Factors Associated With Complete Remission After Rituximab Therapy for Pemphigus
Factors Associated With Complete Remission After Rituximab Therapy for Pemphigus
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DOI：
10.1001/jamadermatol.2019.3236
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发表时间：
2019-12-01
期刊：
影响因子：
10.9
通讯作者：
Payne, Aimee S.
中科院分区：
文献类型：
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作者：
Kushner, Carolyn J.;Wang, Shiyu;Payne, Aimee S.
重要性 利妥昔单抗已成为天疱疮的一线疗法，但通过口服全身药物实现完全缓解 (CROT) 的预后因素仍不清楚。目的 描述 CROT 和复发率，并确定利妥昔单抗治疗天疱疮后实现 CROT 的预后因素。设计、背景和参与者 宾夕法尼亚大学进行了一项单中心、回顾性队列研究，纳入了 112 名接受利妥昔单抗治疗的天疱疮患者，并在开始利妥昔单抗治疗后进行了至少 12 个月的临床随访。对 CROT 预测因素进行多变量回归分析，并对疾病复发进行 Kaplan-Meier 分析。该研究包括2005年3月15日至2016年12月19日接受利妥昔单抗治疗的患者。数据分析于2017年12月至2018年6月进行。 主要结果和措施 主要研究结果是1个周期后的CROT。次要研究结果包括 CROT 率或 CROT 复合终点或 1 个或多个周期后最小治疗完全缓解，以及中位复发时间。对 CROT 的预后变量进行多变量回归分析，包括年龄、性别、天疱疮亚型、体重指数 (BMI)（计算方法为体重公斤数除以身高米数平方）、疾病持续时间和给药方案。结果 共有 112 名天疱疮患者在利妥昔单抗治疗后随访中位时间为 37.8 个月（范围为 12.1-130.7）。其中，65 人为女性（58.0%）。首次输注利妥昔单抗时，中位年龄为 52.3 岁（范围，20.0-89.3）。包括接受多个周期利妥昔单抗的患者，79 名患者 (70.5%) 在中位时间 10.5 个月（范围，2.0-49.8）后达到 CROT，72 名患者中的 36 名 (50.0%) 在中位时间 23.3 个月后出现复发（四分位数范围，10.8-50.4 个月）。仅考虑利妥昔单抗的第一个周期，54 名患者 (48.2%) 实现了 CROT。控制年龄、性别、天疱疮亚型、BMI 和病程后，接受淋巴瘤治疗的患者与类风湿性关节炎患者相比，获得 CROT 的可能性高出 2.70 倍（比值比 [OR]，2.70；95% CI，1.03-7.12；P = 0.04）。年龄增长与实现 CROT 的显着增加相关（Wald 趋势检验，P = .01），而 BMI 大于或等于 35 与实现 CROT 的 0.14 OR（95% CI，0.03-0.63；P = .01）相关，无论给药方案如何。在多变量分析中，CROT 率与性别（OR，1.01；95% CI，0.42-2.50；P = .97）、天疱疮亚型（OR，0.37；95% CI，0.09-1.51；P = .17）或病程（OR，0.99；95% CI， 0.98-1.00；P = .09)。结论和相关性 淋巴瘤剂量和年龄较大可能与 CROT 相关，BMI 大于或等于 35 可能是利妥昔单抗治疗天疱疮后 CROT 的负面预后因素。这些发现有助于为未来前瞻性临床试验中的临床预期和价值评估提供信息。问题 在三级护理中心的一大群天疱疮患者中使用利妥昔单抗的改善率、安全性和预后因素是多少？结果 在这项针对 112 名天疱疮患者的队列研究中，48.2% 的患者在第一个周期的利妥昔单抗治疗后通过口服全身药物治疗获得完全缓解，70.5% 的患者在中位随访时间 10.5 个月的多个周期后获得缓解，50.0% 的患者在中位随访时间 23.3 个月后出现复发。淋巴瘤剂量方案、年龄大于 65 岁以及体重指数大于或等于 35 与治疗完全缓解率显着相关。意义 未接受口服全身治疗时完全缓解的长期结果和预后因素可能会告知患者和临床医生在常规临床实践中对利妥昔单抗治疗天疱疮的预期。本队列研究评估了天疱疮患者使用利妥昔单抗与缓解之间的关联。
Importance Rituximab has emerged as a front-line therapy for pemphigus, but prognostic factors for achieving complete remission off therapy (CROT) with oral systemic agents remain unknown. Objectives To describe rates of CROT and relapse and identify prognostic factors for achieving CROT after rituximab therapy for pemphigus. Design, Setting, and Participants A single-center, retrospective, cohort study was conducted at the University of Pennsylvania including 112 patients with pemphigus treated with rituximab with at least 12 months' clinical follow-up after the start of rituximab therapy. Multivariate regression analysis of factors predictive of CROT and Kaplan-Meier analysis of disease relapse were conducted. The study included patients treated with rituximab from March 15, 2005, until December 19, 2016. Data analysis was performed from December 2017 to June 2018. Main Outcomes and Measures The primary study outcome was CROT after 1 cycle. Secondary study outcomes included rate of CROT or the composite end point of CROT or complete remission on minimal therapy after 1 or more cycle, and median time to relapse. Multivariate regression analysis for prognostic variables for CROT, including age, sex, pemphigus subtype, body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), disease duration, and dosing regimen, was performed. Results A total of 112 patients with pemphigus with median 37.8 months (range, 12.1-130.7) follow-up after rituximab therapy were identified. Of these, 65 were women (58.0%). At the time of first rituximab infusion, median age was 52.3 years (range, 20.0-89.3). Including patients who received multiple cycles of rituximab, 79 patients (70.5%) achieved CROT after a median time of 10.5 months (range, 2.0-49.8), and 36 of 72 patients (50.0%) subsequently experienced relapse after a median of 23.3 months (interquartile range, 10.8-50.4 months). Considering only the first cycle of rituximab, 54 patients (48.2%) achieved CROT. Controlling for age, sex, pemphigus subtype, BMI, and disease duration, patients who received lymphoma vs rheumatoid arthritis dosing were 2.70-fold more likely to achieve CROT (odds ratio [OR], 2.70; 95% CI, 1.03-7.12; P = .04). Increasing age was associated with significant increases in achieving CROT (Wald test for trend, P = .01), whereas BMI greater than or equal to 35 was associated with a 0.14 OR (95% CI, 0.03-0.63; P = .01) for achieving CROT, regardless of the dosing regimen. In multivariate analysis, there was no significant difference in CROT rates with sex (OR, 1.01; 95% CI, 0.42-2.50; P = .97), pemphigus subtype (OR, 0.37; 95% CI, 0.09-1.51; P = .17), or disease duration (OR, 0.99; 95% CI, 0.98-1.00; P = .09). Conclusions and Relevance Lymphoma dosing and older age may be associated with CROT and BMI greater than or equal to 35 may be a negative prognostic factor for CROT after rituximab therapy for pemphigus. These findings help inform clinical expectations and merit evaluation in future prospective clinical trials.Question What are the rates of improvement, safety profile, and prognostic factors for rituximab use in a large cohort of patients with pemphigus at a tertiary care center? Findings In this cohort study of 112 patients with pemphigus, 48.2% of the patients achieved complete remission off therapy with oral systemic agents after the first cycle of rituximab therapy, 70.5% achieved remission following multiple cycles at a median follow-up time of 10.5 months, and 50.0% of patients experienced relapse after a median of 23.3 months. Lymphoma dose regimen, age greater than 65 years, and body mass index greater than or equal to 35 were significantly associated with rate of complete remission off therapy. Meaning Long-term outcomes and prognostic factors for complete remission when not receiving oral systemic therapy may inform patient and clinician expectations for rituximab therapy for pemphigus during routine clinical practice.This cohort study evaluates the association between use of rituximab and remission in patients with pemphigus.