doiSerbia

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

Milić Biljana (Clinical Center of Vojvodina, Clinic for Nephrology and Clinical Immunology Novi Sad, Serbia + University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia), biljana.milic@mf.uns.ac.rs,
Erdeljan Biljana (Special hospital for rheumatic diseases Jodna Banja, Novi Sad, Serbia)
Janković Tanja (University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia + Special hospital for rheumatic diseases Jodna Banja, Novi Sad, Serbia)
Popović Milica (Clinical Center of Vojvodina, Clinic for Nephrology and Clinical Immunology Novi Sad, Serbia + University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia)
Stražmešter-Majstorović Gordana (Clinical Center of Vojvodina, Clinic for Nephrology and Clinical Immunology Novi Sad, Serbia + University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia)
Ilić Katarina (Roche,d.o.o., Belgrade, Serbia)

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-α inhibitor) therapy in HLA-B27 positive and negative patients with AS. This retrospective analysis included AS patients treated with TNF-α inhibitor for at least 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-α-inhibitor therapy. All 59 patients who participated in the study has been administered at least one TNF-α inhibitor. The mean age at introduction of TNF-α inhibitor as well as mean disease duration from diagnosis until start of TNF-α 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-α 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.

Keywords: HLA-B27, ankylosing spondylitis, tumor necrosis factor-alpha inhibitors, clinical features, response to therapy