Open-Label Observation of Addition of Etanercept Versus a Conventional Disease-Modifying Antirheumatic Drug in Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy in the Latin American Region

2014 ◽  
Vol 20 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Daniel A. Machado ◽  
Renato M. Guzman ◽  
Ricardo M. Xavier ◽  
J. Abraham Simon ◽  
Linda Mele ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Latin American ◽  
Active Rheumatoid Arthritis ◽  
Methotrexate Therapy ◽  
Antirheumatic Drug ◽  
Open Label ◽  
Latin American Region ◽  
Disease Modifying ◽  
Disease Modifying Antirheumatic Drug ◽  
American Region

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 Two-Year Safety and Efficacy Experience in Patients with Methotrexate-Resistant Active Rheumatoid Arthritis Treated with Etanercept and Conventional Disease-Modifying Anti-rheumatic Drugs in the Latin American Region

2016 ◽  
Vol 10 (1) ◽  
pp. 13-25
Author(s):  
Daniel A. Machado ◽  
Renato Guzman ◽  
Ricardo M. Xavier ◽  
Jesus A. Simon ◽  
Linda Mele ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Treatment Regimen ◽  
Latin American ◽  
Methotrexate Therapy ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Disease Modifying

Background:Although long-term data are available from biologic studies in North American/European populations with rheumatoid arthritis (RA), long-term findings in Latin American RA populations are limited.Objective:To examine long-term safety/efficacy of etanercept, methotrexate, and/or other disease-modifying anti-rheumatic drugs (DMARDs) in Latin American patients with moderate-to-severe active RA.Methods:In the first phase of this open-label study, patients were randomized to etanercept 50 mg weekly plus methotrexate or conventional DMARD (hydroxychloroquine or sulfasalazine) plus methotrexate for 24 weeks. At the start of the second phase (week 24), investigators selected a treatment regimen that included any combination/dosage of etanercept, methotrexate, hydroxychloroquine, or sulfasalazine based on previous treatment response, preference, and local product labeling, and was continued for the 104-week extension.Results:In the extension, in the group previously randomized to etanercept-plus-methotrexate therapy, etanercept was continued in 259/260 patients; methotrexate continued in 260/260; and hydroxychloroquine and sulfasalazine added in 8/260 and 3/260, respectively. In the group previously randomized to conventional DMARD-plus-methotrexate therapy, conventional DMARD was discontinued in 86/126 and etanercept added in 105/126. Among etanercept-exposed patients (total exposure, 798.1 patient-year [PY]), rates of adverse events, serious adverse events, and serious infections per PY were 1.7, 0.07, and 0.02 events per PY. In both groups, after treatment modification was permitted, clinical response rates and improvements in clinical/patient-reported outcomes from baseline were sustained to week 128.Conclusion:After investigators were permitted to modify treatment, etanercept was part of the treatment regimen in 95% of patients. Continuation or addition of etanercept in the 2-year extension resulted in a consistently good risk:benefit profile.Trial Registration:Open-Label Study Comparing Etanercept to Conventional Disease Modifying Antirheumatic Drug (DMARD) Therapy; ClinicalTrials.gov, number NCT00848354; https://clinicaltrials.gov/ct2/show/NCT00848354

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.

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