Rituximab therapy for refractory orbital inflammation: results of a phase 1/2, dose-ranging, randomized clinical trial.
Rituximab therapy for refractory orbital inflammation: results of a phase 1/2, dose-ranging, randomized clinical trial.
复制标题
DOI：
10.1001/jamaophthalmol.2013.8179
复制
发表时间：
2014-05
影响因子：
8.1
通讯作者：
Rosenbaum, James T.
中科院分区：
文献类型：
--
作者：
Suhler, Eric B.;Lim, Lyndell L.;Beardsley, Robert M.;Giles, Tracy R.;Pasadhilka, Sirichai;Lee, Shelly T.;Saint Sardos, Alexandre de;Butler, Nicholas J.;Smith, Justine R.;Rosenbaum, James T.
眼眶炎症是一种潜在的致盲和毁容的疾病过程，通常用全身性皮质类固醇和免疫抑制剂治疗;需要更好的治疗方法。确定利妥昔单抗（一种抗B淋巴细胞抗原CD 20的单克隆抗体）是否能有效治疗难治性眼眶炎症。前瞻性、剂量范围探索、随机、双盲、I/II期临床试验，三级转诊眼科诊所。从2007年1月至2010年3月，入组了10例全身性皮质类固醇和至少一种其他免疫抑制剂难治性眼眶炎症患者。在研究第1天和第15天输注利妥昔单抗; 500 mg或1000 mg。第24周后炎症复发的初始应答者允许再输注两个开放标签利妥昔单抗1000 mg输注的额外周期。主要：通过经验证的眼眶疾病分级量表（OGS）测量的炎症减轻和皮质类固醇剂量减少至少50%。次要：视力、疼痛减轻以及患者和医生报告的总体健康评估。在10例入组患者中，7例显示OGS改善。在这7例患者中，4例在研究开始时服用皮质类固醇，均成功减量。关于次要结局指标，7/10例患者和8/10例患者的患者和医生总体健康评分分别改善，7/10例患者疼痛减轻25%或更多。4名初始应答者在研究期间经历了突破性炎症，并进行了再输注。所有受试者的视力保持稳定。10例患者中有3例在接受利妥昔单抗输注后2-8周出现明显的短期客观或主观恶化，随后接受围输注期口服皮质类固醇的患者避免了这种情况，并且不影响最终的积极治疗结局。未观察到给药组之间在疗效、毒性或重新开始治疗的可能性方面存在差异。利妥昔单抗在24周内对10例非感染性眼眶疾病患者中的7例安全有效，尽管4例需要再输注利妥昔单抗以维持对眼眶炎症的控制。未观察到显著毒性。口服皮质类固醇成功治疗了输注期炎症加重，且不影响最终的阳性结局。Clinicaltrials.gov标识符NCT 00415506
Orbital inflammation is a potentially blinding and disfiguring disease process which is often treated with systemic corticosteroids and immunosuppression; better treatments are needed. To determine whether rituximab, a monoclonal antibody against the B-lymphocyte antigen CD20, is effective in the treatment of refractory orbital inflammation. Prospective, dose-ranging, randomized, double-masked Phase I/II clinical trial Tertiary referral ophthalmology clinic. 10 patients with orbital inflammation refractory to systemic corticosteroids and at least one other immunosuppressive agent were enrolled from January 2007 to March 2010. Rituximab infusions at study days 1 and 15; either 500 mg or 1000 mg. Initial responders with recurrent inflammation after week 24 were permitted reinfusion with an additional cycle of two open-label rituximab 1000 mg infusions. Primary: reduction of inflammation measured with a validated orbital disease grading scale (OGS) and corticosteroid dose reduction by at least 50%. Secondary: visual acuity, reduction in pain, and patient and physician-reported global health assessment. Of 10 enrolled patients, 7 demonstrated improvement in OGS. Of these 7, 4 were taking corticosteroids at study inception and all achieved successful dose reduction. With regard to secondary outcome measures, 7/10 and 8/10 patients improved in patient and physician global health scores, respectively, and 7/10 had reduction in pain by 25% or more. Four initial responders experienced breakthrough inflammation during the study period and were reinfused. Vision remained stable in all subjects. Three of 10 patients had significant short-term objective or subjective worsening 2-8 weeks after receiving rituximab infusions, which was averted in subsequent patients with peri-infusional oral corticosteroids and did not affect eventual positive treatment outcome. No differences with regard to efficacy, toxicity, or likelihood of retreatment were noted between the dosing arms. Rituximab was safe and effective in 7 of 10 enrolled patients with non-infectious orbital disease within 24 weeks, although 4 required reinfusion with rituximab to maintain control of orbital inflammation. Significant toxicity was not noted. Peri-infusional inflammatory exacerbations were successfully treated with oral corticosteroids and did not affect eventual positive outcomes. Clinicaltrials.gov identifier NCT00415506
登录
查看更多内容
DOI：
10.1097/iop.0b013e3181c4dfde
发表时间：
2010-09-01
影响因子：
2
作者：
Silkiss, Rona Z.;Reier, Alice;Lauer, Simeon A.
通讯作者：
Lauer, Simeon A.
影响因子：
13.7
作者：
Khanna D;Chong KK;Afifiyan NF;Hwang CJ;Lee DK;Garneau HC;Goldberg RA;Darwin CH;Smith TJ;Douglas RS
通讯作者：
Douglas RS
DOI：
10.1080/01676830590912562
发表时间：
2005-01-01
期刊：
ORBIT-AN INTERNATIONAL JOURNAL ON ORBITAL DISORDERS AND FACIAL RECONSTRUCTIVE SURGERY
影响因子：
--
作者：
Durrani, O. M.;Reuser, T. Q.;Murray, P. I.
通讯作者：
Murray, P. I.
影响因子：
158.5
作者：
Edwards, JCW;Szczepanski, L;Shaw, T
通讯作者：
Shaw, T
影响因子：
4.2
作者：
Garrity, JA;Coleman, AW;Waitzman, DM
通讯作者：
Waitzman, DM