Browsing by Author "Damjanov, Nemanja S. (8503557800)"

Objective. To compare an ultrasonographic (US) scoring system of salivary glands with scintigraphy and salivary gland biopsy, in order to evaluate its diagnostic value in primary Sjögren's syndrome (SS). Methods. In 135 patients with suspected SS, the grades of 5 US measures of both parotid and submandibular salivary glands were scored (0-48 scale). Diagnosis of primary SS was established following the American-European Consensus Group criteria of 2002. The patients' total scintigraphic score (0-12 scale) was determined and the histopathological changes of minor salivary glands graded. Area under the receiver-operating characteristic (ROC) curve was employed to evaluate the diagnostic value of the US scoring system. Results. Primary SS was diagnosed in 107 (79.2%) patients and the remaining 28 subjects (20.8%) constituted the control group. US changes of salivary glands were established in 98/107 patients with SS and in 14/28 controls. Mean US score was 26 in SS patients and 6 in controls. Through ROC curves, US arose as the best performer (0.95 ± 0.01), followed by scintigraphy (0.86 ± 0.31). Setting the cutoff score for US at 19 resulted in the best ratio of specificity (90.8%) to sensitivity (87.1%), while setting the cutoff scintigraphic score at 6 resulted in specificity of 86.1% and sensitivity of 67.1%. Among 70 patients with US score ≥ 19, a scintigraphic score > 6 was recorded in 54/70 (77.1%) and positive biopsy findings in 62/70 (88.5%) patients. Conclusion. We show high diagnostic accuracy of a novel US scoring system of salivary glands (0-48) in patients with primary SS comparable to invasive methods, i.e., scintigraphy and salivary gland biopsy. The Journal of Rheumatology Copyright © 2009. All rights reserved.

Objective. To compare an ultrasonographic (US) scoring system of salivary glands with scintigraphy and salivary gland biopsy, in order to evaluate its diagnostic value in primary Sjögren's syndrome (SS). Methods. In 135 patients with suspected SS, the grades of 5 US measures of both parotid and submandibular salivary glands were scored (0-48 scale). Diagnosis of primary SS was established following the American-European Consensus Group criteria of 2002. The patients' total scintigraphic score (0-12 scale) was determined and the histopathological changes of minor salivary glands graded. Area under the receiver-operating characteristic (ROC) curve was employed to evaluate the diagnostic value of the US scoring system. Results. Primary SS was diagnosed in 107 (79.2%) patients and the remaining 28 subjects (20.8%) constituted the control group. US changes of salivary glands were established in 98/107 patients with SS and in 14/28 controls. Mean US score was 26 in SS patients and 6 in controls. Through ROC curves, US arose as the best performer (0.95 ± 0.01), followed by scintigraphy (0.86 ± 0.31). Setting the cutoff score for US at 19 resulted in the best ratio of specificity (90.8%) to sensitivity (87.1%), while setting the cutoff scintigraphic score at 6 resulted in specificity of 86.1% and sensitivity of 67.1%. Among 70 patients with US score ≥ 19, a scintigraphic score > 6 was recorded in 54/70 (77.1%) and positive biopsy findings in 62/70 (88.5%) patients. Conclusion. We show high diagnostic accuracy of a novel US scoring system of salivary glands (0-48) in patients with primary SS comparable to invasive methods, i.e., scintigraphy and salivary gland biopsy. The Journal of Rheumatology Copyright © 2009. All rights reserved.

Background The transition from psoriasis (PsO) to psoriatic arthritis (PsA) and the early diagnosis of PsA is of considerable scientific and clinical interest for the prevention and interception of PsA. Objective To formulate EULAR points to consider (PtC) for the development of data-driven guidance and consensus for clinical trials and clinical practice in the field of prevention or interception of PsA and for clinical management of people with PsO at risk for PsA development. Methods A multidisciplinary EULAR task force of 30 members from 13 European countries was established, and the EULAR standardised operating procedures for development for PtC were followed. Two systematic literature reviews were conducted to support the task force in formulating the PtC. Furthermore, the task force proposed nomenclature for the stages before PsA, through a nominal group process to be used in clinical trials. Results Nomenclature for the stages preceding PsA onset, 5 overarching principles and 10 PtC were formulated. Nomenclature was proposed for three stages towards PsA development, namely people with PsO at higher risk of PsA, subclinical PsA and clinical PsA. The latter stage was defined as PsO and associated synovitis and it could be used as an outcome measure for clinical trials evaluating the transition from PsO to PsA. The overarching principles address the nature of PsA at its onset and underline the importance of collaboration of rheumatologists and dermatologists for strategies for prevention/interception of PsA. The 10 PtC highlight arthralgia and imaging abnormalities as key elements of subclinical PsA that can be used as potential short-term predictors of PsA development and useful items to design clinical trials for PsA interception. Traditional risk factors for PsA development (ie, PsO severity, obesity and nail involvement) may represent more long-term disease predictors and be less robust for short-term trials concerning the transition from PsO to PsA. Conclusion These PtC are helpful to define the clinical and imaging features of people with PsO suspicious to progress to PsA. This information will be helpful for identification of those who could benefit from a therapeutic intervention to attenuate, delay or prevent PsA development. © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Background The transition from psoriasis (PsO) to psoriatic arthritis (PsA) and the early diagnosis of PsA is of considerable scientific and clinical interest for the prevention and interception of PsA. Objective To formulate EULAR points to consider (PtC) for the development of data-driven guidance and consensus for clinical trials and clinical practice in the field of prevention or interception of PsA and for clinical management of people with PsO at risk for PsA development. Methods A multidisciplinary EULAR task force of 30 members from 13 European countries was established, and the EULAR standardised operating procedures for development for PtC were followed. Two systematic literature reviews were conducted to support the task force in formulating the PtC. Furthermore, the task force proposed nomenclature for the stages before PsA, through a nominal group process to be used in clinical trials. Results Nomenclature for the stages preceding PsA onset, 5 overarching principles and 10 PtC were formulated. Nomenclature was proposed for three stages towards PsA development, namely people with PsO at higher risk of PsA, subclinical PsA and clinical PsA. The latter stage was defined as PsO and associated synovitis and it could be used as an outcome measure for clinical trials evaluating the transition from PsO to PsA. The overarching principles address the nature of PsA at its onset and underline the importance of collaboration of rheumatologists and dermatologists for strategies for prevention/interception of PsA. The 10 PtC highlight arthralgia and imaging abnormalities as key elements of subclinical PsA that can be used as potential short-term predictors of PsA development and useful items to design clinical trials for PsA interception. Traditional risk factors for PsA development (ie, PsO severity, obesity and nail involvement) may represent more long-term disease predictors and be less robust for short-term trials concerning the transition from PsO to PsA. Conclusion These PtC are helpful to define the clinical and imaging features of people with PsO suspicious to progress to PsA. This information will be helpful for identification of those who could benefit from a therapeutic intervention to attenuate, delay or prevent PsA development. © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

The aim of this study was to assess the association between Raynaud's phenomenon (RP) and specific capillaroscopic findings in patients with SLE and particular clinical manifestations of the disease. A total of 79 patients with SLE were included in the study: 44 of them (43 women) with RP and 35 (32 women) age-, sex-, and disease- duration-matched patients with SLE without RP. Demographic variables, clinical manifestations, laboratory and nailfold capillaroscopy findings were compared between the two groups. Central nervous systemic involvements (P = 0.0038) and peripheral neuropathy (P = 0.0336) were significantly more common in SLE patients with RP, while secondary Sjögren's syndrome (P = 0.0363) was more common in SLE patients without RP. RP occurred in 52 % of patients before SLE onset while 48 % of patients developed RP after they had been diagnosed with SLE. Arthritis/arthralgia (P = 0.0073) was significantly more common in patients who had been diagnosed with RP before the onset of SLE, while mucosal ulcers were more common in patients who contracted RP after the onset of SLE (P = 0.0258). Enlarged capillaries (P = 0.0482), presence of avascular areas (P = 0.0476), capillary hemorrhages (P = 0.0482), and granular blood flow (P = 0.0482) were more common in patients with SLE who also suffered from RP, than in patients with SLE without RP. The frequency of normal (63.6 vs. 82.9 %, P = 0.100) and nonspecific (25 vs. 17.1 %, P = 0.5696) capillaroscopy findings were similar in either groups. Scleroderma-like pattern of capillaroscopy finding was only found in patients with RP [(11.4 %), P = 0.0482]. RP in our patients with SLE was associated with specific clinical manifestations, indicating that prognostic relevance of RP in SLE should be evaluated. © Springer-Verlag 2012.

The aim of this study was to assess the association between Raynaud's phenomenon (RP) and specific capillaroscopic findings in patients with SLE and particular clinical manifestations of the disease. A total of 79 patients with SLE were included in the study: 44 of them (43 women) with RP and 35 (32 women) age-, sex-, and disease- duration-matched patients with SLE without RP. Demographic variables, clinical manifestations, laboratory and nailfold capillaroscopy findings were compared between the two groups. Central nervous systemic involvements (P = 0.0038) and peripheral neuropathy (P = 0.0336) were significantly more common in SLE patients with RP, while secondary Sjögren's syndrome (P = 0.0363) was more common in SLE patients without RP. RP occurred in 52 % of patients before SLE onset while 48 % of patients developed RP after they had been diagnosed with SLE. Arthritis/arthralgia (P = 0.0073) was significantly more common in patients who had been diagnosed with RP before the onset of SLE, while mucosal ulcers were more common in patients who contracted RP after the onset of SLE (P = 0.0258). Enlarged capillaries (P = 0.0482), presence of avascular areas (P = 0.0476), capillary hemorrhages (P = 0.0482), and granular blood flow (P = 0.0482) were more common in patients with SLE who also suffered from RP, than in patients with SLE without RP. The frequency of normal (63.6 vs. 82.9 %, P = 0.100) and nonspecific (25 vs. 17.1 %, P = 0.5696) capillaroscopy findings were similar in either groups. Scleroderma-like pattern of capillaroscopy finding was only found in patients with RP [(11.4 %), P = 0.0482]. RP in our patients with SLE was associated with specific clinical manifestations, indicating that prognostic relevance of RP in SLE should be evaluated. © Springer-Verlag 2012.

To assess the prognostic value of the age at onset of Raynaud's (RP) and of a history of exacerbation of RP attacks for the development of connective tissue disease (CTD) in patients initially found to have primary Raynaud's. 3,035 patients with primary RP (2,702 women and 333 men) were followed for an average of 4.8 years (range from 1 to 10 years). At baseline and every 6 months, they were screened for signs and symptoms of CTD. At 4.8 years of follow-up, 54.7 % patients remained as primary RP, 8.1 % had developed suspected secondary RP, and 37.2 % had developed a definite CTD. Primary RP patients had an earlier onset of RP (mean age of 32.2 years) than those with suspected (mean age 36.5 years, P = .007) or definite secondary RP associated with CTD (mean age of 39.8 years, P = .004). RP beginning before the age of forty was not significantly associated with the development of CTD. Conversely, the appearance of RP after the age of 40 was significantly associated with the development of CTD (P = .00001). Worsening of RP attacks predicted the development of CTD, especially systemic sclerosis (relative risk [RR] of 1.42), scleroderma overlap syndrome (RR of 1.18), and mixed CTD (RR of 1.18). Patients whose onset of RP occurred past 40 years of age and those with worsening RP attacks were at risk for the future development of CTD. © Springer-Verlag 2012.

To assess the prognostic value of the age at onset of Raynaud's (RP) and of a history of exacerbation of RP attacks for the development of connective tissue disease (CTD) in patients initially found to have primary Raynaud's. 3,035 patients with primary RP (2,702 women and 333 men) were followed for an average of 4.8 years (range from 1 to 10 years). At baseline and every 6 months, they were screened for signs and symptoms of CTD. At 4.8 years of follow-up, 54.7 % patients remained as primary RP, 8.1 % had developed suspected secondary RP, and 37.2 % had developed a definite CTD. Primary RP patients had an earlier onset of RP (mean age of 32.2 years) than those with suspected (mean age 36.5 years, P = .007) or definite secondary RP associated with CTD (mean age of 39.8 years, P = .004). RP beginning before the age of forty was not significantly associated with the development of CTD. Conversely, the appearance of RP after the age of 40 was significantly associated with the development of CTD (P = .00001). Worsening of RP attacks predicted the development of CTD, especially systemic sclerosis (relative risk [RR] of 1.42), scleroderma overlap syndrome (RR of 1.18), and mixed CTD (RR of 1.18). Patients whose onset of RP occurred past 40 years of age and those with worsening RP attacks were at risk for the future development of CTD. © Springer-Verlag 2012.

Objectives Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). Methods The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). Results 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. Conclusions Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. Trial registration number NCT02339441. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Objectives Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). Methods The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). Results 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. Conclusions Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. Trial registration number NCT02339441. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[No abstract available]

[No abstract available]

To assess the prognostic value of scleroderma pattern of nailfold capillary changes for the development of connective tissue diseases (CTD) in subjects with primary Raynaud's phenomenon (RP). The study included 3,029 consecutive patients with primary RP who had been followed at 6-month intervals during the mean of 4.8 years. The pathological features of nailfold capillaroscopy were recorded in all patients who had neither clinical nor serological signs of a CTD. In patients who developed CTD, capillary changes obtained 6 months prior to diagnosis were analyzed. A possible relationship between capillary changes and the presence of associated CTD was assessed. At the end of follow-up, 1,660 (54,8%) patients have still the primary RP, 246 (8,1%) had suspected secondary RP, and 1,123 (37,1%) patients developed CTD (363 undifferentiated CTD, 263 systemic sclerosis, 143 systemic lupus erythematosus, 106 rheumatoid arthritis, 102 Sjögren's syndrome, 61 overlap syndrome, 30 vasculitides, 24 mixed CTD, 19 polymyositis, 7 dermatomyositis, and 5 primary antiphospholipid syndrome). Scleroderma pattern were significantly associated with the development of systemic sclerosis [P = .00001, sensitivity 94%, specificity 92%, positive predictive value 52%, negative predictive value 99%, and odds ratio 163 (95% CI, 97,9-271,5)], as well as dermatomyositis (P = .0004), overlap syndrome with signs of systemic sclerosis (P = .0001), and mixed connective tissue disease (P = .007). Capillary microscopy is effective method for differentiation between primary and secondary RP and useful tool for the prediction of scleroderma spectrum disorders in RP patients. © 2011 Springer-Verlag.

To assess the prognostic value of scleroderma pattern of nailfold capillary changes for the development of connective tissue diseases (CTD) in subjects with primary Raynaud's phenomenon (RP). The study included 3,029 consecutive patients with primary RP who had been followed at 6-month intervals during the mean of 4.8 years. The pathological features of nailfold capillaroscopy were recorded in all patients who had neither clinical nor serological signs of a CTD. In patients who developed CTD, capillary changes obtained 6 months prior to diagnosis were analyzed. A possible relationship between capillary changes and the presence of associated CTD was assessed. At the end of follow-up, 1,660 (54,8%) patients have still the primary RP, 246 (8,1%) had suspected secondary RP, and 1,123 (37,1%) patients developed CTD (363 undifferentiated CTD, 263 systemic sclerosis, 143 systemic lupus erythematosus, 106 rheumatoid arthritis, 102 Sjögren's syndrome, 61 overlap syndrome, 30 vasculitides, 24 mixed CTD, 19 polymyositis, 7 dermatomyositis, and 5 primary antiphospholipid syndrome). Scleroderma pattern were significantly associated with the development of systemic sclerosis [P = .00001, sensitivity 94%, specificity 92%, positive predictive value 52%, negative predictive value 99%, and odds ratio 163 (95% CI, 97,9-271,5)], as well as dermatomyositis (P = .0004), overlap syndrome with signs of systemic sclerosis (P = .0001), and mixed connective tissue disease (P = .007). Capillary microscopy is effective method for differentiation between primary and secondary RP and useful tool for the prediction of scleroderma spectrum disorders in RP patients. © 2011 Springer-Verlag.

The aim of this study is to assess the prognostic value of major provisional criteria for the development of systemic sclerosis (SSc) in primary Raynaud's phenomenon (RP) patients. We retrospectively studied the chart of 497 patients with primary RP in whom anticentromere (ACA) and antitopoisomerase I (ATA) antibodies tests and a capillary reading were available. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratios (LHR?), negative likelihood ratios (LHR-), odds ratio (OR), and area under the receiver operating characteristics curve (AUC) of those criteria were assessed to predict the development of SSc. During the average follow-up of 2.3 ± 1.9 years, 159 (32 %) patients evolved to SSc, 245 (49.3 %) evolved to other connective tissue diseases, and 93 (18.7 %) patients did not progress. The SSc pattern predicted SSc satisfactorily (LHR? 4.12, LHR- 0.07, OR 63, AUC 0.819; P\0.001). ACA were not significantly associated with the development of SSc (LHR? 1.19, LHR- 0.9, OR 1.32, AUC 0.538, P = 0.156). ATA were significantly associated with the development of SSc (LHR? 9.32, LHR- 0.67, OR 15.13, AUC 0.777; P\0.001). Both SSc pattern and ACA or ATA were significantly associated with the development of SSc (LHR? 2.98, LHR- 0.70, OR 4.2, AUC 0.674; P\0.001 vs. LHR? 16, LHR- 0.68, OR 24, AUC 0.819; P\0.001, respectively). SSc pattern or ATA as independent risk factors, as well as following two parameters together (SSc pattern and ATA or SSc pattern and ACA) were good predictors for the development of SSc. © Springer-Verlag Berlin Heidelberg 2013.

The aim of this study is to assess the prognostic value of major provisional criteria for the development of systemic sclerosis (SSc) in primary Raynaud's phenomenon (RP) patients. We retrospectively studied the chart of 497 patients with primary RP in whom anticentromere (ACA) and antitopoisomerase I (ATA) antibodies tests and a capillary reading were available. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratios (LHR?), negative likelihood ratios (LHR-), odds ratio (OR), and area under the receiver operating characteristics curve (AUC) of those criteria were assessed to predict the development of SSc. During the average follow-up of 2.3 ± 1.9 years, 159 (32 %) patients evolved to SSc, 245 (49.3 %) evolved to other connective tissue diseases, and 93 (18.7 %) patients did not progress. The SSc pattern predicted SSc satisfactorily (LHR? 4.12, LHR- 0.07, OR 63, AUC 0.819; P\0.001). ACA were not significantly associated with the development of SSc (LHR? 1.19, LHR- 0.9, OR 1.32, AUC 0.538, P = 0.156). ATA were significantly associated with the development of SSc (LHR? 9.32, LHR- 0.67, OR 15.13, AUC 0.777; P\0.001). Both SSc pattern and ACA or ATA were significantly associated with the development of SSc (LHR? 2.98, LHR- 0.70, OR 4.2, AUC 0.674; P\0.001 vs. LHR? 16, LHR- 0.68, OR 24, AUC 0.819; P\0.001, respectively). SSc pattern or ATA as independent risk factors, as well as following two parameters together (SSc pattern and ATA or SSc pattern and ACA) were good predictors for the development of SSc. © Springer-Verlag Berlin Heidelberg 2013.

Objective. To evaluate the effect of a tumor necrosis factor-α (TNF-α) inhibitor (etanercept) on innate inflammatory and Th17 cytokines in patients with rheumatoid arthritis (RA). Methods. Serum samples were collected from 40 patients with active RA refractory to conventional disease-modifying antirheumatic drugs who initiated therapy with etanercept plus methotrexate (MTX). Treatment response was assessed at Week 24 according to the European League Against Rheumatism response criteria. Serum levels of interleukin 6 (IL-6), TNF-α, IL-32, IL-23, IL-17A, IL-21, and IL-22 were measured in patients with RA and 25 healthy controls. Results. Patients with RA had increased levels of IL-6 (p < 0.001), IL-32 (p < 0.001), IL-23 (p < 0.001), and a trend toward increased IL-21 in the sera compared to controls. At 24 weeks' posttreatment, followup serum samples of etanercept responders had decreased levels of IL-6 (p < 0.001) and increased IL-21 (p < 0.05) and IL-32 (p < 0.001), while there were no differences in cytokine levels in non-responders. Serum IL-6 levels were positively correlated with levels of erythrocyte sedimentation rate (r = 0.458, p < 0.01), C-reactive protein (r = 0.593, p < 0.01), and 28-joint Disease Activity Score (r = 0.432, p < 0.01) at baseline. Serum IL-21 levels were positively correlated with levels of rheumatoid factor (r = 0.513, r = 0.633, both p < 0.01) and antimutated citrullinated vimentin antibodies (r = 0.515, p < 0.01; r = 0.428, p < 0.05) at baseline and after 24 weeks of treatment with etanercept. Conclusion. Multiple inflammatory pathways contribute to persistent chronic inflammation in RA. In contrast to nonresponders, etanercept therapy modulated serum cytokine levels and caused a marked decrease of IL-6 levels in responders. IL-21 might be involved in the regulation of autoantibody production in RA. The Journal of Rheumatology Copyright © 2012. All rights reserved.

Objective. To evaluate the effect of a tumor necrosis factor-α (TNF-α) inhibitor (etanercept) on innate inflammatory and Th17 cytokines in patients with rheumatoid arthritis (RA). Methods. Serum samples were collected from 40 patients with active RA refractory to conventional disease-modifying antirheumatic drugs who initiated therapy with etanercept plus methotrexate (MTX). Treatment response was assessed at Week 24 according to the European League Against Rheumatism response criteria. Serum levels of interleukin 6 (IL-6), TNF-α, IL-32, IL-23, IL-17A, IL-21, and IL-22 were measured in patients with RA and 25 healthy controls. Results. Patients with RA had increased levels of IL-6 (p < 0.001), IL-32 (p < 0.001), IL-23 (p < 0.001), and a trend toward increased IL-21 in the sera compared to controls. At 24 weeks' posttreatment, followup serum samples of etanercept responders had decreased levels of IL-6 (p < 0.001) and increased IL-21 (p < 0.05) and IL-32 (p < 0.001), while there were no differences in cytokine levels in non-responders. Serum IL-6 levels were positively correlated with levels of erythrocyte sedimentation rate (r = 0.458, p < 0.01), C-reactive protein (r = 0.593, p < 0.01), and 28-joint Disease Activity Score (r = 0.432, p < 0.01) at baseline. Serum IL-21 levels were positively correlated with levels of rheumatoid factor (r = 0.513, r = 0.633, both p < 0.01) and antimutated citrullinated vimentin antibodies (r = 0.515, p < 0.01; r = 0.428, p < 0.05) at baseline and after 24 weeks of treatment with etanercept. Conclusion. Multiple inflammatory pathways contribute to persistent chronic inflammation in RA. In contrast to nonresponders, etanercept therapy modulated serum cytokine levels and caused a marked decrease of IL-6 levels in responders. IL-21 might be involved in the regulation of autoantibody production in RA. The Journal of Rheumatology Copyright © 2012. All rights reserved.