2019年9月10日，印度马杜赖眼科医院、美国加州大学等机构的研究人员联合在《美国医学会杂志》发表论文，研究了霉酚酸酯与甲氨蝶呤皮质类固醇维持治疗对葡萄膜炎患者炎症反应的影响。

据悉，甲氨蝶呤和霉酚酸酯常用于免疫调节治疗，以实现皮质类固醇维持控制非感染性葡萄膜炎，但仍不确定哪种药物更有效。

2013年8月22日至2017年8月16日，一线抗代谢药物类固醇维持治疗（FAST）葡萄膜炎试验在印度、美国、澳大利亚、沙特阿拉伯和墨西哥的9个转诊眼科中心招募了216名需要类固醇维持免疫抑制治疗的非感染性葡萄膜炎成人患者，中位年龄为38岁，62.5%为女性。这些参与者被随机分组，107例患者口服甲氨蝶呤，每周25mg；109例患者口服霉酚酸酯，每天3g。

治疗成功定义为双眼炎症得到控制，每天使用强的松不超过7.5毫克，1%的松醋酸酯不超过2滴。根据6个月的治疗结果来决定患者是继续治疗还是换其他抗代谢药，继续随访至12个月。

最终有194名（89.8%）患者完成了6个月的随访。甲氨蝶呤组64例（66.7%）患者治疗成功，霉酚酸酯组为56例（57.1%），优势比为1.50，差异不显著。在后葡萄膜炎或全葡萄膜炎患者中，甲氨蝶呤组58例（74.4%）患者治疗成功，显著高于霉酚酸酯组（42例，55.3%），优势比为2.35；而在中间葡萄膜炎患者中甲氨蝶呤组有6例（33.3%）治疗成功，霉酚酸酯组有14例（63.6%），优势比为0.29。肝酶升高是最常见的非严重实验室不良反应，甲氨蝶呤组中有14例（13.0%）发生，霉酚酸酯组中有8例（7.4%）。

在非感染性葡萄膜炎的成人中，与甲氨蝶呤相比，霉酚酸酯作为一线皮质类固醇维持治疗并没有使炎症得到更好的控制。但根据葡萄膜炎的解剖亚型，仍需进一步研究来确定究竟哪种药物更有效。

附：英文原文

Title: Effect of Corticosteroid-Sparing Treatment With Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients With Uveitis: A Randomized Clinical Trial

Author: S. R. Rathinam, John A. Gonzales, Radhika Thundikandy, Anuradha Kanakath, S. Bala Murugan, R. Vedhanayaki, Lyndell L. Lim, Eric B. Suhler, Hassan A. Al-Dhibi, Thuy Doan, Jeremy D. Keenan, Maya M. Rao, Caleb D. Ebert, Hieu H. Nguyen, Eric Kim, Travis C. Porco, Nisha R. Acharya

Issue&Volume: Vol 322 No 10

Abstract: 

Importance  Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective.

Objective  To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis.

Design, Setting, and Participants  The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018.

Interventions  Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109).

Main Outcomes and Measures  The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome.

Results  Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexate group vs 56 (57.1%) in the mycophenolate group (difference, 9.5% [95% CI, −5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81]; P = .20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in the mycophenolate group (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90]; P = .02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, −30.3% [95% CI, −51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05]; P = .07; P for interaction = .004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in the mycophenolate group.

Conclusions and Relevance  Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis.

DOI: 10.1001/jama.2019.12618

Source: https://jamanetwork.com/journals/jama/article-abstract/2749597