“目标治疗”可持续改善银屑病关节炎

随着抗肿瘤坏死因子抑制剂以及其他高效生物制剂的问世，风湿科医生开始越来越多地使用“目标治疗（treat to target）”，有时也称为“严格控制（tight control）”，这是一种密切监测患者并且对药物治疗做出相应调整直至疾病活动度降到最低的治疗策略。

来自随机对照试验的大量证据表明，对于类风湿性关节炎患者，目标治疗较之标准治疗能改善患者结局。但是对于银屑病关节炎（PsA），这是一种异质性更高的疾病，可能不但有皮肤和指甲表现，而且关节和结缔组织也可能受累，所以过去一直没能很好地定义疾病缓解。到了近几年才制定并确证了代表PsA最低疾病活动度的终点，现在支持目标治疗策略的证据正在慢慢积累中。

在今年的欧洲风湿病学大会上，来自美国加州大学圣地亚哥分校的Arthur Kavanaugh博士报告了一项戈利木单抗（golimumab）治疗PsA随机对照试验的5年扩展期结果。结果显示，通过目标治疗策略达到了最低疾病活动度（MDA）的患者的远期结局更好。

Arthur Kavanaugh博士

Kavanaugh博士及其同事采用的是一项临床试验开放性扩展期的数据，大约有400例患者随机接受了戈利木单抗50 mg、100 mg或安慰剂；第24周时安慰剂组的所有患者均交叉至接受戈利木单抗治疗直至该试验的长期开放性扩展期结束；随访期长达252周。分别于第14、24和52周时对患者进行评估，之后每年评估一次直至第252周。研究者采用的是一个经过确证的复合终点，包括皮肤、关节、肌腱附着点受累等指标。

大约一半的患者（安慰剂组44.2%，阳性治疗组51.7%）在随访期至少连续3个时间点达到了持续MDA；研究者发现无论治疗分组情况如何，达到了MDA的患者在具有临床意义的健康评估问卷（HAQ）评分改善方面显著优于没有达到MDA的患者，影像学进展也显著减少。

交叉后达到了MDA的患者的改善程度与从基线时就开始使用戈利木单抗的患者相似，提示延后治疗启动时间并不会导致身体功能加重或影像学进展。

Kavanaugh博士说：“就患者而言，我们往往无法控制他们会在病程中的什么时候来就诊。上述研究数据表明即使患者来就诊时病情已经失去控制好几个月了，也仍然可以采用目标治疗尽量帮助其达到MDA。”

他总结道：“我认为这项研究的确提供了一些证据表明目标治疗对于PsA患者是很有价值的。”“对于RA，目前有更多的研究证实了这一点。”

Kavanaugh博士表示，还需要针对PsA患者开展进一步的研究以确认目标治疗策略的确能改善疾病的远期结局。他补充道：“和其他医学技术一样，通过多项研究反复验证是十分重要的。还可以采用有着其他作用机制的药物来开展研究以验证目标治疗策略。”

Kavanaugh博士声明接受了雅培、安进、杨森和UCB公司提供的研究经费。该研究的其他作者声明还接受了其他生产厂家提供的经费支持；3名作者为杨森公司员工。

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Thanks to anti–tumor necrosis factor inhibitors and other highly effective biologic therapies, rheumatologists are increasingly embracing treat to target, a strategy in which patients are closely monitored and medications adjusted until a patient has the least disease activity possible.

Ample evidence from randomized, controlled trials has shown treat to target – sometimes referred to as tight control – to result in better outcomes than standard therapy in rheumatoid arthritis patients.

But in psoriatic arthritis (PsA), a more heterogeneous disorder with skin and nail manifestations as well as joint and connective tissue involvement, remission has historically been less well defined. Only in recent years have endpoints been developed and validated for minimal disease activity in PsA, and evidence in support of a treat-to-target approach is now slowly trickling in.

Dr. Arthur Kavanaugh

At the annual European Congress of Rheumatology, Dr. Arthur Kavanaugh of the University of California, San Diego, presented results from a 5-year extension of a randomized, controlled trial of golimumab in patients with PsA that showed better long-term outcomes in those able to achieve minimal disease activity (MDA) through a treat-to-target strategy.

"I think [the study] does provide some evidence suggesting that treat to target could well be a valuable goal for PsA, Dr. Kavanaugh said. "Right now, RA has the advantage of more studies showing this."

Dr. Kavanaugh and his colleagues’ study used data from an open-label extension of a clinical trial in which about 400 patients were randomized to receive golimumab at 50 mg or 100 mg, or placebo; all placebo patients were crossed over to golimumab treatment at 24 weeks and during the long-term, open-label extension of the trial, were followed for as long as 252 weeks. Patients were assessed at 14, 24, and 52 weeks, then yearly until week 252. The investigators used a validated composite endpoint that included measures of skin, joint, and enthesis involvement.

About half of the patients (44.2% of those randomized to placebo and 51.7% of those randomized to active treatment) achieved persistent MDA over three or more consecutive time points during follow-up, and investigators saw significantly better clinically meaningful Health Assessment Questionnaire improvement and less radiographic progression in patients who had achieved MDA, regardless of treatment allocation.

Patients who achieved MDA after crossing over had improvements that were similar to those who started on golimumab at baseline, suggesting that delayed treatment initiation does not result in a worsening of physical function or radiographic progression.

"When it comes to patients, we cannot always control when we will see them in the course of disease," Dr. Kavanaugh said. "These data suggest that even though a patient may show up with months of uncontrolled disease, it is still a viable goal to treat them to try to get MDA."

Dr. Kavanaugh said that further studies in PsA patients were needed to confirm that treat-to-target strategies resulted in better long-term disease outcomes. "As always in medicine, it is important to have verification from multiple studies. It would be helpful to have data from studies using medications with other mechanisms of action to support treat to target," he added.

Dr. Kavanaugh disclosed research and grant support from Abbott, Amgen, Janssen, and UCB. His coauthors on the study disclosed financial support from additional manufacturers, and three were employees of Janssen.