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
Vastesaeger, N.; Heijde, D. van der; Inman, R.D.; Wang, Y.X.; Deodhar, A.; Hsu, B.; ... ; Braun, J. 2011
Objectives To create a model that provides a potential basis for candidate selection for anti-tumour necrosis factor (TNF) treatment by predicting future outcomes relative to the current disease... Show moreObjectives To create a model that provides a potential basis for candidate selection for anti-tumour necrosis factor (TNF) treatment by predicting future outcomes relative to the current disease profile of individual patients with ankylosing spondylitis (AS). Methods ASSERT and GO-RAISE trial data (n=635) were analysed to identify baseline predictors for various disease-state and disease-activity outcome instruments in AS. Univariate, multivariate, receiver operator characteristic and correlation analyses were performed to select final predictors. Their associations with outcomes were explored. Matrix and algorithm-based prediction models were created using logistic and linear regression, and their accuracies were compared. Numbers needed to treat were calculated to compare the effect size of anti-TNF therapy between the AS matrix subpopulations. Data from registry populations were applied to study how a daily practice AS population is distributed over the prediction model. Results Age, Bath ankylosing spondylitis functional index (BASFI) score, enthesitis, therapy, C-reactive protein (CRP) and HLA-B27 genotype were identified as predictors. Their associations with each outcome instrument varied. However, the combination of these factors enabled adequate prediction of each outcome studied. The matrix model predicted outcomes as well as algorithm-based models and enabled direct comparison of the effect size of anti-TNF treatment outcome in various subpopulations. The trial populations reflected the daily practice AS population. Conclusion Age, BASFI, enthesitis, therapy, CRP and HLA-B27 were associated with outcomes in AS. Their combined use enables adequate prediction of outcome resulting from anti-TNF and conventional therapy in various AS subpopulations. This may help guide clinicians in making treatment decisions in daily practice. Show less
Emery, P.; Fleischmann, R.; Heijde, D. van der; Keystone, E.C.; Genovese, M.C.; Conaghan, P.G.; ... ; Rahman, M.U. 2011
Objective. To evaluate the effects of golimumab on radiographic progression in patients with rheumatoid arthritis (RA). Methods. Methotrexate (MTX)-naive patients (in the Golimumab Before Employing... Show moreObjective. To evaluate the effects of golimumab on radiographic progression in patients with rheumatoid arthritis (RA). Methods. Methotrexate (MTX)-naive patients (in the Golimumab Before Employing Methotrexate as the First-Line Option in the Treatment of Rheumatoid Arthritis of Early Onset [GO-BEFORE] study; n = 637) and patients with active RA despite MTX therapy (in the Golimumab in Active Rheumatoid Arthritis Despite Methotrexate Therapy [GO-FORWARD] study; n = 444) were randomly assigned to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Golimumab or placebo was administered subcutaneously every 4 weeks. Radiographs of the hands and feet were taken at baseline, week 28, and week 52 in the GO-BEFORE study and at baseline, week 24 (week 16 for patients who entered early escape), and week 52 in the GO-FORWARD study. Radiographs were scored by 2 independent readers in each study using the van der Heijde modification of the Sharp score. Results. In the GO- BEFORE study, the mean +/- SD changes in the modified Sharp score from baseline to week 52 (control period) were 1.4 +/- 4.6 in group 1, 1.3 +/- 6.2 in group 2 (P = 0.266), 0.7 +/- 5.2 in group 3 (P = 0.015), and 0.1 +/- 1.8 in group 4 (P = 0.025). In the GO-FORWARD study, changes from baseline to week 24 (control period) were 0.6 +/- 2.4 in group 1, 0.3 +/- 1.6 in group 2 (P = 0.361), 0.6 +/- 2.7 in group 3 (P = 0.953), and 0.2 +/- 1.3 in group 4 (P = 0.293). Conclusion. Golimumab in combination with MTX inhibited radiographic progression significantly better than did MTX alone in the GO-BEFORE study. Radiographic progression in the GO-FORWARD study was minimal in all treatment arms, precluding an adequate assessment of the effect of golimumab on radiographic progression in this study. Show less
