霉酚酸酯在系统性硬化症中的安全性和有效性。一项系统评价。
Safety and effectiveness of mycophenolate in systemic sclerosis. A systematic review.
作者信息
Omair Mohammed A, Alahmadi Abdulaziz, Johnson Sindhu R
机构信息
Toronto Scleroderma Program, Division of Rheumatology, Department of Medicine, Toronto Western Hospital, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Rheumatology, Department of Medicine, King Saud University, Riyadh, Saudi Arabia.
Toronto Scleroderma Program, Division of Rheumatology, Department of Medicine, Toronto Western Hospital, Mount Sinai Hospital, Toronto, Ontario, Canada.
出版信息
PLoS One. 2015 May 1;10(5):e0124205. doi: 10.1371/journal.pone.0124205. eCollection 2015.
BACKGROUND
Mycophenolate is increasingly being used in the rheumatic diseases. Its main adverse effects are gastrointestinal, myelosuppression, and infection. These may limit use in systemic sclerosis (SSc) since gastrointestinal involvement is common. The objective of this study is to evaluate gastrointestinal adverse events of mycophenolate in SSc. Secondarily we evaluated other adverse events, and the effectiveness of mycophenolate in skin and lung disease.
METHODS
A literature search of Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL (inception-2013) was performed. Studies reporting use of mycophenolate in SSc patients, adverse events, modified Rodnan skin score (MRSS), forced vital capacity (FVC), or diffusing capacity of carbon monoxide (DLCO) were included. The primary outcome was gastrointestinal events occurring after the initiation of mycophenolate. Secondary safety outcomes included myelosuppression, infection, malignancy, and death after the initiation of mycophenolate.
RESULTS
617 citations were identified and 21 studies were included. 487 patients were exposed to mycophenolate. The mean disease duration ranged between 0.8-14.1 years. There were 18 deaths and 90 non-lethal adverse events. The non-lethal adverse events included 43 (47.7%) gastrointestinal events, 34 (26%) infections, 6 (5%) cytopenias and 2 (2%) malignancies. The most common gastrointestinal events included diarrhea (n=18 (14%)), nausea (n=12 (9%)), and abdominal pain (n=3 (2%)). The rate of discontinuation ranged between 8%-40%. Seven observational studies reported improvement or stabilization in FVC, and 5 studies report stabilization or improvement in MRSS.
CONCLUSION
Mycophenolate-associated gastrointestinal adverse events are common in SSc, but not severe enough to preclude its use. Observational data suggests mycophenolate may be effective in improving or stabilizing interstitial lung disease, and skin involvement.
背景
霉酚酸酯越来越多地用于治疗风湿性疾病。其主要不良反应为胃肠道反应、骨髓抑制和感染。由于系统性硬化症（SSc）常累及胃肠道，这些不良反应可能会限制霉酚酸酯在该病中的应用。本研究的目的是评估霉酚酸酯在SSc患者中的胃肠道不良事件。其次，我们评估了其他不良事件以及霉酚酸酯在皮肤病和肺病中的疗效。
方法
检索了Medline、Embase、Cochrane对照试验中心注册库和CINAHL（建库至2013年）。纳入了报告霉酚酸酯在SSc患者中的应用、不良事件、改良Rodnan皮肤评分（MRSS）、用力肺活量（FVC）或一氧化碳弥散量（DLCO）的研究。主要结局是开始使用霉酚酸酯后发生的胃肠道事件。次要安全性结局包括开始使用霉酚酸酯后的骨髓抑制、感染、恶性肿瘤和死亡。
结果
共检索到617篇文献，纳入21项研究。487例患者使用了霉酚酸酯。平均病程为0.8 - 14.1年。有18例死亡和90例非致命性不良事件。非致命性不良事件包括43例（47.7%）胃肠道事件、34例（26%）感染、6例（5%）血细胞减少和2例（2%）恶性肿瘤。最常见的胃肠道事件包括腹泻（n = 18（14%））、恶心（n = 12（9%））和腹痛（n = 3（2%））。停药率在8% - 40%之间。7项观察性研究报告FVC有所改善或稳定，5项研究报告MRSS有所稳定或改善。
结论
霉酚酸酯相关的胃肠道不良事件在SSc中很常见，但严重程度不足以排除其使用。观察性数据表明，霉酚酸酯可能对改善或稳定间质性肺病及皮肤受累有效。
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