The role of HLA-DRB1 shared epitope alleles in predicting short-term response to leflunomide in rheumatoid arthritis
1Department of Physiology, 2Division of Rheumatology, Istanbul Faculty of Medicine, 3Division of Rheumatology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, 4Division of Rheumatology, 9 Eylul Faculty of Medicine, Izmir, 5Division of Rheumatology, Bursa State Hospital, Bursa, 6Division of Rheumatology, Cukurova University Medical School, Adana, 7Division of Rheumatology, Ankara Numune Hospital, 8Division of Rheumatology, Ankara University Medical School, Ankara, 9Division of Rheumatology, Ege University Medical School, Izmir, 10Division of Rheumatology, GATA Medical School, 11Division of Rheumatology, Baskent University Medical School, Ankara and 12Division of Rheumatology, Marmara University Medical School, Istanbul, Turkey.
Correspondence to: H. Direskeneli, Division of Rheumatology, Marmara University Hospital, Tophanelioglu Cad. 13/15, Altunizade, Istanbul, Turkey. E-mail: direskeneli{at}superonline.com
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Abstract |
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Objectives. To investigate the role of shared epitope (SE) alleles in the short–term clinical response to leflunomide for the treatment of active RA.
Methods. In an open-label, multi-centre study of 16-weeks duration, 93 patients (82% female) fulfilling ARA 1987 RA criteria were treated with leflunomide (100 mg loading dose for 3 days, then 20 mg/day as the maintenance dose). The primary efficacy criterion was the response status according to the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score-28 (DAS28) activity measure. SE determinations have been undertaken by polymerase chain reaction and sequence–specific oligonucleotide genotyping methods.
Results. The mean (S.D.) Disease Activity Score-28 (DAS28) was 5.1 (1.3) before the treatment, which was significantly decreased after 16 weeks [3.0 (1.1), P < 0.001]. According to the EULAR response criteria, 55 patients (59.1%) were classified as good responders. SE was positive in 51 (54.8%) of the patients, with 13 (13.9%) having SE homozygosity or carrying any two SE alleles. Among SE-positive patients, 68.6% (35/51) were good responders, compared with 47.6% (20/42) in SE negatives (P = 0.04). No difference was present according to SE hetero- or homozygosity (68.4 vs 69.2%). RF was also present significantly more frequently in the SE-positive group compared with negatives (78.4 vs 57.1%, P = 0.03). However, no significant difference was observed in the prevalence of RF positivity in patients with a good clinical response (72.7 vs 63.2%, P = 0.32).
Conclusions. The results suggest that HLA–DRB1 SE presence may favourably affect the outcome of leflunomide monotherapy in an unselected group of RA patients with an active disease and naive to leflunomide.
KEY WORDS: Leflunomide, Rheumatoid arthritis, Shared epitope
Submitted 24 December 2006;
revised version accepted 7 September 2007.
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