標簽: 類風濕關節炎; 依那西普; 藥物減停; 復發重治

對RA疾病復發患者, 依那西普按需治療與持續足劑量治療是否存在療效差異？

?Inui K, et al. ACR 2015. Presentation ID: 477.

背景/目的:?生物DMARDs（bDMARDs）對RA治療而言非常重要, 尤其對于有骨侵蝕進展傾向的活動性RA患者。但在日常醫療實踐過程中, 生物制劑高昂的價位使得某些患者不敢嘗試或被迫停藥。為了降低治療費用, bDMARDs的用法往往類似于皮質激素的"橋"治療, 用于高疾病活動度患者的臨時用藥。本研究名為RESUME試驗, 為非盲法、非隨機的前瞻性研究, 旨在探討RA患者反復多次按需重新接受依那西普治療(on-demand)是否能維持療效。

方法:?研究招募自2011年1月1日至2012年12月31日簽署知情同意的31例生物制劑初治的中、重度RA患者(DAS28≥3.2)。患者平均年齡60歲, 平均病程5年。受試者接受依那西普50 mg/周治療直至達到低疾病活動度(LDA, DAS28<3.2), 繼而停用依那西普。每2個月隨訪一次, 如果患者復發則重新開啟足量生物制劑治療。該方案持續應用2年。若患者接受依那西普治療3個月仍無法達到LDA, 可以加用傳統DMARDS, 禁用糖皮質激素和他克莫司。如治療6個月患者仍無法達到LDA則退出研究。在基線、1年和2年隨訪時進行包括DSA28和血液檢查在內的臨床評估和放射學評估（mTSS）。為比較這個小樣本患者人群的關節結構破壞, 另選擇31例接受依那西普持續足量治療患者作為對照。

結果:?對依那西普無應答的13例RA患者退出試驗。5例患者在停藥后的2年間一直無復發。13例患者（8例為女性）接受依那西普按需治療維持LDA。這13例患者接受MTX的平均劑量為10mg/周, 11例患者RF陽性, 平均隨訪20.5個月。該13例患者在數次開啟和停用依那西普治療后仍在末次隨訪時維持LDA。13例患者中的82%在治療1年時達到放射學緩解（△mTSS =<0.5）, 第二年有50%患者維持放射學緩解。按需治療組的1年放射學緩解率與足量治療組無顯著差異（p=0.464, Fisher精確概率檢驗）

結論:?RA復發患者按需接受依那西普治療可在花費低的情況下達到降低疾病活動度、抑制骨破壞的療效。

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原文如下。

On-Demand Use of Etanercept Only for Disease Flares Reduced the Disease ? Activity Score and Structural Damage Equivalent to Fully-Use of Etanercept in ? RA Patients

Sunday, November 8, 2015: 9:00 AM-11:00 AM

Presentation Number:?477

Kentaro Inui¹, Tatsuya Koike¹, Masahiro Tada², Yuko Sugioka¹, ? Kenji Mamoto¹, Tadashi Okano¹, Akira Sakawa³, ? Kenzo Fukushima⁴?and Hiroaki Nakamura¹,?¹Osaka ? City University Graduate School of Medicine, Osaka, Japan,?²Osaka ? City General Hospital, OSAKA, Japan,?³Osaka City Juso ? Hospital, Osaka, Japan,?⁴Fujiidera Municipal Hospital, ? Fujiidera, Japan

Background/Purpose:?Biological ? disease-modifying antirheumatic drugs (bDMARDs) are essential in the ? treatment of rheumatoid arthritis (RA). Biological DMARDs are particularly ? recommended for patients with active RA who may incur further joint damage. ? However, in daily clinical practice, some patients with RA do not accept or ? discontinue bDMARDs because of their high cost. Similar to use of ? glucocorticoids, the use of bDMARDs may be limited to periods of high disease ? activity to help reduce patient costs. For this option to work well, the ? efficacy of a bDMARD should be maintained when restarting the same bDMARDs ? after several periods of discontinuation, bDMARDs holiday. We conducted a ? prospective, nonrandomized, non-blinded study (RESUME study: UMIN000008164) ? to examine the sustained efficacy of etanercept (ETN) after starting and ? stopping ETN several times in the patients with rheumatoid arthritis.

Methods:?Thirty-one bDMARD-naive ? patients with RA with moderate to severe disease activity (Disease Activity ? Score 28 [DAS28] of ≥3.2) were enrolled in this study ? with written consent from 1 January 2011 to 31 December 2012. Their average ? age was 60 years and average disease duration was 5 years. ETN was ? administered at 50 mg/week and discontinued when low disease activity (LDA) ? (DAS28 of <3.2) was achieved. Upon recurrence, the same dose of ETN was ? administered with observation every 2 months. This strategy was maintained ? for 2 years. If patients did not achieve LDA within 3 months of ETN ? administration, other synthetic DMARDs other than glucocorticoids and ? tacrolimus were administered. If LDA was not achieved within 6 months, the ? patients were withdrawn from the trial. Clinical measure by DAS28, blood ? test, radiography (mTSS) was analyzed at baseline, 1 year, and 2year visit. ? In order to compare the structural damage of this study population, another ? series of 31 patients with RA treated with fully-use of ETN were evaluated by ? mTSS.

Results:?Thirteen of the 31 patients ? had an inadequate response to ETN and were withdrawn from the study. Five ? patients had no flare-up of disease activity after discontinuation of ETN ? during the observation period. In the remaining 13 patients (8 women), ? on-demand use of ETN was carried out to maintain LDA. The mean dose of ? methotrexate in these 13 patients was 10 mg/week, rheumatoid factor was ? positive in 11 patients, and the mean follow-up period was 20.5 months. All ? 13 patients achieved LDA at the final follow-up after starting and stopping ? the ETN several times. The cost-saving calculation was approximately 28% ? among the five patients who maintained LDA with no need to restart ETN. ? Structural remission (DmTSS =<0.5) was achieved in 82% of the 13 patients ? as evaluated by the total Sharp score in 1 year, and 50% in 2 years. ? Structural remission rate in this study population in 1 year was equivalent ? to that of full dose use (p=0.464, Fisher's exact probability test).

Conclusion:?On-demand use of ETN for disease flares reduced disease activity ? score and structural damage at low cost.

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