Systematic Review of Effects of Withdrawal of Immunomodulators or Biologic Agents From Patients With Inflammatory Bowel Disease
Systematic Review of Effects of Withdrawal of Immunomodulators or Biologic Agents From Patients With Inflammatory Bowel Disease
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DOI：
10.1053/j.gastro.2015.08.055
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发表时间：
2015-12-01
期刊：
影响因子：
29.4
通讯作者：
Satsangi, Jack
中科院分区：
文献类型：
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作者：
Torres, Joana;Boyapati, Ray K.;Satsangi, Jack
关于炎症性肠病（IBD）患者使用抗肿瘤坏死因子（TNF）药物和/或免疫调节剂治疗的最佳持续时间知之甚少。我们对文献进行了系统检索，以识别IBD缓解患者中报告抗TNF药物和/或免疫调节剂剂量递减（停药或减量）后的研究。根据IBD的类型和药物进行综述。确定复发率、复发相关因素和对再治疗的反应。我们的检索获得了6315篇唯一引文;我们分析了69项研究（18项关于免疫调节剂单药治疗的剂量递减[停药或减量]，8项关于免疫调节剂联合治疗的剂量递减，43项关于抗TNF药物的剂量递减，包括妊娠期间的3项）的结果，包括4672例患者。在克罗恩病或溃疡性结肠炎患者中，缓解期后停止免疫调节剂单药治疗与高复发率相关（约75%的患者在治疗停止后5年内复发）。大多数对联合治疗后停用免疫调节剂的克罗恩病患者的研究发现，复发率与继续服用药物的患者没有差异（55%-60%在停用免疫调节剂后24个月疾病复发）。溃疡性结肠炎患者的唯一研究支持继续使用免疫调节剂。联合治疗后停用抗TNF药物的患者中约有50%在24个月后维持缓解，但缓解比例随时间推移而下降。疾病活动性标志物、不良预后因素和复杂或复发性病程与未来复发相关。总之，基于系统性综述，50%或更多的IBD患者停止治疗后疾病复发。需要进一步的研究来准确地确定哪些患者是停止治疗的良好候选者。停药的决定应根据患者的偏好、疾病标志物、复发的后果、安全性和成本为每个人做出。
Little is known about the optimal duration of therapy with an anti-tumor necrosis factor (TNF) agent and/or an immunomodulator for patients with inflammatory bowel disease (IBD). We performed a systematic search of the literature to identify studies reporting after de-escalation (drug cessation or dose reduction) of anti-TNF agents and/or immunomodulators in patients in remission from IBD. Studies were reviewed according to the type of IBD and drug. Rates of relapse, factors associated with relapse, and response to re-treatment were determined. Our search yielded 6315 unique citations; we analyzed findings from 69 studies (18 on de-escalation [drug cessation or dose reduction] of immunomodulator monotherapy, 8 on immunomodulator de-escalation from combination therapy, and 43 on de-escalation of anti-TNF agents, including 3 during pregnancy) comprising 4672 patients. Stopping immunomodulator monotherapy after a period of remission was associated with high rates of relapse in patients with Crohn disease or ulcerative colitis (approximately 75% of patients experienced a relapse within 5 years after therapy was stopped). Most studies of patients with Crohn disease who discontinued an immunomodulator after combination therapy found that rates of relapse did not differ from those of patients who continued taking the drug (55%-60% had disease relapse 24 months after they stopped taking the immunomodulator). The only study in patients with ulcerative colitis supported continued immunomodulator use. Approximately 50% of patients who discontinued anti-TNF agents after combination therapy maintained remission 24 months later, but the proportion in remission decreased with time. Markers of disease activity, poor prognostic factors, and complicated or relapsing disease course were associated with future relapse. In conclusion, based on a systematic review, 50% or more of patients with IBD who cease therapy have a disease relapse. Further studies are required to accurately identify subgroups of patients who are good candidates for discontinuation of treatment. The decision to withdraw a drug should be made for each individual based on patient preference, disease markers, consequences of relapse, safety, and cost.