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.

scholarly journals Cardiovascular effects of biological versus conventional synthetic disease-modifying antirheumatic drug therapy in treatment-naïve, early rheumatoid arthritis

2020 ◽  
Vol 79 (11) ◽  
pp. 1414-1422 ◽  
Author(s):  
Sven Plein ◽  
Bara Erhayiem ◽  
Graham Fent ◽  
Sarah Horton ◽  
Raluca Bianca Dumitru ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Antirheumatic Drug ◽  
First Line ◽  
Dmard Therapy ◽  
Link Type ◽  
Lv Mass ◽  
Disease Modifying ◽  
Disease Modifying Antirheumatic Drug

ObjectivesTo determine whether patients with early rheumatoid arthritis (ERA) have cardiovascular disease (CVD) that is modifiable with disease-modifying antirheumatic drug (DMARD) therapy, comparing first-line etanercept (ETN) + methotrexate (MTX) with MTX strategy.MethodsPatients from a phase IV ERA trial randomised to ETN+MTX or MTX strategy±month 6 escalation to ETN+MTX, and with no CVD and maximum one traditional risk factor underwent cardiovascular magnetic resonance (CMR) at baseline, years 1 and 2. Thirty matched controls underwent CMR. Primary outcome measure was aortic distensibility (AD) between controls and ERA, and baseline to year 1 AD change in ERA. Secondary analyses between and within ERA groups performed. Additional outcome measures included left ventricular (LV) mass and myocardial extracellular volume (ECV).ResultsEighty-one patients recruited. In ERA versus controls, respectively, baseline (geometric mean, 95% CI) AD was significantly lower (3.0×10−3 mm Hg−1 (2.7–3.3) vs 4.4×10−3 mm Hg−1 (3.7–5.2), p<0.001); LV mass significantly lower (78.2 g (74.0–82.7), n=81 vs 92.9 g (84.8–101.7), n=30, p<0.01); and ECV increased (27.1% (26.4–27.9), n=78 vs 24.9% (23.8–26.1), n=30, p<0.01). Across all patients, AD improved significantly from baseline to year 1 (3.0×10−3 mm Hg−1 (2.7–3.4) to 3.6×10–3 mm Hg−1 (3.1–4.1), respectively, p<0.01), maintained at year 2. The improvement in AD did not differ between the two treatment arms and disease activity state (Disease Activity Score with 28 joint count)-erythrocyte sedimentation rate-defined responders versus non-responders.ConclusionWe report the first evidence of vascular and myocardial abnormalities in an ERA randomised controlled trial cohort and show improvement with DMARD therapy. The type of DMARD (first-line tumour necrosis factor-inhibitors or MTX) and clinical response to therapy did not affect CVD markers.Trial registration numberISRCTN: ISRCTN89222125; ClinicalTrials.gov: NCT01295151.

scholarly journals Continued Benefit of Tocilizumab Plus Disease-modifying Antirheumatic Drug Therapy in Patients with Rheumatoid Arthritis and Inadequate Clinical Responses by Week 8 of Treatment

2014 ◽  
Vol 41 (2) ◽  
pp. 216-226 ◽  
Author(s):  
Edward C. Keystone ◽  
Andrew Anisfeld ◽  
Sarika Ogale ◽  
Jenny N. Devenport ◽  
Jeffrey R. Curtis
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Response ◽  
Antirheumatic Drug ◽  
Joint Disease ◽  
Phase Iii ◽  
Link Type ◽  
Disease Modifying ◽  
Factor Α ◽  
Disease Modifying Antirheumatic Drug

Objective.To evaluate whether patients with rheumatoid arthritis who did not respond sufficiently to tocilizumab (TCZ) plus disease-modifying antirheumatic drug (DMARD) treatment by Week 8 responded at later timepoints when continuing to take their original dose of TCZ.Methods.In this posthoc analysis of data from phase III randomized controlled trials of inadequate responders (IR) to DMARD or tumor necrosis factor-α inhibitors (anti-TNF), percentages of patients meeting early response criteria were calculated by randomized treatment arm (TCZ 4 mg/kg, 8 mg/kg, or placebo in combination with DMARD). Percentages of patients achieving certain disease activity thresholds at later timepoints were calculated for patients who had/had not achieved response by Week 8.Results.In DMARD-IR early nonresponders, 29.0%, 17.2%, and 3.7% of TCZ 8 mg/kg-randomized, TCZ 4 mg/kg-randomized, and placebo-randomized patients, respectively, achieved 28-joint Disease Activity Score (DAS28) ≤ 3.2 by Week 24. Among anti-TNF-IR patients without early response, 26.5%, 8.5%, and 1.9% of TCZ 8 mg/kg-randomized, TCZ 4 mg/kg-randomized, and placebo-randomized patients, respectively, achieved DAS28 ≤ 3.2 at Week 24.Conclusion.A substantial number of DMARD-IR patients taking TCZ 4 or 8 mg/kg and anti-TNF-IR patients taking TCZ 8 mg/kg who failed to respond by 8 weeks benefited from continued TCZ treatment in combination with DMARD. In contrast, the anti-TNF-IR patients without early responses who continued to take TCZ 4 mg/kg were unlikely to experience a cumulative benefit. ClinicalTrials.gov registration numbers: NCT00106548, NCT00106574, NCT00106535, NCT00106522.

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.

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