scholarly journals Gender stratified adjustment of the DAS28-CRP improves inter-score agreement with the DAS28-ESR in rheumatoid arthritis

Rheumatology ◽  
2018 ◽  
Vol 58 (5) ◽  
pp. 831-835 ◽  
Author(s):  
Philip D H Hamann ◽  
Gavin Shaddick ◽  
Kimme Hyrich ◽  
Amelia Green ◽  
Neil McHugh ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
British Society ◽  
Treat To Target ◽  
Low Disease Activity ◽  
Factors Influencing ◽  
Resulting Effect ◽  
The Impact ◽  
Biologics Register

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.

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

scholarly journals POS0455 EFFECT OF ANTI-Ro/SSA ANTIBODIES FOR TREATMENT RESPONSE TO METHOTREXATE IN RHEUMATOID ARTHRITIS: A RETROSPECTIVE MULTICENTER OBSERVATIONAL STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 458.1-458
Author(s):  
R. Yokochi ◽  
H. Tamai ◽  
T. Kido ◽  
Y. Yagyu ◽  
D. Waki ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Disease Activity ◽  
Clinical Response ◽  
Logistic Regression Analysis ◽  
Age At Onset ◽  
Treat To Target ◽  
Low Disease Activity ◽  
Target Strategy

Background:Several previous observational studies have suggested that patients with anti-Ro/SSA antibody-positive rheumatoid arthritis (RA) may respond poorly to treatment, including tumor necrosis factor inhibitors1. However, its influence on methotrexate (MTX) treatment, which is the anchor drug of treat-to-target strategy in RA treatment, remains unclear.Objectives:We compared the clinical response to MTX in both anti-Ro/SSA antibody-positive and -negative patients with MTX-naiive RA and investigated the reasons for the difference in response.Methods:We recruited 210 consecutive patients with RA who were newly started on MTX in this retrospective cohort study. The effect of the presence of anti-Ro/SSA antibodies on achieving low disease activity (LDA) of DAS28-CRP at six months after initiating MTX was investigated by using logistic regression analysis. CDAI, SDAI, concomitant using DMARDs and painkillers, patient’s and evaluator’s VAS, tender joint counts, and swollen joint counts at six months were also compared between the anti-Ro/SSA-positive patients and -negative patients. Missing data were imputed by using multiple imputations before multivariate analysis.Results:32 anti-Ro/SSA antibody-positive patients and 178 anti-Ro/SSA antibody-negative patients were included. The rate of achieving DAS28-LDA at six months was significantly lower in the anti-Ro/SSA antibody-positive patients than those in the anti-Ro/SSA antibody-negative patients (56.2% versus 75.8%, P=0.03). in the logistic regression analysis, the presence of anti-Ro/SSA antibodies was an independent negative predictor for achieving DAS-28-LDA at six months (OR:0.431, 95%CI: 0.190-0.978, P=0.044) (Table1). Anti-Ro/SSA antibody-positive patients had significantly higher patient’s VAS at six months (median [IQR]: 22 [15-41] vs 19 [5-30], P=0.038), and prescribed NSAIDs (37.5% vs 18.0%, P=0.018). CDAI and SDAI after six months were not significantly different between the group.Conclusion:The presence of anti-Ro/SSA antibodies might be one of the predictive factors for the insufficient response to treat to target strategy in RA treatment. Residual pain was suspected as one of the mechanisms contributing to the lesser clinical response of MTX in anti-Ro antibody-positive RA.References:[1]Ran Matsudaira wt al. J Rheumatol 2011;38(11):2346-54Table 1.Logistic regression analysis for the rate of achieving DAS28 low disease activity at six months.Risk factor Odds ratio95%CIP valueAge at onset0.9930.968-1.0180.586Sex (woman)0.6430.300-1.3840.258RF-positive1.9620.853-4.5110.112ACPA-positive0.5520.225-1.3510.192Anti-Ro/SSA antibody-positive0.4310.190-0.9780.044Disclosure of Interests:None declared

scholarly journals O26 Non-serious infections in patients with RA: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Katie Bechman ◽  
Kapil Halai ◽  
Sam Norton ◽  
Andrew P Cope ◽  
Kimme L Hyrich ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
British Society ◽  
Tnf Inhibitor ◽  
Drug Survival ◽  
Increased Risk ◽  
Serious Infections ◽  
The Impact ◽  
Biologics Register

Abstract Background Patients with rheumatoid arthritis (RA) are at an increased risk of infection. Most attention has been given to serious infections, but these are the tip of the iceberg. Non-serious infections (NSI) are far more frequent, and although not life-threatening, have potential to impact treatment outcomes (drug survival) and quality of life. Our objective was to describe frequency of NSI and compare incidence of NSI by biologic drug within the British Society for Rheumatology Biologics Register (BSRBR-RA). Methods The BSRBR-RA is a prospective observational cohort study. NSI was identified as not requiring hospitalisation, intravenous therapy or leading to disability or death. Infections were captured from clinician questionnaires and patient diaries. Individuals were considered ‘at risk’ from the date of commencing biologic treatment for 3 years. Drug exposure was defined by agent; TNF inhibitor, IL-6 inhibitor, anti-CD20 or csDMARD only. To account for a high frequency of events, a multiple-failure Cox model was used. Multivariable adjustment included age, gender, DAS28-ESR, HAQ-DI, disease duration, smoking, steroid usage, year recruited to BSRBR-RA, line of biologic therapy and cumulative infection number. Results There were 17,304 NSI in 10,099 patients, with an event rate of 27.0 per year (95% CI 26.6 to 27.4). Increasing age, female gender, comorbidity burden, corticosteroid therapy, DAS28 and HAQ-DI were associated with an increased risk of NSI. The rate of NSI was numerically lowest with csDMARDs. Compared to TNFi, IL-6 inhibitor had a higher risk of NSI, whilst the csDMARD cohort had a lower risk. Between the TNFi agents, adalimumab had a higher risk than etanercept (Table 1). Conclusion These results confirm that NSI is a frequent occurrence for patients, which historically has received little attention in research literature. The data suggest biologics increase the risk of NSI, especially IL-6 inhibition. Whilst unmeasured confounding must be considered, the magnitude of effects are large and it seems likely that a causal link between targeted immunosuppression and NSI risk exists. Further research is needed to understand the impact of NSI on clinical outcomes including drug survival and quality of life. Disclosures K. Bechman: None. K. Halai: None. S. Norton: None. A.P. Cope: None. K.L. Hyrich: Honoraria; AbbVie paid to the institution and grant income from Pfizer and Bristol-Myers Squibb for activities outside of this work. J.B. Galloway: Honoraria; for speaking or attending conferences from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Pfizer and Union Chimique Belge.

scholarly journals Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique

2015 ◽  
Vol 75 (3) ◽  
pp. 511-518 ◽  
Author(s):  
M van Onna ◽  
D F Ten Cate ◽  
K L Tsoi ◽  
A J L Meier ◽  
J W G Jacobs ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Joint Inflammation ◽  
Imaging Modalities ◽  
Receiver Operating Curve ◽  
Treat To Target ◽  
Spectral Transmission ◽  
Low Disease Activity ◽  
Non Invasive ◽  
Measure Disease Activity

ObjectivesIn rheumatoid arthritis (RA), treat-to-target strategies require instruments for valid detection of joint inflammation. Therefore, imaging modalities are increasingly used in clinical practice. Optical spectral transmission (OST) measurements are non-invasive and fast and may therefore have benefits over existing imaging modalities. We tested whether OST could measure disease activity validly in patients with RA.MethodsIn 59 patients with RA and 10 patients with arthralgia, OST, joint counts, Disease Activity Score (DAS) 28 and ultrasonography (US) were performed. Additionally, MRI was performed in patients with DAS28<2.6. We developed and validated within the same cohort an algorithm for detection of joint inflammation by OST with US as reference.ResultsAt the joint level, OST and US performed similarly inproximal interphalangeal-joints (area under the receiver-operating curve (AUC) of 0.79, p<0.0001) andmetacarpophalangeal joints (AUC 0.78, p<0.0001). Performance was less similar in wrists (AUC 0.62, p=0.006). On the patient level, OST correlated moderately with clinical examination (DAS28 r=0.42, p=0.001), and US scores (r=0.64, p<0.0001). Furthermore, in patients with subclinical and low disease activity, there was a correlation between OST and MRI synovitis score (RAMRIS (Rheumatoid Arthritis MRI Scoring) synovitis), r=0.52, p=0.005.ConclusionsIn this pilot study, OST performed moderately in the detection of joint inflammation in patients with RA. Further studies are needed to determine the diagnostic performance in a new cohort of patients with RA.

scholarly journals The impact of different (rheumatoid) arthritis phenotypes on patients’ lives

Rheumatology ◽  
2020 ◽  
Author(s):  
Nathalie Luurssen-Masurel ◽  
Angelique Elisabeth Adriana Maria Weel ◽  
Johanna Maria Wilhelmina Hazes ◽  
Pascal Hendrik Pieter de Jong
Keyword(s):  
Disease Activity ◽  
Disease Burden ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Daily Practice ◽  
Treat To Target ◽  
Low Disease Activity ◽  
Patient Reported ◽  
The Impact ◽  
Over Time

Abstract Objectives To compare patient-reported outcome (PRO) domains between three arthritis phenotypes [undifferentiated arthritis (UA), autoantibody-negative RA (RA−) and autoantibody-positive RA (RA+)] at diagnosis, after 2 years and over time. Methods All UA (n = 130), RA− (n = 176) and RA+ (n = 331) patients from the tREACH trial, a stratified single-blinded trial with a treat-to-target approach, were used. PRO comparisons between phenotypes at baseline and after 2 years were performed with analysis of variance, while a linear mixed model compared them over time. Effect sizes were weighted against the minimal clinically important differences (MCIDs) for each PRO. Results RA− patients had a higher disease burden compared with RA+ and UA. At baseline and after 2 years, RA− patients had more functional impairment and a poorer Physical Component Summary (PCS) compared with the other phenotypes, while they only scored worse for general health and morning stiffness duration at baseline. The MCIDs were exceeded at baseline, except for functional ability between RA+ and UA, while after 2 years only the MCID of the PCS was exceeded by RA− compared with UA and RA. After 2 years the PROs of all phenotypes improved, but PROs measuring functioning were still worse compared with the general population, even when patients had low disease activity. Conclusion RA− patients had the highest disease burden of all phenotypes. Although most patients have low disease activity after treatment, all clinical phenotypes still have a similar significant impact on patients’ lives, which is mainly physical. Therefore it is important to assess and address PROs in daily practice because of persistent disease burden despite low disease activity. Trial registration ISRCTN26791028.

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