scholarly journals Maintenance of low disease activity and remission with etanercept–disease-modifying antirheumatic drug (DMARD) combination therapy compared with treatment with DMARDs alone in Latin American patients with active rheumatoid arthritis

Medicine ◽  
2018 ◽  
Vol 97 (36) ◽  
pp. e11989
Author(s):  
Cristiano A.F. Zerbini ◽  
Carlos Abud-Mendoza ◽  
Paul Mendez-Patarroyo ◽  
Mauricio De Angelo Andrade ◽  
Ron Pedersen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Combination Therapy ◽  
Disease Activity ◽  
Latin American ◽  
Active Rheumatoid Arthritis ◽  
Antirheumatic Drug ◽  
Low Disease Activity ◽  
Disease Modifying ◽  
Disease Modifying Antirheumatic Drug

scholarly journals Results from a Phase IIA Parallel Group Study of JNJ-40346527, an Oral CSF-1R Inhibitor, in Patients with Active Rheumatoid Arthritis despite Disease-modifying Antirheumatic Drug Therapy

2015 ◽  
Vol 42 (10) ◽  
pp. 1752-1760 ◽  
Author(s):  
Mark C. Genovese ◽  
Elizabeth Hsia ◽  
Stanley M. Belkowski ◽  
Caly Chien ◽  
Tara Masterson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Primary Endpoint ◽  
Active Rheumatoid Arthritis ◽  
Antirheumatic Drug ◽  
Target Engagement ◽  
Dmard Therapy ◽  
Parallel Group ◽  
Disease Modifying ◽  
Disease Modifying Antirheumatic Drug

Objective.To assess the efficacy and safety of JNJ-40346527, a selective inhibitor of colony-stimulating factor-1 (CSF-1) receptor kinase that acts to inhibit macrophage survival, proliferation, and differentiation in patients with active rheumatoid arthritis (RA) despite disease-modifying antirheumatic drug (DMARD) therapy.Methods.In this randomized, double-blind, placebo-controlled, parallel group study, adults were randomized (2:1) to receive oral JNJ-40346527 100 mg or placebo twice daily through Week 12. Patients with RA had disease activity [≥ 6 swollen/≥ 6 tender joints, C-reactive protein (CRP) ≥ 0.8 mg/dl] despite DMARD therapy for ≥ 6 months. The primary endpoint was change from baseline at Week 12 in the 28-joint Disease Activity Score with CRP (DAS28-CRP). Pharmacokinetic/pharmacodynamic analyses were also performed, and safety was assessed through Week 16.Results.Ninety-five patients were treated (63 JNJ-40346527, 32 placebo); 8 patients discontinued treatment (6 JNJ-40346527, 2 placebo) through Week 12. Mean improvements in DAS28-CRP from baseline to Week 12 were 1.15 for the JNJ-40346527 group and 1.42 for the placebo group (p = 0.30); thus, a statistically significant difference was not observed for the primary endpoint. Pharmacokinetic exposure to JNJ-40346527 and its active metabolites was above the projected concentration needed for pharmacologic activity, and effective target engagement and proof of activity were demonstrated by increased levels of CSF-1 and decreased CD16+ monocytes in JNJ-40346527–treated, but not placebo-treated, patients. Thirty-seven (58.7%) JNJ-40346527–treated and 16 (50.0%) placebo-treated patients reported ≥ 1 adverse event (AE); 1 (1.6%) JNJ-40346527–treated and 3 (9.4%) placebo-treated patients reported ≥ 1 serious AE.Conclusion.Although adequate exposure and effective peripheral target engagement were evident, JNJ-40346527 efficacy was not observed in patients with DMARD-refractory active RA. ClinicalTrials.gov identifier: NCT01597739. EudraCT Number: 2011-004529-28.

scholarly journals Lack of association between CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with rheumatoid arthritis

2021 ◽  
Author(s):  
Małgorzata Łączna ◽  
Damian Malinowski ◽  
Agnieszka Paradowska-Gorycka ◽  
Krzysztof Safranow ◽  
Violetta Dziedziejko ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Antirheumatic Drug ◽  
Disease Modifying ◽  
Individual Disease ◽  
Disease Modifying Antirheumatic Drug

Abstract Aim Leflunomide is a disease-modifying antirheumatic drug used in therapy for rheumatoid arthritis (RA). Previous studies indicated that oestrogens and androgens may affect the response to leflunomide in RA patients. The synthesis of androgens is regulated by cytochrome CYB5A. The aim of this study was to examine the association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA. Methods The study included 111 women diagnosed with RA. Leflunomide was administered in monotherapy at a dose of 20 mg/day. All patients underwent a monthly evaluation for 12 months after the initiation of treatment with leflunomide. Results After 12 months of therapy, the changes in individual disease activity parameters, such as: DAS28, ESR, CRP and VAS, were not statistically significantly different between rs1790834 genotypes in the Kruskal–Wallis test. Conclusions The results of our study suggest lack of statistically significant association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA.

Plasma Adiponectin in Patients with Active, Early, and Chronic Rheumatoid Arthritis Who Are Steroid- and Disease-Modifying Antirheumatic Drug-Naive Compared with Patients with Osteoarthritis and Controls

2009 ◽  
Vol 36 (9) ◽  
pp. 1885-1891 ◽  
Author(s):  
TRINE BAY LAURBERG ◽  
JAN FRYSTYK ◽  
TORKELL ELLINGSEN ◽  
IB T. HANSEN ◽  
ANETTE JØRGENSEN ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Antirheumatic Drug ◽  
Joint Disease ◽  
Healthy Controls ◽  
Plasma Adiponectin ◽  
Activity Measures ◽  
Disease Modifying ◽  
Disease Modifying Antirheumatic Drug ◽  
Disease Activity Measures

Objective.Rheumatoid arthritis (RA) is a systemic chronic inflammatory joint disease, whereas osteoarthritis (OA) is a local joint disease with low-level inflammatory activity. The pathogenic role of the adipocytokine adiponectin is largely unknown in these diseases. We hypothesized (1) that plasma adiponectin concentrations differ in healthy controls and patients with early disease-modifying antirheumatic drug (DMARD)-naive RA, chronic RA, and OA; (2) that changes in adiponectin are observed during methotrexate (MTX) treatment of chronic RA; and (3) that adiponectin correlates to disease activity measures in RA.Methods.Plasma adiponectin was analyzed with a validated in-house immunoassay. We measured adiponectin in healthy controls (n = 45) and patients with early DMARD-naive RA (n = 40), chronic RA (n = 74), and OA (n = 35). In a subgroup of patients with chronic RA (n = 31), the longitudinal effect of MTX treatment on adiponectin (Week 0 vs Week 28) was investigated.Results.Adiponectin differed significantly between healthy controls (mean 4.8 ± SD 2.7 mg/l) and the 3 groups, with 8.9 ± 4.8 mg/l in early RA, 11.6 ± 5.6 mg/l in chronic RA, and 14.1 ± 6.4 mg/l in OA. Longitudinally, MTX treatment increased adiponectin significantly from 9.7 ± 4.5 mg/l at Week 0 to 11.0 ± 4.5 mg/l at Week 28 in chronic RA. No correlations to disease activity measures were found.Conclusion.Both early DMARD-naive and chronic RA were associated with higher plasma adiponectin compared to healthy controls, but lower plasma adiponectin than OA. Adiponectin increased 13% during MTX treatment. In patients with RA and OA body mass index, age, sex, and disease activity measures failed to explain the findings.

scholarly journals Disease Activity in Disease Modifying Anti-Rheumatic Drug (DMARD) Naïve Rheumatoid Arthritis Patients in A Subset of Karachi Population

2021 ◽  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Rheumatoid Factor ◽  
Pearson Correlation ◽  
Antirheumatic Drug ◽  
Tender Joint Count ◽  
P Value ◽  
Disease Modifying ◽  
Disease Modifying Antirheumatic Drug ◽  
Activity Variables

Background: Rheumatoid arthritis (RA) is a progressive inflammatory disease affecting the joints with a marked impact upon functional capacity of the patient. The working ability of RA patients can be preserved if the disease modifying antirheumatic drug (DMARD) therapy is initiated early in the course of disease. The objective of our study was to compare the disease activity variables in DMARD-naïve seropositive rheumatoid arthritis (SPRA) and seronegative rheumatoid arthritis (SNRA) patients and to determine correlations between the disease activity variables in RA. Methods: A cross-sectional study recruited n=90 patients from Rheumatology Clinic from May 2020 to October 2020. The rheumatoid factor (RF), anti-cyclic citrullinated peptide levels (ACCP), erythrocyte sedimentation rates (ESR) were clinically measured. Disease activity variables including the tender joint count (TJC), swollen joint count (SJC), health assessment questionnaire-disability index (HAQ-DI) and disease activity score of 28 joints (DAS28) were consistently calculated. Patients were divided into seropositive RA group and seronegative RA group, based on RF and ACCP. Chi squared test and Pearson correlation were applied, p≤0.05 was considered statistically significant. Results: High HAQ-DI and DAS28-ESR scores were found in SPRA than in the SNRA patients and were statistically significant (p=0.000, p=0.054). TJ-28 and SJ-28 counts were higher in SPRA but were not statistically significant. There was a significant correlation of DAS28 with TJ-28 (r=0.816, p-value = 0.000), with SJ-28(r=0.801, p-value = 0.000) and HAQ-DI (r=0.517, p-value = 0.000). Conclusion: Evaluation of inflammatory markers and functional disability was found significant (p=0.000) in determining the disease activity compared to presence of autoantibodies in DMARD naïve RA patients. Keywords: Disease Modifying Antirheumatic Drug; Arthritis; Rheumatoid Factor; Autoimmune Diseases.

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