Home

Current Issue

Archives

Guidelines for Authors & Reviewers

Classified Ads

Links

Search PubMed

Subscriptions

Subscriber Registration

Guidelines for Website Users

JRheum Update Service

Contact Info

NIGIL HAROON, RAJNI SRIVASTAVA, RAMNATH MISRA, and AMITA AGGARWAL

ABSTRACT.

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-a (TNF-a), interferon-g (IFN-g), 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 (ΔDAS) 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 ΔDAS with ID₅₀ values for TNF-a (R = -0.62, p < 0.01) and IFN-g (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-a (sensitivity 93%, specificity 86%) and IFN-g (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-a suppression assay may help predict clinical response to MTX in RA. (J Rheumatol First Release May 1 2008)

Key Indexing Terms:

DRUG RESPONSE
DISEASE MODIFYING ANTIRHEUMATIC DRUGS
CYTOKINES
PROGNOSIS
PREDICTION
EARLY RHEUMATOID ARTHRITIS

From the Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Supported by a grant from Sanjay Gandhi Postgraduate Institute of Medical Sciences to Dr. Aggarwal. Ms. Srivastava is supported by funds from the Department of Science and Technology, Government of India.

N. Haroon, MD, Senior Resident; R. Srivastava, BSc, Technician; R. Misra, MD, Professor; A. Aggarwal, DM, Additional Professor.

Address reprint requests to Dr. A. Aggarwal, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India. E-mail: amita@sgpgi.ac.in

Accepted for publication January 11, 2008.