Evaluation of Serum Biomarkers Associated with Radiographic Progression in Methotrexate-naive Rheumatoid Arthritis Patients Treated with Methotrexate or Golimumab

2013 ◽  
Vol 40 (5) ◽  
pp. 590-598 ◽  
Author(s):  
Carrie Wagner ◽  
Dion Chen ◽  
Hongtao Fan ◽  
Elizabeth C. Hsia ◽  
Michael Mack ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Statistical Significance ◽  
Tumor Necrosis Factor Inhibitor ◽  
Cd40 Ligand ◽  
Joint Space ◽  
Protein Profiling ◽  
Serum Samples ◽  
Markers Of Inflammation ◽  
Factor Inhibitor

Objective.To evaluate associations between biomarkers and radiographic progression in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) treated with MTX or golimumab, a tumor necrosis factor inhibitor (with or without MTX).Methods.Serum samples from 152 MTX-naive adults with active RA who received placebo + MTX (n = 37) or golimumab (combined 50 mg + MTX or 100 mg ± MTX; n = 115) were analyzed for selected markers of inflammation and bone/cartilage turnover. One hundred patients were randomly selected for additional protein profiling using multianalyte profiles (HumanMap v1.6, Rules Based Medicine). Radiographs at baseline, Week 28, and Week 52 were scored using van der Heijde-Sharp (vdH-S) methodology. Correlations were assessed between biomarker levels (baseline and change at Week 4) and joint space narrowing, erosion, and total vdH-S scores (changes at Weeks 28 and 52). Statistical significance was defined as a correlation coefficient with an absolute value ≥ 0.3 and p < 0.05.Results.Biomarker correlations with changes in vdH-S scores at Week 28 and/or 52 were observed predominantly in the placebo + MTX group and rarely in the combined golimumab treatment group. Changes in epidermal growth factor (EGF) and CD40 ligand (CD40L) at Week 4 were positively correlated with changes in total vdH-S scores at Weeks 28 and 52 in the placebo + MTX group.Conclusion.These preliminary findings indicate that EGF and CD40L may have utility in monitoring MTX-treated patients with RA who are more likely to have radiographic progression as measured by increases in vdH-S scores.

scholarly journals AB0245 ANALYSIS OF THE CLINICAL AND ANTIDESTRUCTIVE EFFECTS OF RITUXIMAB DEPENDING ON GENDER IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1147.3-1148
Author(s):  
A. Kudryavtseva ◽  
G. Lukina ◽  
E. Aronova ◽  
G. Gridneva ◽  
S. Glukhova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Effect ◽  
Radiographic Progression ◽  
Statistical Significance ◽  
Joint Space ◽  
Scoring Method ◽  
X Ray ◽  
Effective Inhibition ◽  
High Degree ◽  
The Impact

Background:Rheumatoid arthritis is a chronic autoimmune disease characterized by inflammation of the synovial tissue and destruction of the underlying cartilage and bones. It was found that RA more often affects women than men, with a sex ratio of 3: 1. And the question of the influence of gender on the outcomes and course of RA remains controversial, there is no consensus on whether RA is worse in women or men. Recent reports indicate that women are less likely to achieve remission than men. Women suffer from RA at an earlier age and have higher markers of disease activity such as DAS28 and HAQ. Rituximab is a chimeric monoclonal antibody that targets the CD20 molecule expressed on the surface of B cells, it has been successfully and widely used for the treatment of rheumatoid arthritis, so it is of interest to assess whether gender influences the therapeutic and radiological effects of RTX.Objectives:The aim of this study was to analyze the impact of gender on the response to rituximab (RTX) in patients with RA.Methods:Initially, 221 women(w), 27 men(m), were examined to assess the clinical and X-ray effect (88w/6m), who received RTX treatment (1000 mgx2 or 500 mgx2). Both groups were comparable in terms of the main clinical and laboratory characteristics (age, duration of the disease, the number of preceding DMARDs, in both groups most patients were RF + and ACCP +, a high degree of activity according to DAS 8 - men - 5.6 [4.6-6.7], women - 6.04 [5.2-6.63] Initially, the degree of radiological changes in men is slightly higher than in women (p> 0.05). Clinical effect was scored by EULAR criteria, radiographic progression was assessed using Sharp/van der Heijde modified scoring method.Results:When assessing the clinical effect after 48 weeks in men, a significantly better effect of RTX treatment was noted in comparison with women (Δ DAS28, a significantly better effect was noted in men - Δ DAS28 =3.75[2.8-4.14], and Δ DAS28=1.3[0.37-2.72] in women, (p=0.04). Analyzing the X-ray effect after 48 weeks of RTM treatment: the absence of progression in terms of the total score in 83.33% of men and 60.98% of women; there was no progression in narrowing of the joint space in 83.33% of men and 65.85% of women, noteworthy that the account of erosion practically reaches statistical significance - inhibition of destruction in 100% of men and 74.31% of women (p = 0.06).Conclusion:Thus, having analyzed the clinical and antidestructive effects of RTM therapy depending on gender, we can conclude that the effect is significantly higher in the male group. Also, there is a tendency towards more effective inhibition of radiographic progression in men.Disclosure of Interests:None declared

scholarly journals Increased radiographic progression of distal hand osteoarthritis occurring during biologic DMARD monotherapy for concomitant rheumatoid arthritis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
C. A. Lechtenboehmer ◽  
T. Burkard ◽  
S. Reichenbach ◽  
U. A. Walker ◽  
A. M. Burden ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Space Narrowing ◽  
Radiographic Progression ◽  
Cox Regression ◽  
Joint Space ◽  
Estimating Equation ◽  
Considerable Proportion ◽  
Hand Osteoarthritis ◽  
Increased Risk ◽  
Subchondral Sclerosis

Abstract Objectives A considerable proportion of patients with rheumatoid arthritis (RA) also suffer from hand osteoarthritis (OA). We here assess the association between conventional synthetic (cs) and biological (b) disease-modifying antirheumatic drugs (DMARDs) and radiographic distal interphalangeal-(DIP) OA in patients with RA. Methods Adult RA patients from a longitudinal Swiss registry of rheumatic diseases who had ≥ 2 hand radiographs were included at the first radiograph and followed until the outcome or the last radiograph. Patients were grouped into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Modified Kellgren-Lawrence scores (KLS) were obtained by evaluating DIP joints for the severity of osteophytes, joint space narrowing, subchondral sclerosis, and erosions. KLS ≥ 2 in ≥ 1 DIP joint indicated incident or existing OA, and increase of ≥ 1 in KLS in ≥ 1 DIP joint indicated progression in existing DIP OA. Time-varying Cox regression and generalized estimating equation (GEE) analyses were performed. We estimated hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) of DIP OA incidence (cohort 2), or progression (cohort 1), in bDMARD monotherapy, bDMARD/csDMARD combination therapy, and past or never DMARD use, when compared to csDMARD use. In post hoc analyses, we descriptively and analytically assessed the individual KLS features in cohort 1. Results Among 2234 RA patients with 5928 radiographs, 1340 patients had DIP OA at baseline (cohort 1). Radiographic progression of DIP OA was characterized by new or progressive osteophyte formation (666, 52.4%), joint space narrowing (379, 27.5%), subchondral sclerosis (238, 17.8%), or erosions (62, 4.3%). bDMARD monotherapy had an increased risk of radiographic DIP OA progression compared to csDMARD monotherapy (adjusted HR 1.34 [95% CI 1.07–1.69]). The risk was not significant in csDMARD/bDMARD combination users (HR 1.12 [95% CI 0.96–1.31]), absent in past DMARD users (HR 0.96 [95% CI 0.66–1.41]), and significantly lower among never DMARD users (HR 0.54 [95% CI 0.33–0.90]). Osteophyte progression (HR 1.74 [95% CI 1.11–2.74]) was the most significantly increased OA feature with bDMARD use compared to csDMARD use. In 894 patients without initial DIP OA (cohort 2), the risk of incident OA did not differ between the treatment groups. The results from GEE analyses corroborated all findings. Conclusions These real-world RA cohort data indicate that monotherapy with bDMARDs is associated with increased radiographic progression of existing DIP OA, but not with incident DIP OA.

Effectiveness of a second biologic after failure of a non-tumor necrosis factor inhibitor as first biologic in rheumatoid arthritis

2021 ◽  
pp. jrheum.201467
Author(s):  
Katerina Chatzidionysiou ◽  
Merete Lund Hetland ◽  
Thomas Frisell ◽  
Daniela Di Giuseppe ◽  
Karin Hellgren ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Inhibitor ◽  
Primary Response ◽  
Low Disease Activity ◽  
Factor Inhibitor ◽  
Disease Modifying ◽  
Necrosis Factor

Objective In Rheumatoid Arthritis (RA), evidence regarding the effectiveness of a second biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in patients whose first ever bDMARD was a non-tumor-necrosis-factor-inhibitor (TNFi) bDMARD is limited. The objective of this study was therefore to assess the outcome of the second bDMARD (non-TNFi [rituximab, abatacept or tocilizumab, separately] and TNFi) after failure of a non-TNFi bDMARD as first bDMARD. Methods We identified RA patients from the five Nordic biologics registers started treatment with a non-TNFi as first ever bDMARD but switched to a second bDMARD. For the second bDMARD, we assessed survival-on-drug (at 6 and 12 months), and primary response (at 6 months). Results We included 620 patients starting a second bDMARD (ABA 86, RTX 40, TCZ 67 and TNFi 427) following failure of a first non-TNFI bDMARD. At 6 and 12 months after start of their second bDMARD, around 70% and 50%, respectively, remained on treatment, and at 6 months less than one third of patients were still on their second bDMARD and had reached low disease activity or remission according to DAS28. For those patients whose second bMDARD was a TNFI, the corresponding proportion was slightly higher (40%). Conclusion The survival-on-drug and primary response of a second bDMARD in RA patients switching due to failure of a non-TNFi bDMARD as first bDMARD is modest. Some patients may benefit from TNFi when used after failure of a non-TNFi as first bDMARD.

scholarly journals Perceived clinical utility of a test for predicting inadequate response to TNF inhibitor therapies in rheumatoid arthritis: results from a decision impact study

2020 ◽  
Author(s):  
Dimitrios A. Pappas ◽  
Christine Brittle ◽  
James E. Mossell ◽  
Johanna B. Withers ◽  
Jeraldine Lim-Harashima ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Decision Making ◽  
Clinical Utility ◽  
Tumor Necrosis Factor Inhibitor ◽  
Medical Decision ◽  
Inadequate Response ◽  
Tnf Inhibitor ◽  
Financial Outcomes ◽  
Factor Inhibitor ◽  
Therapeutic Decision Making

AbstractTumor necrosis factor inhibitor (TNFi) therapies are often the first biologic therapy used to treat rheumatoid arthritis (RA) patients. However, a substantial fraction of patients do not respond adequately to TNFi therapies. A test with the ability to predict response would inform therapeutic decision-making and improve clinical and financial outcomes. A 32-question decision-impact survey was conducted with 248 rheumatologists to gauge the perceived clinical utility of a novel test that predicts inadequate response to TNFi therapies in RA patients. Participants were informed about the predictive characteristics of the test and asked to indicate prescribing decisions based on four result scenarios. Overall, rheumatologists had a favorable view of the test: 80.2% agreed that it would improve medical decision-making, 92.3% said it would increase their confidence when making prescribing decisions, and 81.5% said it would be useful when considering TNFi therapies. Rheumatologists would be more likely to prescribe a TNFi therapy when the test reported that no signal of non-response was detected (79.8%) and less likely to prescribe a TNFi therapy when a signal of non-response was detected (11.3%–25.4%). Rheumatologists (84.7%) agreed that payers should provide coverage for such a test. This study shows that rheumatologists support the clinical need for a test to predict inadequate response to TNFi therapies. Test results were perceived to lead to changes in prescribing behaviors as results instill confidence in the ordering rheumatologist.

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