Showing papers by "Ronald F van Vollenhoven published in 2006"

The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment

Abstract: Objective To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment. Methods This was a 2-year, multicenter, double-blind, active comparator–controlled study of 799 RA patients with active disease of <3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co-primary end points at year 1 were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score. Results Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at 1 and 2 years. There was significantly less radiographic progression (P ≤ 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28-joint Disease Activity Score <2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups. Conclusion In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission.

The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial.

Abstract: Objective To examine the efficacy and safety of different rituximab doses plus methotrexate (MTX), with or without glucocorticoids, in patients with active rheumatoid arthritis (RA) resistant to disease-modifying antirheumatic drugs (DMARDs), including biologic agents. Methods A total of 465 patients were randomized into 9 treatment groups: 3 rituximab groups (placebo [n = 149], 500 mg [n = 124], or 1,000 mg [n = 192] on days 1 and 15) each also taking either placebo glucocorticoids, intravenous methylprednisolone premedication, or intravenous methylprednisolone premedication plus oral prednisone for 2 weeks. All patients received MTX (10–25 mg/week); no other DMARDs were permitted. Results Significantly more patients who received 2 500-mg or 2 1,000-mg infusions of rituximab met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 24 (55% and 54%, respectively) compared with placebo (28%; P < 0.0001). ACR50 responses were achieved by 33%, 34%, and 13% of patients, respectively (P < 0.001), and ACR70 responses were achieved by 13%, 20%, and 5% of patients (P < 0.05). Changes in the Disease Activity Score in 28 joints (−1.79, −2.05, −0.67; P < 0.0001) and moderate to good responses on the European League Against Rheumatism criteria (P < 0.0001) reflected the ACR criteria responses. Glucocorticoids did not contribute significantly to the primary efficacy end point, ACR20 response at 24 weeks. Intravenous glucocorticoid premedication reduced the frequency and intensity of first infusion–associated events; oral glucocorticoids conferred no additional safety benefit. Rituximab was well tolerated; the type and severity of infections was similar to those for placebo. Conclusion Both rituximab doses were effective and well tolerated when added to MTX therapy in patients with active RA. The primary end point (ACR20 response) was independent of glucocorticoids, although intravenous glucocorticoid premedication improved tolerability during the first rituximab infusion.

Disconnect between inflammation and joint destruction after treatment with etanercept plus methotrexate: results from the trial of etanercept and methotrexate with radiographic and patient outcomes.

Abstract: Objective To determine the relationship between disease activity and radiographic progression of joint destruction in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), those treated with etanercept, and those treated with the combination of MTX plus etanercept. Methods Baseline, 12-month, and 24-month data from the Trial of Etanercept and Methotrexate with Radiographic and Patient Outcomes database were analyzed. The dependent variable was the 1-year change in the modified Sharp/van der Heijde score (Sharp score); therefore, 2 interval changes per patient were available. Interval change in the Sharp score was modeled by time (years), treatment, disease activity, and the interaction (disease activity × treatment). Disease activity was reflected by the time-averaged Disease Activity Score (taDAS) and the time-averaged C-reactive protein (taCRP) level, which were calculated per 1-year interval. Generalized mixed linear modeling (GMLM) was used to adjust for within-patient correlation. Results GMLM confirmed a significant interaction between treatment and the taCRP level and taDAS with respect to the change in Sharp score (P = 0.012 and P = 0.03, respectively). In patients treated with MTX alone, radiographic progression increased with an increasing taCRP level or taDAS, although progression rates were low in patients whose disease was in remission and in those with low-to-moderate disease activity. This relationship was less clear in patients treated with etanercept and was absent in those who received combination therapy. Conclusion Combination therapy with MTX plus etanercept uncouples the classic relationship between disease activity and radiographic progression in patients with RA.

Why are only 50% of courses of anti-tumor necrosis factor agents continued for only 2 years in some settings? Need for longterm observations in standard care to complement clinical trials.

Abstract: Volume 33, no. 12 care to complement clinical trials. standard for only 2 years in some settings? Need for longterm observations in Why are only 50% of courses of anti-tumor necrosis factor agents continued Theodore Pincus, Yusuf Yazici and Ronald van Vollenhoven http://www.jrheum.org/content/33/12/2372.citation J Rheumatol 2006;33;2372-2375 http://www.jrheum.org/alerts 1. Sign up for TOCs and other alerts http://jrheum.com/faq 2. Information on Subscriptions http://jrheum.com/reprints_permissions 3. Information on permissions/orders of reprints

Rituximab-induced long-term remission of membranous lupus nephritis

Abstract: Sir, Rituximab is a chimeric anti-CD20 monoclonal antibody that has proved to be effective in depleting B-lymphocytes in vivo [1]. We report here a case of a woman with severe membranous lupus nephritis who was treated with rituximab with significant and persistent improvement during a 3 year follow-up. She had previously failed to respond to therapy with cyclophosphamide, prednisolone, cyclosporine and mycophenolate mofetil (MMF). A 16-year-old female with SLE and nephrotic syndrome had a renal biopsy performed showing membranous lupus nephritis (WHO class V). The patient was treated with prednisolone continuously and a sustained remission of the nephrotic syndrome was achieved. At the age of 22, the patient had a relapse and a new renal biopsy showed WHO class V. The prednisolone dose was increased and i.v. cyclophosphamide was administered monthly for 6 months. A re-biopsy showed persistent WHO class V. Cyclophosphamide i.v. pulse therapy was continued but due to incomplete effect and side effects, therapy was stopped after two infusions. The patient was started on oral cyclosporine, 24-h urine albumin was 5.2 g and glomerular filtration rate (GFR) was 59 ml/min. During treatment, proteinuria decreased to approximately 1–2 g/24 h. At � 27 months (before start of rituximab) the then

Infliximab in the treatment of rheumatoid arthritis

Abstract: Rheumatoid arthritis is a chronic inflammatory systemic autoimmune disorder characterized by symmetric inflammation of synovial joints, leading to progressive erosion of cartilage and bone. Tumor necrosis factor-α antagonists have set a new therapeutic standard for rheumatoid arthritis. Tumor necrosis factor-α blocking agents, including infliximab, etanercept and adalimumab, have demonstrated substantial improvement in signs and symptoms, disability and quality of life, while significantly inhibiting joint damage in early and long-standing rheumatoid arthritis. The focus of this article will be the role of infliximab in the treatment of rheumatoid arthritis.