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.

scholarly journals POS0492 A MOLECULAR SIGNATURE RESPONSE CLASSIFIER PREDICTS THE LIKELIHOOD OF EULAR NON-RESPONSE TO TNF INHIBITOR THERAPIES IN RA: RESULTS FROM A RETROSPECTIVE COHORT ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 478.2-479
Author(s):  
L. Zhang ◽  
C. van der Tog ◽  
A. den Broeder ◽  
T. Mellors ◽  
E. Connolly-Strong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Predictive Value ◽  
Molecular Signature ◽  
Response Criteria ◽  
Treat To Target ◽  
Inadequate Response ◽  
Tnf Inhibitor ◽  
Target Setting ◽  
The Impact

Background:Following RA treatment recommendations, most people with rheumatoid arthritis (RA) begin targeted therapy with TNF inhibitors (TNFi), even though inadequate response to TNFi therapies is widespread. Treatment changes from one medication to the next are currently fueled by disease-activity measures and eventually result in disease control for most patients; however, this “trial-and-error” approach wastes precious time on ineffective treatments. A delay in reaching treat-to-target goals has a negative effect on patient burden and, possibly, disease progression.1 Useful predictors for TNFi response have been challenging to identify but a specific molecular signature response classifier (MSRC) test was shown to be predictive for inadequate response to TNFi therapies.2 The impact of such identification has the potential to result in improved patient outcomes, but further validation would be welcome, especially for response criteria other than ACR50, and in a stringent treat-to-target setting with lower baseline disease activity.Objectives:To validate the predictive value of the MSRC test in identifying those patients who do not meet EULAR good response criteria after 6 months of TNFi treatment.Methods:Data from a prospective cohort study conducted in the Sint Maartenskliniek (Nijmegen, the Netherlands) of RA patients who started adalimumab or etanercept TNFi as their first biologic were included.3 Baseline RNA samples and clinical assessments were used to identify patients who had a molecular signature1 of non-response to TNFi therapy. Outcomes were calculated at six months using DAS28-CRP-based EULAR good response, and high and low confidence responders and non-responders were identified using Monte Carlo simulation with 2,000 repeats and 70% precision cut off. Outcome measurements were blinded for test results. Treatment switch before 6 months was imputed as non-response. Odds ratios and area under the ROC curve (AUC) assessments were used to evaluate the ability of the MSRC test to predict inadequate response at 6 months against EULAR good response criteria.Results:A total of 68 out of 88 RA patients were identified to have a high-confidence response status and were included in analyses (Table 1). EULAR good response was observed in 45.5% (31/68) of patients. Patients were stratified according to detection of a molecular signature of non-response with an AUC of 0.61. The odds that a patient with the molecular signature of non-response at baseline failed to achieve a EULAR good response at 6 months was four times greater than that of a patient lacking the molecular signature (odds ratio 4.0, 95% confidence interval 1.2-13.3).Table 1.Patient demographicsCharacteristicRA patients (N = 68)Age, median (SD)57 (11)Female, n (%)43 (63.2)CCP positive, n (%)34 (50.0)RF positive, n (%)38 (55.9)Prescribed adalimumab at baseline, n (%)11 (16.2)Prescribed etanercept at baseline, n (%)57 (83.8)Conclusion:In this validation study, the molecular signature of non-response identified patients who did not fulfill the EULAR good response criteria to TNFi therapies. The patient selection process for this study had limitations; additional analysis in an alternative cohort would further verify the performance of the MSRC test. Nevertheless, the test, previously validated for ACR50, now has been validated using EULAR good response in a treat-to-target setting.References:[1]Schipper LG et al, Time to achieve remission determines time to be in remission. Arthritis Res Ther 201[2]Mellors T, et al. Clinical Validation of a Blood-Based Predictive Test for Stratification of Response to Tumor Necrosis Factor Inhibitor Therapies in Rheumatoid Arthritis Patients. Network and Systems Medicine 2020[3]Tweehuysen L et al. Predictive value of ex-vivo drug-inhibited cytokine production for clinical response to biologic DMARD therapy in rheumatoid arthritis. Clin Exp Rheumatol 2019Disclosure of Interests:Lixia Zhang Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Celeste van der Tog: None declared, Alfons den Broeder Consultant of: Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead., Grant/research support from: Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead., Ted Mellors Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Erin Connolly-Strong Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Johanna Withers Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Alex Jones Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Viatcheslav Akmaev Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation

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.

scholarly journals The effectiveness of leflunomide as a co-therapy of tumour necrosis factor inhibitors in rheumatoid arthritis: a population-based study

2008 ◽  
Vol 68 (1) ◽  
pp. 33-39 ◽  
Author(s):  
A Finckh ◽  
S Dehler ◽  
C Gabay
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Functional Disability ◽  
Drug Discontinuation ◽  
Radiographic Damage ◽  
Conventional Dmards ◽  
Significant Difference ◽  
Necrosis Factor

Background:Randomised trials have demonstrated that the efficacy of anti-tumour necrosis factor (TNF) agents is significantly increased by concomitant methotrexate (MTX) in rheumatoid arthritis (RA). In clinical routine, anti-TNF agents are commonly prescribed with other disease-modifying antirheumatic drugs (DMARDs) than MTX, however their effectiveness in combination with anti-TNF agents is not well established.Objective:To compare the effectiveness of leflunomide (LEF) and other conventional DMARDs with MTX as co-therapy to anti-TNF agents in RA.Methods:All patients on anti-TNF agents and conventional DMARDs within the Swiss Clinical Quality Management (SCQM)-RA database were included (n = 1218) and categorised according to the type of co-therapy into anti-TNF+MTX (n = 842), anti-TNF+LEF (n = 260) and anti-TNF+other DMARDs (n = 116). Drug discontinuation rates and incidence of toxic side effects were analysed using Cox proportional hazard models. Progression of radiographic damage, the evolution of functional disability and the improvement of RA disease activity were analysed using longitudinal regression models, adjusting for potential confounders.Results:The overall discontinuation rates of anti-TNF and conventional DMARD combination therapies were relatively high with a median survival of only 16 months (interquartile range (IQR): 10–37), but they did not differ between the three regimens (p = 0.69). The progression of radiographic damage (p = 0.77), functional disability (p = 0.09) and RA disease activity (p = 0.33) were also similar between the different regimen. In addition, no significant difference in the frequency of adverse events emerged.Conclusion:Overall these results suggest that LEF and potentially other conventional DMARDs offer an effective and safe alternative to MTX as co-therapy in combination with anti-TNF agents.

Predictors of response to methotrexate in early DMARD naïve rheumatoid arthritis: results from the initial open-label phase of the SWEFOT trial

2010 ◽  
Vol 70 (3) ◽  
pp. 469-475 ◽  
Author(s):  
Saedis Saevarsdottir ◽  
Helena Wallin ◽  
Maria Seddighzadeh ◽  
Sofia Ernestam ◽  
Pierre Geborek ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Secondary Response ◽  
Response Criteria ◽  
Symptom Duration ◽  
Eular Response ◽  
Current Smoking ◽  
Predictors Of Response

ObjectiveTo identify predictors of response to methotrexate (MTX) in early rheumatoid arthritis (RA).MethodsIn the SWEFOT trial, patients with RA with symptom duration <1 year started MTX monotherapy (20 mg/weekly) and 405/487 continued until the 3–4- month visit. The primary outcome measure was the DAS28-based European League against Rheumatism (EULAR) response criteria. Multivariate logistic regression was used to study the association between response and the following baseline characteristics: gender, age, symptom duration, cigarette smoking habits, autoantibody status, Health Assessment Questionnaire (HAQ) score, concurrent prednisolone and treatment with non-steroidal anti-inflammatory drugs. Secondary response and remission measures were the American College of Rheumatology and the Simple Disease Activity Index and Clinical Disease Activity Index (SDAI/CDAI)-derived criteria.ResultsAfter 3–4 months of MTX treatment, the frequency of EULAR good/moderate/no response was 34%/41%/25%, respectively. Parameters associated with a decreased likelihood of EULAR response were female gender (adjusted OR (adj OR) 0.50, 95% CI 0.31 to 0.81), symptom duration (adj OR per month increase 0.93, 95% CI 0.88 to 0.99), current smoking (adj OR 0.35, 95% CI 0.20 to 0.63) and higher HAQ (adj OR 0.56, 95% CI 0.40 to 0.80). Parameters associated with an increased likelihood of EULAR response were higher age (adj OR per 10-year increase 1.30, 95% CI 1.11 to 1.51) and prednisolone treatment (adj OR 2.84, 95% CI 1.43 to 5.63). The findings were similar when patients on prednisolone were excluded and other response criteria tested, although current smoking was the only significant predictor using all response criteria, while HAQ was the only significant predictor of all the remission criteria used. A matrix showed up to ninefold differences between subgroups stratified by the main predictors.ConclusionCurrent smoking, female sex, longer symptom duration and younger age predict a worse response to MTX in patients with new-onset RA.TrialRegNo NCT00764725

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

Effectiveness of a Third Tumor Necrosis Factor-α-blocking Agent Compared with Rituximab After Failure of 2 TNF-blocking Agents in Rheumatoid Arthritis

2011 ◽  
Vol 38 (11) ◽  
pp. 2355-2361 ◽  
Author(s):  
MARLIES BLOM ◽  
WIETSKE KIEVIT ◽  
A. ROGIER T. DONDERS ◽  
ALFONS A. den BROEDER ◽  
VINCENT H.H.P. STRATEN ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Functional Disability ◽  
Blocking Agent ◽  
Blocking Agents ◽  
Factor Α ◽  
Necrosis Factor

Objective.To compare the effectiveness of a third tumor necrosis factor-α (TNF-α)-blocking agent with rituximab after failure of 2 TNF-blocking agents in patients with rheumatoid arthritis (RA) in daily clinical practice.Methods.Patients receiving a third TNF-blocking agent or rituximab after failure of 2 TNF-blocking agents were selected from a Dutch biologic registry. The primary outcome was the results from the Disease Activity Score of 28 joints (DAS28) over the first 12 months after start of the third biologic using mixed-model analyses. Secondary outcomes included the course of the Health Assessment Questionnaire (HAQ) and the separate components of the DAS28 over the first 12 months and the change from baseline in DAS28 and HAQ at 3 and 6 months.Results.The overall course of the DAS28 over the first 12 months was significantly better for rituximab (p = 0.0044), as also observed for the HAQ, although the latter results were not statistically significant (p = 0.0537). The erythrocyte sedimentation rates, C-reactive protein, and swollen joint counts showed a better course for rituximab (p = 0.0008, p = 0.0287, p = 0.0547, respectively), but not the tender joint counts or visual analog scale for general health. DAS28 decreased significantly in both groups at 3 and 6 months (p ≤ 0.024), but the change in HAQ was significant for rituximab only at 3 months (p = 0.009).Conclusion.During the first 12 months of therapy, a larger improvement in disease activity and a trend toward a larger decrease in functional disability was observed in patients receiving rituximab. Switching to a biologic with another mechanism of action might be more effective after failure of 2 TNF-blocking agents in RA.

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.

CXCL 9 and CXCL 10 as Sensitive Markers of Disease Activity in Patients with Rheumatoid Arthritis

2009 ◽  
Vol 37 (2) ◽  
pp. 257-264 ◽  
Author(s):  
WOON PANG KUAN ◽  
LAI-SHAN TAM ◽  
CHUN-KWOK WONG ◽  
FANNY W.S. KO ◽  
TENA LI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Concentration ◽  
Disease Activity ◽  
Serum Levels ◽  
Response Criteria ◽  
Clinical Activity ◽  
Healthy Controls ◽  
Eular Response ◽  
Baseline Serum ◽  
Activity Measurements

Objective.To assess whether serum levels of CC and CXC chemokines correlate with disease activity in patients with rheumatoid arthritis (RA), and to determine whether these effects predict clinical response.Methods.Serum levels of the chemokines CC (CCL2, CCL5) and CXC (CXCL8, CXCL9, CXCL10) were quantified at baseline and after 12 weeks of treatment with disease-modifying antirheumatic drugs or biologic agents in 28 patients using flow cytometry. Serum from 40 healthy individuals was collected for comparison at baseline. Response to treatment was classified according to the European League Against Rheumatism (EULAR) response criteria. Remission of disease was defined as a Disease Activity Score < 2.6.Results.The baseline serum concentrations of CC and CXC chemokines were significantly elevated in patients with active RA compared to healthy controls (p < 0.05) except for CCL2. Significant improvement in all disease activity measurements was observed after 12 weeks of treatment. Seventeen (60.7%) patients achieved good to moderate response based on the EULAR response criteria, and 5 (17.9%) patients achieved remission. The improvement in clinical activity in patients with RA was accompanied by a significant reduction in the serum concentration of CXCL9 and CXCL10 (p < 0.001). A significant reduction in the serum level of CXCL10 was also observed in the group that achieved EULAR response. Serum concentration of CCL5 remained significantly elevated in patients with RA (n = 5) who achieved remission compared to the healthy controls (p < 0.05).Conclusion.Serum concentration of CXCL9 and CXCL10 may serve as sensitive biomarkers for disease activity in patients with RA.

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