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[516] - Can We Discontinue Anti-TNF Therapy in Patients with Ankylosing Spondylitis and Remission? A Systematic Literature Review.

Miguel A. Abad¹,Ana M Ortiz²,Estibaliz Loza³,Juan A. Martinez Lopez³,Maria P. Rosario³,Loreto Carmona³. ¹Rheumatology Unit, Hospital Virgen del Puerto, Plasencia, Spain,²Hospital Universitario de la Princesa, Madrid, Spain,³Fundación Española de Reumatología, Madrid, Spain

Background: The introduction of anti-TNF agents has changed the management of patients with Ankylosing spondylitis (AS). At present there is no doubt about the efficacy of anti-TNF agents: Infliximab (IFX), etanercept (ETN) and Adalimumab (ADA) in controlling symptoms of AS. However, it is unclear which should be the attitude once patients have achieved remission.
Objectives: To analyze the effect of discontinuing anti-TNF therapy in AS patients who achieved complete remission, and to assess whether the readministration would be effective and safe in case of relapse.
Methods: We conducted a systematic literature search for studies published up tol January 2009 on the efficacy of IFX, ETN and ADA in AS in Medline, Embase and the Cochrane Central databases. Selection criteria were: a)Type of study: clinical trials with any quality level (according to Jadad scale), b)Participants: patients with AS; c)Intervention: IFX, ETN or ADA d) Outcome: clinical relapse (according to ASAS criteria), time to relapse, effectiveness and safety after readministration of anti-TNFs. Two reviewers screened the titles and abstracts of the retrieved articles for selection criteria independently and collected the data by using ad hoc standard forms. One of them also graded the quality of the selected studies using a modification of the Oxford Centre for Evidence-based Medicine Levels of Evidence in its May 2001 update. A hand search was completed by reviewing the references of the included studies.
Results: We identified a total of 406 titles, of which 390 were excluded after reading the title and abstract. The final number of selected studies for a detailed review was 16. Finally 9 were excluded and 6 included (1 was a randomized controlled trial, 1 an open trial and the other 4 were follow-up studies) 2 evaluated ETN, 4 IFX. We did not found studies regarding ADA.
After the discontinuation of IFX in AS patients who achieved remission, almost 100% relapsed. The mean time to relapse was 17.5 weeks ± 7.9 weeks (range 7-45). Patients who were in partial remission and those with normal C-reactive protein levels at the time point of withdrawal had longer times to relapse. Retreatment with IFX was safe and the clinical improvement was similar to that before the treatment was stopped.
All of AS patients on ETN relapsed after treatment cessation. The median time to recurrence after discontinuation was 6.2 weeks ± 3 weeks, with relapse at 3 months 75% and 100% 9 months. Retreatment with ETN was efficacious and safe after readministration over 1 year in patients with active AS
Conclusion: The discontinuation of IFX leads to a relapse in almost all of AS patients who achieved remission within weeks or few months (level of evidence 1b, grade of recommendation A). The reinfusion of IFX in AS patients is safe, and the clinical improvement is comparable to the observed before the discontinuation (level of evidence 4, grade of recommendation C).
The discontinuation of ETN leads to a relapse in almost all of AS patients who achieved remission within weeks or few months (level of evidence 1b, grade of recommendation A). The reintroduction of ETN achieved similar clinical response to that observed previously (evidence level 4, recommendation grade C).

系统性综述: 达到缓解的AS患者能否停用TNF拮抗剂

Abad MA, et al. ACR2010. Present No:516.

背景：TNF拮抗剂是AS患者治疗的革新。TNF拮抗剂包括英夫利昔单抗（IFX）、依那西普（ETN）和阿达木单抗（ADL），它们对于控制AS症状疗效确切。但是，患者达到缓解后是否应继续治疗尚不明确。

目的：分析达到完全缓解的AS患者停用TNF拮抗剂的影响，评估复发患者再用药的有效性和安全性。

方法：在Medline、Embase和Cochrane中心数据库搜索2009年1月之前发表的有关IFX、ETN和ADL治疗AS的文献。选择标准如下：1）研究类型：各种质量水平的临床试验（根据Jadad评分标准）；2）参与者：AS患者；3）治疗药物：IFX、ETN或ADL；4）结局：临床复发（根据ASAS标准），复发时间，TNF拮抗剂再用药的疗效与安全性。 2名检索者将各标准单独检索到的文献的标题和摘要进行筛选，将数据记录在特制标准表格中。其中一人采用2001年5月修订的哈佛中心循证医学证据水平标准，对所选研究质量进行分级。回顾所选研究的参考文献，完成手工检索。

结果：共检索到406个标题，其中390篇在阅读标题和摘要后进行排除。详细回顾16项研究。最终排除9项，入选6项（1项随机对照研究，1项开放性研究，4项随访研究），2项研究ETN，4项研究IFX。未发现有关ADL的研究。

达到缓解的AS患者在停用IFX后，几乎100%复发。复发的平均时间为17.5±7.9周（7-45周）。停药时达到部分缓解和CRP正常的患者复发时间更长。再次使用IFX安全性好，其临床改善情况与之前相似。

停用ETN的AS患者全部复发。平均复发时间为6.2±3周，75%在3个月内复发，100%在9个月内复发。活动性AS患者再次使用ETN 1年以上安全有效。

结论：达到缓解的AS患者停用IFX后数周或数月内几乎全部复发（1b级证据，推荐级别A）。AS患者再次使用IFX有效，临床改善情况与之前相当（4级证据，推荐级别C）。

达到缓解的AS患者停用ETN后数周或数月内几乎全部复发（1b级证据，推荐级别A）。患者再次使用ETN的疗效与之前相当（4级证据，推荐级别C）。