Non-biologic, steroid-sparing therapies for non-infectious intermediate, posterior, and panuveitis in adults

医学 硫唑嘌呤 他克莫司 霉酚酸 甲氨蝶呤 安慰剂 内科学 临床试验 随机对照试验 移植 疾病 病理 替代医学
作者
Rebecca G Edwards Mayhew,Tianjing Li,Paul McCann,Louis Leslie,Anne Strong Caldwell,Alan G. Palestine
出处
期刊:The Cochrane library [Elsevier]
卷期号:2022 (10) 被引量:4
标识
DOI:10.1002/14651858.cd014831.pub2
摘要

Background Non‐infectious intermediate, posterior, and panuveitis (NIIPPU) represent a heterogenous collection of autoimmune and inflammatory disorders isolated to or concentrated in the posterior structures of the eye. Because NIIPPU is typically a chronic condition, people with NIIPPU frequently require treatment with steroid‐sparing immunosuppressive therapy. Methotrexate, mycophenolate, cyclosporine, azathioprine, and tacrolimus are non‐biologic, disease‐modifying antirheumatic drugs (DMARDs) which have been used to treat people with NIIPPU. Objectives To compare the effectiveness and safety of selected DMARDs (methotrexate, mycophenolate mofetil, tacrolimus, cyclosporine, and azathioprine) in the treatment of NIIPPU in adults. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase, the Latin American and Caribbean Health Sciences database, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, most recently on 16 April 2021. Selection criteria We included randomized controlled trials (RCTs) comparing selected DMARDs (methotrexate, mycophenolate, tacrolimus, cyclosporine, and azathioprine) with placebo, standard of care (topical steroids, with or without oral steroids), or with each other. Data collection and analysis We used standard methodological procedures expected by Cochrane. Main results We included 11 RCTs with a total of 601 participants in this review. DMARDs versus control Two studies compared an experimental DMARD (cyclosporine A or enteric‐coated mycophenolate [EC‐MPS]) plus oral steroid with steroid monotherapy. We did not pool these results into a meta‐analysis because the dose of cyclosporine used was much higher than that used in current clinical practice. The evidence is very uncertain about whether EC‐MPS plus low‐dose oral steroid results in a higher proportion of participants achieving control of inflammation over steroid monotherapy (risk ratio [RR] 2.81, 95% confidence interval [CI] 1.10 to 7.17; 1 study, 41 participants; very low‐certainty evidence). The change in best‐corrected visual acuity (BCVA) was reported separately for right and left eyes. The evidence for improvement (lower logarithm of the minimum angle of resolution (logMAR) indicates better vision) between the groups is very uncertain (mean difference [MD] ‐0.03 and ‐0.10, 95% CI ‐0.96 to 0.90 and ‐0.27 to 0.07 for right and left, respectively; 1 study, 82 eyes; very low‐certainty evidence). No data were available for the following outcomes: proportion of participants achieving a 2‐line improvement in visual acuity, with confirmed macular edema, or achieving steroid‐sparing control. The evidence for the proportion of participants requiring cessation of medication in the DMARD versus control group is very uncertain (RR 2.61, 95% CI 0.11 to 60.51; 1 study, 41 participants; very low‐certainty evidence). Methotrexate versus mycophenolate We were able to combine two studies into a meta‐analysis comparing methotrexate versus mycophenolate mofetil. Methotrexate probably results in a slight increase in the proportion of participants achieving control of inflammation, including steroid‐sparing control, compared to mycophenolate at six months (RR 1.23, 95% CI 1.01 to 1.50; 2 studies, 261 participants; moderate‐certainty evidence). Change in BCVA was reported per eye and the treatments likely result in little to no difference in change in vision (MD 0.01 logMAR higher [worse] for methotrexate versus mycophenolate; 2 studies, 490 eyes; moderate‐certainty evidence). No data were available for the proportion of participants achieving a 2‐line improvement in visual acuity. The evidence is very uncertain regarding the proportion of participants with confirmed macular edema between methotrexate versus mycophenolate (RR 0.49, 95% CI 0.19 to 1.30; 2 studies, 35 eyes; very low‐certainty). Methotrexate versus mycophenolate may result in little to no difference in the proportion of participants requiring cessation of medication (RR 0.99, 95% CI 0.43 to 2.27; 2 studies, 296 participants; low‐certainty evidence). Steroids with or without azathioprine versus cyclosporine A Four studies compared steroids with or without azathioprine (oral steroids, intravenous [IV] steroids, or azathioprine) to cyclosporine A. We excluded two studies from the meta‐analysis because the participants were treated with 8 mg to 15 mg/kg/day of cyclosporine A, a significantly higher dose than is utilized today because of concerns for nephrotoxicity. The remaining two studies were conducted in all Vogt‐Koyanagi‐Harada disease (VKH) populations and compared cyclosporine A to azathioprine or IV pulse‐dose steroids. The evidence is very uncertain for whether the steroids with or without azathioprine or cyclosporine A influenced the proportion of participants achieving control of inflammation (RR 0.84, 95% CI 0.70 to 1.02; 2 studies, 112 participants; very low‐certainty evidence), achieving steroid‐sparing control (RR 0.64, 95% CI 0.33 to 1.25; 1 study, 21 participants; very low‐certainty evidence), or requiring cessation of medication (RR 0.85, 95% 0.21 to 3.45; 2 studies, 91 participants; very low‐certainty evidence). The evidence is uncertain for improvement in BCVA (MD 0.04 logMAR lower [better] with the steroids with or without azathioprine versus cyclosporine A; 2 studies, 91 eyes; very low‐certainty evidence). There were no data available (with current cyclosporine A dosing) for the proportion of participants achieving a 2‐line improvement in visual acuity or with confirmed macular edema. Studies not included in synthesis We were unable to include three studies in any of the comparisons (in addition to the aforementioned studies excluded based on historic doses of cyclosporine A). One was a dose‐response study comparing cyclosporine A to cyclosporine G, a formulation which was never licensed and is not clinically available. We excluded another study from meta‐analysis because it compared cyclosporine A and tacrolimus, considered to be of the same class (calcineurin inhibitors). We were unable to combine the third study, which examined tacrolimus monotherapy versus tacrolimus plus oral steroid, with any group. Authors' conclusions There is a paucity of data regarding which DMARD is most effective or safe in NIIPPU. Studies in general were small, heterogenous in terms of their design and outcome measures, and often did not compare different classes of DMARD with each other. Methotrexate is probably slightly more efficacious than mycophenolate in achieving control of inflammation, including steroid‐sparing control (moderate‐certainty evidence), although there was insufficient evidence to prefer one medication over the other in the VKH subgroup (very low‐certainty evidence). Methotrexate may result in little to no difference in safety outcomes compared to mycophenolate.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
小管完成签到,获得积分10
刚刚
量子星尘发布了新的文献求助100
1秒前
dara完成签到,获得积分10
1秒前
隐形曼青应助西习采纳,获得10
2秒前
2秒前
曾经晓亦发布了新的文献求助20
2秒前
香蕉觅云应助庾稀采纳,获得10
3秒前
岁月轮回发布了新的文献求助10
3秒前
4秒前
4秒前
练习时长两年半应助香菜采纳,获得10
5秒前
1111发布了新的文献求助10
5秒前
7秒前
CipherSage应助澡雪采纳,获得10
8秒前
YOLO发布了新的文献求助10
8秒前
敏感安柏关注了科研通微信公众号
8秒前
所所应助奥暖将采纳,获得10
9秒前
9秒前
cc完成签到,获得积分10
10秒前
11秒前
LittleTT发布了新的文献求助10
11秒前
11秒前
11秒前
所所应助太渊采纳,获得10
12秒前
迷路铸海完成签到,获得积分20
13秒前
cc发布了新的文献求助10
13秒前
lyy关注了科研通微信公众号
14秒前
鱼贝贝完成签到 ,获得积分10
14秒前
小蘑菇应助zyw采纳,获得10
14秒前
linkman发布了新的文献求助10
14秒前
Ava应助岁月轮回采纳,获得10
16秒前
16秒前
刻苦海露发布了新的文献求助30
17秒前
18秒前
Henry发布了新的文献求助30
19秒前
毛哥看文献完成签到 ,获得积分10
19秒前
Dream点壹完成签到,获得积分10
21秒前
平淡南松完成签到,获得积分10
22秒前
狗狗发布了新的文献求助10
23秒前
23秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Effective Learning and Mental Wellbeing 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3975871
求助须知:如何正确求助?哪些是违规求助? 3520207
关于积分的说明 11201502
捐赠科研通 3256611
什么是DOI,文献DOI怎么找? 1798403
邀请新用户注册赠送积分活动 877552
科研通“疑难数据库(出版商)”最低求助积分说明 806430