Rituximab in Patients With Rheumatoid Arthritis
Rituximab in Patients With Rheumatoid Arthritis
This observational study aimed to follow up adult patients with RA treated with RTX in a routine clinical setting in Finland from April 2005 to December 2011. The patients included in these analyses had been treated according to local standard of care, and, for example, visit intervals were not fixed. Data were collected from medical records of a total of 151 patients fulfilling the American College of Rheumatology criteria for RA and treated with RTX. Our data partially extend the earlier report by Valleala et al with longer follow-up times on some patients (cohort 1, n = 56, 37%), but include also data of new patients (cohort 2, n = 95, 63%). Patient distribution during the study course is presented in Figure 1. The shortest follow-up period was set to at least 1 year from the initiation of RTX therapy. Patient's written informed consent was obtained before data collection was initiated. Patients were coded, and the collected data were anonymous. Approval for the study was obtained from the ethical review board of the Hospital District of Helsinki and Uusimaa and by the ethical committees of all 7 participating hospitals.
(Enlarge Image)
Figure 1.
Flowchart of patient distribution during the study.
The information collected included the previous usage of conventional DMARDs and biologics. In addition, concomitant chronic diseases or other factors affecting the choice of RTX therapy were documented. At the onset of RTX therapy and at subsequent follow-up and retreatment visits, data on erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), number of tender and swollen joints, Health Assessment Questionnaire score, and visual analog scale (0–100 mm) scores for patient's assessment of pain and general health status, as well as physician's assessment of disease activity, were collected. Follow-up information after discontinuation of RTX therapy was also obtained. All data were observational and collected when available from the hospital case records.
Rituximab was administered on days 1 and 15 as 1000-mg intravenous infusions with intravenous methylprednisolone premedication. Upon a disease flare, a retreatment course of RTX was administered. For a small proportion of patients (n = 17), RTX therapy was initiated with 500 mg of RTX 2 weeks apart. Subsequently, the majority of these patients received retreatment with the 1000-mg dose of RTX. Treatment response after RTX therapy was defined according to European League Against Rheumatism response criteria at 3 months at the earliest. As the timing of the follow-up visits varied, we chose to use the lowest 28-joint Disease Activity Score (DAS28) value after each RTX course for efficacy analysis. Responses were calculated from the patients' original baseline (BL) values to the indicated time point. Good response was defined as a DAS28 of less than 3.2 and DAS28 score improvement from BL of greater than 1.2. Moderate response was defined as 3.2 ≤ DAS28 ≤ 5.1 and improvement of 0.6 to 1.2, or DAS28 of greater than 5.1 and improvement of greater than 1.2. Low disease activity was defined as DAS28 of less than 3.2 and remission as DAS28 of less than 2.6.
In our previous study, adverse reactions with causality to RTX were collected. During this study, all adverse events (AEs) were collected for the whole follow-up period including the time after RTX discontinuation, because of update in reporting guidelines. Physicians were asked to assess seriousness of the event (nonserious/serious) as well as the causality of the event to RTX.
Descriptive statistics, such as medians and ranges, were used to describe patient demographics and treatment responses. Treatment responses were also evaluated using Wilcoxon signed rank (within group), Wilcoxon rank sum (between group comparisons), and χ tests when appropriate.
Materials and Methods
This observational study aimed to follow up adult patients with RA treated with RTX in a routine clinical setting in Finland from April 2005 to December 2011. The patients included in these analyses had been treated according to local standard of care, and, for example, visit intervals were not fixed. Data were collected from medical records of a total of 151 patients fulfilling the American College of Rheumatology criteria for RA and treated with RTX. Our data partially extend the earlier report by Valleala et al with longer follow-up times on some patients (cohort 1, n = 56, 37%), but include also data of new patients (cohort 2, n = 95, 63%). Patient distribution during the study course is presented in Figure 1. The shortest follow-up period was set to at least 1 year from the initiation of RTX therapy. Patient's written informed consent was obtained before data collection was initiated. Patients were coded, and the collected data were anonymous. Approval for the study was obtained from the ethical review board of the Hospital District of Helsinki and Uusimaa and by the ethical committees of all 7 participating hospitals.
(Enlarge Image)
Figure 1.
Flowchart of patient distribution during the study.
The information collected included the previous usage of conventional DMARDs and biologics. In addition, concomitant chronic diseases or other factors affecting the choice of RTX therapy were documented. At the onset of RTX therapy and at subsequent follow-up and retreatment visits, data on erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), number of tender and swollen joints, Health Assessment Questionnaire score, and visual analog scale (0–100 mm) scores for patient's assessment of pain and general health status, as well as physician's assessment of disease activity, were collected. Follow-up information after discontinuation of RTX therapy was also obtained. All data were observational and collected when available from the hospital case records.
Rituximab was administered on days 1 and 15 as 1000-mg intravenous infusions with intravenous methylprednisolone premedication. Upon a disease flare, a retreatment course of RTX was administered. For a small proportion of patients (n = 17), RTX therapy was initiated with 500 mg of RTX 2 weeks apart. Subsequently, the majority of these patients received retreatment with the 1000-mg dose of RTX. Treatment response after RTX therapy was defined according to European League Against Rheumatism response criteria at 3 months at the earliest. As the timing of the follow-up visits varied, we chose to use the lowest 28-joint Disease Activity Score (DAS28) value after each RTX course for efficacy analysis. Responses were calculated from the patients' original baseline (BL) values to the indicated time point. Good response was defined as a DAS28 of less than 3.2 and DAS28 score improvement from BL of greater than 1.2. Moderate response was defined as 3.2 ≤ DAS28 ≤ 5.1 and improvement of 0.6 to 1.2, or DAS28 of greater than 5.1 and improvement of greater than 1.2. Low disease activity was defined as DAS28 of less than 3.2 and remission as DAS28 of less than 2.6.
In our previous study, adverse reactions with causality to RTX were collected. During this study, all adverse events (AEs) were collected for the whole follow-up period including the time after RTX discontinuation, because of update in reporting guidelines. Physicians were asked to assess seriousness of the event (nonserious/serious) as well as the causality of the event to RTX.
Descriptive statistics, such as medians and ranges, were used to describe patient demographics and treatment responses. Treatment responses were also evaluated using Wilcoxon signed rank (within group), Wilcoxon rank sum (between group comparisons), and χ tests when appropriate.