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.

Prevention of Appearance of Radiological Lesions in Early Rheumatoid Arthritis: A Randomized, Single-Blind Study Comparing Intra-Articular Rifamycin with Auranofin

1992 ◽  
Vol 20 (1) ◽  
pp. 61-77 ◽  
Author(s):  
I Caruso ◽  
S Santandrea ◽  
P Sarzi Puttini ◽  
F Montrone ◽  
L Boccassini ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
Disease Duration ◽  
Blind Study ◽  
Erythrocyte Sedimentation ◽  
Rifamycin Sv ◽  
Number Of Patients ◽  
Single Blind ◽  
Latex Test

In a prospective, randomized, single-blind study of 116 patients with early rheumatoid arthritis (mean disease duration 7 months), therapeutic activity of intra-articular rifamycin SV (525 mg/week) infiltration into each peripheral joint over 10 weeks was compared with that of 3 mg auranofin given orally twice daily. The incidence of side-effects was lower in rifamycin-treated patients. At the end of follow-up, the clinical variables and erythrocyte sedimentation rate showed a significant and persistant improvement both in 16 patients who continued the auranofin treatment regularly and in 55 treated with rifamycin who had completed the therapeutic cycle 62.5 months before; the latex test decreased only in the rifamycin group. In patients treated with auranofin or who changed to other commonly used antirheumatic agents, 57% of those with an initially negative radiological picture developed new radiological lesions in at least one of the small joints compared with 9% in the rifamycin group. Although the number of patients treated with rifamycin was small and the follow-up relatively short, the results of the study indicated that treatment with intra-articular rifamycin SV may prevent the appearance of radiological lesions in patients with early rheumatoid arthritis and normal radiographs initially.

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 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 Associations between APOE Genotypes and Disease Susceptibility, Joint Damage and Lipid Levels in Patients with Rheumatoid Arthritis

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e60970 ◽  
Author(s):  
Marthe T. Maehlen ◽  
Sella A. Provan ◽  
Diederik P. C. de Rooy ◽  
Annette H. M. van der Helm - van Mil ◽  
Annemarie Krabben ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Susceptibility ◽  
Joint Damage ◽  
Lipid Levels ◽  
Apoe Genotypes

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 Predictive Factors Related to the Efficacy of Golimumab in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 8 ◽  
pp. CMAMD.S22155 ◽  
Author(s):  
Katsuaki Kanbe ◽  
Junji Chiba ◽  
Yasuo Inoue ◽  
Masashi Taguchi ◽  
Akiko Yabuki
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Predictive Factors ◽  
Disease Duration ◽  
Radiographic Progression ◽  
Serum Levels ◽  
Serum Concentrations ◽  
Regression Analyses ◽  
Tnf Α ◽  
Baseline Characteristics

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.

scholarly journals The impact of therapies as monotherapy with combined therapy on novel and traditional biomarkers in patients with rheumatoid arthritis

2020 ◽  
Vol 24 (3) ◽  
pp. 325-332
Author(s):  
Asmaa Haydar ◽  
Ijlal Abdullah
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Markers ◽  
Combined Therapy ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Erythrocyte Sedimentation ◽  
Group I ◽  
Group Ii ◽  
Citrullinated Protein ◽  
Citrullinated Peptide

Background and objectives: Rheumatoid arthritis is an autoimmune and inflammatory disease that influences many tissues and organs. Inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate, anti-cyclic citrullinated protein, rheumatoid factor, and 14-3-3η protein have been found to play an important role in both the diagnosis and progression of rheumatoid arthritis. This study aimed to elucidate the effect of anti-rheumatoid medication, as mono- and combined therapy, on these inflammatory mediators. Methods: A cross-sectional study was performed at Hawler Medical University, College of Pharmacy, Erbil, Iraq. Forty-two patients of both genders with rheumatoid arthritis participated in the study as group I. Forty-four age–gender matched adults (with no rheumatoid arthritis) were included as a comparison group or group II. Serum levels of biomarkers were determined by enzyme linked immune sorbent assay. Results: There was a statistically significant (P <0.05) increased level of serum anti-cyclic citrullinated peptide, 14-3-3η protein, erythrocyte sedimentation rate, C-reactive protein, and rheumatic factor levels in group I compared with group II. The serum level of the anti-cyclic citrullinated peptide significantly decreased in rheumatoid patients treated with combined therapy compared with mono remedy. However, the mean of body mass index, age, and gender of group I was non-significantly different from group II (P >0.05). Conclusion: Therapeutic regimen of mono or combined therapy played a role in changing levels of inflammatory markers. Anti-cyclic citrullinated protein significantly decreased with the combined therapy in comparison with the monotherapy regimen. Keywords: Rheumatic arthritis; Monotherapy; Combined therapy; Anti-rheumatoid; Inflammatory markers.

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