Patients chosen for treatment with CSA because of severe RA

February 18, 2002

J Rheumatol 2002 Feb;29(2):271-5

Patients chosen for treatment with cyclosporine because of severe

rheumatoid arthritis are more likely to carry HLA-DRB1 shared epitope

alleles, and have earlier disease onset.

-Gay MA, Hajeer AH, -Porrua C, Dababneh A, Thomson W,

Ollier WE, Mattey DL.

Staffordshire Rheumatology Centre, Stoke-on-Trent, Staffordshire, UK.

OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA)

selected for treatment with cyclosporin A (CSA) because of severe

disease are more likely to carry HLA-DRB1 alleles encoding the conserved

" shared epitope " (SE) sequence. METHODS: The majority of patients (n =

178) were currently being treated with methotrexate (MTX), either alone

or in combination with chloroquine and/or CSA. In about 30% of patients,

treatment with CSA had been initiated because of limited response to MTX

or MTX and chloroquine. Patients were treated as clinically indicated

without knowledge of their HLA-DRB1 status. HLA-DRB1 typing was by a

reverse dot blot method. RESULTS: Patients that had been treated with

CSA were significantly more likely to carry an SE allele than patients

not treated with CSA (81.5% vs 60.5%; OR 2.9, p = 0.006). Patients with

2 SE alleles were the most likely to have been treated with CSA. Results

were still significant after correction for age, sex, and disease

duration in a logistic regression model. There was no association

between rheumatoid factor positivity and requirement for CSA therapy.

Examination of individual SE alleles by multiple logistic regression

analysis indicated that the strongest association was with presence of

HLA-DRB1**0401 (p = 0.004). The DRB1*0401/*0404 genotype provided the

greatest risk of requiring CSA treatment. Patients selected for CSA

treatment had developed RA at a significantly earlier age than those not

requiring CSA (44.4 vs 51.3 yrs; p = 0.004). CONCLUSION: Patients

requiring treatment with CSA because of severe RA were significantly

more likely to carry an SE allele than patients not requiring such

treatment. CSA treated patients were also more likely to have had

earlier age of disease onset. These data provide further evidence that

bearing the SE (particularly 2 alleles) is associated with development

of severe RA.

Recommended Posts