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A novel predictor of clinical response to methotrexate in patients with rheumatoid arthritis: a pilot study of in vitro T cell cytokine suppression.| Autores: | Nigil Haroon, Rajni Srivastava, Ramnath Misra, Amita Aggarwal | | Língua: | Eng. | | Data: | 05-06-2008 | | Jornal: | The Journal of rheumatology
(0315-162X)
| | Release: | J Rheumatol. 2008 Jun;35(6):975-8 | |
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Abstract:
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OBJECTIVE:
Methotrexate (MTX) is an important drug for treatment of rheumatoid arthritis; however, there is variation in the clinical response. MTX inhibits T cell cytokine production, with significant interindividual variability in the dose required. We investigated if the variability in clinical response was related to variability in the in vitro assay. METHODS:Patients with disease modifying antirheumatic drug-naive, active RA [1982 American College of Rheumatology (ACR) criteria] seen from September 2005 through January 2006 were enrolled. MTX was started at 10 mg/week and increased monthly by 2.5 mg/week. Baseline whole-blood cultures were set up with anti-CD3, anti-CD28, and increasing doses of MTX. Supernatants were harvested at 96 hours and tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin 10 (IL-10) concentrations were estimated by ELISA. The dose of MTX (ID50) required for 50% suppression of production of cytokines and the change in Disease Activity Score-28 (DeltaDAS) at 4 months were noted.
RESULTS:
T cell stimulation resulted in significant increase in cytokine release, and addition of MTX led to a dose-dependent suppression of all 3 cytokines. There was significant negative correlation of DeltaDAS with ID50 values for TNF-alpha (R = -0.62, p < 0.01) and IFN-gamma (R = -0.43, p = 0.04). At 4 months, EULAR moderate and ACR 20% responses were achieved by 13 and 16 patients, respectively. EULAR moderate response could be predicted using ROC curves for TNF-alpha (sensitivity 93%, specificity 86%) and IFN-gamma (60% specificity, 71% sensitivity). ACR response was correctly predicted in 14 of 16 ACR 20% responders and in all ACR 50% and ACR 70% responders.
CONCLUSION:
An in vitro TNF-alpha suppression assay may help predict clinical response to MTX in RA.
| | Copyright: | The Journal of rheumatology
Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. | | Full text: |  EBSCO - HTML (necessita a subscrição) | | |
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Artigos de outros especialidades: Dermatologia, Cirurgia Pediátrica, Microbiologia Clinica, Hematologia, Ortopedia e traumatologia, Otorrinolaringologia, Neurologia, Cirurgia Plástica, Cirurgia torácica, Oftalmologia, Urologia, Neurofisiologia Clinica |
