Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial.

Objective: Tumor necrosis factor (TNF) is an important proinflammatory cytokine that mediates inflammatory synovitis and articular matrix degradation in rheumatoid arthritis (RA). We investigated the ability of adalimumab, a human anti-TNF monoclonal antibody, to inhibit the progression of structural joint damage, reduce the signs and symptoms, and improve physical function in patients with active RA receiving concomitant treatment with methotrexate (MTX).

Methods: In this multicenter, 52-week, double-blind, placebo-controlled study, 619 patients with active RA who had an inadequate response to MTX were randomized to receive adalimumab 40 mg subcutaneously every other week (n = 207), adalimumab 20 mg subcutaneously every week (n = 212), or placebo (n = 200) plus concomitant MTX.

Once-weekly administration of 50 mg etanercept in patients with active rheumatoid arthritis: results of a multicenter, randomized, double-blind, placebo-controlled trial.

Objective: To evaluate the safety, efficacy, and pharmacokinetics of 50 mg etanercept administered subcutaneously once weekly in adult patients with active rheumatoid arthritis (RA).

Methods: Four hundred twenty RA patients were randomized to receive, in a blinded manner, the study drug for up to 16 weeks: 214 patients received 50 mg etanercept once weekly, 153 received 25 mg etanercept twice weekly, and 53 received placebo for 8 weeks followed by 25 mg etanercept twice weekly for 8 weeks. Efficacy and safety were assessed at weeks 8 and 16.

Appropriate and effective rheumatoid arthritis control: role of TNF antagonists.

There are several unmet needs for the appropriate and effective control of rheumatoid arthritis (RA), namely rapid onset of action; effectiveness in disease-modifying antirheumatic drug (DMARD)-resistant disease, including improvements in signs and symptoms, disability, quality of life and radiographic progression; sustainability of response; and a good risk/benefit ratio. Tumor necrosis factor (TNF) antagonists appear to address these needs and consequently have set a new therapeutic standard for the treatment of RA and have made it possible for rheumatologists to target remission as a primary therapeutic goal.

Mutant p53 in bone marrow stromal cells increases VEGF expression and supports leukemia cell growth.

Objective: Genetic alterations, including p53 mutations, have been identified in the stroma of solid tumors and are thought be involved in the induction of tumor growth and metastasis. We tested the hypothesis that somatic molecular alterations in bone marrow stromal cells provide a favorable growth environment for leukemic cells.

Materials And Methods: We established an in vitro model consisting of stroma expressing mutant p53 (Cys135Ser) to study its ability to support growth of cells from a pre-B acute lymphoblastic leukemia (ALL) cell line.

Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor necrosis factor-alpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate: a pilot study.

Background: Because traditional therapies for rheumatoid arthritis (RA) such as methotrexate (MTX) do not produce an adequate response in many patients, newer therapies that block the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) are increasingly being used in combination with MTX.

Objective: This study evaluated the efficacy, pharmacokinetics, and safety profile of adalimumab, a fully human anti-TNF alpha monoclonal antibody, when added to continuing MTX therapy.

Methods: This Phase I, randomized, dose-titration study consisted of a 4-week, double-blind, placebo-controlled treatment phase and a 26-month, open-label continuation phase.

Therapeutic implications for interferon-alpha in arthritis: a pilot study.

Objective: To evaluate the therapeutic potential of interferon-a (IFN-a) in osteoarthritis (OA) and rheumatoid arthritis (RA) by examining regulation of cytokine antagonist expression.

Methods: Expression of interleukin 1 receptor antagonist (IL-1Ra) and soluble tumor necrosis factor receptor (sTNFR) was examined by ELISA in cells from freshly isolated synovial fluids (SF) and synovial tissues (ST) from patients with OA or RA, either left untreated or treated with IFN-a. Single (7) and paired (5) SF and ST cells from OA and RA patients were examined.

Abandoned therapies and unpublished trials in rheumatoid arthritis.

The capability of selectively targeting pathogenic elements of disease with biologic therapies has created a new therapeutic repertoire. Although a substantial number of biologic agents have been developed for treatment of rheumatoid arthritis, few have been approved for use. Most of the agents have failed to reach the approval stage because of inadequate clinical benefit.

Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management.

Cases of active tuberculosis have been reported worldwide with the use of therapeutic agents that inhibit tumour necrosis factor (TNF) alpha. TNFalpha has a central role in mycobacterial infection and disease. Accordingly, progression of recently acquired tuberculosis infection or reactivation of remotely acquired infection should be expected with the use of anti-TNF agents.

Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial.

Objective: To evaluate the efficacy and safety of adalimumab (D2E7), a fully human monoclonal tumor necrosis factor alpha antibody, in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite treatment with MTX.

Methods: In a 24-week, randomized, double-blind, placebo-controlled study, 271 patients with active RA were randomly assigned to receive injections of adalimumab (20 mg, 40 mg, or 80 mg subcutaneously) or placebo every other week while continuing to take their long-term stable dosage of MTX. The primary efficacy end point was the American College of Rheumatology criteria for 20% improvement (ACR20) at 24 weeks.

The relationship of serum infliximab concentrations to clinical improvement in rheumatoid arthritis: results from ATTRACT, a multicenter, randomized, double-blind, placebo-controlled trial.

Objective: To investigate the relationship between serum concentrations of infliximab, a monoclonal anti-tumor necrosis factor alpha antibody, and clinical improvement from infliximab therapy for rheumatoid arthritis (RA).

Methods: Multiple blood samples were obtained from each of 428 subjects with active RA who were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (ATTRACT [Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy]) evaluating the clinical efficacy and safety of infliximab therapy. Serum levels of infliximab were measured by enzyme-linked immunosorbent assay.

Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes.

Objective: To compare the clinical and radiographic outcomes in patients with rheumatoid arthritis (RA) who received monotherapy with either etanercept or methotrexate (MTX) for 2 years and to assess the safety of this therapy.

Methods: In the Enbrel ERA (early rheumatoid arthritis) trial, 632 patients with early, active RA were randomized to receive either twice-weekly subcutaneous etanercept (10 mg or 25 mg) or weekly oral MTX (mean dosage 19 mg per week) for at least 1 year in a double-blind manner. Following the blinded phase of the trial, 512 patients continued to receive the therapy to which they had been randomized for up to 1 additional year, in an open-label manner.

CD4 coating, but not CD4 depletion, is a predictor of efficacy with primatized monoclonal anti-CD4 treatment of active rheumatoid arthritis.

Objective: Double blind studies were conducted with the anti-CD4 monoclonal antibody (Mab) keliximab in patients with active, stable rheumatoid arthritis (RA), to confirm preliminary evidence of efficacy and safety from open. uncontrolled studies.

Methods: We enrolled 136 and 186 patients into 2 consecutive, randomized, double blind trials, with similar populations [apart from inclusion of disease modifying antirheumatic drug (DMARD)-naïve patients in Study 2].