scholarly journals HLA-DRB1 Amino Acid Positions 11/13, 71, and 74 Are Associated With Inflammation Level, Disease Activity, and the Health Assessment Questionnaire Score in Patients With Inflammatory Polyarthritis

2016 ◽  
Vol 68 (11) ◽  
pp. 2618-2628 ◽  
Author(s):  
Stephanie F. Ling ◽  
Sebastien Viatte ◽  
Mark Lunt ◽  
Alper M. Van Sijl ◽  
Lucia Silva-Fernandez ◽  
...  

2008 ◽  
Vol 68 (1) ◽  
pp. 57-62 ◽  
Author(s):  
S L Hider ◽  
A J Silman ◽  
W Thomson ◽  
M Lunt ◽  
D Bunn ◽  
...  

Purpose:Methotrexate (MTX) is the first choice conventional disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis. It is not universally effective, however; although to date it is not possible to predict with any accuracy which patients will respond to treatment. The aim of this analysis was to examine whether clinical and genetic variables could be used to predict response to MTX.Methods:Patients recruited to the Norfolk Arthritis Register (NOAR), a primary care based inception cohort of patients with inflammatory polyarthritis, were eligible for this analysis if they were commenced on MTX as their first DMARD within 3 months of their baseline visit and had at least 2 years of follow-up data. Outcome on MTX was defined as: (1) stopped for adverse events; (2) stopped for inefficacy or second DMARD added; (3) stopped for other reasons; or (4) remained on MTX monotherapy. Multiple logistic regression was used to establish which variables (including demographics, disease activity and Health Assessment Questionnaire score) predicted stopping monotherapy for inefficacy or adverse event (with those remaining on treatment taken as the referent category). The area under the Receiver Operating Characteristic curves (AUC ROC), were used to determine how accurate the model was at predicting outcome.Results:309 patients were included in this analysis. At 1 year (2 years), 34 (46) patients had stopped for adverse events and 25 (49) had either stopped monotherapy for inefficacy or had a second DMARD added. 231 (188) patients remained on MTX monotherapy. The strongest predictor of inefficacy at both time points was shared epitope positivity: odds ratios (OR) 5.8 (95% confidence intervals (CI) 1.3 to 25.6) at 1 year, OR 3.0 (95% CI 1.3 to 7.3) at 2 years. High Health Assessment Questionnaire score (OR 1.84 95% CI 1.12 to 3.01) and female gender (OR 2.2, 95% CI 0.92 to 5.28) were associated with adverse events on MTX at 1 year. However, even the most optimal combinations of the factors analysed were only weakly predictive of treatment outcome: AUC ROC for adverse events 0.68 (95% CI 0.58 to 0.78) and for inefficacy AUC ROC 0.71 (95% CI 0.6 to 0.81).Conclusions:Within this cohort, routine clinical and laboratory factors were poor at predicting outcome of treatment with MTX. Given the major therapeutic advantage to be derived from accurate prediction of treatment outcome, further studies will need to investigate novel biological and other markers.



2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1097.2-1098
Author(s):  
V. Strand ◽  
S. Cohen ◽  
L. Zhang ◽  
T. Mellors ◽  
A. Jones ◽  
...  

Background:Therapy choice and therapy change depend on the ability to accurately assess patients’ disease activity. The clinical assessments used to evaluate treatment response in rheumatoid arthritis have inherent variability, normally considered as measurement error, intra-observer variability or within subject variability. Each contribute to variability in deriving response status as defined by composite measures such as the ACR or EULAR criteria, particularly when a one-time observed measurement lies near the boundary defining response or non-response. To select an optimal therapeutic strategy in the burgeoning age of precision medicine in rheumatology, achieve the lowest disease activity and maximize long-term health outcomes for each patient, improved treatment response definitions are needed.Objectives:Develop a high-confidence definition of treatment response and non-response in rheumatoid arthritis that exceeds the expected variability of subcomponents in the composite response criteria.Methods:A Monte Carlo simulation approach was used to assess ACR50 and EULAR response outcomes in 100 rheumatoid arthritis patients who had been treated for 6 months with a TNF inhibitor therapy. Monte Carlo simulations were run with 2000 iterations implemented with measurement variability derived for each clinical assessment: tender joint count, swollen joint count, Health Assessment Questionnaire disability index (HAQ-DI), patient pain assessment, patient global assessment, physician global assessment, serum C-reactive protein level (CRP) and disease activity score 28-joint count with CRP.1-3 Each iteration of the Monte Carlo simulation generated one outcome with a value of 0 or 1 indicating non-responder or responder, respectively.Results:A fidelity score, calculated separately for ACR50 and EULAR response, was defined as an aggregated score from 2000 iterations reported as a fraction that ranges from 0 to 1. The fidelity score depicted a spectrum of response covering strong non-responders, inconclusive statuses and strong responders. A fidelity score around 0.5 typified a response status with extreme variability and inconclusive clinical response to treatment. High-fidelity scores were defined as >0.7 or <0.3 for responders and non-responders, respectively, meaning that the simulated clinical response status label among all simulations agreed at least 70% of the time. High-confidence true responders were considered as those patients with high-fidelity outcomes in both ACR50 and EULAR outcomes.Conclusion:A definition of response to treatment should exceed the expected variability of the clinical assessments used in the composite measure of therapeutic response. By defining high-confidence responders and non-responders, the true impact of therapeutic efficacy can be determined, thus forging a path to development of better treatment options and advanced precision medicine tools in rheumatoid arthritis.References:[1]Cheung, P. P., Gossec, L., Mak, A. & March, L. Reliability of joint count assessment in rheumatoid arthritis: a systematic literature review. Semin Arthritis Rheum43, 721-729, doi:10.1016/j.semarthrit.2013.11.003 (2014).[2]Uhlig, T., Kvien, T. K. & Pincus, T. Test-retest reliability of disease activity core set measures and indices in rheumatoid arthritis. Ann Rheum Dis68, 972-975, doi:10.1136/ard.2008.097345 (2009).[3]Maska, L., Anderson, J. & Michaud, K. Measures of functional status and quality of life in rheumatoid arthritis: Health Assessment Questionnaire Disability Index (HAQ), Modified Health Assessment Questionnaire (MHAQ), Multidimensional Health Assessment Questionnaire (MDHAQ), Health Assessment Questionnaire II (HAQ-II), Improved Health Assessment Questionnaire (Improved HAQ), and Rheumatoid Arthritis Quality of Life (RAQoL). Arthritis Care Res (Hoboken) 63 Suppl 11, S4-13, doi:10.1002/acr.20620 (2011).Disclosure of Interests:Vibeke Strand Consultant of: Abbvie, Amgen, Arena, BMS, Boehringer Ingelheim, Celltrion, Galapagos, Genentech/Roche, Gilead, GSK, Ichnos, Inmedix, Janssen, Kiniksa, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Setpoint, UCB, Stanley Cohen: None declared, Lixia Zhang Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Ted Mellors Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Alex Jones Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Johanna Withers Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Viatcheslav Akmaev Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation



2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 267.1-267
Author(s):  
K. W. Moon

Background:Low disease activity (LDA) in patients with rheumatoid arthritis (RA) are usually recognized as stable state. In according to most guidelines for RA, monotherapy of disease modifying anti-rheumatic drug (DAMRD) was recommended for RA patents with LDA. But some of patients with LDA suffer from flare in their disease course. Until now, we don’t have enough data on factors that can predict flare in RA patients with LDA.Objectives:The aim of this study is to evaluate predictor of flare in RA patient with LDA from long-term (3 year) cohort data.Methods:Korean observational study network for arthritis (KORONA) registry is a nationwide Korean RA specific cohort registry that collecting data annually from 5,376 RA patients in 23 centers across South Korea. We include the data from 1, 801 RA patients with LDA (28 –joint disease activity score (DAS 28) < 3.2 at enrollment) who had consecutive data of DAS28 for 3 years. Flare was defined as an increase in DAS28 compared with baseline of >1.2 or >0.6 if concurrent DAS28 ≥3.2. Cox regression analysis was used to identify baseline predictors of flare.Results:Among 1,801 RA patients, 673 patients (37.4%) experienced flare in 3 years. When we compare the baseline characteristics of both flare and non-flare group, more women and more non-adherent patients for medication were observed in flare group. Flare group had longer disease duration, lower EuroQol 5D score, higher health assessment questionnaire (HAQ) score, and higher erythrocyte sedimentation rate (ESR) than non-flare group at baseline. In multivariate analysis, physician’s VAS, HAQ score, ESR, and poor adherence for medication were significant predictors of flare (Table 1).Table 1.Multivariate analysis of prediction of flare with baseline variablesMeasureHazard ratio95% Confidence IntervalP-valueFemale1.1300.906-1.4090.280Age0.9960.988-1.0050.414Physician’s VAS1.0081.002-1.013<0.01Pain VAS1.0020.998-1.0060.34EQ5D0.9520.534-1.6960.87HAQ1.4071.109-1.786<0.01ESR1.0081.002-1.014<0.01Poor adherence1.2721.047-1.545<0.05VAS: Visual Analogue Scale; EQ5D: EuroQol 5D; HAQ: Health Assessment Questionnaire; ESR: Erythrocyte Sedimentation RateConclusion:RA patient who have risk factors for flare, even though their disease activity was low, require more proactive treatment.References:[1]Bechman K, Tweehuysen L, Garrood T, Scott DL, Cope AP, Galloway JB, et al. Flares in Rheumatoid Arthritis Patients with Low Disease Activity: Predictability and Association with Worse Clinical Outcomes. J Rheumatol. 2018;45(11):1515-21.[2]Singh JA, Saag KG, Bridges SL, Jr., Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26.[3]Sung YK, Cho SK, Choi CB, Park SY, Shim J, Ahn JK, et al. Korean Observational Study Network for Arthritis (KORONA): establishment of a prospective multicenter cohort for rheumatoid arthritis in South Korea. Semin Arthritis Rheum. 2012;41(6):745-51.Disclosure of Interests:None declared



2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maria Chiara Ditto ◽  
Simone Parisi ◽  
Marta Priora ◽  
Silvia Sanna ◽  
Clara Lisa Peroni ◽  
...  

Abstract AntiTNF-α biosimilars are broadly available for the treatment of inflammatory arthritis. There are a lot of data concerning the maintenance of clinical efficacy after switching from originators to biosimilars; therefore, such a transition is increasingly encouraged both in the US and Europe. However, there are reports about flares and adverse events (AE) as a non-medical switch remains controversial due to ethical and clinical implications (efficacy, safety, tolerability). The aim of our work was to evaluate the disease activity trend after switching from etanercept originator (oETA-Enbrel) to its biosimilar (bETA-SP4/Benepali) in a cohort of patients in Turin, Piedmont, Italy. In this area, the switch to biosimilars is stalwartly encouraged. We switched 87 patients who were in a clinical state of stability from oETA to bETA: 48 patients were affected by Rheumatoid Arthritis (RA),26 by Psoriatic Arthritis (PsA) and 13 by Ankylosing Spondylitis (AS).We evaluated VAS-pain, Global-Health, CRP, number of swollen and tender joints, Disease Activity Score on 28 joints (DAS28) for RA, Disease Activity in Psoriatic Arthritis (DAPSA) for PsA, Health Assessment Questionnaire (HAQ) and Health Assessment Questionnaire for the spondyloarthropathies (HAQ-S),Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS patients. 11/85 patients (12.6%) stopped treatment after switching to biosimilar etanercept. No difference was found between oETA and bETA in terms of efficacy. However, some arthritis flare and AE were reported. Our data regarding maintenance of efficacy and percentage of discontinuation were in line with the existing literature.



Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Fiammetta Danzo ◽  
Klodian Gjeloshi ◽  
Giovanni Lettieri ◽  
Giuseppina Abignano ◽  
Mark Hinton ◽  
...  

Abstract Background Neointima proliferation is a key pathologic feature of systemic sclerosis (SSc), causing arterial vessel narrowing and being the recognised culprit pathological lesion in digital ulcers (DUs), pulmonary artery hypertension and renal crisis. Nevertheless, there are no validated imaging techniques to assess the severity of vascular involvement in SSc. We have previously shown digital artery volume index (DAVIX©) assessed with time of right MRI angiography, is a reliable measure of neointima proliferation in the hands. The purpose of our study was to identify the value of DAVIX© in predicting worsening of patient reported outcomes (PROs) and clinical parameters in SSc. Methods Cross-sectional data were available for 91 patients and complete 12 months follow-up data for 68 patients. Data collected included: modfied Rodnan skin score (mRSS), pulmonary function tests (PFTs), echocardiography, nailfold capillaroscopy, Health Assessment Questionnaire Disability Index (HAQ-DI), and Scleroderma Health Assessment Questionnaire (sHAQ). DAVIX© of the dominant hand was calculated as the % mean of the 4 fingers, employing MeVisLab software. Following analysis of distribution, Spearman or Pearson test were used to determine correlation coefficients, as appropriate (Prism 7). Results 56/68 were female and median of disease duration was 4 years (IQR 1.91-9). As previously reported DAVIX© correlated with the presence of DUs (p = 0.0093). Considering all patients, DAVIX© correlated with mRSS (r=-0.258, p = 0.017), DLCO% (r = 0.338, p = 0.008) and the pattern of capillaroscopy (r=-0.388, p = 0.001). In patients with DUs, DAVIX© showed a stronger correlation with DLCO% (r = 0.786, p = 0.048). Most importantly, DAVIX© predicted the worsening of HAQ-DI (r=-0.295, p = 0.029), sHAQ (r =-0.333, p = 0.029) and VAS pain (r=-0.269, p = 0.038) independently of the presence of DUs. Conclusion The quantitative assessment of neointima proliferation in the hand by DAVIX© is a useful imaging biomarker of vascular disease activity. The value of DAVIX© in predicting the worsening of PROs and clinical parameters in overall patients, may offer insights on the role of vascular disease activity in the global progression of SSc. The validation of our data in an independent cohort and the sensitivity to change over time of DAVIX© may aid to the implementation of hand MRI as imaging outcome measure of vascular severity in SSc. Disclosures F. Danzo None. K. Gjeloshi None. G. Lettieri None. G. Abignano None. M. Hinton None. A. Dean None. G. Cuomo None. O. Kubassova None. F. del Galdo None.



2011 ◽  
Vol 38 (7) ◽  
pp. 1309-1316 ◽  
Author(s):  
ANCA DINU ASKANASE ◽  
ISABEL CASTREJÓN ◽  
THEODORE PINCUS

Objective.To analyze quantitative data in patients with systemic lupus erythematosus (SLE), seen in usual care, from a patient Multidimensional Health Assessment Questionnaire (MDHAQ) with routine assessment of patient index data (RAPID3) scores and from a physician global estimate of noninflammatory symptoms; and to compare results to self-report Systemic Lupus Activity Questionnaire (SLAQ) scores and 4 SLE indices: SLE Disease Activity Index-2K (SLEDAI-2K), British Isles Lupus Assessment Group (BILAG), Systemic Lupus Activity Measure (SLAM), and European Consensus Lupus Activity Measurement (ECLAM).Methods.Fifty consecutive patients with SLE were studied in usual care of one rheumatologist. All patients completed an MDHAQ/RAPID3 in this setting. Each patient also completed a SLAQ. The rheumatologist scored SLEDAI-2K, BILAG, SLAM, ECLAM, and 2 physician global estimates, one for overall status and one for noninflammatory symptoms. Patients were classified into 2 groups: “few” or “many” noninflammatory symptoms. Scores and indices were compared using correlations, cross-tabulations and t tests.Results.The patients included 45 women and 5 men. MDHAQ/RAPID3 and SLAQ scores were significantly correlated. RAPID3 scores were significantly higher in patients with SLE index scores above median levels, and in 34 patients scored by the rheumatologist as having “few” noninflammatory symptoms. MDHAQ/RAPID3 and SLAQ were significantly higher in 16 patients scored as having many noninflammatory symptoms.Conclusion.MDHAQ/RAPID3 and SLAQ subscale scores appear to reflect disease activity in patients with SLE, but not in patients with many noninflammatory symptoms. A physician scale for noninflammatory symptoms is useful to interpret MDHAQ/RAPID3, SLAQ, and SLE index scores.



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