Achieving drug-free remission: elucidating the role of TNF in rheumatoid arthritisinhibitors

Abstract

inhibitors (e.g., infliximab) has accumulated, including our RECONFIRM studies and many others [1–5], there is no well-established evidence regarding biologic-free remission. We conducted a study, remission induction by Remicade in RA patients (RRR), of RA patients from 26 centers and reported that 55% of patients, who achieved low disease activity (Disease Activity Score [DAS] 28 < 3.2) for more than 24 weeks during treatment with infliximab, were able to discontinue infliximab for more than 1 year without flaring. In addition, 43% had scores below 2.6 after discontinuation, indicating that they were in remission. The study registered patients with established disease. Their mean age was 51.4 years, mean disease duration was 5.9 years, mean total Sharp score was 63 and baseline DAS28 was 5.5. Furthermore, yearly progression of total Sharp score was less than 0.5 points in 67% and the health assessment questionnaire score was only 0.174 in patients who maintained low disease activity for 1 year after discontinuation. Therefore, we concluded that more than half of the patients who maintained low disease state for more than 24 weeks on infliximab could discontinue the drug and keep low disease activity for a year without radiographic or functional disease progression. These results suggest that the biologic-free remission is possible using infliximab and that the treatment may change or modify the course of disease. The potential for biologic-free remission in RA patients was initially reported by a British group (TNF20 study). The combination of infliximab and MTX in early RA patients who had less than 12 months of symptoms provided tight control of the disease activity and a significant reduction in MRI evidence of synovitis and erosions at 1 year. At 2 years, functional and quality-of-life benefits were sustained, despite withdrawal of infliximab therapy. On the other Rheumatoid arthritis (RA) is a systemic inflammatory disease that causes significant morbidity and mortality. RA patients should be started with disease-modifying antirheumatic drugs such as methotrexate (MTX) as early as possible. However, the use of MTX often fails to control disease activity and prevent structural damage, and more effective treatment strategies are needed. TNF plays a pivotal role in the pathological processes of RA through the accumulation of inflammatory cells and the self-perpetuation of inflammation, leading to joint destruction. The combinational use of MTX and biologics targeting TNF, including infliximab, etanercept and adalimumab, has revolutionized the treatment of RA, producing significant improvements in clinical, radiographic and functional outcomes that were not previously observed, as well as producing the emerging outcome and upcoming end point for treatment [1–5]: