tacrolimus and Arthritis--Psoriatic

Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory disorders of unknown etiology characterized by a wide range of abnormalities of the immune system that may compromise the function of several organs, such as kidney, heart, joints, brain and skin. Corticosteroids (CCS), synthetic and biologic immunosuppressive agents have demonstrated the capacity to improve the course of autoimmune diseases. However, a significant number of patients do not respond or develop resistance to these therapies over time. P-glycoprotein (P-gp) is a transmembrane protein that pumps several drugs out of the cell, including CCS and immunosuppressants; thus, its over-expression or hyper-function has been proposed as a possible mechanism of drug resistance in patients with autoimmune disorders. Recently, different authors have demonstrated that P-gp inhibitors, such as cyclosporine A (CsA) and its analogue Tacrolimus, are able to reduce P-gp expression and or function in SLE, RA and PsA patients. These observations suggest that P-gp antagonists could be adopted to revert drug resistance and improve disease outcome. The complex inter-relationship among drug resistance, P-gp expression and autoimmunity still remains elusive.

Topics: Adrenal Cortex Hormones; Arthritis, Psoriatic; Arthritis, Rheumatoid; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cyclosporine; Drug Resistance; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Tacrolimus

Immunomodulatory agents represent a unique group of therapies that are not biologics and have relatively specific, noncytotoxic effects on the immune system. Cyclosporine has been the most widely tested of the immunomodulatory agents and shown efficacy in a variety of autoimmune diseases as well as monotherapy in established rheumatoid arthritis. FK-506 and rapamycin, agents similar to cyclosporine, are being tested in human transplantation, with only arthritis studies having been done in animals. Tilomisole, imuthiol, and mycophenolate mofetil have been studied in limited rheumatoid arthritis trials with positive effects. Although more specific and with manageable short-term side effects, this group of therapies requires more studies to establish their efficacy and long-term safety.

Topics: Arthritis, Psoriatic; Arthritis, Rheumatoid; Clinical Trials as Topic; Cyclosporine; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Polyenes; Sirolimus; Tacrolimus

Psoriasis, a disease of unknown etiology, is in some patients severe, extremely debilitating, and unresponsive to conventional therapies, including UV-B, oral psoralen with long-wave UV radiation in the A range (PUVA), oral retinoids, and methotrexate. We report the results from our study of seven patients with refractory psoriasis who were treated with the new immunosuppressive drug, tacrolimus (FK 506).. All seven patients showed a dramatic resolution of psoriasis that remained in remission as long as they received full-dose therapy. Serial skin biopsy specimens demonstrated a rapid disappearance of the inflammatory infiltrate and a slower resolution of the epidermal changes. Tacrolimus was well tolerated during the 5.5 to 14 months of observation. Side effects, including nephrotoxicity and hypertension, were controlled by appropriate modification of drug dosage.. Tacrolimus, a new immunosuppressive agent, is effective in treating patients with severe recalcitrant psoriasis. The mechanism of its action in psoriasis is unknown, but it may be related to its ability to modulate immune function. Further studies will establish criteria for patient selection and drug dosage, to maximize efficacy of this agent in psoriasis, while minimizing its toxicity.

Topics: Administration, Oral; Adult; Arthritis, Psoriatic; Blood Urea Nitrogen; Creatinine; Female; Follow-Up Studies; Heart Transplantation; Humans; Liver Transplantation; Male; Middle Aged; Psoriasis; Remission Induction; Severity of Illness Index; Tacrolimus