Background Since initial approval for the treatment of rheumatoid arthritis (RA), rituximab has been evaluated in clinical trials involving various populations with RA. Information has also been... Show moreBackground Since initial approval for the treatment of rheumatoid arthritis (RA), rituximab has been evaluated in clinical trials involving various populations with RA. Information has also been gathered from registries. This report therefore updates the 2007 consensus document on the use of rituximab in the treatment of RA. Methods Preparation of this new document involved many international experts experienced in the treatment of RA. Following a meeting to agree upon the core agenda, a systematic literature review was undertaken to identify all relevant data. Data were then interrogated by a drafting committee, with subsequent review and discussion by a wider expert committee leading to the formulation of an updated consensus statement. These committees also included patients with RA. Results The new statement covers wide-ranging issues including the use of rituximab in earlier RA and impact on structural progression, and aspects particularly pertinent to rituximab such as co-medication, optimal dosage regimens, repeat treatment cycles and how to manage non-response. Biological therapy following rituximab usage is also addressed, and safety concerns including appropriate screening for hepatitis, immunoglobulin levels and infection risk. This consensus statement will support clinicians and inform patients when using B-cell depletion in the management of RA, providing up-to-date information and highlighting areas for further research. Conclusion New therapeutic strategies and treatment options for RA, a chronic destructive and disabling disease, have expanded over recent years. These have been summarised in general strategic suggestions and specific management recommendations, emphasising the importance of expedient disease-modifying antirheumatic drug implementation and tight disease control. This consensus statement is in line with these fundamental principles of management. Show less
Heijde, D. van der; Landewe, R.; Guerette, B.; Roy, S.; Patra, K.; Keystone, E. 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
Heijde, D. van der; Schiff, M.; Keystone, E.; Landewe, R.; Kvien, T.; Curtis, J.; ... ; Furst, D. 2011
Objectives To determine whether MRI and conventional (clinical and laboratory) measures of inflammation can predict 3-year radiographic changes measured by the van der Heijde Sharp score in... Show moreObjectives To determine whether MRI and conventional (clinical and laboratory) measures of inflammation can predict 3-year radiographic changes measured by the van der Heijde Sharp score in patients with early rheumatoid arthritis (RA). Methods 55 patients with RA with disease duration <1 year participated in this 3-year follow-up study. Patients were evaluated at baseline, 3, 6, 12 and 36 months by swollen and tender joint count, disease activity score based on 28-joint count, erythrocyte sedimentation rate (ESR), C reactive protein, MRI measures of synovitis, bone marrow oedema and tenosynovitis of the dominant wrist, as well as conventional x-rays of the hands and wrists. Results All measures of inflammation decreased during the follow-up period. ESR, MRI synovitis and MRI bone marrow oedema were independent predictors of 3-year radiographic progression adjusted for age, sex and anti-citrullinated protein antibodies. The 1-year cumulative measures of MRI synovitis and bone marrow oedema provided an improved explanation of variation (adjusted R-2) in radiographic change compared with the baseline MRI values (adjusted R-2 = 0.32 and 0.20 vs 0.11 and 0.04, respectively). Conclusions Both baseline and 1-year cumulative measures of MRI synovitis and bone marrow oedema independently predicted 3-year radiographic progression. These results confirm that MRI synovitis and MRI bone marrow oedema precede radiographic progression in patients with early RA. Show less
Both erosions and joint space narrowing (JSN) are aspects of structural damage in rheumatoid arthritis. Most information is available on structural damage as one concept. However, the differential... Show moreBoth erosions and joint space narrowing (JSN) are aspects of structural damage in rheumatoid arthritis. Most information is available on structural damage as one concept. However, the differential aspect of the effects on bone and cartilage could yield interesting information. Comparative information of these aspects can be based only on radiographic data on erosions and JSN. Both erosions and JSN are the consequence of inflammation, and their progression is inhibited by drugs that inhibit inflammation. These two processes often occur in parallel but joints in which erosions are present show a preference for progression of erosions and, to a lesser extent, development of JSN. The reverse is true for joints with JSN present, where there is a preference for worsening of JSN over development of erosions. Repair is possible for erosions as well as JSN and this is related to the absence of inflammation and effective treatment (especially methotrexate in combination with a tumour necrosis factor blocker). 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 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
Dougados, M.; Simon, P.; Braun, J.; Burgos-Vargas, R.; Maksymowych, W.P.; Sieper, J.; Heijde, D. van der 2011
The amount of NSAID intake could be considered as a clinically relevant outcome measure in ankylosing spondylitis. The information should include at least the following: (1) the type of NSAID; (2)... Show moreThe amount of NSAID intake could be considered as a clinically relevant outcome measure in ankylosing spondylitis. The information should include at least the following: (1) the type of NSAID; (2) the dose; (3) the number of days taking NSAID during the period of interest. The objectives of this initiative were to propose both an NSAID equivalent score and a way of collecting and analysing this information in longitudinal clinical studies/trials. For the NSAID equivalent scoring system, the recommendations are (1) to refer to a scale in which 0 = no intake, 100 = 150 mg diclofenac, 1000 mg naproxen, 200 mg aceclofenac, 400 mg celecoxib, 600 mg etodolac, 90 mg etoricoxib, 200 mg flurbiprofen, 2400 mg ibuprofen, 150 mg indometacin, 200 mg ketoprofen, 15 mg meloxicam, 400 mg phenylbutazone, 20 mg piroxicam, 20 mg tenoxicam; (2) to present the results as mean daily intake by considering the number of days on which NSAID has been taken during a period of interest. This initiative should facilitate the conduct and analysis of clinical studies/trials. Show less
