scholarly journals THU0060 ELEVATED SYNOVIAL MUC1 EXPRESSION IS ASSOCIATED WITH JOINT DAMAGE AND ONE-YEAR RADIOGRAPHIC PROGRESSION IN RHEUMATOID ARTHRITIS

2019 ◽  
Author(s):  
Yaoyao Zou ◽  
Jun Jing ◽  
Jiale Qin ◽  
Feng Zhou ◽  
Ting Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Muc1 Expression ◽  
One Year

scholarly journals Baricitinib inhibits structural joint damage progression in patients with rheumatoid arthritis—a comprehensive review

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Paul Emery ◽  
Patrick Durez ◽  
Axel J. Hueber ◽  
Inmaculada de la Torre ◽  
Esbjörn Larsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Janus Kinase ◽  
X Rays ◽  
Phase 3 ◽  
Once Daily ◽  
Positive Effects ◽  
Damage Progression ◽  
Structural Joint

AbstractBaricitinib is an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 that has proved effective and well tolerated in the treatment of rheumatoid arthritis (RA) in an extensive programme of clinical studies of patients with moderate-to-severe disease. In a phase 2b dose-ranging study of baricitinib in combination with traditional disease-modifying antirheumatic drugs (DMARDs) in RA patients, magnetic resonance imaging showed that baricitinib 2 mg or 4 mg once daily provided dose-dependent suppression of synovitis, osteitis, erosion and cartilage loss at weeks 12 and 24 versus placebo. These findings correlated with clinical outcomes and were confirmed in three phase 3 studies (RA-BEGIN, RA-BEAM and RA-BUILD) using X-rays to assess structural joint damage. In patients naïve to DMARDs (RA-BEGIN study), baricitinib 4 mg once daily as monotherapy or combined with methotrexate produced smaller mean changes in structural joint damage than methotrexate monotherapy at week 24. Differences versus methotrexate were statistically significant for combined therapy. In patients responding inadequately to methotrexate (RA-BEAM study), baricitinib 4 mg plus background methotrexate significantly inhibited structural joint damage at week 24 versus placebo, and the results were comparable to those observed with adalimumab plus background methotrexate. In patients responding inadequately to conventional synthetic DMARDs (csDMARDs; RA-BUILD study), baricitinib 4 mg again significantly inhibited radiographic progression compared with placebo at week 24. Benefits were also observed with baricitinib 2 mg once daily, but the effects of baricitinib 4 mg were more robust. The positive effects of baricitinib 4 mg on radiographic progression continued over 1 and 2 years in the long-term extension study RA-BEYOND, with similar effects to adalimumab and significantly greater effects than placebo. Findings from the phase 3 studies of patients with RA were supported by preclinical studies, which showed that baricitinib has an osteoprotective effect, increasing mineralisation in bone-forming cells. In conclusion, baricitinib 4 mg once daily inhibits radiographic joint damage progression in patients with moderate-to-severe RA who are naïve to DMARDs or respond inadequately to csDMARDs, including methotrexate, and the beneficial effects are similar to those observed with adalimumab.

scholarly journals OP0185 RADIOGRAPHIC PROGRESSION DESPITE PERSISTENT LDA OR REMISSION IS INFLUENCED BY CURRENT SMOKING RATHER THAN THE RESPECTIVE DAS 28 LEVEL, RESULTS OF THE SWISS RHEUMATOID ARTHRITIS REGISTER (SCQM)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 112.1-112
Author(s):  
L. Brandt ◽  
H. Schulze-Koops ◽  
T. Hügle ◽  
M. J. Nissen ◽  
H. Paul ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Radiographic Progression ◽  
X Rays ◽  
Das28 Score ◽  
Das 28 ◽  
Significant Difference ◽  
Control Disease ◽  
One Year ◽  
Ratingen Score

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

scholarly journals Low rates of radiographic progression of structural joint damage over 2 years of baricitinib treatment in patients with rheumatoid arthritis

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000898 ◽  
Author(s):  
Desirée van der Heijde ◽  
Michael Schiff ◽  
Yoshiya Tanaka ◽  
Li Xie ◽  
Gabriella Meszaros ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Combination Therapy ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Phase Iii ◽  
Inadequate Response ◽  
Smallest Detectable Change ◽  
Structural Joint ◽  
Synthetic Dmards ◽  
Modified Total Sharp Score

ObjectivesTo evaluate radiographic progression of structural joint damage over 2 years in patients with rheumatoid arthritis from baricitinib clinical trials who were disease-modifying antirheumatic drug (DMARD)–naïve or had an inadequate response to conventional synthetic DMARDs (csDMARD-IR).MethodsPatients had completed one of three phase III studies and entered a long-term extension (LTE) study, continuing on the same baricitinib dose as at originating study completion. At 52 weeks, DMARD-naïve patients receiving methotrexate (MTX) or combination therapy (baricitinib 4 mg+MTX) were switched to baricitinib 4 mg monotherapy (±MTX per investigator opinion); MTX-IR patients receiving adalimumab were switched to baricitinib 4 mg on background MTX. At 24 weeks, csDMARD-IR patients receiving placebo were switched to baricitinib 4 mg on background csDMARD. Radiographs at baseline, year 1 and year 2 were scored using the van der Heijde modified Total Sharp Score. Linear extrapolation was used for missing data.ResultsOf 2573 randomised patients, 2125 (82.6%) entered the LTE, of whom 1893 (89.1%) entered this analysis. At year 2, progression was significantly lower with initial baricitinib (monotherapy or combination therapy) versus initial MTX in DMARD-naïve patients (proportion with non-progression defined by ≤smallest detectable change (SDC): 87.3% baricitinib 4 mg+MTX; 70.6% MTX; p≤ 0.001). In MTX-IR patients, progression with initial baricitinib was significantly lower than with initial placebo and similar to initial adalimumab (≤SDC: 82.7% baricitinib 4 mg; 83.5% adalimumab; 70.6% placebo; p≤0.001). In csDMARD-IR patients, significant benefit was seen with baricitinib 4 mg (≤SDC: 87.2% vs 73.2% placebo; p≤0.01).ConclusionsTreatment with once-daily baricitinib resulted in low rates of radiographic progression for up to 2 years.

Effect on efficacy and safety trial outcomes of also enrolling patients on ongoing glucocorticoid therapy in rheumatoid arthritis clinical trials of tocilizumab or adalimumab or methotrexate monotherapy

2020 ◽  
Vol 79 (4) ◽  
pp. 460-463 ◽  
Author(s):  
Mary Safy-Khan ◽  
Johannes W G Jacobs ◽  
Maria J H de Hair ◽  
Paco M J Welsing ◽  
Michael D Edwardes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Incidence Rates ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety Outcomes ◽  
Trial Outcomes

BackgroundIn rheumatoid arthritis (RA) trials, inclusion of patients on background treatment with glucocorticoids (GCs) might impact efficacy and safety outcomes.ObjectivesTo determine if inclusion of patients on background GC use influenced efficacy and safety outcomes of RA randomised clinical trials on initiation of tocilizumab (TCZ) or adalimumab (ADA) or methotrexate (MTX) monotherapy.MethodsData of four double-blind RA randomised controlled trials (AMBITION, ACT-RAY, ADACTA and FUNCTION) with in total four TCZ, one ADA and two MTX monotherapy arms were analysed. Analyses of covariance of changes from baseline to week 24 in efficacy endpoints and radiographic progression up to week 104 were performed, correcting for relevant covariates. Incidence rates of serious adverse events (SAEs) were assessed.ResultsNo statistically significant differences were found in efficacy parameters between background GC users and non-GC users, except for less radiographic progression associated with GC usage in one MTX arm. SAE rates were not statistically significantly different between GC users and non-GC users in the treatment arms.ConclusionNo effect of including patients on background GC treatment on efficacy and safety trial outcomes was found, with the exception of reduced radiological joint damage in one MTX arm.

scholarly journals Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of joint damage in Japanese patients with early rheumatoid arthritis: the HOPEFUL 1 study

2013 ◽  
Vol 73 (3) ◽  
pp. 536-543 ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Hisashi Yamanaka ◽  
Naoki Ishiguro ◽  
Nobuyuki Miyasaka ◽  
Masaya Mukai ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Japanese Patients ◽  
High Disease Activity ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Modified Total Sharp Score

ObjectivesTo evaluate the efficacy and safety of adalimumab+methotrexate (MTX) in Japanese patients with early rheumatoid arthritis (RA) who had not previously received MTX or biologics.MethodsThis randomised, double-blind, placebo-controlled, multicentre study evaluated adalimumab 40 mg every other week+MTX 6–8 mg every week versus MTX 6–8 mg every week alone for 26 weeks in patients with RA (≤2-year duration). The primary endpoint was inhibition of radiographic progression (change (Δ) from baseline in modified total Sharp score (mTSS)) at week 26.ResultsA total of 171 patients received adalimumab+MTX (mean dose, 6.2±0.8 mg/week) and 163 patients received MTX alone (mean dose, 6.6±0.6 mg/week, p<0.001). The mean RA duration was 0.3 years and 315 (94.3%) had high disease activity (DAS28>5.1). Adalimumab+MTX significantly inhibited radiographic progression at week 26 versus MTX alone (ΔmTSS, 1.5±6.1 vs 2.4±3.2, respectively; p<0.001). Significantly more patients in the adalimumab+MTX group (62.0%) did not show radiographic progression (ΔmTSS≤0.5) versus the MTX alone group (35.4%; p<0.001). Patients treated with adalimumab+MTX were significantly more likely to achieve American College of Rheumatology responses and achieve clinical remission, using various definitions, at 26 weeks versus MTX alone. Combination therapy was well tolerated, and no new safety signals were observed.ConclusionsAdalimumab in combination with low-dose MTX was well tolerated and efficacious in suppressing radiographic progression and improving clinical outcomes in Japanese patients with early RA and high disease activity.

scholarly journals Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients

2019 ◽  
Vol 78 (6) ◽  
pp. 761-772 ◽  
Author(s):  
Frances Humby ◽  
Myles Lewis ◽  
Nandhini Ramamoorthi ◽  
Jason A Hackney ◽  
Michael R Barnes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
B Cells ◽  
Disease Activity ◽  
Treatment Response ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Molecular Signatures ◽  
Early Ra ◽  
Treatment Naïve

ObjectivesTo unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally.Methods144 consecutive treatment-naïve early RA patients (<12 months symptoms duration) underwent ultrasound-guided synovial biopsy before and 6 months after disease-modifying antirheumatic drug (DMARD) initiation. Synovial biopsies were analysed for cellular (immunohistology) and molecular (NanoString) characteristics and results compared with clinical and imaging outcomes. Differential gene expression analysis and logistic regression were applied to define variables correlating with treatment response and predicting radiographic progression.ResultsCellular and molecular analyses of synovial tissue demonstrated for the first time in early RA the presence of three pathology groups: (1) lympho-myeloid dominated by the presence of B cells in addition to myeloid cells; (2) diffuse-myeloid with myeloid lineage predominance but poor in B cells nd (3) pauci-immune characterised by scanty immune cells and prevalent stromal cells. Longitudinal correlation of molecular signatures demonstrated that elevation of myeloid- and lymphoid-associated gene expression strongly correlated with disease activity, acute phase reactants and DMARD response at 6 months. Furthermore, elevation of synovial lymphoid-associated genes correlated with autoantibody positivity and elevation of osteoclast-targeting genes predicting radiographic joint damage progression at 12 months. Patients with predominant pauci-immune pathology showed less severe disease activity and radiographic progression.ConclusionsWe demonstrate at disease presentation, prior to pathology modulation by therapy, the presence of specific cellular/molecular synovial signatures that delineate disease severity/progression and therapeutic response and may pave the way to more precise definition of RA taxonomy, therapeutic targeting and improved outcomes.

FCRL3 –169C/C Genotype Is Associated with Anti-citrullinated Protein Antibody-positive Rheumatoid Arthritis and with Radiographic Progression

2011 ◽  
Vol 38 (11) ◽  
pp. 2329-2335 ◽  
Author(s):  
MARTHE T. MAEHLEN ◽  
GRY B. NORDANG ◽  
SILJE W. SYVERSEN ◽  
DÉSIRÉE M. van der HEIJDE ◽  
TORE K. KVIEN ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Susceptibility ◽  
Disease Duration ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Promoter Polymorphism ◽  
Erythrocyte Sedimentation ◽  
Number Of Patients ◽  
Autoantibody Status ◽  
Citrullinated Protein

Objective.Studies of Caucasian populations have shown conflicting results concerning the association between a promoter polymorphism –169T>C of the Fc receptor-like 3 (FCRL3) gene and rheumatoid arthritis (RA). It is unknown whether FCRL3 is associated with autoantibody status and disease severity. We investigated associations between FCRL3 –169T>C and autoantibody status and joint damage in patients with RA.Methods.A total of 652 Norwegian patients with RA from 2 cohorts and 981 Norwegian controls, previously genotyped for FCRL3 –169T>C (rs7528684), were studied. Data on anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) were available. The EURIDISS cohort (disease duration ≤ 4 yrs at baseline) was followed longitudinally, with assessment of radiographic hand damage at baseline and after 10 years (n = 117) according to the van der Heijde-modified Sharp score.Results.We found significant associations with ACPA-positive RA for both the C allele (OR 1.28, 95% CI 1.08–1.52, p = 0.004) and the C/C genotype (OR 1.57, 95% CI 1.18–2.10, p = 0.002). Similar associations were seen with RF-positive RA. No association was found with ACPA-negative or RF-negative RA. The C/C genotype was found to be associated with 10-year radiographic progression in multivariate linear and logistic regression analyses, after adjustment for ACPA, erythrocyte sedimentation rate, age, and sex.Conclusion.The promoter polymorphism of FCRL3 was associated with autoantibody-positive RA. Despite the low number of patients, the C/C genotype of the FCRL3 polymorphism consistently and independently predicted radiographic progression. These findings suggest that FCRL3 is involved in both disease susceptibility and progression.

scholarly journals Predictive value of anti-CarP and anti-PAD3 antibodies alone or in combination with RF and ACPA for the severity of rheumatoid arthritis

Rheumatology ◽  
2021 ◽  
Author(s):  
Celine Lamacchia ◽  
Delphine S Courvoisier ◽  
Matthias Jarlborg ◽  
Sylvette Bas ◽  
Pascale Roux-Lombard ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
High Risk ◽  
Quality Management ◽  
Predictive Value ◽  
Radiographic Progression ◽  
Axial Spondyloarthritis ◽  
Joint Damage ◽  
Arginine Deiminase ◽  
Radiographic Damage ◽  
Type 3

Abstract Objectives The objective of this study was to analyse the predictive value of anti-carbamylated protein (anti-CarP) and anti-peptidyl-arginine deiminase type-3 (anti-PAD3) antibodies, alone or in combination with RF and ACPA, to identify patients at high risk of developing severe RA outcomes. Methods Patients within the Swiss Clinical Quality Management registry with a biobank sample were tested for RF, ACPA, anti-CarP, and anti-PAD3 antibodies. We examined the association of each autoantibody with DAS28, HAQ and radiographic damage (Ratingen) at baseline and longitudinally. Results Analyses included 851 established RA patients and 516 disease controls [axial spondyloarthritis (axSpA = 320) and PsA (196)]. Anti-CarP and anti-PAD3 antibodies were, respectively, present in 22.4% and 10.7% of the whole RA population, and in 13.2% and 3.8% of the RF and ACPA double seronegative patients. At baseline, RA patients with anti-PAD3 had higher DAS28 (4.2 vs 3.7; P= 0.005) and significantly more radiographic damage (14.9 vs 8.8; P= 0.02) than anti-PAD3-negative patients. In the ACPA-negative subgroup, baseline Ratingen scores were significantly higher in anti-PAD3-positive patients (P= 0.01). The combination of anti-PAD3, RF IgM, and ACPA was associated with significantly higher baseline radiographic scores than the double seropositive group (P= 0.04). The presence of any two of the previous autoantibodies was associated with significantly greater radiographic progression over 10 years than if all were absent (P= 0.02). There were no differences in RA outcome measures with regards to anti-CarP. Conclusions Anti-PAD3 antibodies are associated with higher disease activity and joint damage scores in RA patients.

Sign in / Sign up

Export Citation Format

Share Document