Phenotype differences in HLA-b27 positive versus negative patients with ankylosing spondylitis treated with tumor necrosis factor alpha inhibitors

摘要

The human leukocyte antigen (HLA)-B27 is one of the strongest known genetic factorsassociated with the development of ankylosing spondylitis (AS), but approximately10% of AS patients are HLA-B27 negative. The aim of this study was to compareclinical features and response to tumor necrosis factor-alpha inhibitor (TNF-α inhibitor)therapy in HLA-B27 positive and negative patients with AS. This retrospective analysisincluded AS patients treated with TNF-α inhibitor for at least 12 weeks in two referralcenters for biologic therapy in Vojvodina province, Serbia. Clinical and demographicparameters were compared between HLA-B27 positive and negative patients. Data from59 patients (59.32% male) were collected: 49 (83.05%) were HLA-B27 positive and 10 (16.95%) HLA-B27 negative. HLA-B27-positive patients showed higher familyaggregation (49% vs. 10%; p=0.033) compared with those who were HLA-B27negative. In contrast, HLA-B27 negative patients showed a higher prevalence ofperipheral arthritis (49% vs. 90%; p =0.032) and longer diagnosis delay (8.42 vs. 5.73years; p=0.016) but there were no differences regarding dactylitis, enthesitis, uveitis orinflammatory bowel disease (IBD). Also, no differences were observed between HLAB27-positive and negative patients regarding disease activity prior to TNF-α-inhibitortherapy. All 59 patients who participated in the study has been administered at least oneTNF-α inhibitor. The mean age at introduction of TNF-α inhibitor as well as meandisease duration from diagnosis until start of TNF-α inhibitor were similar betweengroups. HLA-B27 positive patients had a significantly longer drug survival time for firstbiologics (49.06±29.22 months), whereas HLA-B27 negative received it for 24.8±12.25months (p<0.0000). 4/49 HLA-B27 positive (8.2%) and 1/10 HLA-B27 negativepatients (10%) fail to demonstrate efficacy in AS (primary or secondary treatmentfailure) with no difference between groups. One HLA-B27 positive patient on etanerceptdeveloped IBD. All 6 non-responders switched to second TNF-α inhibitor and showed agood clinical response. In our cohort, presence of HLA-B27 was related to greaterfamily occurrence, shorter diagnosis delay and lower peripheral arthritis rate. Moreover,HLA-B27 positive patients demonstrated significantly longer drug survival time for thefirst biologic then HLA-B27 negative, but non-response rate was similar betweengroups.