Treatment of rheumatoid arthritis: state of the art 2009

Abstract

Few, if any, areas of medical therapeutics have witnessed such dramatic changes as those that have occurred in the therapy of rheumatoid arthritis (RA) during the past two decades. Improvements in clinical trials methodologies, the introduction of no fewer than nine biologic agents with distinct mechanisms of action, and the development of better strategies for the use of such agents have all contributed to the new age in RA therapeutics. Here, we review these developments and attempt to describe the current landscape of RA therapy in terms of available treatments, agreed-upon principles of RA management, as well as some important controversies in this field. Despite the great pace at which developments are moving, a treatment-free remission for patients with RA remains an elusive goal and unmet medical needs remain. The quest for better therapies for this potentially devastating disease is still as important as ever; research in this exciting area is ongoing, and it is reasonable to hope that, during the next decade, developments will lead to improved, rationally designed, targeted therapies for RA.

Pharmacokinetics, Safety, and Tolerability of GLPG0259, a Mitogen-Activated Protein Kinase-Activated Protein Kinase 5 (MAPKAPK5) Inhibitor, Given as Single and Multiple Doses to Healthy Male Subjects

“…A considerable advance in the effective treatment of RA came from the introduction of the biologic therapeutics that neutralize cytokines or their receptors (TNFa and interleukin [IL]-6) or that inhibit cellular activation (B-cell or T-cell activation). [4,5] However, because of the high production costs, inconvenience of parenteral administration, increased risk of infections, and potential immunogenicity of biologics, there is still a need for less expensive and orally administered drugs. [4] Hence, the development of small-molecule inhibitors targeting disease-relevant signal transduction pathways is being pursued by various companies.…”

“…[4,5] However, because of the high production costs, inconvenience of parenteral administration, increased risk of infections, and potential immunogenicity of biologics, there is still a need for less expensive and orally administered drugs. [4] Hence, the development of small-molecule inhibitors targeting disease-relevant signal transduction pathways is being pursued by various companies. [6] GLPG0259 is a small-molecule inhibitor of mitogen-activated protein kinase-activated protein kinase 5 (MAPKAPK5), a kinase enzyme that plays a role in important inflammatory pathways.…”

Atacicept in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor antagonist therapy: Results of a phase II, randomized, placebo-controlled, dose-finding trial

“…The introduction of biologic agents has represented a considerable advance in the treatment of RA, but treatment-free remission is still not achieved in most patients (3). In many cases, the disease is resistant to existing therapies, or patients may be unable to continue treatment because of intolerance.…”

EFFICACY OF ETANERCEPT TREATMENT AS a SECOND TNF Α INHIBITOR IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS AND PRIMARY AND SECONDARY INEFFICIENCY OR INTOLERANCE OF INFLIXIMAB

“…В последнее время появилось немало работ, посвя-щенных оценке «выживаемости», эффективности и безо-пасности второго и даже третьего биологического препарата при ревматоидном артрите у взрослых больных [7,[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”

“…Анализ эффективности генно-инженерных препаратов у взрослых показал, что анти-ФНО ␣-терапия была пер-вым биологическим направлением в лечении пациентов со среднетяжелым и тяжелым ревматоидным артритом [7,[15][16][17][18][19]25]. Однако в клинической практике у 30% пациентов ингибиторы ФНО ␣ отменяют из-за недоста-точной эффективности или развития побочных эффектов [26].…”