The role of HLA-DRB1 shared epitope alleles in predicting short-term response to leflunomide in rheumatoid arthritis.
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.
Saruhan-Direskeneli
G
G
Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Inanc
M
M
Fresko
I
I
Akkoc
N
N
Dalkilic
E
E
Erken
E
E
Karaaslan
Y
Y
Kinikli
G
G
Oksel
F
F
Pay
S
S
Yucel
E
E
Yentür
S P
SP
Duymaz-Tozkir
J
J
Yilmaz
V
V
Inanc
N
N
Yazici
H
H
Konice
M
M
Direskeneli
H
H
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
D015415:Biomarkers; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007555:Isoxazoles; D000077339:Leflunomide