Chatzidionysiou Katerina, Lie Elisabeth, Lukina Galina, Hetland Merete L, Hauge Ellen-Margrethe, Pavelka Karel, Gabay Cem, Scherer Almut, Nordström Dan, Canhao Helena, Santos Maria José, Tomsic Matija, Rotar Ziga, Hernández M Victoria, Gomez-Reino Juan, Ancuta Ioan, Kvien Tore K, van Vollenhoven Ronald
From the Karolinska Institute, Department of Medicine, Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID), Stockholm, Sweden; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway; ARBITER, Institute of Rheumatology, Moscow, Russia; DANBIO, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Rigshospitalet, Glostrup; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen; Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; Institute of Rheumatology, Prague, Czech Republic; Swiss Clinical Quality Management (SCQM) Registry, University Hospital of Geneva, Geneva; SCQM Foundation, Zurich, Switzerland; National Register for Biologic Treatment in Finland (ROB-FIN), Helsinki University Central Hospital, Helsinki, Finland; Reuma.pt Registry, Instituto de Medicina Molecular da Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; BioRx.si University Medical Centre, Ljubljana, Ljubljana, Slovenia; Rheumatology Department, Hospital Clinic of Barcelona, Barcelona; Hospital Clinico Universidad De Santiago, Santiago, Spain; Cantacuzino Hospital, Bucharest, Romania.
K. Chatzidionysiou, MD, PhD, Karolinska Institute, Department of Medicine, Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID); E. Lie, MD, PhD, Department of Rheumatology, Diakonhjemmet Hospital; G. Lukina, MD, PhD, ARBITER, Institute of Rheumatology; M.L. Hetland, MD, PhD, Professor, DANBIO, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Rigshospitalet, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen; E.M. Hauge, MD, PhD, Department of Rheumatology, Aarhus University Hospital; K. Pavelka, MD, PhD, Professor, Institute of Rheumatology; C. Gabay, MD, PhD, Professor, SCQM Registry, University Hospital of Geneva; A. Scherer, PhD, SCQM Foundation; D. Nordström, MD, PhD, Professor, ROB-FIN, Helsinki University Central Hospital; H. Canhao, MD, PhD, Professor, Reuma.pt Registry, Instituto de Medicina Molecular da Faculdade de Medicina, Universidade de Lisboa; M.J. Santos, MD, PhD, Reuma.pt Registry, Instituto de Medicina Molecular da Faculdade de Medicina, Universidade de Lisboa; M. Tomsic, MD, PhD, Professor, BioRx.si University Medical Centre; Z. Rotar, MD, BioRx.si University Medical Centre; M.V. Hernández, MD, PhD, Rheumatology Department, Hospital Clinic of Barcelona; J. Gomez-Reino, MD, PhD, Professor, Hospital Clinico Universidad De Santiago; I. Ancuta, MD, Cantacuzino Hospital; T.K. Kvien, MD, PhD, Professor, Department of Rheumatology, Diakonhjemmet Hospital; R. van Vollenhoven, MD, PhD, Professor, Karolinska Institute, Department of Medicine, Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID).
J Rheumatol. 2017 Feb;44(2):162-169. doi: 10.3899/jrheum.160460. Epub 2017 Jan 15.
Several aspects of rituximab (RTX) retreatment in rheumatoid arthritis (RA) need to be further elucidated. The aim of this study was to describe the effect of repeated courses of RTX on disease activity and to compare 2 retreatment strategies, fixed-interval versus on-flare retreatment, in a large international, observational, collaborative study.
In the first analysis, patients with RA who received at least 4 cycles with RTX were included. In the second analysis, patients who received at least 1 RTX retreatment and for whom information about the strategy for retreatment was available were identified. Two retreatment strategies (fixed-interval vs on-flare) were compared by fitting-adjusted, mixed-effects models of 28-joint Disease Activity Score (DAS28) over time for first and second retreatment.
A total of 1530 patients met the eligibility criteria for the first analysis. Significant reductions of mean DAS28 between the starts of subsequent treatment cycles were observed (at start of first treatment cycle: 5.5; second: 4.3; third: 3.8; and fourth: 3.5), suggesting improved response after each additional cycle (p < 0.0001 for all pairwise comparisons). A total of 800 patients qualified for the second analysis: 616 were retreated on flare and 184 at fixed interval. For the first retreatment, the fixed-interval retreatment group yielded significantly better results than the on-flare group (estimated marginal mean DAS28 = 3.8, 95% CI 3.6-4.1 vs 4.6, 95% CI 4.5-4.7, p < 0.0001). Similar results were found for the second retreatment.
Repeated treatment with RTX leads to further clinical improvement after the first course of RTX. A fixed-interval retreatment strategy seems to be more effective than on-flare retreatment.
类风湿关节炎（RA）中利妥昔单抗（RTX）再治疗的几个方面需要进一步阐明。本研究的目的是描述RTX重复疗程对疾病活动的影响，并在一项大型国际观察性合作研究中比较两种再治疗策略，即固定间隔再治疗与发作时再治疗。
在首次分析中，纳入接受至少4个RTX疗程的RA患者。在第二次分析中，确定接受至少1次RTX再治疗且有再治疗策略信息的患者。通过对首次和第二次再治疗时28个关节疾病活动评分（DAS28）随时间变化拟合调整后的混合效应模型，比较两种再治疗策略（固定间隔与发作时）。
共有1530例患者符合首次分析的纳入标准。在后续治疗周期开始之间观察到平均DAS28显著降低（第一个治疗周期开始时：5.5；第二个：4.3；第三个：3.8；第四个：3.5），表明每个额外周期后反应有所改善（所有两两比较p<0.0001）。共有800例患者符合第二次分析的条件：616例在发作时进行再治疗，184例采用固定间隔再治疗。对于首次再治疗，固定间隔再治疗组的结果明显优于发作时再治疗组（估计边际平均DAS28 = 3.8，95%CI 3.6 - 4.1 vs 4.6，95%CI 4.5 - 4.7，p<0.0001）。第二次再治疗也发现了类似结果。
RTX重复治疗在首次RTX疗程后可带来进一步的临床改善。固定间隔再治疗策略似乎比发作时再治疗更有效。
