标签: 类风湿关节炎;
依那西普; 药物减停; 复发重治

对RA疾病复发患者, 依那西普按需治疗与持续足剂量治疗是否存在疗效差异？

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

背景/目的: 生物DMARDs（bDMARDs）对RA治疗而言非常重要,
尤其对于有骨侵蚀进展倾向的活动性RA患者。但在日常医疗实践过程中,
生物制剂高昂的价位使得某些患者不敢尝试或被迫停药。为了降低治疗费用, bDMARDs的用法往往类似于皮质激素的"桥"治疗,
用于高疾病活动度患者的临时用药。本研究名为RESUME试验, 为非盲法、非随机的前瞻性研究,
旨在探讨RA患者反复多次按需重新接受依那西普治疗(on-demand)是否能维持疗效。

方法: 研究招募自2011年1月1日至2012年12月31日签署知情同意的31例生物制剂初治的中、重度RA患者(DAS28≥3.2)。患者平均年龄60岁,
平均病程5年。受试者接受依那西普50 mg/周治疗直至达到低疾病活动度(LDA, DAS28<3.2),
继而停用依那西普。每2个月随访一次,
如果患者复发则重新开启足量生物制剂治疗。该方案持续应用2年。若患者接受依那西普治疗3个月仍无法达到LDA, 可以加用传统DMARDS,
禁用糖皮质激素和他克莫司。如治疗6个月患者仍无法达到LDA则退出研究。在基线、1年和2年随访时进行包括DSA28和血液检查在内的临床评估和放射学评估（mTSS）。为比较这个小样本患者人群的关节结构破坏,
另选择31例接受依那西普持续足量治疗患者作为对照。

结果: 对依那西普无应答的13例RA患者退出试验。5例患者在停药后的2年间一直无复发。13例患者（8例为女性）接受依那西普按需治疗维持LDA。这13例患者接受MTX的平均剂量为10mg/周,
11例患者RF阳性,
平均随访20.5个月。该13例患者在数次开启和停用依那西普治疗后仍在末次随访时维持LDA。13例患者中的82%在治疗1年时达到放射学缓解（△mTSS
=<0.5）,
第二年有50%患者维持放射学缓解。按需治疗组的1年放射学缓解率与足量治疗组无显著差异（p=0.464,
Fisher精确概率检验）

结论: RA复发患者按需接受依那西普治疗可在花费低的情况下达到降低疾病活动度、抑制骨破坏的疗效。

图1.     试验设计示意图

图2.     关节破坏放射学进展的累积概率

蓝色点代表按需治疗组在第1年评估是mTSS变化值,
红色点代表第2年评估结果。黑色点线代表接受依那西普标准剂量治疗1年时的mTSS变化值。第1年随访时,
13例患者中放射学缓解(DmTSS≤0.5)达标率为82%,
第2年时为50%。按需治疗组的第1年放射学缓解率与依那西普标准剂量组相似(P=0.464,
Fisher精确概率检验。

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.