RESEARCH - A novel predictor of clinical response to MTX in patients wih RA

[Guest guest]

J Rheumatol. 2008 May 1 [Epub ahead of print]

A Novel Predictor of Clinical Response to Methotrexate in Patients

with Rheumatoid Arthritis: A Pilot Study of in Vitro T Cell Cytokine

Suppression.

Haroon N, Srivastava R, Misra R, Aggarwal A.

From the Department of Clinical Immunology, Sanjay Gandhi Postgraduate

Institute of Medical Sciences, Lucknow, India.

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.

PMID: 18464312

http://www.ncbi.nlm.nih.gov/pubmed/18464312

--

Not an MD