Full Text: Can Gold Therapy Be Used More Safely in Rheumatoid Arthritis? Adverse Drug Reactions Are More Likely in Patients with Nodular Disease, Independent of HLA-DR3 Status

Can Gold Therapy Be Used More Safely in Rheumatoid Arthritis? Adverse Drug Reactions Are More Likely in Patients with Nodular Disease, Independent of HLA-DR3 Status

PREETI SHAH, SIAN M. GRIFFITH, MICHAEL F. SHADFORTH, JUNE FISHER, PETER T. DAWES, KAY V. POULTON, WENDY THOMSON, WILLIAM E.R. OLLIER, and DEREK L. MATTEY

ABSTRACT.

Objective. To investigate whether features associated with severe rheumatoid arthritis (RA) are predictive of adverse drug reactions (ADR) to gold salts, independent of HLA-DR3 status.

Methods. A cohort of patients with RA (n = 41) who developed thrombocytopenia (platelets < 100 ´ 10⁶/l) or proteinuria (> 1.0 g/24 h) upon treatment with gold sodium thiomalate was identified from patient records and matched for age, sex, and disease duration with 41 RA controls treated with gold without development of ADR. A second group of 161 random RA patients that had received gold therapy for at least as long without development of an ADR was also compared. All patients were typed for HLA-DRB1, and the presence of rheumatoid factor (RF), antinuclear antibodies (ANA), and nodules before initiation of therapy was recorded. Association of clinical or genetic factors with ADR was investigated using the McNemar test and logistic regression analysis.

Results. Patients with ADR were more likely to have nodular disease than their matched controls (51.3% vs 25.6%; odds ratio, OR = 3.0, p = 0.02) and more likely to be HLA-DR3 positive (41.2% vs 17.6%; OR = 3.0, p = 0.045). No difference between the groups was found for RF or ANA. Nodular disease was associated with development of ADR independently of HLA-DR3, although a combination of both factors significantly increased the likelihood of an ADR.

Conclusion. Our data suggest that nodular disease may be a predictor of gold-induced ADR independent of HLA-DR3. (J Rheumatol 2004;31:1903-5)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
GOLD THERAPY
ADVERSE REACTIONS
HLA
NODULES

From the Staffordshire Rheumatology Centre, University Hospital of North Staffordshire NHS Trust, The Haywood, Burslem, Stoke-on-Trent, Staffordshire; and the Centre for Integrated Genomic Medical Research, Manchester University Medical School, Oxford Road, Manchester, UK.

Supported by the Haywood Rheumatism Research and Development Foundation and the Arthritis Research Campaign.

P. Shah, MRCP; S.M. Griffith, FRCP; M.F. Shadforth, FRCP; J. Fisher, SRN; P.T. Dawes, FRCP, K.V. Poulton, PhD; W. Thomson, PhD, Staffordshire Rheumatology Centre; W.E.R. Ollier, PhD, Centre for Integrated Genomic Medical Research; D.L. Mattey, PhD, Staffordshire Rheumatology Centre.

Address reprint requests to Dr. D.L. Mattey, Department of Rheumatology, Staffordshire Rheumatology Centre, The Haywood, Burslem, Stoke-on-Trent, ST6 7AG, UK. E-mail: d.l.mattey@keele.ac.uk

Submitted November 24, 2003; revision accepted April 28, 2004.