, etanercept, adalimumab, golimumab and certolizumab has accumulated in many clinical randomized controlled trials. Treatment with any of these TNF inhibitors and MTX leads to clinical remission in approximately 20–50% of RA patients. Effective treatments using TNF inhibitors have led to more stringent criteria for the clinical remission. Furthermore, induction and/or maintenance of clinical remission with TNF inhibitors and MTX can potentially lead to structural remission, reduction of radiographic progress in joint destruction and its maintenance, and thereby functional remission, improvement and keeping physical functions and abilities. For instance, structural remission defined with yearly changes of modified total Sharp score (DmTSS) can be achieved in approximately 60–90% of patients treated with any TNF inhibitors and MTX. Thus, TNF inhibitors brought about a paradigm shift in the treatment of RA, and structural and functional remission has become possible in a considerable percentage of patients (Fig. 1).
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Figure 1.
A paradigm shift in the treatment of rheumatoid arthritis (RA). Biologics targeting TNF has revolutionized the treatment of RA and clinical, structural and functional remission becomes a realistic treatment goal. After maintaining remission, discontinuation of TNF inhibitors and biologic-free remission is an important issue from viewing points of safety and economy.
Maintenance of Remission by Tumor Necrosis Factor Inhibitors
With the increasingly widespread and prolonged use of TNF inhibitors, assessments of their longterm safety and efficacy are important. The most important study regarding maintenance of TNF inhibitors was reported by Weinblatt et al.. In the study etanercept maintained disease activity and functional abilities beyond 10 years of therapy in both early RA and longstanding RA patients; a total of 163 (29%) of 558 early RA patients and 264 (37%) of 714 longstanding RA patients followed through year 10. After 10 years of open-label etanercept treatment, improvements in ACR20, ACR50, and ACR70 responses were maintained in both groups and 77, 52, and 38%, respectively, for early RA patients and 71, 51, and 24%, respectively, for longstanding RA patients at year 11. Also, at year 10, 42% of early RA patients and 29% of longstanding RA patients achieved a disease activity score 28 (DAS28) remission, defined as a DAS28-C-reactive protein below 2.6. It is noteworthy that reduction of Health Assessment Questionnaire disability index (HAQ-DI) score in early RA and longstanding RA patients was clinically significant and sustained at each observation point through 10 years; 24–33% of early RA patients and 13– 20% of longstanding RA patients achieved a HAQDI score of 0 at any given yearly assessment during the 10-year period and 0.4 (range 0–2.4) for the early RA patients and 0.9 (range 0–2.9) for the longstanding RA patients at year 11.
In terms of its safety, 5 opportunistic infections and 21 cases of sepsis (10 early RA, 19 longstanding RA) were reported. Occurrence of all malignancies was similar to that expected in the general population, but 14 lymphomas (7 early RA, 7 longstanding RA) were reported, indicating the occurrence of lymphomas was higher than expected in the general population. Deaths occurred in 18 early RA patients and 43 longstanding RA patients.
Thus, etanercept maintained disease activity and functional abilities beyond 10 years of therapy in both early RA and longstanding RA patients. The way in which etanercept has prevented structure and function from its progress is the most dramatic revolution during the long history of the treatment of RA.