Department of Internal Medicine, Bridgeport Hospital-Yale New Haven Health, Bridgeport, Connecticut, USA.
Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
Inflamm Bowel Dis. 2020 Mar 4;26(4):515-523. doi: 10.1093/ibd/izz193.
We summarized the protocol-specified corticosteroid tapering regimens in clinical trials of moderate-severe ulcerative colitis (UC) and Crohn's disease (CD) and calculated differences in rates of clinical remission vs corticosteroid-free clinical remission (CSF-CR).
Through a systematic literature review through February 28, 2019, we identified 16 randomized controlled trials (RCTs) of biologics or small molecules in patients with moderate-severe UC or CD who reported CSF-CR as an outcome. We estimated the relative risk and 95% confidence interval of achieving CSF-CR vs overall clinical remission in patients treated with active intervention or placebo through random-effects meta-analysis.
Across trials of UC (11 trials) and CD (5 trials), a median of 53% and 49% of participants were on corticosteroids at the time of trial entry, respectively. Participants were allowed to enter trials at a median corticosteroid dose (range) of 35 (20-40) mg/d. Doses were kept stable for a median (range) of 8 (5-10) weeks during induction therapy, after which a mandatory and structured taper was implemented, albeit with the investigators' discretion depending on clinical status. Pooled rates of CSF-CR in patients with UC and CD treated with placebo were 9.7% and 19.1%, respectively. In UC and CD trials, the rate of CSF-CR was 24% and 18% lower than the rate of overall clinical remission, respectively.
Protocol-specified corticosteroid tapering regimens vary across trials. These findings will help to inform the design and interpretation of future clinical trials and highlight the need for standardization.
我们总结了中度至重度溃疡性结肠炎（UC）和克罗恩病（CD）的临床试验中规定的皮质类固醇减量方案，并计算了临床缓解与无皮质类固醇临床缓解（CSF-CR）之间的差异率。
通过系统的文献综述，截至 2019 年 2 月 28 日，我们确定了 16 项关于中度至重度 UC 或 CD 患者使用生物制剂或小分子治疗的随机对照试验（RCT），这些试验报告了 CSF-CR 作为结局。我们通过随机效应荟萃分析估计了接受活性干预或安慰剂治疗的患者达到 CSF-CR 与总体临床缓解的相对风险和 95%置信区间。
在 UC（11 项试验）和 CD（5 项试验）的试验中，分别有中位数 53%和 49%的参与者在试验入组时正在使用皮质类固醇。参与者入组时的皮质类固醇剂量（范围）中位数为 35（20-40）mg/d。在诱导治疗期间，剂量保持稳定，中位数（范围）为 8（5-10）周，之后实施了强制性和结构化的减量，但取决于临床状况，由研究者自行决定。接受安慰剂治疗的 UC 和 CD 患者的 CSF-CR 率分别为 9.7%和 19.1%。在 UC 和 CD 试验中，CSF-CR 的发生率分别比总体临床缓解率低 24%和 18%。
试验中皮质类固醇减量方案各不相同。这些发现将有助于为未来的临床试验提供设计和解释信息，并强调标准化的必要性。
