Rheumatoid Arthritis: Stern RL

Fleischmann R, Iqbal I, Stern RL. · University of Texas Southwestern Medical Centre at Dallas, USA. · Expert Opin Pharmacother. · Pubmed #16370926 No free full text.

Abstract: Tacrolimus is an immunosuppressive drug that has been used widely in organ transplantation and topically for atopic dermatitis. Tacrolimus exerts its immunosuppressive effects by the inhibition of calcineurin, leading to interference with T-cell activation. As T-cell activation plays a major role in the pathogenesis of rheumatoid arthritis, there has been an interest in the use of tacrolimus for the treatment of rheumatoid arthritis. The pharmacological properties of tacrolimus have the potential of suppressing the production of inflammatory cytokines, improvement of joint inflammation, improvement of bone and cartilage destruction, improvement of functional status and relief from arthritic pain. This article reviews the pharmacodynamics, pharmacokinetics, clinical efficacy, safety and role of tacrolimus in the treatment of rheumatoid arthritis.

Fleischmann RM, Iqbal I, Stern RL. · University of Texas Southwestern Medical Center, 5939 Harry Hines Boulevard, Suite 400, Dallas, Texas 75235-5360, USA. · Expert Opin Drug Saf. · Pubmed #15335295 No free full text.

Abstract: The treatment of rheumatoid arthritis (RA) has changed dramatically over the past 15 years with the realisation that earlier, aggressive therapy limits progression. There is evidence that biological response modifiers (BRMs), which target specific cytokines such as TNF-alpha and IL-1, are more effective than traditional disease-modifying antirheumatic drugs (DMARDs), especially in combination with methotrexate. Four therapies are approved for use in RA; three target TNF-alpha (etanercept [Enbrel, Amgen Inc.], infliximab [Remicade, Centocor Inc.], and adalimumab [Humira, Abbott]), and one targets IL-1 (anakinra [Kineret, Amgen Inc.]). It is clear from both the clinical trials and postmarketing reports that all four agents have a different safety profile compared with traditional DMARDs. There are several areas of concern with the use of the BRMs, which include serious and opportunistic infections, malignancy/lymphoma, congestive heart failure, demyelination, injection/infusion reactions, development of autoantibodies and lupus-like disease. It is important to be fully aware of the safety profile and differences between BRMs in order to use them appropriately.

Fleischmann RM, Stern RL, Iqbal I. · University of Texas Southwestern Medical Center at Dallas, Radiant Research - Dallas, 5939 Harry Hines Boulevard, Suite 400, Dallas, TX 75235-5360, USA. · Mod Rheumatol. · Pubmed #17029055 No free full text.

Abstract: Recent advances in the understanding of the pathophysiology, aggressive treatment, and early detection of rheumatoid arthritis (RA) have changed the clinical, pathologic, and functional outcomes in patients with RA. Early aggressive treatment of RA has now become the norm in clinical practice rather than the use of the traditional pyramid approach of the last half of the twentieth century. Early treatment with monotherapy of traditional disease-modifying antirheumatic drugs (DMARDs) or biologics, combination traditional DMARD therapy and, especially, combination of biologic therapy and methotrexate, have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic, and functional outcomes not seen previously. For the individual patient, we still cannot determine which medication or combination of medications will give the most complete response. There have been a number of recent, well-designed clinical trials that have tried to answer this question. Herein we review the evidence-based medicine that addresses these issues.