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Abatacept for the treatment of rheumatoid arthritis: A review.

ABSTRACT: Rheumatoid arthritis (RA) is a chronic, inflammatory disease affecting synovial joints. Patients with persistent, active disease have traditionally been treated with disease-modifying antirheumatic drugs (DMARDs) (eg, methotrexate) or biologic agents (eg, tumor necrosis factor [TNF] antagonists). However, patients may discontinue these treatments due to toxicity, infection, or lack of efficacy. Two additional biologic therapies-rituximab and abatacept-are currently available for TNF-antagonist inadequate responders. Abatacept is also indicated for inadequate responders to traditional DMARDs.The aims of this review was to provide an overview of the issues surrounding the treatment of RA patients experiencing inadequate responses to current treatment and to discuss the current and future impact of abatacept on the RA treatment armamentarium.The MEDLINE, EMBASE, and BIOSIS databases were searched (search dates: January 1, 2000-September 19, 2007) using the terms abatacept or CTLA-4 or Orencia with rheumatoid arthritis. Full text articles in English were selected for relevance, and only articles presenting primary clinical trial data from randomized, placebo-controlled, clinical trials of abatacept were included. This review focused on the Phase III trials of abatacept in methotrexate and/or TNF-antagonist inadequate responders, as these trials had the largest number of patients and the longest study durations.The literature search initially yielded 848 papers. A total of 12 articles fulfilled the inclusion criteria. Abatacept is a novel agent that has been reported to reduce the signs and symptoms of RA in patients with active RA with an inadequate response to DMARDs and/or TNF-antagonist treatment. In both of these patient populations, treatment with abatacept was found to provide clinically meaningful health-related quality-of-life benefits, such as improvements in physical function, activity limitation, sleep, and fatigue. Abatacept was reported to have a consistent safety and tolerability profile, with a low rate (3.5%-4.2%) of discontinuation due to adverse events.The efficacy and tolerability data from Phase III clinical trials suggest that abatacept is an effective and generally well tolerated treatment option for RA patients with an inadequate response to methotrexate and/or TNF antagonists.

SUBMITTER: Kaine JL

PROVIDER: S-EPMC3969965 | biostudies-other | 2007 Nov

REPOSITORIES: biostudies-other

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Abatacept for the treatment of rheumatoid arthritis: A review.

Kaine Jeffrey L JL

Current therapeutic research, clinical and experimental 20071101 6

<h4>Background</h4>Rheumatoid arthritis (RA) is a chronic, inflammatory disease affecting synovial joints. Patients with persistent, active disease have traditionally been treated with disease-modifying antirheumatic drugs (DMARDs) (eg, methotrexate) or biologic agents (eg, tumor necrosis factor [TNF] antagonists). However, patients may discontinue these treatments due to toxicity, infection, or lack of efficacy. Two additional biologic therapies-rituximab and abatacept-are currently available f ...[more]

PMID: 24692770

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Project description:In 15 patients with rheumatoid arthritis the baseline expression (t=0) of type I IFN-regulated genes was determined in peripheral blood cells (PAXgene) using cDNA-microarrays and compared to levels one month after (t=1) anti-TNF treatment (infliximab). Therefore, we used 43K cDNA microarrays from the Stanford Functional Genomics Facility (http://microarray.org/sfgf/) printed on aminosilane-coated slides containing ~20.000 unique genes. Only one batch of arrays was used for all experiments. First DNA spots were UV-cross linked to the slide using 150-300 mJoules. Sample preparation and microarray hybridization were performed as described previously (1,2). Data storage and filtering was performed using the Stanford Microarray Database (http://genome-www5.stanford.edu//) as described previously. 1. van der Pouw Kraan TC, Wijbrandts CA, van Baarsen LG, Voskuyl AE, Rustenburg F, Baggen JM et al.: Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients. Ann Rheum Dis 2007, 66: 1008-1014. 2. van der Pouw Kraan TC, van Baarsen LG, Rustenburg F, Baltus B, Fero M, Verweij CL: Gene expression profiling in rheumatology. Methods Mol Med 2007, 136: 305-327. Abbreviations: - Bnrs are the different patients analyzed - PAX or Paxgene indicates the total RNA was isolated from peripheral blood obtained in PAXgene tubes - CRS: common reference sample: We made a common reference that consisted of a mixture of mRNAs isolated from 11 different cell lines (Perou CM, Jeffrey SS, van de RM et al. Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc Natl Acad Sci U S A. 1999; 96:9212-9217) supplemented with RNA from rheumatoid synovial tissue, fibroblasts, and activated peripheral blood mononuclear cells (PBMCs). - PMT: photomultiplier tube: the sensitivity/intensity of the scanner can be adjusted to prevent spot saturation. Compound Based Treatment: anti-TNF (infliximab)

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Abatacept for the treatment of rheumatoid arthritis: A review.

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Abatacept for the treatment of rheumatoid arthritis: A review.

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