Rheumatoid Arthritis: Díaz-Borjón A

Díaz-Borjón A. · Department of Medicine, Division of Rheumatology, Hospital Angeles Lomas, Huixquilucan, Estado de México, Mexico. · Drugs Aging. · Pubmed #19476397 No free full text.

Abstract: Treatment strategies in the management of rheumatoid arthritis (RA) have significantly changed in the past decade. The early use of disease-modifying antirheumatic drugs (DMARDs) is the basis of this new treatment strategy. Because these agents alter the natural disease course of RA, early aggressive intervention results in better outcomes with respect to future structural damage and disability. The arrival of the 'biologic agents' era in rheumatology has further improved the therapeutic options in patients with RA. A significant portion of individuals with this ailment are elderly, with approximately one-third of patients experiencing their first symptoms after the age of 60 years. Yet, many elderly patients with RA do not receive optimal treatment. Although the reasons for this have not been completely defined, it seems clinicians are reluctant to use DMARDs in the elderly because of uncertainty regarding their efficacy and safety in this population. The aging process is associated with important changes in drug pharmacokinetics and pharmacodynamics. It appears that the former, mainly through decreased renal clearance, is responsible for an increased incidence of adverse effects with some DMARDs. The old are also more susceptible to infection than the young, making prevention of infectious disease through vaccination of particular importance; however, healthcare professionals should be aware that some DMARDs, including biologic agents, may interfere with responses to vaccination. The available data, although limited, suggest that DMARDs, including some biologic agents, are similarly effective in the old and the young, while maintaining very good adverse effect profiles. Therefore, the elderly with RA should not be excluded from receiving optimal treatment with these medications. At the same time, clinicians must be aware of the possible increased risk of drug toxicities, recognize the need to adjust therapy to match individual patient characteristics (i.e. renal function, co-morbidities, concomitant medication use or polypharmacy), and use the lowest possible effective dosage. This review describes the special considerations to be taken into account when administering conventional (synthetic) or biologic DMARDs to elderly patients with RA.

Llorente L, Richaud-Patin Y, Díaz-Borjón A, Alvarado de la Barrera C, Jakez-Ocampo J, de la Fuente H, Gonzalez-Amaro R, Diaz-Jouanen E. · Department of Immunology and Rheumathology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City, Mexico. · Joint Bone Spine. · Pubmed #10773966 No free full text.

Abstract: BACKGROUND: Multidrug resistance (MDR) is characterized by overexpression of P-glycoprotein, a pump molecule that decreases intracellular drug concentrations by increasing drug efflux from cells. OBJECTIVE: To look for correlations between clinical status and P-glycoprotein activity and/or TNF-alpha mRNA levels in patients with rheumatoid arthritis. METHODS: Sixteen patients were studied. Based on response to therapy, eight were refractory and eight nonrefractory to treatment. Findings were compared to those in 24 healthy controls. Flow cytometry was used to evaluate P-glycoprotein activity in peripheral blood mononuclear cells isolated by gradient centrifugation and incubated with the P-glycoprotein substrate daunorubicin. TNF-alpha mRNA levels were determined using quantitative PCR. RESULTS: Patients with rheumatoid arthritis showed an increased number of lymphocytes with high P-glycoprotein activity (p = 0.0001) as compared to the normal controls. P-glycoprotein activity was higher in the refractory than in the non-refractory patient subgroup (p = 0.006). Also, TNF-alpha mRNA levels were markedly higher in the refractory subgroup than in the nonrefractory subgroup, and were undetectable in the normal controls. CONCLUSIONS: Enhanced P-glycoprotein activity may be closely related to an unfavorable clinical course and a poor response to treatment. Increased TNF-alpha expression and chronic exposure to various drugs, including glucocorticoids, may contribute to increase P-glycoprotein activity. Both high P-glycoprotein activity and excessive amounts of TNF-alpha seem associated with poor outcome in rheumatoid arthritis.