Circulating Leptin and Adiponectin Concentrations During Tumor Necrosis Factor Blockade in Patients with Active Rheumatoid Arthritis

2009 ◽  
Vol 36 (4) ◽  
pp. 724-730 ◽  
Author(s):  
CALIN POPA ◽  
MIHAI G. NETEA ◽  
JACQUELINE de GRAAF ◽  
FRANK H.J. van den HOOGEN ◽  
TIMOTHY R.D.J. RADSTAKE ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Active Rheumatoid Arthritis ◽  
Disease Activity Score ◽  
Serum Levels ◽  
Plasma Leptin ◽  
Necrosis Factor

Objective.Adipocytokines, including leptin and adiponectin, may play an important role in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of longterm therapeutic tumor necrosis factor (TNF) blockade on adipocytokine concentrations in patients with RA.Methods.We studied 58 RA patients starting anti-TNF therapy and 58 healthy controls matched for age, sex, and body mass index (BMI). Fasting blood samples were drawn at baseline, 2 weeks, and 6 months after the start of anti-TNF therapy and serum levels of leptin and adiponectin were measured.Results.Patients with RA had increased adiponectin (p < 0.001) and similar leptin concentrations compared with the controls. Leptin concentrations were significantly higher in patients with high BMI (p < 0.001) and correlated positively with BMI at all timepoints (r > 0.75). In contrast, serum adiponectin tended to be higher in lean RA patients and did not correlate with BMI at any timepoint. There were no clear correlations between serum concentrations of adipocytokines and disease activity (Disease Activity Score 28). Short or longterm TNF blockade alone had no influence on circulating leptin and adiponectin concentrations. Patients treated with anti-TNF and concomitant corticosteroids on a stable basis showed a significant decrease in adiponectin levels after 6 months of therapy (p < 0.025).Conclusion.In patients with RA, chronic inflammation and its suppression during anti-TNF therapy have limited influence on plasma leptin concentrations, while significantly decreasing circulating adiponectin levels. Our findings question the suggested key role of inflammatory markers in regulating adipocytokine patterns in RA.

scholarly journals Heterogeneity of Anticitrullinated Peptide Antibodies and Response to Anti-Tumor Necrosis Factor Agents in Rheumatoid Arthritis

2012 ◽  
Vol 39 (5) ◽  
pp. 929-932 ◽  
Author(s):  
BENJAMIN A. FISHER ◽  
DARREN PLANT ◽  
KARIN LUNDBERG ◽  
PETER CHARLES ◽  
ANNE BARTON ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Disease Activity Score ◽  
Activity Score ◽  
Fine Specificity ◽  
Citrullinated Peptide ◽  
Necrosis Factor ◽  
Peptide Antibodies

Objective.To examine fine specificity of anticitrullinated peptide antibodies (ACPA) in relation to responsiveness to anti-tumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA).Methods.Samples from 450 patients with RA treated with anti-TNF agents were analyzed for antibodies to citrullinated α-enolase, vimentin, and fibrinogen peptides. The Disease Activity Score-28 was measured at baseline and 6 months.Results.Both anti-cFib antibodies and the number of citrullinated peptides recognized were associated with a poorer response. These findings were not significant following stratification for anti-cyclic citrullinated peptide 2 antibodies.Conclusion.The presence of any ACPA rather than individual ACPA specificities was associated with a poorer response to anti-TNF agents. We suggest that this reflects distinctive differences in the pathogenesis of ACPA-positive and negative RA.

Determinants Associated with Work Participation in Patients with Established Rheumatoid Arthritis Taking Tumor Necrosis Factor Inhibitors

2014 ◽  
Vol 41 (7) ◽  
pp. 1263-1269 ◽  
Author(s):  
Sofie H.M. Manders ◽  
Wietske Kievit ◽  
Annemarie L.M.A. Braakman-Jansen ◽  
Herman L.M. Brus ◽  
Lidy Hendriks ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Functional Status ◽  
Tumor Necrosis ◽  
Work Participation ◽  
P Value ◽  
Retirement Pension ◽  
Patient Reported ◽  
Necrosis Factor

Objective.Reduced work participation (WP) is a common problem for patients with rheumatoid arthritis (RA) and generates high costs for society. Therefore, it is important to explore determinants of WP at the start of tumor necrosis factor inhibitor (TNFi) treatment, and for changes in WP after 2 years of TNFi treatment.Methods.Within the Dutch Rheumatoid Arthritis Monitoring (DREAM) biologic register, WP data were available from 508 patients with RA younger than 65 years and without an (early) retirement pension. WP was registered at start of TNFi treatment and after 2 years of followup and was measured by single patient-reported binary questions whether they had work, paid or voluntary, or had a disability allowance or a retirement pension. Determinants measured at baseline were age, sex, disease duration, functional status [through Health Assessment Questionnaire-Disability Index (HAQ-DI)], 28-joint Disease Activity Score (DAS28), rheumatoid factor, presence of erosions, number of previous disease-modifying antirheumatic drugs, and number of comorbidities. During the 2 years of followup, HAQ-DI response and European League Against Rheumatism response were measured. Univariate analyses (excluded if p value was > 0.2) and multivariate (excluded if p value was > 0.1) logistic regression analyses were used.Results.Determinants associated with WP at baseline were having a better HAQ-DI (OR 0.32, p = 0.000) and male sex (OR 0.65, p = 0.065). After 2 years of TNFi therapy, 11.8% (n = 60) started to work and 13.6% (n = 69) stopped working. Determinants associated with starting to work were better baseline HAQ-DI (OR 0.58), positive RF (OR 2.73), and young age (OR 0.96); and for stopping work, worse baseline HAQ-DI (OR 2.74), low HAQ-DI response (OR 0.31), and comorbidity (OR 2.67), all with p < 0.1.Conclusion.Young patients with RA and a high functional status without any comorbidity will have a better chance of working. This supports the main goal in the management of RA: to suppress disease activity as soon and as completely as possible to prevent irreversible destruction of the joints, and thus maintain a good functional status of the patient. Because of the low proportion of variance explained by the models in this study, other factors besides the ones studied are associated with WP.

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.

Which Factors Influence Radiographic Progression During Treatment with Tumor Necrosis Factor Inhibitors in Clinical Practice? Results from 930 Patients with Rheumatoid Arthritis in the Nationwide Danish DANBIO Registry

2014 ◽  
Vol 41 (12) ◽  
pp. 2352-2360 ◽  
Author(s):  
Lykke Midtbøll Ørnbjerg ◽  
Mikkel Østergaard ◽  
Pernille Bøyesen ◽  
Niels Steen Krogh ◽  
Anja Thormann ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Regression Analysis ◽  
Clinical Practice ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Radiographic Progression ◽  
Tnf Inhibitor ◽  
Baseline Characteristics ◽  
Necrosis Factor

Objective.To investigate baseline characteristics associated with radiographic progression and the effect of disease activity, drug, switching, and withdrawal on radiographic progression in tumor necrosis factor (TNF) inhibitor-naive patients with rheumatoid arthritis (RA) followed for about 2 years after anti-TNF initiation in clinical practice.Methods.DANBIO-registered patients with RA who had available radiographs (anti-TNF initiation and ∼2 yrs followup) were included. Radiographs were scored, blinded to chronology with the Sharp/van der Heijde method and linked with DANBIO data. Baseline characteristics were investigated with univariate regression and significant variables included in a multivariable logistic regression analysis with ± radiographic progression [Δ total Sharp score (TSS) > 0] as dependent variable. Effect of time-averaged C-reactive protein (CRP), 28-joint Disease Activity Score with CRP (DAS28-CRP), and treatment status at followup were investigated with univariate regression analysis.Results.The study included 930 patients. They were 75% women, 79% positive for IgM-rheumatoid factor (IgM-RF), median age was 57 yrs (range 19–88), disease duration 9 yrs (1–59), DAS28-CRP 5.0 (1.4–7.8), TSS median 15 [3–45 interquartile range (IQR)] and mean 31 (SD 40). Patients started treatment with infliximab (59%), etanercept (18%), or adalimumab (23%). At followup (median 526 days, IQR 392–735), 61% were treated with the initial anti-TNF, 29% had switched TNF inhibitor, and 10% had withdrawn. Twenty-seven percent of patients had progressed radiographically. ΔTSS was median 0.0 [0.0–0.5 IQR/mean 0.6 (SD 2.4)] units/year. Higher TSS, older age, positive IgM-RF, and concomitant prednisolone at baseline were associated with radiographic progression. Time-averaged DAS28-CRP and time-averaged CRP, but not type of TNF inhibitor, were associated with radiographic progression. Patients who stopped/switched during followup progressed more than patients who continued treatment.Conclusion.High TSS, older age, IgM-RF positivity, and concomitant prednisolone were associated with radiographic progression during 2 years of followup of 930 anti-TNF–treated patients with RA in clinical practice. High disease activity and switching/stopping anti-TNF treatment were associated with radiographic progression.

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