Objective To evaluate changes in baseline patient characteristics and entry criteria of randomised, controlled studies of tumour necrosis factor alpha (TNF alpha) inhibitors in rheumatoid arthritis... Show moreObjective To evaluate changes in baseline patient characteristics and entry criteria of randomised, controlled studies of tumour necrosis factor alpha (TNF alpha) inhibitors in rheumatoid arthritis (RA) patients. Methods A systematic literature review was performed using predefined inclusion criteria to identify randomised, double-blind, controlled trials that evaluated TNF alpha inhibitors in adult RA patients. Entry criteria and baseline clinical characteristics were evaluated over time for methotrexate-experienced and methotrexate-naive study populations. Enrolment start date for each trial was the time metric. The anchor time was the study with the earliest identifiable enrolment start date. Results 44 primary publications (reporting the primary study endpoint) from 1993 to 2008 met the inclusion criteria. Enrolment start dates of August 1993 and May 1997 were identified as time anchors for the 37 methotrexate-experienced studies and the seven methotrexate-naive studies, respectively. In methotrexate-experienced trials, no significant change was observed over the years included in this study in any inclusion criteria (including swollen joint counts and C-reactive protein (CRP)), but a significant decrease over time was observed in the baseline swollen joint count, CRP and total Sharp or van der Heijde modified Sharp score, but not in baseline tender joint counts. In the methotrexate-naive studies, significant decreases over the years were observed in swollen joint and tender joint inclusion criteria, but not in baseline tender joint count, baseline CRP, CRP inclusion criteria or baseline total Sharp or van der Heijde modified Sharp score. Conclusion Inclusion criteria and baseline characteristics of RA patients enrolled in studies of TNF alpha inhibitors have changed, with more recent trials enrolling cohorts with lower disease activity, especially in methotrexate-experienced trials. Show less
Landewe, R.; Keystone, E.; Smolen, J.; Goldring, M.; Guerette, B.; Patra, K.; ... ; Heijde, D. van der 2011
Objective. Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied... Show moreObjective. Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a definition. Methods. A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecified analyses from RA clinical trials. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to define remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate definitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analyzed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes. Results. Survey results for the definition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (e. g., tender and swollen joint counts, C-reactive protein [CRP] level, and global assessments on a 0-10 scale). Analyses suggested the need to include a patientreported measure. Examination of 2-year followup data suggested that many candidate definitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score-based measures of remission did not predict good radiographic outcomes as well as the other candidate definitions did. Given these and other considerations, we propose that a patient's RA can be defined as being in remission based on one of two definitions: (a) when scores on the tender joint count, swollen joint count, CRP (in mg/dl), and patient global assessment (0-10 scale) are all <= 1, or (b) when the score on the Simplified Disease Activity Index is <= 3.3. Conclusion. We propose two new definitions of remission, both of which can be uniformly applied and widely used in RA clinical trials. We recommend that one of these be selected as an outcome measure in each trial and that the results on both be reported for each trial. Show less
Objective Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied... Show moreObjective Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a definition. Methods A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecified analyses from RA clinical trials. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to define remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate definitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analysed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes. Results Survey results for the definition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (eg, tender and swollen joint counts, C reactive protein (CRP) level, and global assessments on a 0-10 scale). Analyses suggested the need to include a patient-reported measure. Examination of 2-year follow-up data suggested that many candidate definitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score-based measures of remission did not predict good radiographic outcomes as well as the other candidate definitions did. Given these and other considerations, we propose that a patient's RA can be defined as being in remission based on one of two definitions: (1) when scores on the tender joint count, swollen joint count, CRP (in mg/dl), and patient global assessment (0-10 scale) are all <= 1, or (2) when the score on the Simplified Disease Activity Index is <= 3.3. Conclusion We propose two new definitions of remission, both of which can be uniformly applied and widely used in RA clinical trials. The authors recommend that one of these be selected as an outcome measure in each trial and that the results on both be reported for each trial. Show less
Keystone, E.; Kavanaugh, A.; Heijde, D. van der; Sinisi, S.; Guerette, B. 2010
