scholarly journals POS0452 SYNOVIAL MYELOID-STROMAL PATHOTYPE PREDICTS ONE-YEAR RADIOGRAPHIC PROGRESSION IN ACTIVE RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 456.1-456
Author(s):  
X. Zhang ◽  
J. D. Ma ◽  
D. H. Zheng ◽  
C. Chen ◽  
T. Wu ◽  
...  

Background:Rheumatoid arthritis (RA) is a heterogeneous disease with variable prognosis. The cellular composition in synovium is the driving force of joint destruction in RA, and the predictive values of histopathological assessments on the clinical outcomes of RA have been identified. However, current synovial histopathological assessments mainly focus on the infiltrated immunocytes to distinguish RA synovium into different synovial pathotypes. Whether addition of stromal cells improve the accuracy of histopathological assessments remains unknow.Objectives:To distinguish synovial pathotypes of RA based on intercellular connection and explore their predictive value on one-year radiographic progression.Methods:Active RA patients who underwent needle synovial biopsy at baseline were recruited from a real-world prospective cohort. Clinical data were evaluated at baseline and 1, 3, 6, 12 months. Histopathologic assessments included Krenn synovitis score and semiquantitative score of immunohistochemical staining for CD20, CD38, CD4, CD8, CD68, CD31 and CD90. Cluster analysis was used to distinguish synovial pathotypes. The primary outcome was one-year radiographic progression defined as a change in total Sharp/van der Heijde modified score≥0.5 units.Results:1. Among 134 RA patients who received synovial biopsy at baseline and finished one-year follow-up, 105 had qualified synovial tissue. The mean age was 50.2±13.3 years with 77.1% female. The median disease duration was 24 (9-120) months. All patients were active RA, and 64.8%, 26.7% and 8.6% patients in high, moderate and low disease activity, respectively. There were 41 (39%) patients who have never been treated with corticosteroids or disease-modifying anti-rheumatic drugs.2. During one-year follow-up, there were 48.6%, 63.8%, 71.4%, and 69.5% patients achieved CDAI LDA target, and 12.4%, 30.5%, 34.3%, and 32.4% patients achieved CDAI remission after 1, 3, 6, and 12 months, respectively. A total of 33 (31.4%) patients had radiographic progression.3. All patients were divided into three clusters using cluster analysis based on the seven synovial cellular scores. Patients in cluster 1 (n=50, 47.6%) had higher scores of sublining CD68+ macrophages, CD31+ endothelial cells and CD90+ fibroblasts, thus named as myeloid-stromal pathotype. Patients in cluster 2 (n=26, 24.8%) had higher scores of CD20+ B cells, CD38+ plasma cells, CD4+ T cells and CD8+ T cells, thus named as lymphoid pathotype. Patients in cluster 3 (n=29, 27.6%) had lower scores of all seven cell types, thus named as pauci-cellular pathotype (Figure 1).4. RA patients with baseline synovial myeloid-stromal pathotype showed higher rate of one-year radiographic progression versus lymphoid and pauci-cellular pathotypes (48% vs. 16.4%, P<0.001), whereas there was no difference between lymphoid and pauci-cellular pathotypes (11.5% vs. 20.7, P=0.475). Adjusted for confounding factors including age, sex, smoking, disease duration, RF status, ACPA status, CDAI, HAQ-DI and mTSS at baseline, multivariate logistic regression analysis showed that baseline synovial myeloid-stromal pathotype independently predicted one-year radiographic progression (AOR=3.602, 95%CI:1.257-10.324, P=0.017, Table 1).Conclusion:Baseline synovial myeloid-stromal pathotype in RA can predict one-year radiographic progression.Funding:This work was supported by National Natural Science Foundation of China (no. 81971527, 81801606 and 81801605), Guangdong Natural Science Foundation (no. 2018A030313541 and 2018A030313690), Guangdong Medical Scientific Research Foundation (no. A2018062), Guangdong Basic and Applied Basic Research Foundation (no. 2019A1515011928 and 2020A1515110061), and Science and Technology Program of Guangzhou (no. 201904010088).Acknowledgements:We thank all subjects and medical staff who generously contributed to this study.Disclosure of Interests:None declared

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Ahmad A Sherbini ◽  
James M Gwinnutt ◽  
Kimme L Hyrich ◽  
Suzanne M M Verstappen ◽  

Abstract Background/Aims  Methotrexate (MTX) is the most common treatment for rheumatoid arthritis (RA). The prevalence of adverse events (AEs) associated with MTX treatment for RA have been studied extensively, but there are limited data on the predictors of these AEs. This study aims to summarise the prevalence rates of MTX AEs, including gastrointestinal (GI), neurological, mucocutaneous, and elevated alanine transaminase (ALT) enzyme, and to identify baseline demographic and clinical predictors of these AEs. Methods  The Rheumatoid Arthritis Medication Study (RAMS) is a UK multi-centre prospective cohort study of patients with RA starting MTX for the first time. Relevant demographic, medication, clinical and disease related data were collected at baseline. AEs were reported at six and twelve months follow-ups. The prevalence rates of AEs were calculated based on the proportions of patients who reported having had an AE within one year of follow-up. The associations between candidate baseline predictors and AEs were assessed using multivariable logistic regression. Results  A total of 2,089 patients were included with a mean age of 58.4 (standard deviation: 13.5) years, 1390 (66.5%) were women. 1,814 and 1,579 patients completed the 6 and 12 months follow-up visits, respectively. The prevalence rates of the AEs within one year of follow-up were: GI = 777 (40.6%), mucocutaneous = 441 (23.1%), neurological = 487 (25.5%), elevated ALT (&gt; upper limit of normal [ULN]) = 286 (15.5%). Younger age and being a woman were associated with increased risk of GI AEs, (age: OR 0.97 per year increase in age, 95% CI 0.98, 1.00; male sex: OR 0.58 vs female, 95% CI 0.46, 0.74) (Table 1). Higher baseline Health Assessment Questionnaire (HAQ) score was an independent predictor of GI, mucocutaneous, and neurological AEs. Furthermore, having ALT &gt;1xULN at baseline or history of diabetes was associated with increased risk of subsequent ALT elevation during the study follow-up. Conclusion  In patients with RA starting MTX, GI AEs were the most commonly reported AEs during the first year of follow-up. The identified predictors of AEs may facilitate discussions between clinicians and patients prior to commencing MTX, and may lead to increased adherence and consequently improved effectiveness. Disclosure  A.A. Sherbini: None. J.M. Gwinnutt: Grants/research support; BMS. K.L. Hyrich: Member of speakers’ bureau; Abbvie. Grants/research support; Pfizer, UCB, BMS. S.M.M. Verstappen: Consultancies; Celltrion. Member of speakers’ bureau; Pfizer. Grants/research support; BMS.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1463.2-1464
Author(s):  
S. Bayat ◽  
K. Tascilar ◽  
V. Kaufmann ◽  
A. Kleyer ◽  
D. Simon ◽  
...  

Background:Recent developments of targeted treatments such as targeted synthetic DMARDs (tsDMARDs) increase the chances of a sustained low disease activity (LDA) or remission state for patients suffering rheumatoid arthritis (RA). tsDMARDs such as baricitinib, an oral inhibitor of the Janus Kinases (JAK1/JAK2) was recently approved for the treatment of RA with an inadequate response to conventional (cDMARD) and biological (bDMARD) therapy. (1, 2).Objectives:Aim of this study is to analyze the effect of baricitinb on disease activity (DAS28, LDA) in patients with RA in real life, to analyze drug persistance and associate these effects with various baseline characteristics.Methods:All RA patients were seen in our outpatient clinic. If a patient was switched to a baricitinib due to medical reasons, these patients were included in our prospective, observational study which started in April 2017. Clinical scores (SJC/TJC 76/78), composite scores (DAS28), PROs (HAQ-DI; RAID; FACIT), safety parameters (not reported in this abstract) as well as laboratory biomarkers were collected at each visit every three months. Linear mixed effects models for repeated measurements were used to analyze the time course of disease activity, patient reported outcomes and laboratory results. We estimated the probabilities of continued baricitinib treatment and the probabilities of LDA and remission by DAS-28 as well as Boolean remission up to one year using survival analysis and explored their association with disease characteristics using multivariable Cox regression. All patients gave informed consent. The study is approved by the local ethics.Results:95 patients were included and 85 analyzed with available follow-up data until November 2019. Demographics are shown in table 1. Mean follow-up duration after starting baricitinib was 49.3 (28.9) weeks. 51 patients (60%) were on monotherapy. Baricitinib survival (95%CI) was 82% (73% to 91%) at one year. Cumulative number (%probability, 95%CI) of patients that attained DAS-28 LDA at least once up to one year was 67 (92%, 80% to 97%) and the number of patients attaining DAS-28 and Boolean remission were 31 (50%, 34% to 61%) and 12(20%, 9% to 30%) respectively. Median time to DAS-28 LDA was 16 weeks (Figure 1). Cox regression analyses did not show any sufficiently precise association of remission or LDA with age, gender, seropositivity, disease duration, concomitant DMARD use and number of previous bDMARDs. Increasing number of previous bDMARDs was associated with poor baricitinib survival (HR=1.5, 95%CI 1.1 to 2.2) while this association was not robust to adjustment for baseline disease activity. Favorable changes were observed in tender and swollen joint counts, pain-VAS, patient and physician disease assessment scores, RAID, FACIT and the acute phase response.Conclusion:In this prospective observational study, we observed high rates of LDA and DAS-28 remission and significant improvements in disease activity and patient reported outcome measurements over time.References:[1]Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Annals of the rheumatic diseases. 2015 Feb;74(2):333-40.[2]Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. The New England journal of medicine. 2016 Mar 31;374(13):1243-52.Figure 1.Cumulative probability of low disease activity or remission under treatment with baricitinib.Disclosure of Interests:Sara Bayat Speakers bureau: Novartis, Koray Tascilar: None declared, Veronica Kaufmann: None declared, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Johannes Knitza Grant/research support from: Research Grant: Novartis, Fabian Hartmann: None declared, Susanne Adam: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 112.1-112
Author(s):  
L. Brandt ◽  
H. Schulze-Koops ◽  
T. Hügle ◽  
M. J. Nissen ◽  
H. Paul ◽  
...  

Background:The therapeutic aim for rheumatoid arthritis (RA) is to control disease activity and prevent radiographic progression. Various clinical scores are utilized to describe disease activity in RA patients. The DAS28 score can define states of low disease activity (LDA) and remission. Despite achieving LDA or remission, radiographic progression may nevertheless occur. However, the rates and frequency of this occurrence have not been analyzed in detail.Objectives:To describe the frequency and rate of radiographic progression in patients with persistent LDA or remission.Methods:Analysis of RA patients from the SCQM cohort. Persistent LDA or remission were defined as DAS 28 ≤3.2 or <2.6 respectively, at two subsequent follow up time points in the database. We included patients with at least two sets of radiographs within these intervals of LDA and/or remission. Radiographic progression was measured with the Ratingen-score (range 0-190), which describes joint erosions numerically. Repair was defined as an improvement in the Ratingen score >5 points/year and progression as >2 or >5 points change in the Ratingen score within one year.Results:Among 10’141 RA patients, 4’342 episodes of remission occurred in 3’927 patients with 1’776 sets of X rays available within these episodes. Similarly, 8’136 episodes of LDA in 6’765 patients and 2’358 sets of X rays were present within these intervals. For patients in LDA or remission, rates of repair were 5.5% and 4.8%, respectively, while for radiographic progression >5 points in the Ratingen score/year were 10.3% in both groups and for >2 points change of Ratingen score/year were 27.7 and 25.4%, respectively).No differences for demographic factors or measures of disease activity, rheumatoid factor or ACPA were found comparing patients with radiographic progression or non-progression despite LDA or remission at the beginning of the episode of LDA and/or remission.Interestingly, 42.9% of patients in LDA with progression of >5 points in the Ratingen score/year were current smokers vs 29.4% among the non-progressors (X2 = 6.55, p = 0.01). This significant difference vanished when the cut-off for radiographic progression was set at >2 points yearly change in Ratingen score or in patients in remission.Conclusion:Radiographic progression despite LDA or remission are more frequent than expected. No differences in radiographic progression were found comparing LDA and remission suggesting that the goal of LDA is appropriate. Smoking seems to be an independent risk factor for radiographic progression despite LDA. Why the effect of smoking could was not demonstrated in patients in remission, remains unclear.Disclosure of Interests:Lena Brandt: None declared, Hendrik Schulze-Koops: None declared, Thomas Hügle Consultant of: GSK, Abbvie, Pfizer, Jansen, Novartis, Eli Lilly., Michael J. Nissen Consultant of: Abbvie, Celgene, Eli-Lilly, Janssen, Novartis and Pfizer, Hasler paul Consultant of: Abbvie, Lilly, Rudiger Muller Consultant of: AbbVie, Novartis, Grant/research support from: Gebro


2010 ◽  
Vol 70 (3) ◽  
pp. 428-433 ◽  
Author(s):  
Pernille Bøyesen ◽  
Espen A Haavardsholm ◽  
Mikkel Østergaard ◽  
Désirée van der Heijde ◽  
Sølve Sesseng ◽  
...  

ObjectivesTo determine whether MRI and conventional (clinical and laboratory) measures of inflammation can predict 3-year radiographic changes measured by the van der Heijde Sharp score in patients with early rheumatoid arthritis (RA).Methods55 patients with RA with disease duration <1 year participated in this 3-year follow-up study. Patients were evaluated at baseline, 3, 6, 12 and 36 months by swollen and tender joint count, disease activity score based on 28-joint count, erythrocyte sedimentation rate (ESR), C reactive protein, MRI measures of synovitis, bone marrow oedema and tenosynovitis of the dominant wrist, as well as conventional x-rays of the hands and wrists.ResultsAll measures of inflammation decreased during the follow-up period. ESR, MRI synovitis and MRI bone marrow oedema were independent predictors of 3-year radiographic progression adjusted for age, sex and anti-citrullinated protein antibodies. The 1-year cumulative measures of MRI synovitis and bone marrow oedema provided an improved explanation of variation (adjusted R2) in radiographic change compared with the baseline MRI values (adjusted R2=0.32 and 0.20 vs 0.11 and 0.04, respectively).ConclusionsBoth baseline and 1-year cumulative measures of MRI synovitis and bone marrow oedema independently predicted 3-year radiographic progression. These results confirm that MRI synovitis and MRI bone marrow oedema precede radiographic progression in patients with early RA.


Cephalalgia ◽  
2016 ◽  
Vol 38 (2) ◽  
pp. 265-273 ◽  
Author(s):  
Jasna J Zidverc-Trajkovic ◽  
Tatjana Pekmezovic ◽  
Zagorka Jovanovic ◽  
Aleksandra Pavlovic ◽  
Milija Mijajlovic ◽  
...  

Objective To evaluate long-term predictors of remission in patients with medication-overuse headache (MOH) by prospective cohort study. Background Knowledge regarding long-term predictors of MOH outcome is limited. Methods Two hundred and forty MOH patients recruited from 2000 to 2005 were included in a one-year follow-up study and then subsequently followed until 31 December 2013. The median follow-up was three years (interquartile range, three years). Predictive values of selected variables were assessed by the Cox proportional hazard regression model. Results At the end of follow-up, 102 (42.5%) patients were in remission. The most important predictors of remission were lower number of headache days per month before the one-year follow-up (HR-hazard ratio = 0.936, 95% confidence interval (CI) 0.884–0.990, p = 0.021) and efficient initial drug withdrawal (HR = 0.136, 95% CI 0.042–0.444, p = 0.001). Refractory MOH was observed in seven (2.9%) and MOH relapse in 131 patients (54.6%). Conclusions Outcome at the one-year follow-up is a reliable predictor of MOH long-term remission.


2014 ◽  
Vol 153 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Natalia Marek-Trzonkowska ◽  
Małgorzata Myśliwiec ◽  
Anita Dobyszuk ◽  
Marcelina Grabowska ◽  
Ilona Derkowska ◽  
...  

2015 ◽  
Vol 8 ◽  
pp. CMAMD.S22155 ◽  
Author(s):  
Katsuaki Kanbe ◽  
Junji Chiba ◽  
Yasuo Inoue ◽  
Masashi Taguchi ◽  
Akiko Yabuki

In order to investigate the predictive factors related to clinical efficacy and radiographic progression at 24 weeks by looking at the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 including baseline characteristics in patients with rheumatoid arthritis (RA) treated with golimumab, serum concentrations of TNF-α and IL-6 were analyzed every 4 weeks up to 24 weeks in 47 patients treated with golimumab. Baseline levels of the Disease Activity Score 28 C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI) scores were also assessed. Radiographic progression using the van der Heijde-modified Sharp (vdH-S) score was assessed in 29 patients. Multiple regression analyses related to the DAS28-CRP score and delta total sharp score at 24 weeks was undertaken using the baseline characteristics of patients and serum concentrations of matrix metalloproteinase (MMP)-3, TNF-α, and IL–6. The DAS28-CRP score and SDAI decreased significantly at 4 weeks up to 24 weeks compared with baseline. Serum levels of TNF-α were not changed significantly up to 24 weeks compared with baseline, but those of IL-6 decreased significantly at 4 weeks up to 8 weeks. Multiple regression analyses showed that disease duration and serum levels of MMP-3 were related significantly to the DAS28-CRP score at 24 weeks. Radiographic progression was related significantly to disease duration with regard to joint space narrowing and bone erosion. However, serum levels of TNF-α and IL-6 were not correlated significantly with the DAS28-CRP score and radiographic progression. These data suggest that decreasing serum levels of IL-6 significantly, MMP-3, and disease duration are predictive factors for RA activity in patients taking golimumab.


2020 ◽  
pp. jrheum.200743
Author(s):  
Alan M. Rathbun ◽  
Bryant R. England ◽  
Ted R. Mikuls ◽  
Alice S. Ryan ◽  
Jennifer L. Barton ◽  
...  

Objective Depression is common in rheumatoid arthritis (RA) patients, exacerbates disease activity, and may decrease response to first-line disease-modifying antirheumatic drugs. This study aimed to determine if depression affects disease activity among Veterans with early RA prescribed methotrexate (MTX). Methods Participants included Veterans enrolled in the Veterans Affairs Rheumatoid Arthritis registry with early RA (onset < 2 years) prescribed MTX. Depression was assessed at enrollment using International Classification of Diseases codes (296.2-296.39, 300.4, 311). Disease activity was measured using the 28 joint count disease activity score (DAS-28) and other core measures of RA disease activity. Propensity score weights were used to adjust depressed (n=48) and non-depressed (n=220) patients on baseline confounders within imputed datasets. Weighted estimating equations were used to assess standardized mean differences in disease activity between depressed and non-depressed patients at six months and one- and two-years follow-up. Results The analytic sample was composed of 268 Veterans with early RA prescribed MTX who were predominantly male (n=239; 89.2%) and older (62.7 years ± 10.6) than general population RA patients. Adjusted estimates indicated that depression was associated with significantly higher DAS-28 at six months (β=0.345; 95% CI: 0.007, 0.682) but not at one- or two-years follow-up. Also, depression was associated with significantly worse pain at six months (β=0.385; 95% CI: 0.040, 0.730) and one-year (β=0.396; 95% CI: 0.042, 0.750) follow-up. Conclusion In early RA, depression is associated with greater short-term disease activity during MTX treatment, as well as more persistent and severe pain.


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