Phenotype differences in HLA-b27 positive versus negative patients with ankylosing spondylitis treated with tumor necrosis factor alpha inhibitors
The human leukocyte antigen (HLA)-B27 is one of the strongest known genetic factors associated with the development of ankylosing spondylitis (AS), but approximately 10% of AS patients are HLA-B27 negative. The aim of this study was to compare clinical features and response to tumor necrosis factor-alpha inhibitor (TNF-? inhibitor) therapy in HLA-B27 positive and negative patients with AS. This retrospective analysis included AS patients treated with TNF-? inhibitor for at least 12 weeks in two
... ast 12 weeks in two referral centers for biologic therapy in Vojvodina province, Serbia. Clinical and demographic parameters were compared between HLA-B27 positive and negative patients. Data from 59 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 family aggregation (49% vs. 10%; p=0.033) compared with those who were HLA-B27 negative. In contrast, HLA-B27 negative patients showed a higher prevalence of peripheral arthritis (49% vs. 90%; p =0.032) and longer diagnosis delay (8.42 vs. 5.73 years; p=0.016) but there were no differences regarding dactylitis, enthesitis, uveitis or inflammatory bowel disease (IBD). Also, no differences were observed between HLA-B27-positive and negative patients regarding disease activity prior to TNF-?-inhibitor therapy. All 59 patients who participated in the study has been administered at least one TNF-? inhibitor. The mean age at introduction of TNF-? inhibitor as well as mean disease duration from diagnosis until start of TNF-? inhibitor were similar between groups. HLA-B27 positive patients had a significantly longer drug survival time for first biologics (49.06?29.22 months), whereas HLA-B27 negative received it for 24.8?12.25 months (p<0.0000). 4/49 HLA-B27 positive (8.2%) and 1/10 HLA-B27 negative patients (10%) fail to demonstrate efficacy in AS (primary or secondary treatment failure) with no difference between groups. One HLA-B27 positive patient on etanercept developed IBD. All 6 non-responders switched to second TNF-? inhibitor and showed a good clinical response. In our cohort, presence of HLA-B27 was related to greater family occurrence, shorter diagnosis delay and lower peripheral arthritis rate. Moreover, HLA-B27 positive patients demonstrated significantly longer drug survival time for the first biologic then HLA-B27 negative, but non-response rate was similar between groups.