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

Genetika ◽  
2020 ◽  
Vol 52 (3) ◽  
pp. 1193-1202
Author(s):  
Biljana Milic ◽  
Biljana Erdeljan ◽  
Tanja Jankovic ◽  
Milica Popovic ◽  
Gordana Strazmester-Majstorovic ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Tumor Necrosis ◽  
Diagnosis Delay ◽  
Tnf Inhibitor ◽  
Hla B27 ◽  
Peripheral Arthritis ◽  
Necrosis Factor Alpha ◽  
Drug Survival ◽  
Factor Alpha ◽  
Necrosis Factor

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 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.

scholarly journals AB0653 SURVIVAL OF BIOLOGIC THERAPHY AS SECOND LINE IN PATIENTS WITH ANKYLOSING SPONDYLITIS. EXPERIENCE IN A TERTIARY CARE CENTRE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1621.3-1621
Author(s):  
F. López Gutiérrez ◽  
V. García García ◽  
Á. Andreu-Suárez ◽  
B. A. Blanco Cáceres ◽  
J. Bachiller-Corral ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Second Line ◽  
Hla B27 ◽  
First Line ◽  
Peripheral Arthritis ◽  
Drug Survival ◽  
The Impact ◽  
Necrosis Factor

Background:In ankylosing spondylitis (AS) patients with lack of response to a first line of biologic disease modifying antirheumatic drugs (bDMARD), switching to another bDMARD is recommended, aiming either to the same or different therapeutic target. In several previous studies a decrease in drug survival has been noted when tumor necrosis factor alfa inhibitors (TNFai) are used as second or third treatment line (1,2).Objectives:Primary endpoint: To evaluate survival of bDMARD as second line treatment in patients with AS non responding to TNFai either because of lack or loss of efficacy. Secondary: To evaluate the impact on drug survival of several variables such as sex, HLA, peripheral arthritis, radiologic sacroiliitis, CRP, BASFI, BASDAI or bDMARD class.Methods:Observational, longitudinal and retrospective observational study. We included 67 patients diagnosed with AS who received treatment on second line with bDMARD (TNFai or anti IL7) after discontinuation of TNFai as first line of treatment. We analyze patients older than 18 yo, with at least 3 months of continuous treatment before and after switch, seen in our Hospital from 2006 to 2019. Data were collected regarding to demographics, HLA B27 positivity and functionality and activity index, CRP and treatment with cDMARDs.Results:All 67 patients included were still on follow up after switching to second bDMARD. Median age was 37 yo, 56.7% were male and 31%, smokers. 35.8% patients had axial AS; 1.5% peripheral arthritis; 62.7%, mixed and 9%, dactilitis. 76.1% had radiographic sacroiliitis and 74.6%, HLA B 27+. As first bDMARD, the most common was Infliximab (IFX) (47.8%), followed by Adalimumab (ADA) (19.4%) and Etanercept (ETN 14.9%). Mean survival was 32.4 months (IFX, 37 months; ETN, 45; Golimumab, 32.3 and ADA, 24.1). The commonest cause of treatment suspension was loss of efficacy (LoE) (56.7%), followed by lack of efficacy (LaE) (17.6%) and adverse effects (AE) (16.4%).As second bDMARD the most frequent was ADA (35.8%), followed by ETN (34.3%), Golimumab (9%), IFX (7.5%) and Secukinumab (6%) with a mean survival of 45 months (ETN 63.8, ADA 45.7, Golimumab 32). Treatment was discontinued in 47.8% of patients because of LoE (17.9%), LaE (17.9%) and EA (11.9%). A total of 16 AE were recorded, of which 6% were infections and 9%, allergic reactions. Regarding the analysis of the impact of other variables on drug survival, there was statistically significant differences on HLA B 27 carrier status (p=0.012), in which we observed an increase on survival when the patient is HLA B27 + and in whom BASDAI is higher before switching (p=0.02).Conclusion:In our study, we did not observe differences in survival of second line bDMARD in patients with AS regarding type of TNFai, case of discontinuation or type of radiographic involvement in the first line of treatment. Patients with HLA B27+ and high value of BASDAI at the beginning of second bDMARD showed an increased on drug survival. Contrary to literature, we did not see significant differences regarding CRP.References:[1]Glintborg B, Østergaard M, Krogh NS, Tarp U, Manilo N, Loft AGR, et al. Clinical response, drug survival and predictors thereof in 432 ankylosing spondylitis patients after switching tumour necrosis factor α inhibitor therapy: results from the Danish nationwide DANBIO registry. Ann Rheum Dis. 2013 Jul;72(7):1149–55.[2]Deodhar A, Yu D. Switching tumor necrosis factor inhibitors in the treatment of axial spondyloarthritis. Semin Arthritis Rheum. 2017 Dec;47(3):343–50.Disclosure of Interests:None declared

scholarly journals Comparative Analysis and Predictors of 10-year Tumor Necrosis Factor Inhibitors Drug Survival in Patients with Spondyloarthritis: First-year Response Predicts Longterm Drug Persistence

2018 ◽  
Vol 45 (6) ◽  
pp. 785-794 ◽  
Author(s):  
Irini D. Flouri ◽  
Theodora E. Markatseli ◽  
Kyriaki A. Boki ◽  
Ioannis Papadopoulos ◽  
Fotini N. Skopouli ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Disease Activity Score ◽  
First Year ◽  
Peripheral Arthritis ◽  
Drug Survival ◽  
Axial Disease ◽  
Necrosis Factor

Objective.To evaluate the 10-year drug survival of the first tumor necrosis factor inhibitor (TNFi) administered to patients with spondyloarthritis (SpA) overall and comparatively between SpA subsets, and to identify predictors of drug retention.Methods.Patients with SpA in the Hellenic Registry of Biologic Therapies, a prospective multicenter observational cohort, starting their first TNFi between 2004–2014 were analyzed. Kaplan-Meier curves and Cox regression models were used.Results.Overall, 404 out of 1077 patients (37.5%) discontinued treatment (followup: 4288 patient-yrs). Ten-year drug survival was 49%. In the unadjusted analyses, higher TNFi survival was observed in patients with ankylosing spondylitis (AS) compared to undifferentiated SpA and psoriatic arthritis [PsA; significant beyond the first 2.5 (p = 0.003) years and 7 years (p < 0.001), respectively], and in patients treated for isolated axial versus peripheral arthritis (p = 0.001). In all multivariable analyses, male sex was a predictor for longer TNFi survival. Use of methotrexate (MTX) was a predictor in PsA and in patients with peripheral arthritis. Absence of peripheral arthritis and use of a monoclonal antibody (as opposed to non-antibody TNFi) independently predicted longer TNFi survival in axial disease because of lower rates of inefficacy. Achievement of major responses during the first year in either axial or peripheral arthritis was the strongest predictor of longer therapy retention (HR 0.33, 95% CI 0.26–0.41 for Ankylosing Spondylitis Disease Activity Score inactive disease, and HR 0.35, 95% CI 0.24–0.50 for 28-joint Disease Activity Score remission).Conclusion.The longterm retention of the first TNFi administered to patients with SpA is high, especially for males with axial disease. The strongest predictor of longterm TNFi survival is a major response within the first year of treatment.

scholarly journals Comparison of the effects of rituximab, tumor necrosis factor alpha inhibitors and non-steroidal antiinflammatory drugs on ankylosing spondylitis clinical activity and sacroileitis intensity on magnetic resonance imaging

2013 ◽  
Vol 94 (6) ◽  
pp. 870-876
Author(s):  
M S Protopopov ◽  
Sh F Erdes ◽  
S A Lapshina ◽  
L I Myasoutova ◽  
R Kh Zakirov ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Clinical Activity ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Inflammatory Drugs ◽  
Necrosis Factor

Aim. To investigate the effect of rituximab in ankylosing spondylitits on disease activity and on intensity of sacroileitis detected by magnetic resonance imagigng compared to tumor necrosis factor alpha inhibitors and non-steroidal anti-inflammatory drugs. Methods. The study included 91 patient [14 (15.4%) females, 77 (84.6%) males, mean age - 34.4±9.13 years, disease duration - 6.6±3.8 years] with established diagnosis of ankylosing spondylitits. The main group included 20 patients (17 males, mean age 36.9±9.9 years) who were treated with rituximab. The comparison group included 36 patients (30 males, mean age 34.3±8.6 years) treated with tumor necrosis factor alpha inhibitors. The control group consisted of 35 patients (30 males, mean age 33.4±9.3 years) treated with non-steroidal anti-inflammatory drugs and sulfasalazine. Disease activity was measured by BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and ASDASESR (Ankylosing Spondylitis Disease Activity Score) scores before the treatment initiation, at the 2nd, 8th, 16th and 24th weeks of treatment. Magnetic resonance imaging of sacroiliac joints was performed before the treatment initiation and at the 24th week of treatment, T1 and STIR sequences were analyzed. Results were processed using the SPARCC (Spondyloarthritis Research Consortium of Canada) scoring methodology. Results. There was a significant reduction of the disease clinical activity measured by BASDAI score (from 6.19±1.48 to 3.70±0.91, p 0.01) and ASDASESR score (form 3.43±0.72 tо 2.11±0.46, p 0.01) in patients treated with rituximab at the week 24. Mean SPARCC score reduced from 15.9±7.2 to 4.6±8.2 (p 0.01). The influence of rituximab on clinical activity of the disease was superior over the effect of the standard treatment (BASDAI and SPARCC scores 5.22±1.14 and 7.8±7.1 accordingly at the week 24, p 0.05), but inferior over the effect of tumor necrosis factor alpha inhibitors (BASDAI and SPARCC scores 2.03±0.64 и 4.9±7.0 accordingly at the week 24, p 0.01). Conclusion. Anti B-cell therapy is effective in treating active ankylosing spondylitis and leads to the decrease of the clinical symptoms intensity and disease activity measured by BASDAI и ASDASESR scores. The effect of rituximab was superior over the effect of non-steroidal anti-inflammatory drugs and sulfasalazine and inferior over the effect of tumor necrosis factor alpha inhibitors.

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