scholarly journals POS0914 IS THERE AN ASSOCIATION BETWEEN AUTOANTIBODIES INDUCTION AND LOSS OF THERAPEUTIC EFFICACY IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS AND PSORIATIC ARTHRITIS TREATED WITH ANTI-TNF-α AGENTS?

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 718.1-718
Author(s):  
A. Martins ◽  
D. Santos Oliveira ◽  
F. R. Martins ◽  
M. Rato ◽  
F. Oliveira Pinheiro ◽  
...  

Background:Induction of autoantibodies is frequently observed in patients treated with a TNF-α blocker. According to other authors, the incidence of induction of antinuclear antibodies (ANA) and anti-double stranded DNA antibodies (anti-dsDNA) varies between 23-57% and 9-33%, respectively. However, it is unknown whether the induction of these autoantibodies affects the pharmacokinetics and bioavailability of biotherapy and, consequently, reduces the efficacy and safety of the drug.Objectives:To analyze if there is an association between autoantibodies induction and therapeutic efficacy in a monocentric cohort of patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) treated with anti-TNF-α agents.Methods:The authors performed a retrospective analysis of patients with axSpA and PsA treated in our University Hospital with a TNF-α blocker as first biologic agent, and analysed the autoantibodies induction rate after 12 (T12) and 24 (T24) months of therapy. Then, they investigated the influence of autoantibodies in therapeutic efficacy at T12 and T24. Clinical evaluation, laboratory findings including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and disease activity and functional scores (Bath Ankylosing Spondylitis Disease Activity Index – BASDAI, AS Disease Activity Score with CPR - ASDAS-CRP, Bath AS Functional Index - BASFI) were collected from reuma.pt and medical records. For PsA patients, Disease Activity Score-28-CRP (DAS28-CRP), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire (HAQ) scores were also collected. Patients with positive ANA (titer > 1/100) prior to anti-TNF-α therapy were excluded. Continuous variables were analyzed using a t-test and categorical variables using a Chi-square test. P-value <0.05 was considered statistically significant.Results:In the axSpA group, 235 patients were included, 44.5% were females, mean age at diagnosis of 42.3 ± 12.4 years and median disease duration of 11.5 (IQR 6.0-21.0) years. Positive ANA were observed in 16.9% at T12 and 26.3% at T24 and positive anti-dsDNA in 3.4% at T12 and 3.8% at T24, with similar conversion rates between different anti-TNF drugs and no significant gender difference. A significant difference in ASDAS-CPR was found in axSpA patients with and without ANA at T12 (p=0.047). ASDAS-CPR was 1.16 times higher in patients with ANA comparing to patients without them. However, no difference was found in the others disease activity and functional scores at T12. Furthermore, no significant difference, including ASDAS-CPR, was found at T24. Also, there was no significant difference found when comparing patients with and without anti-dsDNA.In the PsA group, 94 patients were included, 46.8% were females, mean age at diagnosis of 46.7 ± 11.7 years and median disease duration of 11.5 (IQR 6.5-16.5) years. Positive ANA were found in 14.9% at T12 and 21.3% at T24 and positive anti-dsDNA in 2.1% at T12 and 3.2% at T24. When comparing the groups with and without ANA and with and without anti-dsDNA at T12 and T24, no significant difference in disease activity and functional scores was found.Conclusion:This study revealed high rates of serology conversion, similar to the rates described before. The authors found that ASDAS-CPR was higher in axSpA patients with ANA after 12 months of therapy. However, this difference was no longer evident after 24 months. No other significant difference was found between patients with and without ANA or with and without anti-dsDNA. The authors consider that the induction of autoantibodies may interfere with the response to anti-TNF-α therapy in a short and initial period of time. Long-term follow-up data are lacking to say whether that influence will disappear consistently over the long run, as they observed after 12 months of therapy. However, they can state that, a priori, seroconversion should not lead to treatment suspension because of concerns about loss of efficacy.Disclosure of Interests:None declared

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1629.2-1629
Author(s):  
K. Ben Abdelghani ◽  
Y. Gzam ◽  
A. Fazaa ◽  
S. Miladi ◽  
K. Ouenniche ◽  
...  

Background:Axial spondyloarthritis (ax-SpA) is a chronic rheumatic disease that mainly affects men. However, the female form of ax-SpA remains insufficiently studied.Objectives:The aim of this study was to determine the clinical characteristics, the disease activity and the functional impact of female ax-SpA in comparison with male ax-SpA.Methods:This is a retrospective study including patients diagnosed with ax-SpA fulfilling the criteria of the Assessment of SpondyloArthritis international Society (ASAS) 2009.Clinical parameters, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath ankylosing spondylitis disease activity index (BASDAI) and Bath ankylosing spondylitis functional index (BASFI) were compared between groups of female and male ax-SpA.Results:Two hundred ax-SpA patients were included with 31% of female (n=62) and a mean age of 43,3 ± 11,2 years.The mean age at onset of symptoms was 31,8 ± 8,9 years for women and 25,3 ± 9,1 years for men (p <0,0001). The mean age at diagnosis was 36,4 ± 9,6 years for women and 31,7 ± 10,4 years for men (p = 0,003). Ax-SpA with juvenile onset was noted in 1,7% of women and 12,1% of men (p = 0,02). Male ax-SpA were significantly more smokers (46.8% vs 5.4%; p <0.001). The mean duration of morning stiffness was 11,3 ± 9,2 minutes for women versus 21,6 ± 19,3 minutes for men (p = 0,005).The mean ESR was 42,4 ± 29,8 mm for women and 28,3 ± 23,4 mm for men (p = 0,001). Radiographic sacroiliitis was present in 69,3% of women versus 84,7% of men (p = 0,01). The use of anti-TNF alpha was less frequent in women (29% vs 48,5%; p = 0,01).Our study didn’t found a statistically significant difference in peripheral manifestations, extraarticular manifestations, CRP, BASDAI and BASFI between the two groups.Conclusion:Female ax-SpA seems to have a better prognosis than male with older age in disease onset, less inflammation, less radiographic sacroiliitis and less use of biological treatments.References:[1]Rusman T, et al. Curr Rheumatol Rep. 2018; 20(6).[2]Siar N, et al. Curr Rheumatol Rev. 2019;Disclosure of Interests:None declared


2021 ◽  
Author(s):  
Ozkan Yukselmis ◽  
Pelin Oktayoğlu ◽  
Mehmet Caglayan ◽  
Nuriye Mete

Abstract Objectives Spondyloarthritis refers to a group of chronic inflammatory diseases that particularly involve the sacroiliac joints and spine but may also have an influence on extra-articular involvement in some patients. Oxytocin is a peptide hormone released from the hypothalamus and stored in the pituitary gland. It is known to have anti-inflammatory effects. The aim of this study was to investigate the serum levels of oxytocin and their potential association with disease activity and spinal mobility in patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nrAxSpA). Material and Methods Seventy-one patients with nrAxSpA, 38 patients with AS and 67 healthy control subjects were included in this study. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index, and spinal mobility by the Bath Ankylosing Spondylitis Metrologic Index. Laboratory examinations included complete blood count, ESR, CRP and oxytocin tests. Results There was no significant difference in serum levels of oxytocin among the 3 groups (p=0.973). However, serum levels of oxytocin correlated negatively with both ESR (r=− 0.359, p=0.027), CRP (r=− 0.316, p=0.056) and BASDAI scores (r=− 0,448, p=0.005) in patients with AS. On the other hand, serum levels of oxytocin had a negative correlation only with ESR in patients with nrAxSpA (r=− 0.321 p=0.009).Conclusion This study lays the foundation for further studies that may aim to investigate how addition of oxytocin to the treatment regimen impacts on disease activity in patients with AS who exhibit particularly low levels of oxytocin during the active disease period.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1129.1-1129
Author(s):  
A. Baillet ◽  
X. Romand ◽  
A. Pfimlin ◽  
M. Dalecky ◽  
M. Dougados

Background:Standardization of clinical practice has been proven to be effective in management of chronic diseases. This is particularly true at the time where the concept of treat to target is becoming more and more important in the field of axial spondyloarthritis (ax-SpA).Objectives:To propose a list of variables to be collected at the time of the diagnosis and over the follow-up of patients with axial spondyloarthritis (ax-SpA) for an optimal management in daily practice.Methods:The process comprised (1) the evaluation of the interest of 51 variables proposed for the assessment of axSpA via a systematic literature research, (2) a consensus process involving 78 hospital-based or office-based rheumatologists, considering the collection of the variable in a 4 grade scale from ”potentially useful” to “mandatory”, (3) a consensus on optimal timeline for periodic assessment of the selected variables on a 5 grade scale from “at each visit” to “never to be re-collected”.Results:The systematic literature research retrieved a total of 14,133 abstracts, of which 213 were included in the final qualitative synthesis. Concerning the data to be collected at the time of the diagnosis and during follow-up, we proposed to differentiate the results based on a) the way of collection of the variables (e.g. questionnaires by the patient, interview by the physician, physical examination, investigations) b) the usefulness these variables in daily practice based on the opinion of the rheumatologists ” c) the optimal timeline between 2 evaluations of the variable based on the opinion of the rheumatologists. In the initial systematic review, symptoms of heart failure history of inflammatory bowel disease, psoriasis or uveitis, patient global visual analogic scale, spine radiographs, modified Schöber test, coxo-femoral rotations, swollen joint count, urine strip test, BASDAI and ASDAS global scores were considered very useful and nocturnal back pain/morning stiffness, sacro-iliac joints radiographs and CRP were considered mandatory (Figure 1). Timeline between 2 evaluations of variables to collect in the periodic review are summarized inFigure 2.Figure 1.Core sets of items to collect and report in the systematic review in axial spondyloarthritis management in daily practice ASDAS=Ankylosing Spondylitis Disease Activity Score, BASDAI=Bath Ankylosing Spondylitis Disease Activity Index, BASFI=Bath Ankylosing Spondylitis Functionnal Index, BASMI=Bath Ankylosing Spondylitis Metrology Index, CRP=C Reactive Protein, CT=computerized tomography, FIRST=Fibromyalgia Rapid Screening Tool, HLA=Human Leukocyte Antigen, MRI=Magnetic resonance imaging, PET=positron emission tomography.Figure 2.Periodic review timeline of variables to collectASDAS=Ankylosing Spondylitis Disease Activity Score, BASDAI=Bath Ankylosing Spondylitis Disease Activity Index, Spondylitis Metrology Index, CRP=C Reactive Protein, IBD = inflammatory bowel diseases, PRO = Patient Reported OutcomesConclusion:Using an evidence-based and an expert consensus approaches, this initiative defined a core set of variables to be collected and reported at the time of the diagnosis and during follow-up of patients with ax-SpA in daily practice.Acknowledgments:this study has been conducted in two parts: the first one (evidence-based) was conducted thanks to a support from Abbvie France. AbbVie did not review the content or have influence on this manuscript. The second part of this initiative (consensus) has been conducted thanks to a support from the scientific non-profit organization: Association de Recherche Clinique en RhumatologieDisclosure of Interests:Athan Baillet Consultant of: Athan BAILLET has received honorarium fees from Abbvie for his participation as the coordinator of the systematic literature review, Xavier Romand Consultant of: Xavier ROMAND has received honorarium fees from Abbvie, Arnaud Pfimlin Consultant of: Arnaud PFIMLIN has received honorarium fees from Abbvie, Mickael Dalecky Consultant of: Mickael DALECKY has received honorarium fees from Abbvie, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ji-Young Lim ◽  
Byung-Su Kim ◽  
Da-Bin Ryu ◽  
Tae Woo Kim ◽  
Gyeongsin Park ◽  
...  

Abstract Background Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSCs) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods To compare the therapeutic effects between the unstimulated MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9. Results Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 upregulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.


2010 ◽  
Vol 37 (11) ◽  
pp. 2299-2306 ◽  
Author(s):  
JENNIFER G. WALKER ◽  
RUSSELL J. STEELE ◽  
MIREILLE SCHNITZER ◽  
SUZANNE TAILLEFER ◽  
MURRAY BARON ◽  
...  

Objective.The absence of a standardized disease activity index has been an important barrier in systemic sclerosis (SSc) research. We applied the newly derived Valentini Scleroderma Disease Activity Index (SDAI) among our cohort of patients with SSc to document changes in disease activity over time and to assess possible differences in activity between limited and diffuse disease.Methods.Cross-sectional study of a national cohort of patients enrolled in the Canadian Scleroderma Research Group Registry. Disease activity was measured using the SDAI. Depression scores were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D).Results.A total of 326 out of 639 patients had complete datasets at the time of this analysis; 87% were female, of mean age 55.6 years, with mean disease duration 14.1 years. SDAI declined steeply in the first 5 years after disease onset and patients with diffuse disease had 42% higher SDAI scores than patients with limited disease with the same disease duration and depression scores (standardized relative risk 1.42, 95% CI 1.21, 1.65). Patients with higher CES-D scores had higher SDAI scores relative to patients with the same disease duration and disease subset (standardized RR 1.22, 95% CI 1.14, 1.31). Among the 10 components that make up the SDAI, only skin score (standardized OR 0.59, 95% CI 0.43, 0.82) and patient-reported change in skin (standardized OR 0.64, 95% CI 0.45, 0.92) decreased with increasing disease duration. High skin scores (standardized OR 32.2, 95% CI 15.8, 72.0) were more likely and scleredema (standardized OR 0.58, 95% CI 0.37, 0.92) was less likely to be present in patients with diffuse disease. High depression scores were associated with positive responses for patient-reported changes in skin and cardiopulmonary function.Conclusion.Disease activity declined with time and patients with diffuse disease had consistently higher SDAI scores. Depression was found to be associated with higher patient activity scores and strongly associated with patient self-response questions. The role of depression should be carefully considered in future applications of the SDAI, particularly as several components of the score rely upon patient recall.


Rheumatology ◽  
2020 ◽  
Author(s):  
Laura C Coates ◽  
Joseph F Merola ◽  
Philip J Mease ◽  
Alexis Ogdie ◽  
Dafna D Gladman ◽  
...  

Abstract Objectives To examine which composite measures are most sensitive to change when measuring psoriatic arthritis (PsA) disease activity, analyses compared the responsiveness of composite measures used in a 48-week randomized, controlled trial of MTX and etanercept in patients with PsA. Methods The trial randomised 851 patients to receive weekly: MTX (20 mg/week), etanercept (50 mg/week) or MTX plus etanercept. Dichotomous composite measures examined included ACR 20/50/70 responses, minimal disease activity (MDA) and very low disease activity (VLDA). Continuous composite measures examined included Disease Activity Score (28 joints) using CRP (DAS28-CRP), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS). Results At week 24, etanercept-treated groups were significantly more effective than MTX monotherapy to achieve ACR 20 (primary end point) and MDA (key secondary end point). When examining score changes from baseline at week 24 across the five continuous composite measures, PASDAS demonstrated relatively greater changes in the etanercept-treated groups compared with MTX monotherapy and had the largest effect size and standardized response. Joint count changes drove overall score changes at week 24 from baseline in all the continuous composite measures except for PASDAS, which was driven by the Physician and Patient Global Assessments. Conclusion PASDAS was the most sensitive continuous composite measure examined with results that mirrored the protocol-defined primary and key secondary outcomes. Composite measures with multiple domains, such as PASDAS, may better quantify change in PsA disease burden. Trail registration https://ClinicalTrials.gov, number NCT02376790.


2018 ◽  
Vol 77 (10) ◽  
pp. 1421-1425 ◽  
Author(s):  
Nina Paulshus Sundlisæter ◽  
Anna-Birgitte Aga ◽  
Inge Christoffer Olsen ◽  
Hilde Berner Hammer ◽  
Till Uhlig ◽  
...  

ObjectiveTo explore associations between remission, based on clinical and ultrasound definitions, and future good radiographic and physical outcome in early rheumatoid arthritis (RA).MethodsNewly diagnosed patients with RA followed a treat-to-target strategy incorporating ultrasound information in the Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen (ARCTIC) trial. We defined 6-month remission according to Disease Activity Score, Disease Activity Score in 28 joints-erythrocyte sedimentation rate, American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean criteria, Simplified Disease Activity Index, Clinical Disease Activity Index and two ultrasound definitions (no power Doppler signal, grey scale score ≤2). Two outcomes were defined: no radiographic progression and good outcome (no radiographic progression+physical function≥general population median), both sustained 12–24 months. We calculated the ORs of these outcomes for the remission definitions.ResultsOf 103 patients, 42%–82% reached remission at 6 months, dependent on definition. Seventy-one per cent of patients had no radiographic progression and 37% had good outcome. An association between 6-month remission and no radiographic progression was observed for ACR/EULAR Boolean remission (44 joints, OR 3.2, 95% CI 1.2 to 8.4), ultrasound power Doppler (OR 3.6, 95% CI 1.3 to 10.0) and grey scale remission (OR 3.2, 95% CI 1.2 to 8.0). All clinical, but not ultrasound remission criteria were associated with achievement of a good outcome.ConclusionsOur data support ACR/EULAR Boolean remission based on 44 joints as the preferred treatment target in early RA. Absence of ultrasound inflammation was associated with no radiographic progression.Trial registration numberNCT01205854; Post-results.


2019 ◽  
Vol 78 (12) ◽  
pp. 1609-1615 ◽  
Author(s):  
Daniel Aletaha ◽  
Jen-fue Maa ◽  
Su Chen ◽  
Sung-Hwan Park ◽  
Dave Nicholls ◽  
...  

ObjectivesTo determine if disease duration and number of prior disease-modifying antirheumatic drugs (DMARDs) affect response to therapy in patients with established rheumatoid arthritis (RA).MethodsAssociations between disease duration or number of prior DMARDs and response to therapy were assessed using data from two randomised controlled trials in patients with established RA (mean duration, 11 years) receiving adalimumab+methotrexate. Response to therapy was assessed at week 24 using disease activity outcomes, including 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)), Simplified Disease Activity Index (SDAI) and Health Assessment Questionnaire Disability Index (HAQ-DI), and proportions of patients with 20%/50%/70% improvement in American College of Rheumatology (ACR) responses.ResultsIn the larger study (N=207), a greater number of prior DMARDs (>2 vs 0–1) was associated with smaller improvements in DAS28(CRP) (–1.8 vs –2.2), SDAI (–22.1 vs –26.9) and HAQ-DI (–0.43 vs –0.64) from baseline to week 24. RA duration of >10 years versus <1 year was associated with higher HAQ-DI scores (1.1 vs 0.7) at week 24, but results on DAS28(CRP) and SDAI were mixed. A greater number of prior DMARDs and longer RA duration were associated with lower ACR response rates at week 24. Data from the second trial (N=67) generally confirmed these findings.ConclusionsNumber of prior DMARDs and disease duration affect responses to therapy in patients with established RA. Furthermore, number of prior DMARDs, regardless of disease duration, has a limiting effect on the potential response to adalimumab therapy.


2011 ◽  
Vol 38 (4) ◽  
pp. 723-729 ◽  
Author(s):  
NÓRA BODNÁR ◽  
GYÖRGY KEREKES ◽  
ILDIKÓ SERES ◽  
GYÖRGY PARAGH ◽  
JÁNOS KAPPELMAYER ◽  
...  

Objective.Studies indicate that ankylosing spondylitis (AS), as well as rheumatoid arthritis, may be associated with accelerated atherosclerosis and vascular disease. We assessed endothelial dysfunction, carotid atherosclerosis, and aortic stiffness in AS in context with clinical and laboratory measurements.Methods.Forty-three patients with AS and 40 matched healthy controls were studied. We assessed common carotid intima-media thickness (ccIMT), flow-mediated vasodilation (FMD), and pulse-wave velocity (PWV) in association with age, disease duration, smoking habits, body mass index, patient’s assessment of pain and disease activity, Bath AS Disease Activity Index, Bath AS Functional Index (BASFI), metric measurements, erythrocyte sedimentation rate, C-reactive protein, and HLA-B27 status.Results.We found impaired FMD (6.85 ± 2.98% vs 8.30 ± 3.96%; p = 0.005), increased ccIMT (0.65 ± 0.15 vs 0.54 ± 0.15 mm; p = 0.01), and higher PWV (8.64 ± 2.44 vs 8.00 ± 1.46 m/s; p = 0.03) in patients with AS compared to controls, respectively. We also found that ccIMT negatively correlated with FMD (r = −0.563; p = 0.0001) and positively correlated with PWV (r = 0.374; p = 0.018). Both ccIMT and PWV correlated with disease duration (r = 0.559; p = 0.013 and r = 0.520; p = 0.022, respectively), BASFI (r = 0.691; p = 0.003 and r = 0.654; p = 0.006), decreased lumbar spine mobility (r = −0.656; p = 0.006 and r = −0.604; p = 0.013), chest expansion (r = −0.502; p = 0.047 and r = −0.613; p = 0.012), and increased wall-occiput distance (r = 0.509; p = 0.044 and r = 0.614; p = 0.011).Conclusion.In this well characterized AS population, impaired FMD and increased ccIMT and PWV indicate abnormal endothelial function and increased atherosclerosis and aortic stiffness, respectively. The value of noninvasive diagnostic tools needs to be further characterized.


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