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Daniel Aletaha - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of newly proposed remission cut points for disease activity score in 28 joints DAS28 in rheumatoid arthritis patients upon il 6 pathway inhibition
    Arthritis Research & Therapy, 2017
    Co-Authors: Monika Schoels, Josef S. Smolen, F Alasti, Daniel Aletaha
    Abstract:

    Stringent remission criteria are crucial in rheumatoid arthritis (RA) assessment. Disease activity score in 28 joints (DAS28)-remission has not been included among American College of Rheumatology/European League Against Rheumatism definitions, because of its association with significant residual disease activity, partly due to high weighting of acute-phase reactants (APR). New, more stringent cut-points for DAS28-remission have recently been proposed that are suggested to reflect remission by clinical and simplified disease activity indices (clinical disease activity index (CDAI), simple disease activity index (SDAI)). However, their stringency in therapies directly influencing APR, like IL-6-blockers, has not been tested. We tested the new cut-points in patients with RA receiving tocilizumab. We used data from randomised controlled trials of tocilizumab and evaluated patients in remission according to new DAS28-C-reactive protein (DAS-CRP) and DAS-erythrocyte sedimentation rate (DAS-ESR) cut-points (1.9 and 2.2). We assessed their disease activity state using the CDAI, SDAI and Boolean criteria and analysed their individual residual core set variables, like swollen joint counts (SJC28). About 50% of patients in DAS28-CRP-remission (<1.9) fell into higher disease activity states when assessed with CDAI, SDAI or Boolean criteria. Also, 15% had three or more (up to eight) SJC. Even higher disease activity was seen in patients classified as being in DAS28-ESR-remission (<2.2). Even with new, more stringent cut-points, DAS28-remission is frequently associated with considerable residual clinical disease activity, indicating that this limitation of the DAS28 is related to score construction rather than the choice of cut-points.

  • joint damage in rheumatoid arthritis progresses in remission according to the disease activity score in 28 joints and is driven by residual swollen joints
    Arthritis & Rheumatism, 2011
    Co-Authors: Daniel Aletaha, Josef S. Smolen
    Abstract:

    Objective Remission has been defined as the ultimate target for patients with rheumatoid arthritis. The Disease Activity Score in 28 joints (DAS28) has been criticized for the amount of disease activity that remains in patients despite their achieving DAS28 remission. This study was undertaken to investigate the significance of residual inflammation in remission in relation to radiographic progression. Methods We pooled 1-year clinical data, kindly provided by the respective sponsors, on 864 patients in methotrexate monotherapy arms of recent pivotal trials. We identified patients who had attained persistent DAS28 remission from month 6 through month 12 (a DAS286–12 of <2.6). Among these patients we then assessed radiographic progression in total Sharp/van der Heijde scores (SHS) from baseline to 12 months between those with residual joint swelling (defined as a swollen joint count from month 6 through month 12 [SJC6–12] of ≥2) and those without residual joint swelling (defined as an SJC6–12 of <2). Results One hundred fourteen patients (13.2%) achieved a DAS286–12 of 0.5/year was significantly lower among those without joint swelling than among those with joint swelling (27.2% versus 50.0%; P = 0.039). DAS28 remitters without joint swelling showed progression comparable to that in the total group of remitters by the Simplified Disease Activity Index (remission defined as ≤3.3) and Clinical Disease Activity Index (remission defined as ≤2.8), namely, 0.2 versus −0.07 versus 0.16, respectively (P = 0.66). Conclusion Radiographic progression with nonbiologic treatment is minimal only when patients in DAS28 remission have no persistent residual joint swelling. Under these conditions, progression is comparable to that in patients with disease in remission according to other disease activity indices.

  • interleukin 6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis the role of acute phase reactants
    Arthritis & Rheumatism, 2011
    Co-Authors: Josef S. Smolen, Daniel Aletaha
    Abstract:

    Objective To determine the effects of tocilizumab on rheumatoid arthritis (RA) disease activity and remission assessment, using measures that do or do not comprise acute-phase reactants. Methods Simplified Disease Activity Index (SDAI) scores, Clinical Disease Activity Index (CDAI) scores, and the Disease Activity Score in 28 joints (DAS28) were calculated using data from tocilizumab trials in patients with RA in whom disease had remained active despite treatment with disease-modifying antirheumatic drugs. The CDAI does not contain an acute-phase reactant component. Disease activity states, including remission, were defined using established cut points; for the DAS28, an alternative cut point of <2.4 was also used. Results Changes in the DAS28, the SDAI score, and the CDAI score among patients receiving tocilizumab were significantly higher than those among patients receiving placebo, and the magnitude of these changes was similar for the SDAI and the CDAI. Among patients who achieved 50% improvement in disease activity according to the American College of Rheumatology criteria, only ∼20% required a reduction in acute-phase reactant values in order to fulfill the criteria. However, DAS28 remission rates were higher (even when using the lower cut point) than the SDAI and CDAI remission rates. Only a minority of tocilizumab-treated patients with DAS28 remission also had disease remission according to the SDAI (26%) or CDAI (∼21%). With infliximab treatment, SDAI and CDAI remission rates were of the same magnitude as those observed with tocilizumab treatment, and DAS28 remission rates were lower. Tocilizumab-treated patients with DAS28 remission but without CDAI remission had significantly higher swollen joint counts but lower erythrocyte sedimentation rates (ESRs) compared with patients with SDAI or CDAI remission. Conclusion Disease activity in RA is reduced by tocilizumab treatment, irrespective of the type of composite measure used to evaluate disease activity. Remission rates were much higher using the DAS28 compared with the SDAI and CDAI, due to the high weight of the ESR in the DAS28 and the effect of tocilizumab on the ESR. Using the stringent SDAI and CDAI criteria, however, remission rates in patients treated with tocilizumab were in the same range as those seen in patients treated with tumor necrosis factor inhibitors.

  • validation of the 28 joint disease activity score DAS28 and european league against rheumatism response criteria based on c reactive protein against disease progression in patients with rheumatoid arthritis and comparison with the DAS28 based on eryt
    Annals of the Rheumatic Diseases, 2009
    Co-Authors: George A Wells, Daniel Aletaha, M Dougados, Michael Schiff, Jc Becker, Julie Teng, J S Smolen, P L C M Van Riel
    Abstract:

    Objective: To validate and compare the definition of the Disease Activity Score 28 based on C-reactive protein (DAS28 (CRP)) to the definition based on erythrocyte sedimentation rate (ESR). Methods: Data were analysed from two randomised, double-blind, placebo-controlled trials of abatacept of 6-month and 12-month duration in patients with rheumatoid arthritis. European League Against Rheumatism (EULAR) response criteria and the proportion of patients in remission (DAS28 Results: There was general agreement in determining the EULAR responder state using both DAS28 definitions (κ = 0.80, 95% CI 0.76 to 0.83). Overall, there was 82.4% agreement on the EULAR response criteria; when disagreements occurred, the DAS28 (CRP) yielded a better EULAR response more often then DAS28 (ESR) (12.6% vs 4.9%, respectively). There was also agreement in determining remission: κ = 0.69 (95% CI 0.60 to 0.78). Radiographic progression decreased in patients treated with abatacept across EULAR states (from none to moderate to good) based on both definitions. For patients treated with placebo, the trend was not as pronounced, with radiographic scores higher for moderate vs non-responders. For physical function, similar trends were observed across the EULAR states for both DAS28 definitions. Conclusions: The DAS28 (CRP) has been validated against radiographic progression and physical function. While the DAS28 (CRP) yielded a better EULAR response more often than the DAS28 (ESR), the validation profile was similar to the DAS28 (ESR), indicating that both measures are useful for assessing disease activity in patients with rheumatoid arthritis.

  • validation of the 28 joint disease activity score DAS28 and european league against rheumatism response criteria based on c reactive protein against disease progression in patients with rheumatoid arthritis and comparison with the DAS28 based on eryt
    Annals of the Rheumatic Diseases, 2009
    Co-Authors: George A Wells, Daniel Aletaha, Josef S. Smolen, M Dougados, Michael Schiff, Jc Becker, Julie Teng, P L C M Van Riel
    Abstract:

    OBJECTIVE: To validate and compare the definition of the Disease Activity Score 28 based on C-reactive protein (DAS28 (CRP)) to the definition based on erythrocyte sedimentation rate (ESR). METHODS: Data were analysed from two randomised, double-blind, placebo-controlled trials of abatacept of 6-month and 12-month duration in patients with rheumatoid arthritis. European League Against Rheumatism (EULAR) response criteria and the proportion of patients in remission (DAS28 <2.6) based on the two DAS28 definitions were examined. Trends in radiographic progression (erosion score, joint space narrowing score and total score) and physical function (Health Assessment Questionnaire Disability Index (HAQ-DI)) across the EULAR responder states (none, moderate and good) were analysed. RESULTS: There was general agreement in determining the EULAR responder state using both DAS28 definitions (kappa = 0.80, 95% CI 0.76 to 0.83). Overall, there was 82.4% agreement on the EULAR response criteria; when disagreements occurred, the DAS28 (CRP) yielded a better EULAR response more often then DAS28 (ESR) (12.6% vs 4.9%, respectively). There was also agreement in determining remission: kappa = 0.69 (95% CI 0.60 to 0.78). Radiographic progression decreased in patients treated with abatacept across EULAR states (from none to moderate to good) based on both definitions. For patients treated with placebo, the trend was not as pronounced, with radiographic scores higher for moderate vs non-responders. For physical function, similar trends were observed across the EULAR states for both DAS28 definitions. CONCLUSIONS: The DAS28 (CRP) has been validated against radiographic progression and physical function. While the DAS28 (CRP) yielded a better EULAR response more often than the DAS28 (ESR), the validation profile was similar to the DAS28 (ESR), indicating that both measures are useful for assessing disease activity in patients with rheumatoid arthritis.

Brian C Sauer - One of the best experts on this subject based on the ideXlab platform.

  • utility of administrative and clinical data to predict major change in medical treatment in us veterans enrolled in the veterans affairs rheumatoid arthritis vara registry
    Clinical and Experimental Rheumatology, 2019
    Co-Authors: Jacob R Stever, Grant W Cannon, Chiachen Teng, Neil A Accortt, David H Collier, Brian C Sauer
    Abstract:

    OBJECTIVES To examine factors associated with major therapeutic changes (MTC) among US Veterans with moderate/severe rheumatoid arthritis (RA) based on Disease Activity Score based on 28 joints (DAS28). METHODS We used data from patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry from 1/1/2006 through 12/31/2014. The index date was a clinic visit with DAS28 >3.2 (moderate/severe disease) following an 18-month pre-index period that included ≥2 DAS28 measurements ≥60 days apart. The patients were followed for MTC from 7 days pre-index through 90 days post-index. Poisson multivariable regression models were used to identify associations with MTC. Chart review of a subset of randomly selected patients explored factors that impacted therapeutic decisions. RESULTS Among 941 patients, 396 (42.1%) had MTC. Of these, 369 (39.2%) patients had worsening DAS28 at index, 118 (12.5%) had DAS28 improvements, and 454 (48.2%) patients had no change in DAS28 versus pre-index DAS28. Of the patients with worsening DAS28, no change in DAS28, and improved DAS28, respectively, 50.5%, 62.6%, and 70.3% had no MTC. Regression analyses showed index DAS28, oral steroid or non-biologic disease-modifying anti-rheumatic drug (nbDMARD) use in the previous year were associated with an increased likelihood of MTC; use of nbDMARDs in the previous 90 days was associated with a decreased likelihood of MTC. The most common reason for not modifying therapy despite DAS28 >3.2 was a judgement of mild disease. CONCLUSIONS Clinicians frequently do not institute major therapeutic changes despite DAS28 indicating moderate/severe disease activity; multiple factors are involved in real-world treatment decisions.

  • thu0102 clinical disease activity measures are important drivers of major change in medical treatment in us veterans enrolled in the veterans affairs rheumatoid arthritis vara registry
    Annals of the Rheumatic Diseases, 2017
    Co-Authors: Grant W Cannon, Neil A Accortt, David H Collier, Cc Teng, S Mehrotra, Brian C Sauer
    Abstract:

    Background Current guidelines encourage the measurement of rheumatoid arthritis (RA) disease activity and directing therapy to achieve a low disease state or remission (treat-to-target). Many RA patients with documented moderate to severe disease activity remain on their current therapy without change. Objectives This study investigated Veterans Affairs (VA) clinical data to identify patient factors associated with a major change in RA therapy and to determine the relative importance of these different factors. Methods US Veterans enrolled in the VARA registry were included if they had: 1) high/moderate disease activity (DAS28≥3.2) at index date, 2) 18 months of VA data prior to the index date and 3) two or more other DAS28 measured during the preceding 18 months separated by at least three months. A major change was report if within 7 days before to 90 days after the index date there was either: 1) initiation or escalation of DMARDs, 2) initiation or increase dose of prednisone and/or 3) ≥2 joint injections. Baseline DAS28 was estimated during the observation period prior to the index date using an area under the curve calculation and compared to the DAS28 at the index date. Patients were categorized as have a worsening or improvement of disease if the DAS28 at index date was 0.6 higher or lower than the average DAS28 during the observation period respectively. Other patients were categorized as no change in DAS28. Analyses of clinical variables including components of the DAS28 and patient and physician reported measures were compared in patients with and patients without a major change in therapy. Results Of 941 patients who met study criteria, only 388/941 (41.2%) had a major change of therapy. Patients with worsening DAS28 were more likely to have a major change 183/369 (49.5%) than no DAS28 change 170/454 (37.4%) and improved DAS28 35/118 (29.6%) (P Conclusions More than half of the patients with moderate disease activity did not have a major change in therapy. The likelihood of a major change in therapy increased with worsening disease activity. The clinical variables assessed were more strongly associated with change in therapy in patients with worsening of disease. Clinical disease activity measures are highly associated with the decision to initiate major changes. Future work will investigate the potential added value of administrative variables. This work emphasizes the need for methods to systematically collect and utilize clinical disease activity measurements, particularly longitudinally, to improve the treat-to-target strategy. Acknowledgements Work Sponsored by VA Specialty Care Centers of Innovation, VA Health Service Research and Development, and Amgen. Disclosure of Interest G. Cannon Grant/research support from: Amgen, C.-C. Teng Grant/research support from: Amgen, N. Accortt Shareholder of: Amgen, Employee of: Amgen, D. Collier Shareholder of: Amgen, Employee of: Amgen, S. Mehrotra Grant/research support from: Amgen, B. Sauer Grant/research support from: Amgen

Josef S. Smolen - One of the best experts on this subject based on the ideXlab platform.

  • predictors of remission with etanercept methotrexate induction therapy and loss of remission with etanercept maintenance reduction or withdrawal in moderately active rheumatoid arthritis results of the preserve trial
    Arthritis Research & Therapy, 2018
    Co-Authors: Josef S. Smolen, Andrew S Koenig, A Szumski, Thomas V Jones, L Marshall
    Abstract:

    The aim was to analyze characteristics that predict remission induction and subsequent loss of remission in patients with moderately active rheumatoid arthritis (RA) who received full-dose combination etanercept plus methotrexate induction therapy followed by reduced-dose etanercept or etanercept withdrawal. Patients with Disease Activity Score based on 28-joint count (DAS28) >3.2 and ≤5.1 received open-label etanercept 50 mg once weekly (QW) plus methotrexate for 36 weeks. Those who achieved DAS28 low disease activity by 36 weeks were randomized to double-blind treatment with etanercept 50 mg or 25 mg QW plus methotrexate or placebo plus methotrexate for 52 weeks. All analyses were adjusted for the continuous baseline variables of their respective remission outcomes. Younger age, body mass index (BMI) <30 kg/m2, and lower Health Assessment Questionnaire (HAQ) score at baseline were significant predictors of week-36 remission (P < 0.05) based on DAS28, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI). Baseline DAS28, SDAI, and CDAI were significantly predictive of all three remission endpoints (P < 0.05). For all three treatments, the strongest predictors of loss of DAS28 remission included failure to achieve sustained remission (DAS28 < 2.6 at weeks 12, 20, 28, and 36) with induction therapy, higher DAS28/SDAI/CDAI at randomization and at 1 month, increase in DAS28/SDAI/CDAI at 1 month, and increase in DAS28/CDAI/SDAI components and patient-reported outcomes (PROs) at 1 month. With the exception of not achieving sustained remission, very similar significant predictors were observed for loss of SDAI and CDAI remission. These findings suggest that patients with moderately active RA who are younger and have lower BMI, lower HAQ, and lower disease activity at baseline are most likely to achieve remission when receiving combination etanercept and methotrexate induction therapy. In addition, patients who fail to achieve sustained remission with induction therapy and those with worse disease activity and PROs at early time points after initiating maintenance therapy with a full-dose or reduced-dose etanercept-methotrexate regimen or methotrexate monotherapy are most likely to lose remission across all treatment arms. These findings may help guide clinicians’ decision-making as they treat patients to remission and beyond. ClinicalTrials.gov, NCT00565409 . Registered on 28 November 2007

  • evaluation of newly proposed remission cut points for disease activity score in 28 joints DAS28 in rheumatoid arthritis patients upon il 6 pathway inhibition
    Arthritis Research & Therapy, 2017
    Co-Authors: Monika Schoels, Josef S. Smolen, F Alasti, Daniel Aletaha
    Abstract:

    Stringent remission criteria are crucial in rheumatoid arthritis (RA) assessment. Disease activity score in 28 joints (DAS28)-remission has not been included among American College of Rheumatology/European League Against Rheumatism definitions, because of its association with significant residual disease activity, partly due to high weighting of acute-phase reactants (APR). New, more stringent cut-points for DAS28-remission have recently been proposed that are suggested to reflect remission by clinical and simplified disease activity indices (clinical disease activity index (CDAI), simple disease activity index (SDAI)). However, their stringency in therapies directly influencing APR, like IL-6-blockers, has not been tested. We tested the new cut-points in patients with RA receiving tocilizumab. We used data from randomised controlled trials of tocilizumab and evaluated patients in remission according to new DAS28-C-reactive protein (DAS-CRP) and DAS-erythrocyte sedimentation rate (DAS-ESR) cut-points (1.9 and 2.2). We assessed their disease activity state using the CDAI, SDAI and Boolean criteria and analysed their individual residual core set variables, like swollen joint counts (SJC28). About 50% of patients in DAS28-CRP-remission (<1.9) fell into higher disease activity states when assessed with CDAI, SDAI or Boolean criteria. Also, 15% had three or more (up to eight) SJC. Even higher disease activity was seen in patients classified as being in DAS28-ESR-remission (<2.2). Even with new, more stringent cut-points, DAS28-remission is frequently associated with considerable residual clinical disease activity, indicating that this limitation of the DAS28 is related to score construction rather than the choice of cut-points.

  • joint damage in rheumatoid arthritis progresses in remission according to the disease activity score in 28 joints and is driven by residual swollen joints
    Arthritis & Rheumatism, 2011
    Co-Authors: Daniel Aletaha, Josef S. Smolen
    Abstract:

    Objective Remission has been defined as the ultimate target for patients with rheumatoid arthritis. The Disease Activity Score in 28 joints (DAS28) has been criticized for the amount of disease activity that remains in patients despite their achieving DAS28 remission. This study was undertaken to investigate the significance of residual inflammation in remission in relation to radiographic progression. Methods We pooled 1-year clinical data, kindly provided by the respective sponsors, on 864 patients in methotrexate monotherapy arms of recent pivotal trials. We identified patients who had attained persistent DAS28 remission from month 6 through month 12 (a DAS286–12 of <2.6). Among these patients we then assessed radiographic progression in total Sharp/van der Heijde scores (SHS) from baseline to 12 months between those with residual joint swelling (defined as a swollen joint count from month 6 through month 12 [SJC6–12] of ≥2) and those without residual joint swelling (defined as an SJC6–12 of <2). Results One hundred fourteen patients (13.2%) achieved a DAS286–12 of 0.5/year was significantly lower among those without joint swelling than among those with joint swelling (27.2% versus 50.0%; P = 0.039). DAS28 remitters without joint swelling showed progression comparable to that in the total group of remitters by the Simplified Disease Activity Index (remission defined as ≤3.3) and Clinical Disease Activity Index (remission defined as ≤2.8), namely, 0.2 versus −0.07 versus 0.16, respectively (P = 0.66). Conclusion Radiographic progression with nonbiologic treatment is minimal only when patients in DAS28 remission have no persistent residual joint swelling. Under these conditions, progression is comparable to that in patients with disease in remission according to other disease activity indices.

  • interleukin 6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis the role of acute phase reactants
    Arthritis & Rheumatism, 2011
    Co-Authors: Josef S. Smolen, Daniel Aletaha
    Abstract:

    Objective To determine the effects of tocilizumab on rheumatoid arthritis (RA) disease activity and remission assessment, using measures that do or do not comprise acute-phase reactants. Methods Simplified Disease Activity Index (SDAI) scores, Clinical Disease Activity Index (CDAI) scores, and the Disease Activity Score in 28 joints (DAS28) were calculated using data from tocilizumab trials in patients with RA in whom disease had remained active despite treatment with disease-modifying antirheumatic drugs. The CDAI does not contain an acute-phase reactant component. Disease activity states, including remission, were defined using established cut points; for the DAS28, an alternative cut point of <2.4 was also used. Results Changes in the DAS28, the SDAI score, and the CDAI score among patients receiving tocilizumab were significantly higher than those among patients receiving placebo, and the magnitude of these changes was similar for the SDAI and the CDAI. Among patients who achieved 50% improvement in disease activity according to the American College of Rheumatology criteria, only ∼20% required a reduction in acute-phase reactant values in order to fulfill the criteria. However, DAS28 remission rates were higher (even when using the lower cut point) than the SDAI and CDAI remission rates. Only a minority of tocilizumab-treated patients with DAS28 remission also had disease remission according to the SDAI (26%) or CDAI (∼21%). With infliximab treatment, SDAI and CDAI remission rates were of the same magnitude as those observed with tocilizumab treatment, and DAS28 remission rates were lower. Tocilizumab-treated patients with DAS28 remission but without CDAI remission had significantly higher swollen joint counts but lower erythrocyte sedimentation rates (ESRs) compared with patients with SDAI or CDAI remission. Conclusion Disease activity in RA is reduced by tocilizumab treatment, irrespective of the type of composite measure used to evaluate disease activity. Remission rates were much higher using the DAS28 compared with the SDAI and CDAI, due to the high weight of the ESR in the DAS28 and the effect of tocilizumab on the ESR. Using the stringent SDAI and CDAI criteria, however, remission rates in patients treated with tocilizumab were in the same range as those seen in patients treated with tumor necrosis factor inhibitors.

  • validation of the 28 joint disease activity score DAS28 and european league against rheumatism response criteria based on c reactive protein against disease progression in patients with rheumatoid arthritis and comparison with the DAS28 based on eryt
    Annals of the Rheumatic Diseases, 2009
    Co-Authors: George A Wells, Daniel Aletaha, Josef S. Smolen, M Dougados, Michael Schiff, Jc Becker, Julie Teng, P L C M Van Riel
    Abstract:

    OBJECTIVE: To validate and compare the definition of the Disease Activity Score 28 based on C-reactive protein (DAS28 (CRP)) to the definition based on erythrocyte sedimentation rate (ESR). METHODS: Data were analysed from two randomised, double-blind, placebo-controlled trials of abatacept of 6-month and 12-month duration in patients with rheumatoid arthritis. European League Against Rheumatism (EULAR) response criteria and the proportion of patients in remission (DAS28 <2.6) based on the two DAS28 definitions were examined. Trends in radiographic progression (erosion score, joint space narrowing score and total score) and physical function (Health Assessment Questionnaire Disability Index (HAQ-DI)) across the EULAR responder states (none, moderate and good) were analysed. RESULTS: There was general agreement in determining the EULAR responder state using both DAS28 definitions (kappa = 0.80, 95% CI 0.76 to 0.83). Overall, there was 82.4% agreement on the EULAR response criteria; when disagreements occurred, the DAS28 (CRP) yielded a better EULAR response more often then DAS28 (ESR) (12.6% vs 4.9%, respectively). There was also agreement in determining remission: kappa = 0.69 (95% CI 0.60 to 0.78). Radiographic progression decreased in patients treated with abatacept across EULAR states (from none to moderate to good) based on both definitions. For patients treated with placebo, the trend was not as pronounced, with radiographic scores higher for moderate vs non-responders. For physical function, similar trends were observed across the EULAR states for both DAS28 definitions. CONCLUSIONS: The DAS28 (CRP) has been validated against radiographic progression and physical function. While the DAS28 (CRP) yielded a better EULAR response more often than the DAS28 (ESR), the validation profile was similar to the DAS28 (ESR), indicating that both measures are useful for assessing disease activity in patients with rheumatoid arthritis.

Kimme L Hyrich - One of the best experts on this subject based on the ideXlab platform.

  • pharmacogenetics of tnf inhibitor response in rheumatoid arthritis utilizing the two component disease activity score
    Pharmacogenomics, 2020
    Co-Authors: Syed Gilani, Nisha Nair, Darren Plant, Kimme L Hyrich, Ann W Morgan, Andrew P Morris, Anthony G Wilson, John D Isaacs, Anne Barton, James Bluett
    Abstract:

    Aim: TNF inhibitor drugs are a treatment option for rheumatoid arthritis, but response is not universal. Response is typically measured using the composite 4-component (4C) disease activity score 28 (DAS28) which contains more subjective measures. This study used a validated 2-component (2C) DAS28 score to determine whether SNPs associated with response were replicated in the UK population. Materials & methods: A literature review identified TNF inhibitor response SNPs. Linear regression was conducted to replicate associations with 4C or 2C-DAS28 response. Results: Eighteen independent SNPs were analyzed in 1828 patients. One and four associations with 4C and 2C-DAS28 response respectively were identified (p ≤ 0.05). Conclusion: Further genetic associations were replicated using the 2C-DAS28 which may reflect the objective nature of 2C-AS28.

  • early response to anti tnf predicts long term outcomes including sustained remission an analysis of the bsrbr ra
    Rheumatology, 2020
    Co-Authors: Philip D H Hamann, Kimme L Hyrich, Neil Mchugh, John D Pauling, Gavin Shaddick
    Abstract:

    OBJECTIVE To identify different trajectories of disease activity in patients with RA following initiation of a first anti-TNF. METHODS Patients with RA starting their first anti-TNF between 2001 and 2013 were selected from the British Society for Rheumatology Biologics Register for RA. Six-monthly DAS28-ESR scores were used to identify trajectories of disease activity using latent class modelling. Data were included for six follow-ups after registration (approximately 3 years). Subgroup analysis examined changes in disease activity profiles over time. RESULTS A total of 14 436 patients with RA starting their first anti-TNF were enrolled between 2001 and 2013 (13 115 between 2001 and 2008, 1321 between 2010 and 2013). The mean number of DAS28-ESR scores was 3.5/patient (s.d. 2.1), with a mean of 184.9 days (s.d. 69.9) between scores. The DAS28-ESR nadir was achieved within 250 days of commencing anti-TNF, although apparent trajectory divergence emerged by first 6-monthly follow-up at 180 days. Four distinct response trajectories comprised the most stable model. Most patients fitted into 'modest' (7986 patients; 55.3%) or 'substantial' (4676 patients; 32.4%) response trajectories. Of the remainder, 1254 (8.7%) and 520 (3.6%) fitted 'maximal' and 'minimal' response trajectories, respectively. There was a significant (P < 0.01) increase in proportion achieving 'maximal' response between 2001-2008 and 2010-2013. CONCLUSION This is the largest study to identify long-term response trajectories with anti-TNF. By 6 months, longer-term trajectory profiles of DAS28 could already be identified, with many patients identified earlier. The majority of patients had persistent moderate response, equivalent to maintained DAS28-ESR moderate disease activity. The maximal response trajectory (equivalent to sustained DAS2-ESR remission) was only achieved by approximately one-third of patients.

  • fri0684 novel mapping function illustrates nonlinearity between trial acr response DAS28 change and eular response criteria
    Annals of the Rheumatic Diseases, 2019
    Co-Authors: Nuria Navarro Coy, Kimme L Hyrich, Sue Pavitt, Robert West, Maya H Buch
    Abstract:

    Background The American College of Rheumatology (ACR) definition of improvement is a standardised, widely used outcome measure for clinical trials in rheumatoid arthritis. In routine clinical practice (and registries), improvement is assessed by the DAS28 (Disease Activity Score 28), particularly in the UK, where it is the basis of current NICE guidance1. Objectives To develop a mapping function that charts ACR20/50/70 and ACRn to ΔDAS28 and EULAR response, and determine the relationship between the response measures. Methods Individual patient-level data from the 428 participants randomised to the ATTRACT2 trial were used. The proportion of participants with ACRn (ACR10-ACR90) response and the change in DAS28 (ΔDAS28) at 30 weeks from baseline were calculated and analysed analysed in participants with complete data. The cut points in ΔDAS28 that provided the equivalent proportion of participants achieving ACR10 to ACR90 at 30 weeks overall and per individual arm were searched for through tabulation. Regression models were conducted and misclassification rates calculated to test the accuracy of the mapping function. The minimum and maximum ACRn achieved per EULAR response category were also determined to establish the correlation of these two response criteria. R version 3.4.3 (2017-11-30) was used for all statistical analyses. Results 53%/27%/12% of all trial participants achieved ACR-ESR 20/50/70 responses, respectively. The mapping function shows that at 30 weeks a 20% improvement in ACR is equivalent to a 27.3% and 27.8% improvement from baseline in DAS28 calculated using ESR and CRP, respectively. 50% improvement in ACR is equivalent to a 45% and 46.2% improvement in DAS28-ESR and DAS28-CRP, respectively. 70% improvement in ACR is equivalent to a lower improvement in the DAS28, at 55.8% for ESR and 59.3% for CRP. Similar results were obtained when analysing the individual arms (Table 1 & Figure 1). Baseline DAS28 for all analysed groups was ≥ 6.0. Moderate or good EULAR responses correspond to 80% and 90% improvement in ACR, respectively, whereas the no response EULAR category showed a maximum improvement in ACR-ESR/CRP of 30%-50%, respectively (Figure 2). Conclusion This novel mapping function enables the comparison of trials reporting ACR20/50/70 with those reporting ΔDAS28. The results imply nonlinearity in the relationship between ACR20/50/70, ΔDAS28 and EULAR response criteria. Limitations: The mapping is dependent on the population chosen to examine it, which in this analysis comprised trial participants with very active disease. References [1] National Institute for Health and Care Excellence (NICE), Technology Appraisal Guidance (TA375) 2016. 2Maini R, et al. Lancet 1999. Disclosure of Interests Nuria Navarro Coy: None declared, Kimme Hyrich Grant/research support from: Grants to institution: BMS, Pfizer, UCB, Sue Pavitt: None declared, Robert West: None declared, Maya Buch Grant/research support from: Pfizer LTD, UCB, Consultant for: AbbVie, Eli Lilly, EMD Serono, Pfizer Ltd., Sanofi

  • gender stratified adjustment of the DAS28 crp improves inter score agreement with the DAS28 esr in rheumatoid arthritis
    Rheumatology, 2019
    Co-Authors: Philip D H Hamann, Kimme L Hyrich, Neil Mchugh, Gavin Shaddick, John D Pauling, Amelia Green
    Abstract:

    OBJECTIVES To evaluate determinants of discordance between DAS28-ESR and DAS28-CRP and resulting impact on disease activity stratification in RA. METHODS Paired DAS28-ESR and DAS28-CRP readings (n = 31 074) were obtained from the British Society for Rheumatology Biologics Register for RA. Factors influencing discordance between DAS28-ESR and DAS28-CRP were evaluated alongside the resulting effect on disease activity stratification. The impact of gender adjustment to the DAS28-CRP was evaluated. RESULTS DAS28-CRP scores were ∼0.3 lower than DAS28-ESR overall, with greatest differences for women (-0.35) and patients over 50 years old (-0.34). Mean male DAS28-CRP scores were 0.15 less than corresponding DAS28-ESR scores. Discordance between DAS28-ESR and DAS28-CRP significantly impacted disease activity stratification at low disease activity and remission thresholds (32.0% and 66.6% concordance, respectively). Adjusting DAS28-CRP scores by gender significantly (P < 0.001) improved agreement with the DAS28-ESR. CONCLUSION Discordance between DAS28-ESR and DAS28-CRP is greatest for women and patients over 50 years of age, and influences disease activity stratification. The proposed gender-adjusted DAS28-CRP improves inter-score agreement with DAS28-ESR, supporting more reliable disease activity stratification in treat-to-target approaches for RA.

  • op0174 the development of the modified DAS28 crp to improve agreement with DAS28 esr and ensure appropriate disease activity stratification in ra
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: Philip D H Hamann, Kimme L Hyrich, Amelia Jobling, Neil Mchugh, Gavin Shaddick, John D Pauling
    Abstract:

    Background Disease activity in rheumatoid arthritis (RA) has traditionally been measured using the 28-joint count disease activity score (DAS28) using ESR. Use of DAS28 with CRP in place of ESR is increasing. Evidence suggests these scores are not truly interchangeable and agreement varies dependant on disease activity. This study uses the BSRBR-RA to investigate agreement between these scores, proposing an optimised method to calculate the estimated DAS28-ESR using CRP (mDAS28-CRP) that offers higher interscore agreement than currently. Objectives To investigate and optimise agreement between the DAS28-ESR and DAS28-CRP scores using the BSRBR-RA. Methods Patients with concurrent measures of ESR and CRP were identified from the BSRBR-RA, enabling paired calculation of DAS28-ESR and DAS28-CRP using existing formulae. A non-linear regression model enabled prediction of ESR from CRP. Resulting values were used in the existing DAS28-ESR formula to calculate estimated disease activity (mDAS28-CRP). A Bayesian approach was used to acknowledge the uncertainty associated with the predictions and correctly propagate it through to mDAS28-CRP. Inference, including constructing credible intervals for predicted ESR and mDAS28-CRP, was performed using Markov-Chain-Monte-Carlo. Bland-Altman analysis and agreement matrices were used to compare agreement levels between mDAS28-CRP, DAS28-CRP and DAS28-ESR. Results 5457 patients (mean age 56 yrs, 76% female) with 31,084 data entries were identified where paired DAS28-ESR/DAS28-CRP scores could be calculated. Mean DAS28-ESR was 0.3 points greater than DAS28-CRP (4.4 (SD 1.7), 4.1 (SD 1.6) respectively) compared with mean mDAS28-CRP of 4.6 (SD 1.6; Fig 1). mDAS28-CRP had superior agreement with DAS28-ESR across remission, low and moderate disease activity, with only a 6.8% reduction in agreement at high disease activity when compared with the DAS28-CRP (Table 1). Conclusions The mDAS28-CRP (online calculator pending) allows calculation of a disease activity score, using the same component parts of the DAS28-CRP, and has higher agreement levels with the original validated DAS28-ESR, than the current DAS28-CRP in this cohort. Disease activity scores are fundamental in clinical trials and practice, forming a central role in guiding availability of therapeutic agents. It is therefore essential that scores used are both valid and, if used interchangeably, have high agreement levels. Disclosure of Interest None declared

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  • evaluation of the disease activity score in twenty eight joints based flare definitions in rheumatoid arthritis data from a three year clinical trial
    Arthritis Care and Research, 2015
    Co-Authors: M Dougados, Ernest Choy, Tom W J Huizinga, Clifton O Bingham, Maher Aassi, Corrado Bernasconi
    Abstract:

    OBJECTIVE To assess the flare rate using published criteria (Disease Activity Score in 28 joints [DAS28-2] increase between visits of >1.2 or >0.6 if current DAS28 ≥3.2) in patients receiving constant treatment, and to compare published flare criteria to criteria used by study investigators after biologic treatment discontinuation in the ACT-RAY study. METHODS Patients with rheumatoid arthritis (n = 553) were randomized to add tocilizumab to ongoing methotrexate, or switch to tocilizumab plus placebo. If DAS28 ≤3.2 occurred at week 24, treatment remained constant until week 52; here we assessed the DAS28-2 flare rate. Between weeks 52 and 104, patients in sustained remission (DAS28 <2.6 at 2 consecutive visits 12 weeks apart) discontinued tocilizumab and were assessed every 4 weeks. Per protocol, flare was defined as a worsening of disease activity that required treatment beyond the permitted therapy based on investigator opinions (investigator flare) and was compared with the DAS28-2 definition. RESULTS After tocilizumab discontinuation, DAS28-2 was sensitive (88-100%), but not specific (57-65%), for detecting investigator flare. Under constant treatment, DAS28-2 criteria were met in 136 cases per 100 patient-years despite stable disease activity. Sustained flares were infrequent. Other DAS28-based criteria led to similar conclusions. CONCLUSION DAS28-based flare occurred more often than investigator-defined flares after biologic agent discontinuation. More stringent criteria may be more appropriate for clinical practice.

  • sat0094 superior results in the guepard tight control versus espoir routine care cohorts are documented similarly according to disease activity score DAS28 clinical disease activity index cdai and routine assessment of patient index data rapid3
    Annals of the Rheumatic Diseases, 2013
    Co-Authors: Isabel Castrejon, Theodore Pincus, M Soubrier, M Dougados
    Abstract:

    Background Treat-to-target with intensification of therapy according to DAS28 is documented to be an effective strategy to manage rheumatoid arthritis (RA) 1. However, DAS28 and CDAI require formal joint counts, which are not performed at most rheumatology visits. RAPID3, an index of only the 3 Core Data Set patient-reported outcomes (PROs), does not include a formal joint count, and is calculated on a multidimensional health assessment questionnaire (MDHAQ) in 5 seconds. Objectives To compare changes for DAS28, CDAI, and RAPID3 from baseline to 6 months, and the proportions of patients in 4 categories for high, moderate, low activity/severity and remission at 6 months according to each index, in the GUEPARD treat-to-target clinical trial versus ESPOIR usual care cohort. Methods Post-hoc analyses were performed on 2 databases: 65 RA patients from the GUEPARD tight control trial and 130 matched patients from the ESPOIR usual care cohort, all with baseline DAS28≥5.1 2 . DAS28, CDAI, and RAPID3 were compared for mean changes from baseline to 6 months for differences between the two cohorts. The numbers and proportions of patients at 6 months in 4 categories: high, moderate, low activity/severity, and remission, were computed according to DAS28 >5.1, 3.2-5.1, 2.6-3.2, ≤2.6; CDAI >22, 10.1-22, 2.9-10, ≤2.8; RAPID3 >12, 6.1-12, 3.1-6, ≤3. Statistical significance was analyzed with Student’s t tests and kappa values. Results Baseline demographic and clinical characteristics and DAS28, CDAI, and RAPID3, did not differ between study groups, other than disease duration (5.6 months in GUEPARD versus 3.5 months in ESPOIR); a higher percentage of GUEPARD patients took glucocorticoids, biological agents, and a higher mean dose of glucocorticoids. After 6 months, substantial improvement was seen in both groups. However, mean improvement was greater in GUEPARD compared to ESPOIR for each index: -3.3 vs -2.2 for DAS28, -29.5 versus -20.8 for CDAI and -12.1 vs -7.2 for RAPID3 (all p Conclusions DAS28, CDAI and RAPID3 distinguish GUEPARD from ESPOIR similarly. Because of the moderate to low level of agreement between these instruments and in particular between the strict PRO one (e.g. RAPID3) and the composite indices including clinical evaluation of synovitis (e.g. DAS28), both evaluations might guide a treat to target strategy in daily practice. References Smolen J, et al. Ann Rheum Dis 2010;69: 631-637. Soubrier M, et al. Ann Rheum Dis 2011;70:611-5. Disclosure of Interest None Declared

  • validation of the 28 joint disease activity score DAS28 and european league against rheumatism response criteria based on c reactive protein against disease progression in patients with rheumatoid arthritis and comparison with the DAS28 based on eryt
    Annals of the Rheumatic Diseases, 2009
    Co-Authors: George A Wells, Daniel Aletaha, M Dougados, Michael Schiff, Jc Becker, Julie Teng, J S Smolen, P L C M Van Riel
    Abstract:

    Objective: To validate and compare the definition of the Disease Activity Score 28 based on C-reactive protein (DAS28 (CRP)) to the definition based on erythrocyte sedimentation rate (ESR). Methods: Data were analysed from two randomised, double-blind, placebo-controlled trials of abatacept of 6-month and 12-month duration in patients with rheumatoid arthritis. European League Against Rheumatism (EULAR) response criteria and the proportion of patients in remission (DAS28 Results: There was general agreement in determining the EULAR responder state using both DAS28 definitions (κ = 0.80, 95% CI 0.76 to 0.83). Overall, there was 82.4% agreement on the EULAR response criteria; when disagreements occurred, the DAS28 (CRP) yielded a better EULAR response more often then DAS28 (ESR) (12.6% vs 4.9%, respectively). There was also agreement in determining remission: κ = 0.69 (95% CI 0.60 to 0.78). Radiographic progression decreased in patients treated with abatacept across EULAR states (from none to moderate to good) based on both definitions. For patients treated with placebo, the trend was not as pronounced, with radiographic scores higher for moderate vs non-responders. For physical function, similar trends were observed across the EULAR states for both DAS28 definitions. Conclusions: The DAS28 (CRP) has been validated against radiographic progression and physical function. While the DAS28 (CRP) yielded a better EULAR response more often than the DAS28 (ESR), the validation profile was similar to the DAS28 (ESR), indicating that both measures are useful for assessing disease activity in patients with rheumatoid arthritis.

  • validation of the 28 joint disease activity score DAS28 and european league against rheumatism response criteria based on c reactive protein against disease progression in patients with rheumatoid arthritis and comparison with the DAS28 based on eryt
    Annals of the Rheumatic Diseases, 2009
    Co-Authors: George A Wells, Daniel Aletaha, Josef S. Smolen, M Dougados, Michael Schiff, Jc Becker, Julie Teng, P L C M Van Riel
    Abstract:

    OBJECTIVE: To validate and compare the definition of the Disease Activity Score 28 based on C-reactive protein (DAS28 (CRP)) to the definition based on erythrocyte sedimentation rate (ESR). METHODS: Data were analysed from two randomised, double-blind, placebo-controlled trials of abatacept of 6-month and 12-month duration in patients with rheumatoid arthritis. European League Against Rheumatism (EULAR) response criteria and the proportion of patients in remission (DAS28 <2.6) based on the two DAS28 definitions were examined. Trends in radiographic progression (erosion score, joint space narrowing score and total score) and physical function (Health Assessment Questionnaire Disability Index (HAQ-DI)) across the EULAR responder states (none, moderate and good) were analysed. RESULTS: There was general agreement in determining the EULAR responder state using both DAS28 definitions (kappa = 0.80, 95% CI 0.76 to 0.83). Overall, there was 82.4% agreement on the EULAR response criteria; when disagreements occurred, the DAS28 (CRP) yielded a better EULAR response more often then DAS28 (ESR) (12.6% vs 4.9%, respectively). There was also agreement in determining remission: kappa = 0.69 (95% CI 0.60 to 0.78). Radiographic progression decreased in patients treated with abatacept across EULAR states (from none to moderate to good) based on both definitions. For patients treated with placebo, the trend was not as pronounced, with radiographic scores higher for moderate vs non-responders. For physical function, similar trends were observed across the EULAR states for both DAS28 definitions. CONCLUSIONS: The DAS28 (CRP) has been validated against radiographic progression and physical function. While the DAS28 (CRP) yielded a better EULAR response more often than the DAS28 (ESR), the validation profile was similar to the DAS28 (ESR), indicating that both measures are useful for assessing disease activity in patients with rheumatoid arthritis.

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