Contribution of patient related differences to multidrug resistance in RA

December 17, 2002

Ann Rheum Dis 2003 Jan;62(1):15-19

Contribution of patient related differences to multidrug resistance in

rheumatoid arthritis.

C, Lunt M, Brightwell H, Bradburn P, Fallow W, Lay M, Silman A,

Bruce IN.

Arthritis Research Campaign (ARC) Epidemiology Unit, University of

Manchester Medical School, Oxford Road, Manchester, M13 9PT, UK

University of Manchester Rheumatism Research Centre, Central Manchester

and Manchester Children's University Hospital Trust, Oxford Road,

Manchester, M13 4UL, UK.

BACKGROUND: There is a wide variation in responses to standard disease

modifying antirheumatic drug (DMARD) treatment in rheumatoid arthritis

(RA). Whether multidrug resistance, failure to respond to several

DMARDs, is a specific entity over and above that expected by chance

alone is unclear. OBJECTIVE: To identify patients with RA who

demonstrate a multidrug resistant phenotype and to determine what

proportion of the variance in drug responses is due to patient related

factors. METHODS: Patients with RA (1987 American College of

Rheumatology criteria) were identified from clinics at Manchester Royal

Infirmary and through the Arthritis Research Campaign National RA

Repository. The clinic records were reviewed and multidrug resistance

was defined as stopping three or more DMARDs owing to lack of efficacy

after an adequate trial of the drug. Logistic regression measured by a

random effects model was used to determine the relative contribution of

the drug and subject related differences to the multidrug resistance.

RESULTS: 265 patients (210 (79.3%) female) were studied. The mean (SD)

age and disease duration were 52.2 (12.9) and 10.7 (8.8) years,

respectively. Patients had a median (range) of 2 (1-8) DMARD courses.

Failure of at least one DMARD due to inefficacy occurred in 105 (40%)

and 13 (5%) were multidrug resistant. Overall, 35% of the variance in

drug responses was due to between-subject differences (p=0.02).

Rheumatoid factor (RF) status contributed significantly to this

(OR=2.15, 95% confidence interval (95% CI) 1.00 to 4.62) but explained

only 3% of the total variance in drug inefficacy. CONCLUSION: Multidrug

resistance occurs in an uncommon (5%) but important subgroup of patients

with RA. The between-subject variance is not fully explained by

demographics and RF status. Understanding the biological mechanisms that

contribute to multidrug resistance may suggest new therapeutic

approaches and targets in RA.

PMID: 12480663

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