Adalimumab: 8 Years of Experience in Rheumatoid Arthritis
Adalimumab: 8 Years of Experience in Rheumatoid Arthritis
Rheumatoid arthritis is the most common autoimmune inflammatory arthritis. TNF-α has a pivotal role in its pathogenesis. Adalimumab was the first fully human antibody against TNF-α to be approved for active rheumatoid arthritis. Its pharmacological characteristics, clinical efficacy, effectiveness and safety are discussed in this article. Based on the summarized studies, adalimumab was shown to be effective in patients with active disease. Its beneficial effect can start as early as 1 week after the first dose, and be maintained in responders for up to 5 years. Adalimumab is generally well tolerated. The most common adverse event is injection site reactions. There is no increased rate of serious adverse events in trials, but serious infections, such as tuberculosis, have been reported in larger observational studies and remain a concern to screen and watch for.
Rheumatoid arthritis (RA) is the most common chronic autoimmune inflammatory arthritis, with a prevalence of approximately 1%, with women being affected twice as often as men. The pathogenesis of RA involves an overexpression of many inflammatory cytokines, including TNF-α, certain other interleukins (ILs) and proteinases. This results in the formation and perpetuation of an inflammatory synovitis that may lead to cartilage and bone destruction, and most patients will have evidence of joint erosions in the first year of the disease. The progression of RA leads to a variety of characteristic signs and symptoms, including pain and swelling of the synovial joints, constitutional symptoms and extra-articular involvement. RA can ultimately lead to functional decline and disability, with reduced quality of life and premature mortality, causing a great economic impact to society. The objective of RA treatment is to control the clinical symptoms and slow or stop the radiographic progression and structural damage to improve function and quality of life. Traditional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, remain the basis of RA therapy, and should be initiated early in the course of the disease. In the last few decades, advances in the understanding of the pathogenesis of RA and the inflammatory cascade led to the introduction of biologic response modifiers (BRMs), also known as biologic DMARDs, a class of medication that can further improve clinical outcomes. These agents work by selective blockade of certain molecules of the inflammatory cascade, resulting in a significant reduction of inflammation. They are mostly used in conjunction with methotrexate for patients who fail with, or are unable to tolerate, traditional DMARDs. Available BRMs include TNF-α inhibitors (infliximab, etanercept, adalimumab, golimumab and certolizumab), which are currently the most commonly used biologic agents. Other BRMs are anakinra (IL-1 receptor antagonist), abatacept (cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin), rituximab (anti-CD20 antibody) and tocilizumab (IL-6 inhibitor). Newer BRM agents are continually being evaluated. This article focuses on adalimumab, a commonly used TNF-α inhibitor that has been on the market for 8 years.
Abstract and Introduction
Abstract
Rheumatoid arthritis is the most common autoimmune inflammatory arthritis. TNF-α has a pivotal role in its pathogenesis. Adalimumab was the first fully human antibody against TNF-α to be approved for active rheumatoid arthritis. Its pharmacological characteristics, clinical efficacy, effectiveness and safety are discussed in this article. Based on the summarized studies, adalimumab was shown to be effective in patients with active disease. Its beneficial effect can start as early as 1 week after the first dose, and be maintained in responders for up to 5 years. Adalimumab is generally well tolerated. The most common adverse event is injection site reactions. There is no increased rate of serious adverse events in trials, but serious infections, such as tuberculosis, have been reported in larger observational studies and remain a concern to screen and watch for.
Introduction
Rheumatoid arthritis (RA) is the most common chronic autoimmune inflammatory arthritis, with a prevalence of approximately 1%, with women being affected twice as often as men. The pathogenesis of RA involves an overexpression of many inflammatory cytokines, including TNF-α, certain other interleukins (ILs) and proteinases. This results in the formation and perpetuation of an inflammatory synovitis that may lead to cartilage and bone destruction, and most patients will have evidence of joint erosions in the first year of the disease. The progression of RA leads to a variety of characteristic signs and symptoms, including pain and swelling of the synovial joints, constitutional symptoms and extra-articular involvement. RA can ultimately lead to functional decline and disability, with reduced quality of life and premature mortality, causing a great economic impact to society. The objective of RA treatment is to control the clinical symptoms and slow or stop the radiographic progression and structural damage to improve function and quality of life. Traditional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, remain the basis of RA therapy, and should be initiated early in the course of the disease. In the last few decades, advances in the understanding of the pathogenesis of RA and the inflammatory cascade led to the introduction of biologic response modifiers (BRMs), also known as biologic DMARDs, a class of medication that can further improve clinical outcomes. These agents work by selective blockade of certain molecules of the inflammatory cascade, resulting in a significant reduction of inflammation. They are mostly used in conjunction with methotrexate for patients who fail with, or are unable to tolerate, traditional DMARDs. Available BRMs include TNF-α inhibitors (infliximab, etanercept, adalimumab, golimumab and certolizumab), which are currently the most commonly used biologic agents. Other BRMs are anakinra (IL-1 receptor antagonist), abatacept (cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin), rituximab (anti-CD20 antibody) and tocilizumab (IL-6 inhibitor). Newer BRM agents are continually being evaluated. This article focuses on adalimumab, a commonly used TNF-α inhibitor that has been on the market for 8 years.
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