Background Tumor necrosis factor (TNF) inhibitors enable tight control of disease activity in patients with rheumatoid arthritis (RA). Discontinuation of TNF inhibitors after achievement of clinical remission is important for safety and economic reasons. However there is limited data to confirm the effectiveness and safety over a longer time period after discontinuation of etanercept (ETN).
Objectives We studied 2-year outcome in RA patients who achieved clinical remission (Disease activity score in 28 joints (DAS28) <2.6) by ETN and maintained without ETN to evaluate the clinical, radiographic and functional progression rate.
Methods After patients had achieved DAS28<2.6, informed consent to discontinue ETN was obtained from 23 patients. Mean of characteristics at ETN addition time were as follows: age, 63.1 years; duration of disease, 49.9 months; CRP, 1.83 mg/dl; ESR, 30.6 mm/h; DAS-28, 4.93; simplified disease activity index (SDAI), 24.0; percentage taking methotrexate, 78% (mean dose, 6.19 mg/week); percentage taking prednisolone, 22% (mean dose, 4.0 mg/day); percentage taking DMARDs, 26%. After ETN was discontinued, DAS was measured every one to three months for 2 years. The following data were collected: relapse rate at year 2; the rate of radiographic remission (Dmodified total Sharp score (DTSS) ≤0.5) and functional remission (modified health assessment questionnaire score (mHAQ) <0.5) of patients with continued remission and those with relapse. Re-treatment with TNF inhibitors (including ETN) was considered as clinical relapse. TSS was determined using modified van der Heijde-sharp score.
Results 9 (39.1%) patients maintained clinical remission and clinical relapse was observed in 14 patients (60.9%) at 2years. Re-treatment with TNF inhibitors in 4 patients (2 patients, ETN; 2 patients, adalimumab) was effective and the majority of patients reached DAS28<2.6 within 8weeks. Mean DAS, SDAI, mHAQ and TSS of patients with continued remission at year 2 were 2.03, 3.82, 0.09, and -2.26 respectively, those of patients with relapse were 3.11, 7.36, 0.27, and 0.37. Radiographic and functional remission rates of patients with continued remission at year 2 were 55.6%, 77.8% respectively, those of patients with relapse were 50%, 64.3%.
Conclusions Some patients could maintain clinical, radiographic and functional remission upto two years after discontinuation of ETN. This study result proves that discontinuation of ETN after achieving of DAS<2.6, subsequently could lead to the possibility of bio-free remission in RA. Even if relapse occurred, remission could be achieved again with monitoring of disease activity and adequate treatment after ETN discontinuation.
Brocq O, Millasseau E, Albert C, et al. Effect of discontinuing TNFalpha antagonist therapy in patients with remission of rheumatoid arthritis. Joint Bone Spine. 2009;76:350-5.
Miyamura T, Sonomoto K, Nakamura M, et al. Discontinuationof etanercept in patients with rheumatoid arthritis who were in clinical remission. Clin Rheumatol. 2010;29:87-90.
Tanaka Y, Takeuchi T, Mimori T, et al. Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study. Ann Rheum Dis. 2010;69:1286-91.
van Vollenhoven RF. Unresolved issues in biologic therapy for rheumatoid arthritis. Nat Rev Rheumatol. 2011;7:205-15.
Disclosure of Interest None Declared