title: The role of HLA-DRB1 shared epitope alleles in predicting short-term response to leflunomide in rheumatoid arthritis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: G
authors.initials: G
authors.lastname: Saruhan-Direskeneli
authors.forename: M
authors.initials: M
authors.lastname: Inanc
authors.forename: I
authors.initials: I
authors.lastname: Fresko
authors.forename: N
authors.initials: N
authors.lastname: Akkoc
authors.forename: E
authors.initials: E
authors.lastname: Dalkilic
authors.forename: E
authors.initials: E
authors.lastname: Erken
authors.forename: Y
authors.initials: Y
authors.lastname: Karaaslan
authors.forename: G
authors.initials: G
authors.lastname: Kinikli
authors.forename: F
authors.initials: F
authors.lastname: Oksel
authors.forename: S
authors.initials: S
authors.lastname: Pay
authors.forename: E
authors.initials: E
authors.lastname: Yucel
authors.forename: S P
authors.initials: SP
authors.lastname: Yentür
authors.forename: J
authors.initials: J
authors.lastname: Duymaz-Tozkir
authors.forename: V
authors.initials: V
authors.lastname: Yilmaz
authors.forename: N
authors.initials: N
authors.lastname: Inanc
authors.forename: H
authors.initials: H
authors.lastname: Yazici
authors.forename: M
authors.initials: M
authors.lastname: Konice
authors.forename: H
authors.initials: H
authors.lastname: Direskeneli
mesh_terms: D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000939:Epitopes; D005260:Female; D005500:Follow-Up Studies; D006684:HLA-DR Antigens / Q000032:analysis / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage*; D000077339:Leflunomide; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007555:Isoxazoles; D000077339:Leflunomide