scholarly journals Which subgroup of patients with rheumatoid arthritis benefits from switching to rituximab versus alternative anti-tumour necrosis factor (TNF) agents after previous failure of an anti-TNF agent?

2009 ◽  
Vol 69 (2) ◽  
pp. 387-393 ◽  
Author(s):  
A Finckh ◽  
A Ciurea ◽  
L Brulhart ◽  
B Möller ◽  
U A Walker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Multivariate Regression ◽  
Regression Models ◽  
Primary Outcome ◽  
Disease Activity Score ◽  
Clinical Settings ◽  
Inadequate Response ◽  
Tnf Antagonists ◽  
Necrosis Factor

Background:Patients with rheumatoid arthritis (RA) with an inadequate response to TNF antagonists (aTNFs) may switch to an alternative aTNF or start treatment from a different class of drugs, such as rituximab (RTX). It remains unclear in which clinical settings these therapeutic strategies offer most benefit.Objective:To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients.Methods:A prospective cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF, nested within the Swiss RA registry (SCQM-RA) was carried out. The primary outcome, longitudinal improvement in 28-joint count Disease Activity Score (DAS28), was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders.Results:Of the 318 patients with RA included; 155 received RTX and 163 received an alternative aTNF. The relative benefit of RTX varied with the type of prior aTNF failure: when the motive for switching was ineffectiveness to previous aTNFs, the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF (p = 0.03; at 6 months, −1.34 (95% CI −1.54 to −1.15) vs −0.93 (95% CI −1.28 to −0.59), respectively). When the motive for switching was other causes, the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs (p = 0.40). These results were not significantly modified by the number of previous aTNF failures, the type of aTNF switches, or the presence of co-treatment with a disease-modifying antirheumatic drug.Conclusion:This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF.

scholarly journals Levels of CXCL13 and sICAM-1 correlate with disease activity score in patients with rheumatoid arthritis treated with tocilizumab

2019 ◽  
Vol 59 (1) ◽  
Author(s):  
Katie Tuckwell ◽  
Cem Gabay ◽  
Thierry Sornasse ◽  
Ruediger Paul Laubender ◽  
Jianmei Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Serum Levels ◽  
Activity Score ◽  
Intercellular Adhesion Molecule ◽  
Inadequate Response ◽  
Intercellular Adhesion Molecule 1 ◽  
Baseline Serum ◽  
Early Ra

Abstract Background Tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 receptor, has been proven to be a safe and effective treatment for rheumatoid arthritis (RA). Because RA is a heterogenous disease and patient response to treatments can vary, identifying characteristics that predict which patients are more likely to respond to TCZ is important for optimal patient care. Serum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with response to TCZ in patients with RA. Objectives To evaluate the association of CXCL13 and sICAM-1 with disease activity and response to TCZ in patients with early RA and those with inadequate response to disease-modifying antirheumatic drugs (DMARD-IR). Methods Baseline and week 24 serum CXCL13 and sICAM-1 levels were measured using available patient samples from the FUNCTION (early RA) and LITHE (DMARD-IR) trials. Correlations between CXCL13 and sICAM-1 levels and Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR) at baseline and between change in CXCL13 and sICAM-1 and change in DAS28-ESR at week 24 were estimated. CXCL13 and sICAM-1 changes from baseline to week 24 were compared between treatment arms. The effects of TCZ treatment and baseline DAS28-ESR, CXCL13 and sICAM-1 levels on DAS28-ESR remission and 50% improvement per the American College of Rheumatology (ACR50) response at week 24 were determined. Results Overall, 458 patients from FUNCTION and 287 patients from LITHE were included. Correlation of baseline serum CXCL13 and sICAM-1 levels with DAS28-ESR was weak to moderate. CXCL13 and sICAM-1 levels decreased significantly at week 24 in TCZ-treated patients in both the early-RA and DMARD-IR populations. CXCL13 and sICAM-1 changes correlated moderately to weakly with DAS28-ESR changes at week 24 in both populations. The treatment regimen, but not baseline CXCL13 and sICAM-1 levels, had a significant effect on the likelihood of DAS28-ESR remission and ACR50 response. Conclusions Although CXCL13 and sICAM-1 are modestly associated with RA disease activity, they do not predict response to TCZ in all RA populations.

Longterm Safety and Efficacy of Abatacept Through 5 Years of Treatment in Patients with Rheumatoid Arthritis and an Inadequate Response to Tumor Necrosis Factor Inhibitor Therapy

2012 ◽  
Vol 39 (8) ◽  
pp. 1546-1554 ◽  
Author(s):  
MARK C. GENOVESE ◽  
MICHAEL SCHIFF ◽  
MICHAEL LUGGEN ◽  
MANUELA LE BARS ◽  
RICHARD ARANDA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Physical Function ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Inhibitor ◽  
Malignant Neoplasms ◽  
Inadequate Response ◽  
Safety And Efficacy ◽  
Necrosis Factor

Objective.To evaluate abatacept safety and efficacy over 5 years in patients with rheumatoid arthritis (RA) who had inadequate response to anti-tumor necrosis factor (TNF) therapy in the ATTAIN trial.Methods.Patients completing the 6-month, double-blind (DB) placebo-controlled period were eligible to enter the longterm extension (LTE), where all patients received abatacept every 4 weeks (∼10 mg/kg, according to weight range). Safety, efficacy, physical function, and health-related quality of life were monitored throughout.Results.In total, 317 patients (218 DB abatacept, 99 DB placebo) entered the LTE; 150 (47.3%) completed it. Overall incidences of serious adverse events, infections, serious infections, malignant neoplasms, and autoimmune events did not increase during the LTE versus the DB period. American College of Rheumatology responses with abatacept at Month 6 were maintained over 5 years. At Year 5, among patients who received abatacept for 5 years and had available data, 38/103 (36.9%) achieved low disease activity as defined by the 28-joint Disease Activity Score (DAS28)/C-reactive protein (CRP); 23/103 (22.3%) achieved DAS28/CRP-defined remission. Health Assessment Questionnaire response was achieved by 62.5% of patients remaining on treatment at Year 5; mean improvements from baseline in physical component summary and mental component summary scores were 7.34 and 6.42, respectively. High proportions of patients maintained efficacy and physical function benefits or improved their disease state at each timepoint throughout the LTE, if remaining on abatacept treatment.Conclusion.Safety remained consistent, and abatacept efficacy was maintained from 6 months to 5 years, demonstrating the benefits of switching to abatacept in this difficult-to-treat population of patients with RA previously failing anti-TNF therapy.

Triple Oral Therapy Versus Antitumor Necrosis Factor Plus Methotrexate (MTX) in Patients with Rheumatoid Arthritis and Inadequate Response to MTX: A Systematic Literature Review

2017 ◽  
Vol 44 (6) ◽  
pp. 773-779 ◽  
Author(s):  
Julia Mary ◽  
Michel De Bandt ◽  
Cédric Lukas ◽  
Jacques Morel ◽  
Bernard Combe
Keyword(s):  
Rheumatoid Arthritis ◽  
Prognostic Factors ◽  
Disease Activity ◽  
Functional Disability ◽  
Relative Effectiveness ◽  
Response Criteria ◽  
Cochrane Library ◽  
Inadequate Response ◽  
Eular Response ◽  
Necrosis Factor

Objective.For patients with rheumatoid arthritis (RA) who have an inadequate response to methotrexate (MTX), the relative effectiveness of the combination of conventional disease-modifying antirheumatic drugs (DMARD) compared with the combination of tumor necrosis factor (TNF) inhibitors and MTX, as second-line therapy, is uncertain. The aim of this study was to compare the efficacy and tolerance of triple oral DMARD therapy versus anti-TNF agents associated with MTX in patients with RA after MTX failure.Methods.We performed a systematic search of the literature up to November 2015 in MEDLINE, Embase, the Cochrane library, and abstracts from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) meetings from 2006 to 2015. Articles were included if they were of randomized controlled trials of patients receiving triple oral combination therapy (TT; MTX + sulfasalazine + hydroxychloroquine) compared with anti-TNF agents plus MTX. Treatment effects were examined by disease activity [Disease Activity Score in 28 joints (DAS28)], ACR and EULAR response criteria, structural damage by the modified total Sharp score, and functional disability by the Health Assessment Questionnaire (HAQ).Results.Our search identified 263 articles; only 5 fulfilled the selection criteria. Analysis of ACR and EULAR response criteria, DAS28, and modified Sharp scores favored anti-TNF agents combined with MTX. Functional disability (HAQ) and rates of adverse events did not differ between treatments.Conclusion.In patients with RA in whom MTX has failed, the addition of a TNF antagonist to MTX may be a valid option, with better clinical outcomes and better radiographic results in the presence of poor prognostic factors. In the absence of poor prognostic factors and/or with contraindications to biologic agents, TT retains its place in the therapeutic strategy for RA in a currently restricted economic context.

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 Relationship Between Pack-year History of Smoking and Response to Tumor Necrosis Factor Antagonists in Patients with Rheumatoid Arthritis

2009 ◽  
Vol 36 (6) ◽  
pp. 1180-1187 ◽  
Author(s):  
DEREK L. MATTEY ◽  
ANN BROWNFIELD ◽  
PETER T. DAWES
Keyword(s):  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Disease Activity Score ◽  
Response To Therapy ◽  
Activity Score ◽  
Smoking History ◽  
Tnf Antagonists ◽  
History Of ◽  
Necrosis Factor

Objective.To determine whether there is a quantitative relationship between smoking history and response to therapy with tumor necrosis factor (TNF) antagonists.Methods.A history of cigarette smoking was obtained from a questionnaire completed by each patient starting therapy with TNF antagonists since 2002 (n = 154). A core set of demographic and clinical variables was recorded at baseline and at 3 and 12 months. The extent of smoking was quantified in pack-years (py), with 1 py equivalent to 20 cigarettes per day for 1 year. The association between smoking intensity and response was assessed using contingency tables and logistic regression analysis. Response to therapy was defined according to the European League Against Rheumatism improvement criteria.Results.There was an increasing trend of no response at 3 and 12 months with increasing py history [p (trend) = 0.008 and 0.003, respectively]. The change in Disease Activity Score (DAS)28 over the first 3 months was inversely associated with the number of py (r = −0.28, p = 0.002). The association of py history with response failure was independent of age, sex, disease duration, baseline disease activity score (DAS28), Health Assessment Questionnaire (HAQ) score, IgM rheumatoid factor, and smoking at baseline. The most significant effect was seen in patients treated with infliximab.Conclusion.RA patients with a history of smoking were more likely to show a poor response to TNF antagonists. Response failure was associated with the intensity of previous smoking, irrespective of smoking status at initiation of anti-TNF therapy.

scholarly journals Genetic Polymorphisms Modifying Oxidative Stress Are Associated with Disease Activity in Rheumatoid Arthritis Patients

2009 ◽  
Vol 26 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Petra Bohanec Grabar ◽  
Dušan Logar ◽  
Matija Tomšič ◽  
Blaž Rozman ◽  
Vita Dolžan
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Disease Activity Score ◽  
No Synthase ◽  
Superoxide Dismutases ◽  
Necrosis Factor Alpha ◽  
Low Disease Activity ◽  
Factor Alpha ◽  
Necrosis Factor

Reactive oxygen and nitrogen species are involved in the pathology of rheumatoid arthritis (RA). Polymorphisms in genes coding for superoxide dismutases (SOD2 and SOD3), catalase (CAT), tumor necrosis factor-alpha (TNFA) and inducible NO synthase (NOS2A) may influence RA activity. We determined SOD2 Ala-9Val, SOD3 Arg213Gly, CAT C-262T, TNFA G-308A, TNFA C-857T and NOS2A (CCTTT)npolymorphisms in 327 RA patients. Carriers of CAT -262T and TNFA -308A allele had lower mean disease activity score of 28 joint count (DAS28) values than patients with CAT -262CC and TNFA -308GG genotypes (p= 0.014 andp= 0.046, respectively). Patients with the combination of CAT -262T and TNFA -308A allele had lower mean DAS28 values and a higher probability for low disease activity than non-carriers (p= 0.003, OR = 3.585, 95% CI = 1.538–8.357). Our results suggest that CAT and TNFA polymorphisms alone and in combination influence the activity of RA.

scholarly journals Adherence to Treat-to-target Management in Rheumatoid Arthritis and Associated Factors: Data from the International RA BIODAM Cohort

2019 ◽  
Vol 47 (6) ◽  
pp. 809-819 ◽  
Author(s):  
Alexandre Sepriano ◽  
Sofia Ramiro ◽  
Oliver FitzGerald ◽  
Mikkel Østergaard ◽  
Joanne Homik ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Treat To Target ◽  
Longitudinal Model ◽  
Low Disease Activity ◽  
Optimal Outcomes ◽  
Link Type ◽  
Target Management ◽  
Necrosis Factor

Objective.Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where adherence to T2T is protocol-specified. We aimed to assess clinical factors that associate with failure to adhere to T2T.Methods.Patients with RA from 10 countries who were starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required per protocol to adhere to the T2T strategy. Factors influencing adherence to T2T low disease activity (T2T-LDA; 44-joint count Disease Activity Score ≤ 2.4) were analyzed in 2 types of binomial generalized estimating equations models: (1) including only baseline features (baseline model); and (2) modeling variables that inherently vary over time as such (longitudinal model).Results.A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. Failure of adherence to T2T-LDA was noted in 1765 visits (40.5%). In the baseline multivariable model, a high number of comorbidities (OR 1.10, 95% CI 1.02–1.19), smoking (OR 1.32, 95% CI 1.08–1.63) and high number of tender joints (OR 1.03, 95% CI 1.02–1.04) were independently associated with failure to implement T2T, while anticitrullinated protein antibody/rheumatoid factor positivity (OR 0.63, 95% CI 0.50–0.80) was a significant facilitator of T2T. Results were similar in the longitudinal model.Conclusion.Lack of adherence to T2T in the RA BIODAM cohort was evident in a substantial proportion despite being a protocol requirement, and this could be predicted by clinical features. [Rheumatoid Arthritis (RA) BIODAM cohort; ClinicalTrials.gov: NCT01476956].

scholarly journals SAT0118 COMPARATIVE EFFECTIVENESS OF TOCILIZUMAB IN COMBINATION WITH METHOTREXATE VERSUS TUMOR NECROSIS FACTOR INHIBITORS (TNFIS) IN COMBINATION WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS WITH PRIOR EXPOSURE TO TNFIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 993.2-993
Author(s):  
D. A. Pappas ◽  
T. Blachley ◽  
S. Zlotnick ◽  
J. H. Best ◽  
K. Emeanuru ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Prior Exposure ◽  
World Population ◽  
Inadequate Response ◽  
Tumor Necrosis Factor Inhibitors ◽  
The Mean ◽  
Necrosis Factor

Background:Clinical studies have demonstrated the efficacy of tocilizumab (TCZ) administered with methotrexate (MTX) in improving rheumatoid arthritis (RA) disease activity in patients who have had an inadequate response to tumor necrosis factor inhibitors (TNFis).Objectives:To compare the effectiveness of TCZ + MTX with that of TNFis + MTX in patients with RA who had prior exposure to TNFis in routine clinical practice.Methods:Eligible participants were TCZ-naïve patients from the Corrona RA registry who initiated TCZ + MTX or a TNFi + MTX after January 1, 2010 and had a 6-month follow-up visit. Patients in both groups must have used ≥ 1 TNFi, had a Clinical Disease Activity Index (CDAI) score available at initiation (baseline) and 6 months and had a CDAI score > 10 at baseline. The primary outcome was mean change in CDAI from baseline to 6 months. Secondary outcomes included achievement of low disease activity (LDA; CDAI ≤ 10) and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients were grouped by baseline MTX dose (≤ 10 mg; > 10 to ≤ 15 mg; > 15 to ≤ 20 mg; > 20 mg); outcomes were compared between patients initiating TCZ and those initiating a TNFi overall and within each MTX dose group using propensity score (PS)-trimmed populations. As a sensitivity analysis, TCZ and TNFi initiators in each group were PS-matched 1:1 and outcomes were assessed in the matched populations. Linear and logistic regression models were estimated in the trimmed and matched populations, adjusting for covariates not balanced after PS trimming or matching, respectively.Results:A total of 415 TCZ + MTX initiators and 725 TNFi + MTX initiators met the inclusion criteria prior to PS trimming or matching. The overall trimmed population included 402 TCZ + MTX initiators and 703 TNFi + MTX initiators. In the trimmed population, patient demographics were generally comparable between TCZ + MTX and TNFi + MTX initiators; the mean age was 57.1 years in the TCZ + MTX group and 57.7 years in the TNFi + MTX group, the majority of patients in both groups were female (≥ 80%) and white (≥ 82%) and the mean duration of RA was 11.8 and 10.5 years in the TCZ + MTX and TNFi + MTX groups, respectively. Higher proportions of patients initiating TCZ had received ≥ 2 prior biologics (66.0% to 76.3%) compared with those initiating a TNFi (33.2% to 42.2%) across all MTX dose groups. Patients initiating TCZ had higher mean baseline CDAI scores (26.5 to 29.3) than those initiating a TNFi (24.7 to 27.5). Patients in both cohorts had improvements in CDAI and mHAQ scores and achieved LDA in similar proportions at 6 months regardless of baseline MTX dose (Fig 1). Results were comparable between TCZ and TNFi initiators across all MTX groups in the trimmed population after adjustment for potential confounding variables. Similar results were observed in the PS-matched cohorts.Conclusion:In this real-world population of US patients with RA who had prior TNFi exposure, there was no statistically significant or clinically meaningful difference in the effectiveness of therapy in patients who initiated TCZ + MTX compared with TNFi + MTX.Acknowledgments :This study was sponsored by Corrona, LLC. Corrona is supported through contracted subscriptions with multiple pharmaceutical companies. The abstract was a collaborative effort between Corrona and Genentech, Inc., with financial support provided by Genentech, Inc.Disclosure of Interests: :Dimitrios A Pappas: None declared, Taylor Blachley Employee of: Corrona, LLC, Steve Zlotnick Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Jennie H. Best Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Kelechi Emeanuru Employee of: Corrona, LLC – employment, Joel M Kremer Shareholder of: May own stocks and opinions, Grant/research support from: Research and consulting fees from AbbVie Inc., Consultant of: AbbVie, Amgen, BMS, Genentech, Inc., Gilead, GSK, Lilly, Pfizer, Regeneron and Sanofi, Employee of: Corrona, LLC employee

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