Rheumatoid Arthritis: Refractory to Infliximab, a Tumor Necrosis Factor Inhibitor (original) (raw)
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Infliximab in the treatment of rheumatoid arthritis
Aging Health, 2006
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.
Infliximab treatment of rheumatoid arthritis
Rheumatic Disease Clinics of North America, 2004
The characterization of tumor necrosis factor a (TNF-a) and other cytokines as molecular entities in the mid-1980s provided experimental tools for evaluating their role in the pathogenesis of rheumatoid arthritis (RA) [1]. The accumulating evidence that TNF-a played a unique role in regulating the cytokine network and other inflammatory pathways and therefore was an attractive therapeutic target met with considerable skepticism at the time [2,3]. The first trial of TNF-blockade-performed by our group in London in 1992-1993 with favorable results-dispelled these concerns. It encouraged and set the scene for the development of the three anti-TNF biodrugs that have established a place in the contemporary options available for the treatment of rheumatoid arthritis and other immune-inflammatory diseases. Proof of principle trials The initial experience of the treatment of RA with infliximab (Remicade, originally known as cA2) was planned in an open-label phase I/II trial conducted in 1992-1993 [4]. A dose of 20 mg/kg was derived by extrapolation of the dose of a monoclonal anti-TNF antibody used in a study in murine collagen-induced arthritis in which anti-inflammatory effects and protection of cartilage and bones
Tumor necrosis factor (TNF) inhibitor therapy for rheumatoid arthritis
Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, 2008
Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by inflammation involving large and small joints. Systemic manifestations as well as involvement of paraoral tissues contribute to morbidity. Tumor necrosis factor (TNF) plays a central role in RA by amplifying inflammation in multiple pathways that lead to joint destruction. Tumor necrosis factor inhibitors were first licensed for clinical use in 1998; 3 have been approved for the treatment of RA: Iinfliximab, etanercept, and adalimumab. The purpose of this paper is to review the pathogenesis of RA, the state of the art of therapy, and the most current information on the safety and efficacy of TNF inhibitors for treatment of RA.
Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis
New England Journal of Medicine, 2000
Background Neutralization of tumor necrosis factor a (TNFa) for three to six months reduces the symptoms and signs of rheumatoid arthritis. However, the capacity of this approach to effect a more sustained benefit and its effect on joint damage are not known. Methods We treated 428 patients who had active rheumatoid arthritis despite methotrexate therapy with placebo or infliximab, a chimeric monoclonal antibody against TNFa , in intravenous doses of 3 or 10 mg per kilogram of body weight every 4 or 8 weeks in combination with oral methotrexate for 54 weeks. We assessed clinical responses with use of the criteria of the American College of Rheumatology, the quality of life with a health-status questionnaire, and the effect on joint damage radiographically. Results The combination of infliximab and methotrexate was well tolerated and resulted in a sustained reduction in the symptoms and signs of rheumatoid arthritis that was significantly greater than the reduction associated with methotrexate therapy alone (clinical response, 51.8 percent vs. 17.0 percent; P<0.001). The quality of life was also significantly better with infliximab plus methotrexate than with methotrexate alone. Radiographic evidence of joint damage increased in the group given methotrexate, but not in the groups given infliximab and methotrexate (mean change in radiographic score, 7.0 vs. 0.6; P<0.001). Radiographic evidence of progression of joint damage was absent in infliximab-treated patients whether or not they had a clinical response. Conclusions In patients with persistently active rheumatoid arthritis despite methotrexate therapy, repeated doses of infliximab in combination with methotrexate provided clinical benefit and halted the progression of joint damage.
Current rheumatology reports, 2003
Tumor necrosis factor-alpha (TNFa) plays a central role in rheumatoid arthritis (RA) pathogenesis. There are currently three available anti-TNFa agents for the treatment of RA--adalimumab, etanercept, and infliximab. These targeted therapies have select advantages over traditional disease-modifying antirheumatic drugs (DMARDs), agents that have long been the mainstay of RA treatment. Compared with conventional DMARDs, TNFa inhibitors display a rapid onset of action and have shown a significant effect in retarding the radiographic joint destruction that often characterizes RA disease progression. Although anti-TNFa drugs represent an important advance in RA treatment, postmarketing reports of serious infections, as well as other adverse events, highlight the need for continued postmarketing vigilance with the use of these agents. This review evaluates the unique attributes of the available TNFa inhibitors, focusing specifically on recent reports providing important insight into the u...
Emerging role of anti-tumor necrosis factor therapy in rheumatic diseases
Arthritis Research & Therapy, 2002
S34 ACR = American College of Rheumatology response criteria; AOSD = adult-onset Still's disease; AS = ankylosing spondylitis; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; CRP = C-reactive protein; DMARD = disease-modifying antirheumatic drug; ESR = erythrocyte sedimentation rate; Fc = crystallizable fragment; IL = interleukin; MTX = methotrexate; PASI = Psoriasis Area and Severity Index; PGA = physician's global assessment; PsA = psoriatic arthritis; RA = rheumatoid arthritis; TNF-α = tumor necrosis factor alpha.
The European journal of health economics : HEPAC : health economics in prevention and care, 2014
The aim of this meta-analysis was to compare the efficacy and safety of infliximab-biosimilar and other available biologicals for the treatment of rheumatoid arthritis (RA), namely abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab and tocilizumab. A systematic literature review of MEDLINE database until August 2013 was carried out to identify relevant randomized controlled trials (RCTs). Bayesian mixed treatment comparison method was applied for the pairwise comparison of treatments. Improvement rates by the American College of Rheumatology criteria (ACR20 and ACR50) at week 24 were used as efficacy endpoints, and the occurrence of serious adverse events was considered to assess the safety of the biologicals. Thirty-six RCTs were included in the meta-analysis. All the biological agents proved to be superior to placebo. For ACR20 response, certolizumab pegol showed the highest odds ratio (OR) compared to placebo, OR 7.69 [95% CI 3.69-14.26], foll...