scholarly journals OP0300 USE OF THERMOGRAPHY OF HANDS AND MACHINE LEARNING TO QUANTIFY JOINT INFLAMMATION AND ESTIMATE DAS28, CDAI, SDAI IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 184.1-184
Author(s):  
I. Morales-Ivorra ◽  
C. Gómez Vaquero ◽  
C. Moragues Pastor ◽  
J. M. Nolla ◽  
J. Narváez ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Machine Learning ◽  
Linear Regression ◽  
Disease Activity ◽  
Joint Inflammation ◽  
Training Dataset ◽  
Test Dataset ◽  
Thermal Images ◽  
Joint Assessment

Background:Disease activity scores such as DAS28, CDAI and SDAI are used in the follow-up of patients with rheumatoid arthritis (RA). These scores include variables obtained on physical examination such as the tender joint count (TJC) and the swollen joint count (SJC). In telematic consultations, it is not possible to determine these variables by physical joint assessment. Therefore, it is necessary to develop new tools that allow detecting joint inflammation in places close to the patient. Thermography is a safe and fast technique that measures heat through infrared imaging. Inflammation of the joints causes an increase in temperature and can therefore be detect by thermography. Machine learning methods are highly accurate in analyzing medical images automatically.Objectives:To develop an algorithm that, based on thermographic images of hands and machine learning, learn to quantify joint inflammation in patients with RA and estimate the DAS28, CDAI, SDAI by including the patient global health (PGH).Methods:Multicenter observational study conducted in the rheumatology and radiology service of two hospitals. Patients with RA, psoriatic arthritis (PA), undifferentiated arthritis (UA) and arthritis of hands secondary to other diseases (SA) that attended the follow-up visits were recruited. Companions of patients and healthcare professionals were also recruited as healthy subjects (HS). In all cases, a thermographic image of the hands was taken using a Flir One Pro or a Thermal Expert TE-Q1 camera connected to a smartphone. Ultrasound (US) of both hands was performed in patients with RA, PA, UA and SA. The degree of synovial hypertrophy (SH) and power doppler (PD) was assessed for each joint (score from 0 to 3). Machine learning was used to quantify joint inflammation (SH+PD) from the thermal images using US as ground truth. RA patients whose thermal image was taken with the Thermal Expert TE-Q1 camera were used to evaluate the performance (test dataset). The other participants were used as training dataset. The TJC, SJC, PGH, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were also assessed in the test dataset. A linear regression was used to estimate the DAS28, CDAI and SDAI with the resultant joint inflammation quantification from the thermal images and the PGH. Performance was evaluated by means of Pearson’s correlation coefficient. The study was approved by the Clinical Ethics and Research Committee of both centers.Results:The total number of recruited subjects was 521 (422 for the training and 99 for the testing dataset). In the training dataset, the thermography of 296 patients was taken with the Flir One Pro (163 RA, 17 PA, 22 UA, 12 SA and 82 HS) and 126 with the Thermal Expert TE-Q1 camera (6 RA without clinical data, 20 PA, 7 UA, 23 SA and 70 HS).We found higher correlations between joint inflammation variables (US and SJC) and thermography (0.48, p<0.01 for US and 0.48, p<0.01 for SJC) than between joint inflammation variables (US and SJC) and the PGH (0.29, p<0.01 for US and 0.35, p<0.01 for SJC). Thermography did not show statistically significant correlation with the PGH (0.14, p=0.164). The linear regression of thermography and the PGH showed strong correlation with the DAS28 (0.73, p<0.01), CDAI (0.84, p<0.01) and SDAI (0.82, p<0.01).Conclusion:Thermography of hands and machine learning can effectively quantify joint inflammation and can be used in combination with the PGH to estimate disease activity scores. These results open an opportunity to develop tools that facilitate telematic consultations in patients with RA.References:[1]Brenner M, Braun C, Oster M, Gulko PS. Thermal signature analysis as a novel method for evaluating inflammatory arthritis activity. Ann Rheum Dis. 2006;65(3):306-11[2]Lynch CJ, Liston C. New machine-learning technologies for computer-aided diagnosis. Nat Med. 2018;24(9):1304-1305[3]Tan YK, Hong C, Li H, Allen JC Jr, Thumboo J. Thermography in rheumatoid arthritis: a comparison with ultrasonography and clinical joint assessment. Clin Radiol. 2020;75(12):963Disclosure of Interests:None declared.

Evaluating the efficacy of intra-articular injections of platelet rich plasma (PRP) in rheumatoid arthritis patients and its impact on inflammatory cytokines, disease activity and quality of life.

2020 ◽  
Vol 16 ◽  
Author(s):  
Dalia S. Saif ◽  
Nagwa N. Hegazy ◽  
Enas S. Zahran
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Platelet Rich Plasma ◽  
Joint Inflammation ◽  
Monthly Interval ◽  
Post Injection ◽  
Tnf Α

Background: Among rheumatoid arthritis patients (RA), general disease activity is well regulated by diseasemodifying anti-rheumatic medications (DMARDS), but sometimes local inflammation still persists among a few joints. Adjuvant modern molecular interventions as Platelet Rich Plasma (PRP) with a suggested down regulating effect on inflammatory mediators has a proven effect in management of RA. We aim to evaluate the therapeutic effect of intra-articular PRP versus steroid in RA patients and their impact on inflammatory cytokines IL1B , TNF α, local joint inflammation, disease activity and quality of life (QL). Methods: Open labeled parallel randomized control clinical trial was carried out on 60 RA patients randomly divided into 2 groups, Group 1: included 30 patients received 3 intra-articular injections of PRP at monthly interval, Group 2: included 30 patients received single intra-articular injection of steroid. They were subjected to clinical, laboratory, serum IL1B and TNF α assessment at baseline and at 3, 6 months post injection. Results: Patients of both groups showed improvements in their scores of evaluating tools at 3months post injection and this improvement was persistent in the PRP group up to 6 months post injection while it was continued only for 3 months in the steroid group. Conclusions: PRP is a safe, effective and useful therapy in treating RA patients who had insufficient response and persistent pain and inflammation in just one or two joints through its down regulating effect on inflammatory cytokines IL1B, TNF α with subsequent improvement of local joint inflammation, disease activity and QL.

scholarly journals POS0677 THE ROLE OF MUSCULOSKELETAL ULTRASOUND IN PREDICTING THE RESPONSE TO JAK INHIBITORS: RESULTS FROM A LARGE MONOCENTRIC COHORT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 583-583
Author(s):  
C. Garufi ◽  
F. Ceccarelli ◽  
F. R. Spinelli ◽  
S. Mancuso ◽  
C. Pirone ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Structural Damage ◽  
Power Doppler ◽  
Response To Treatment ◽  
Jak Inhibitors ◽  
Inflammatory Score ◽  
Inflammatory Status

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos

scholarly journals POS1234 IMPACT OF THE CHANGE IN ADMINISTRATION ROUTE OF TOCILIZUMAB AND ABATACEPT, DUE TO THE COVID-19 LOCKDOWN ON DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 900.1-900
Author(s):  
L. Diebold ◽  
T. Wirth ◽  
V. Pradel ◽  
N. Balandraud ◽  
E. Fockens ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Physical Activity ◽  
Disease Activity ◽  
Univariate Analysis ◽  
Route Of Administration ◽  
Anxiety And Depression ◽  
Administration Route ◽  
Factors Associated ◽  
The Impact

Background:Among therapeutics used to treat rheumatoid arthritis (RA), Tocilizumab (TCZ) and Abatacept (ABA) are both biologic agents that can be delivered subcutaneously (SC) or intravenously (IV). During the first COVID-19 lockdown in France, all patients treated with IV TCZ or IV ABA were offered the option to switch to SC administration.Objectives:The primary aim was to assess the impact of changing the route of administration on the disease activity. The second aim was to assess whether the return to IV route at the patient’s request was associated with disease activity variation, flares, anxiety, depression and low physical activity during the lockdown.Methods:We conducted a prospective monocentric observational study. Eligibility criteria: Adult ≥ 18 years old, RA treated with IV TCZ or IV ABA with a stable dose ≥3 months, change in administration route (from IV to SC) between March 16, 2020, and April 17, 2020. The following data were collected at baseline and 6 months later (M6): demographics, RA characteristics, treatment, history of previous SC treatment, disease activity (DAS28), self-administered questionnaires on flares, RA life repercussions, physical activity, anxiety and depression (FLARE, RAID, Ricci &Gagnon, HAD).The primary outcome was the proportion of patients with a DAS28 variation>1.2 at M6. Analyses: Chi2-test for quantitative variables and Mann-Whitney test for qualitative variables. Factors associated with return to IV route identification was performed with univariate and multivariate analysis.Results:Among the 84 patients who were offered to switch their treatment route of administration, 13 refused to change their treatment. Among the 71 who switched (48 TCZ, 23 ABA), 58 had a M6 follow-up visit (13 lost of follow-up) and DAS28 was available for 49 patients at M6. Main baseline characteristics: female 81%, mean age 62.7, mean disease duration: 16.0, ACPA positive: 72.4%, mean DAS28: 2.01, previously treated with SC TCZ or ABA: 17%.At M6, the mean DAS28 variation was 0.18 ± 0.15. Ten (12.2%) patients had a DAS28 worsening>1.2 (ABA: 5/17 [29.4%] and TCZ: 5/32 [15.6%], p= 0.152) and 19 patients (32.8%) had a DAS28 worsening>0.6 (ABA: 11/17 [64.7%] and TCZ: 8/32 [25.0%], p= 0.007).At M6, 41 patients (77.4%) were back to IV route (26 TCZ, 15 ABA) at their request. The proportion of patients with a DAS28 worsening>1.2 and>0.6 in the groups return to IV versus SC maintenance were 22.5%, 42.5% versus 11.1% and 22.2% (p=0.4), respectively. The univariate analysis identified the following factors associated with the return to IV route: HAD depression score (12 vs 41, p=0.009), HAS anxiety score (12 vs 41, p=0.047) and corticosteroid use (70% vs 100%, p=0.021), in the SC maintenance vs return to IV, respectively.Conclusion:The change of administration route of TCZ and ABA during the first COVID-19 lockdown was infrequently associated with a worsening of RA disease. However, the great majority of the patients (77.4%) request to return to IV route, even without disease activity worsening. This nocebo effect was associated with higher anxiety and depression scores.Disclosure of Interests:None declared

scholarly journals Study on Influence of Range of Data in Concrete Compressive Strength with Respect to the Accuracy of Machine Learning with Linear Regression

2021 ◽  
Vol 11 (9) ◽  
pp. 3866
Author(s):  
Jun-Ryeol Park ◽  
Hye-Jin Lee ◽  
Keun-Hyeok Yang ◽  
Jung-Keun Kook ◽  
Sanghee Kim
Keyword(s):  
Machine Learning ◽  
Compressive Strength ◽  
Linear Regression ◽  
Coarse Aggregate ◽  
Learning Algorithm ◽  
Linear Regression Analysis ◽  
Aggregate Size ◽  
Training Dataset ◽  
Machine Learning Algorithm ◽  
Concrete Compressive Strength

This study aims to predict the compressive strength of concrete using a machine-learning algorithm with linear regression analysis and to evaluate its accuracy. The open-source software library TensorFlow was used to develop the machine-learning algorithm. In the machine-earning algorithm, a total of seven variables were set: water, cement, fly ash, blast furnace slag, sand, coarse aggregate, and coarse aggregate size. A total of 4297 concrete mixtures with measured compressive strengths were employed to train and testing the machine-learning algorithm. Of these, 70% were used for training, and 30% were utilized for verification. For verification, the research was conducted by classifying the mixtures into three cases: the case where the machine-learning algorithm was trained using all the data (Case-1), the case where the machine-learning algorithm was trained while maintaining the same number of training dataset for each strength range (Case-2), and the case where the machine-learning algorithm was trained after making the subcase of each strength range (Case-3). The results indicated that the error percentages of Case-1 and Case-2 did not differ significantly. The error percentage of Case-3 was far smaller than those of Case-1 and Case-2. Therefore, it was concluded that the range of training dataset of the concrete compressive strength is as important as the amount of training dataset for accurately predicting the concrete compressive strength using the machine-learning algorithm.

scholarly journals AB0330 HIGH REMISSION RATES IN RA – REAL LIFE DATA FROM BARITICINIB

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1463.2-1464
Author(s):  
S. Bayat ◽  
K. Tascilar ◽  
V. Kaufmann ◽  
A. Kleyer ◽  
D. Simon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Cox Regression ◽  
Real Life ◽  
Inadequate Response ◽  
Research Support ◽  
Das 28 ◽  
Patient Reported ◽  
One Year

Background:Recent developments of targeted treatments such as targeted synthetic DMARDs (tsDMARDs) increase the chances of a sustained low disease activity (LDA) or remission state for patients suffering rheumatoid arthritis (RA). tsDMARDs such as baricitinib, an oral inhibitor of the Janus Kinases (JAK1/JAK2) was recently approved for the treatment of RA with an inadequate response to conventional (cDMARD) and biological (bDMARD) therapy. (1, 2).Objectives:Aim of this study is to analyze the effect of baricitinb on disease activity (DAS28, LDA) in patients with RA in real life, to analyze drug persistance and associate these effects with various baseline characteristics.Methods:All RA patients were seen in our outpatient clinic. If a patient was switched to a baricitinib due to medical reasons, these patients were included in our prospective, observational study which started in April 2017. Clinical scores (SJC/TJC 76/78), composite scores (DAS28), PROs (HAQ-DI; RAID; FACIT), safety parameters (not reported in this abstract) as well as laboratory biomarkers were collected at each visit every three months. Linear mixed effects models for repeated measurements were used to analyze the time course of disease activity, patient reported outcomes and laboratory results. We estimated the probabilities of continued baricitinib treatment and the probabilities of LDA and remission by DAS-28 as well as Boolean remission up to one year using survival analysis and explored their association with disease characteristics using multivariable Cox regression. All patients gave informed consent. The study is approved by the local ethics.Results:95 patients were included and 85 analyzed with available follow-up data until November 2019. Demographics are shown in table 1. Mean follow-up duration after starting baricitinib was 49.3 (28.9) weeks. 51 patients (60%) were on monotherapy. Baricitinib survival (95%CI) was 82% (73% to 91%) at one year. Cumulative number (%probability, 95%CI) of patients that attained DAS-28 LDA at least once up to one year was 67 (92%, 80% to 97%) and the number of patients attaining DAS-28 and Boolean remission were 31 (50%, 34% to 61%) and 12(20%, 9% to 30%) respectively. Median time to DAS-28 LDA was 16 weeks (Figure 1). Cox regression analyses did not show any sufficiently precise association of remission or LDA with age, gender, seropositivity, disease duration, concomitant DMARD use and number of previous bDMARDs. Increasing number of previous bDMARDs was associated with poor baricitinib survival (HR=1.5, 95%CI 1.1 to 2.2) while this association was not robust to adjustment for baseline disease activity. Favorable changes were observed in tender and swollen joint counts, pain-VAS, patient and physician disease assessment scores, RAID, FACIT and the acute phase response.Conclusion:In this prospective observational study, we observed high rates of LDA and DAS-28 remission and significant improvements in disease activity and patient reported outcome measurements over time.References:[1]Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Annals of the rheumatic diseases. 2015 Feb;74(2):333-40.[2]Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. The New England journal of medicine. 2016 Mar 31;374(13):1243-52.Figure 1.Cumulative probability of low disease activity or remission under treatment with baricitinib.Disclosure of Interests:Sara Bayat Speakers bureau: Novartis, Koray Tascilar: None declared, Veronica Kaufmann: None declared, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Johannes Knitza Grant/research support from: Research Grant: Novartis, Fabian Hartmann: None declared, Susanne Adam: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

scholarly journals FRI0094 SIGNIFICANT IMPROVEMENT OF NT-PROBNP LEVELS IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TOCILIZUMAB AND TOFACITINIB

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 625.2-626
Author(s):  
H. Gerasimova ◽  
T. Popkova ◽  
I. Kirillova ◽  
M. Cherkasova ◽  
A. Martynova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Cardiovascular Death ◽  
Control Group ◽  
Activity Levels ◽  
Das 28 ◽  
Interleukin 6 Receptor ◽  
Inflammatory Drugs ◽  
Roche Diagnostics

Background:N-terminal pro-brain natriuretic peptide (NT-proBNP) is a recognized predictor of congestive heart failure (CHF) and cardiovascular death. Rheumatoid arthritis (RA) patients (pts) were shown to have higher NT-proBNP concentrations than in general population, but it remains unclear, whether NT-proBNP levels are related to RA duration, activity or treatment.Objectives:To investigate the effect of interleukin 6 receptor inhibitor - tocilizumab (TCZ) and JAK inhibitor - tofacitinib (TOFA) on NT-proBNP levels in RA pts during a 12-month (m) follow-up period.Methods:The study enrolled 60pts (50women/10men) with the lack of efficacy/resistance and/or intolerance of basic anti-inflammatory drugs (DMARDs); median age was 55[42;61] years, median disease duration 55[29;120]m, with moderate to high activity (DAS28-5,1[4,6;6,1], serum positivity for rheumatoid factor (RF)(85%)/ anti-cyclic citrullinated peptide antibodies (ACCP)(80%). The study did not include RA pts with CHF and clinically overt cardiovascular disease (CVD). Twenty nine RA pts received TCZ(8mg/kg) every 4 weeks: 61% received TCZ in combination with methotrexate (MTX), 35% - with low-dose glucocorticoids (GCs). Thirty one RA pts were prescribed oral TOFA at 5 mg BID with dose escalation to 10 mg BID in 8 (26%)pts. TOFA was used in combination with MTX in 90% pts, with GCs – in 29% pts. Pts treated with TCZ and TOFA were comparable in terms of age, sex, body mass index. RA activity rates (DAS28, SDAI, ESR, CRP) were higher in pts on TCZ -therapy compared with pts treated with TOFA. Echocardiography data and NT-proBNP levels using electrochemiluminescence method Elecsys proBNP II (Roche Diagnostics, Switzerland) were obtained at baseline and after 12m.Results:Significant positive changes in major disease activity, clinical and laboratory parameters were found in RA pts after 12 m of TCZ infusion and TOFA intake: remission (DAS28<2,6) was achieved in 54% and 39% pts, low activity levels (DAS28<3,2) – in 46% and 51% pts, respectively.The NT-proBNP levels were significantly higher in RA pts than in the control group (median 69,1 (37,9;105,8) pg/mL vs 55,3 (36,6;67,3) pg/mL,p<0.05).Six pts (10%) (three in each pts group) had NT-proBNP levels over 125pg/ml, but were asymptomatic and had unremarkable echocardiography.There was a good correlation between NT-proBNP level at baseline with age (r=0,55,p<0,001), SDAI (r=0,5, h=0,01), ACCP (r=0,23,p=0,01).Decrease of median NT-proBNP levels was documented after 12m of TCZ therapy (81,5[43,0;102,0]vs41,6[25,4;64,2]pg/ml (p<0,01) and after 12m TOFA therapy (66,1[30,5;105,0]vs16,8 [5,0;81,0]pg/ml,p=0,001).After 12m of TCZ correlations of ΔNT-proBNP were established with ΔESR (R=0,43;p<0,05], ΔСRP (R=0,46;p<0,05], ΔEe left ventricle (LV) (r=0,88,p=0,03).In the group of pts treated with TOFA ΔNT-proBNP level significantly correlated with the percentage change in DAS 28 (r=0,41,p=0,038), there was no direct correlation with changes in the parameters of the LV diastolic function.Conclusion:TCZ and TOFA treatment for 12 m reduced NT-proBNP levels in RA pts without clinically manifest CVD and CHF. Falling NT-proBNP concentrations are associated with positive dynamics of RA activity (DAS 28) and inflammatory markers (CRP, ESR), therefore allowing to suggest that increased NT-proBNP levels should be considered as a component of disease activity. Correlation between ΔNT-proBNP and ΔEeLF may be indicative as possible impact of these biomarkers on the LV diastolic function’s development in RA pts.Disclosure of Interests:None declared

scholarly journals POS0517 A LONGITUDINAL STUDY OF SARCOPENIA, LOCOMOTIVE SYNDROME, AND FRAILTY IN PATIENTS WITH RHEUMATOID ARTHRITIS: FROM THE CHIKARA STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 492.2-492
Author(s):  
K. Mandai ◽  
M. Tada ◽  
Y. Yamada ◽  
T. Koike ◽  
T. Okano ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Multivariate Logistic Regression Analysis ◽  
Locomotive Syndrome ◽  
Chi Squared ◽  
Higher Doses ◽  
Rheumatoid Arthritis Data ◽  
Onset Rate ◽  
New Onset

Background:Rheumatoid arthritis (RA) patients have a high frequency of sarcopenia, and they commonly have reduced physical function. We previously reported that the prevalence of sarcopenia was 28%, that of frailty was 18.9%, and that of pre-frailty was 38.9% in RA patients1,2, and 13.2% of RA patients developed sarcopenia within a year 3.Objectives:To investigate the risk factors for new onset of sarcopenia, locomotive syndrome, and frailty in patients with RA and the course of each disease.Methods:Two-year follow-up data from the rural group of the prospective, observational CHIKARA study were used. Sarcopenia was diagnosed using the criteria of the Asian Working Group for Sarcopenia 2014, locomotive syndrome was diagnosed using locomotive 5, and frailty was diagnosed using the basic checklist. New onset of the disease over the 2-year follow-up period was studied, excluding cases that had the disease at baseline. Improvement was defined as cases with disease at baseline that no longer met the diagnostic criteria after 2 years. Differences in the characteristics of each disease were tested using the Chi-squared test and the paired t-test.Results:The 81 patients with RA (82.7% female) had mean age 66.9±11.5 years, mean DAS28-ESR 2.9±1.2, methotrexate use in 81.5% (with a dose of 9.9±2.7 mg/week), and glucocorticoid (GC) use in 22.2% (with a dose of 3.1±1.7 mg/week). The baseline prevalence was 44.4% for sarcopenia, 35.8% for locomotive syndrome, and 25.9% for frailty, and the new onset rate was 4.4% for sarcopenia, 15.4% for locomotive syndrome, and 13.3% for frailty. Of the patients with each disease at baseline, 36.1% had sarcopenia, 20.7% had locomotive syndrome, and 33.3% had frailty, and of those with each disease at 2 years, 36.1% had sarcopenia, 20.7% had locomotive syndrome, and 33.3% had frailty. The new onset sarcopenia and locomotive syndrome groups had significantly higher rates of GC use (p=0.036, p=0.007, paired t-test) and significantly higher doses (p=0.01, p=0.001, paired t-test) than the groups without new onset sarcopenia and locomotive syndrome. High baseline disease activity was an independent predictor of new onset of locomotive syndrome on multivariate logistic regression analysis (OR=3.21, p=0.015).Conclusion:The new onset rates at 2 years were 4.4% for sarcopenia, 15.4% for locomotive syndrome, and 13.3% for frailty. In the new onset sarcopenia and locomotive syndrome groups, both GC use and dosage were significantly higher.References:[1]Tada M, et al. Matrix metalloprotease 3 is associated with sarcopenia in rheumatoid arthritis - results from the CHIKARA study. Int J Rheum Dis. 2018 Nov;21(11):1962-1969.[2]Tada M, et al. Correlation between frailty and disease activity in patients with rheumatoid arthritis: Data from the CHIKARA study. Geriatr Gerontol Int. 2019 Dec;19(12):1220-1225.[3]Yamada Y, et al. Glucocorticoid use is an independent risk factor for developing sarcopenia in patients with rheumatoid arthritis: from the CHIKARA study. Clin Rheumatol. 2020 Jun;39(6):1757-1764.Disclosure of Interests:None declared

scholarly journals FRI0046 PHARMACOGENOMICS-DRIVEN INDIVIDUALIZED PREDICTION OF TREATMENT RESPONSE TO METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS: A MACHINE LEARNING APPROACH

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 598.2-598
Author(s):  
E. Myasoedova ◽  
A. Athreya ◽  
C. S. Crowson ◽  
R. Weinshilboum ◽  
L. Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Machine Learning ◽  
Supervised Machine Learning ◽  
Research Support ◽  
Eular Response ◽  
Learning Methods ◽  
Machine Learning Methods ◽  
Early Ra ◽  
Genome Wide

Background:Methotrexate (MTX) is the most common anchor drug for rheumatoid arthritis (RA), but the risk of missing the opportunity for early effective treatment with alternative medications is substantial given the delayed onset of MTX action and 30-40% inadequate response rate. There is a compelling need to accurately predicting MTX response prior to treatment initiation, which allows for effectively identifying patients at RA onset who are likely to respond to MTX.Objectives:To test the ability of machine learning approaches with clinical and genomic biomarkers to predict MTX response with replications in independent samples.Methods:Age, sex, clinical, serological and genome-wide association study (GWAS) data on patients with early RA of European ancestry from 647 patients (336 recruited in United Kingdom [UK]; 307 recruited across Europe; 70% female; 72% rheumatoid factor [RF] positive; mean age 54 years; mean baseline Disease Activity Score with 28-joint count [DAS28] 5.65) of the PhArmacogenetics of Methotrexate in RA (PAMERA) consortium was used in this study. The genomics data comprised 160 genome-wide significant single nucleotide polymorphisms (SNPs) with p<1×10-5 associated with risk of RA and MTX metabolism. DAS28 score was available at baseline and 3-month follow-up visit. Response to MTX monotherapy at the dose of ≥15 mg/week was defined as good or moderate by the EULAR response criteria at 3 months’ follow up visit. Supervised machine-learning methods were trained with 5-repeats and 10-fold cross-validation using data from PAMERA’s 336 UK patients. Class imbalance (higher % of MTX responders) in training was accounted by using simulated minority oversampling technique. Prediction performance was validated in PAMERA’s 307 European patients (not used in training).Results:Age, sex, RF positivity and baseline DAS28 data predicted MTX response with 58% accuracy of UK and European patients (p = 0.7). However, supervised machine-learning methods that combined demographics, RF positivity, baseline DAS28 and genomic SNPs predicted EULAR response at 3 months with area under the receiver operating curve (AUC) of 0.83 (p = 0.051) in UK patients, and achieved prediction accuracies (fraction of correctly predicted outcomes) of 76.2% (p = 0.054) in the European patients, with sensitivity of 72% and specificity of 77%. The addition of genomic data improved the predictive accuracies of MTX response by 19% and achieved cross-site replication. Baseline DAS28 scores and following SNPs rs12446816, rs13385025, rs113798271, and rs2372536 were among the top predictors of MTX response.Conclusion:Pharmacogenomic biomarkers combined with DAS28 scores predicted MTX response in patients with early RA more reliably than using demographics and DAS28 scores alone. Using pharmacogenomics biomarkers for identification of MTX responders at early stages of RA may help to guide effective RA treatment choices, including timely escalation of RA therapies. Further studies on personalized prediction of response to MTX and other anti-rheumatic treatments are warranted to optimize control of RA disease and improve outcomes in patients with RA.Disclosure of Interests:Elena Myasoedova: None declared, Arjun Athreya: None declared, Cynthia S. Crowson Grant/research support from: Pfizer research grant, Richard Weinshilboum Shareholder of: co-founder and stockholder in OneOme, Liewei Wang: None declared, Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking

scholarly journals THU0207 SUSTAINABILITY OF RESPONSE TO UPADACITINIB AS MONOTHERAPY OR IN COMBINATION AMONG PATIENTS WITH RHEUMATOID ARTHRITIS AND PRIOR INADEQUATE RESPONSE TO CONVENTIONAL SYNTHETIC DMARDS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 327.1-328
Author(s):  
A. Kavanaugh ◽  
M. H. Buch ◽  
B. Combe ◽  
L. Bessette ◽  
I. H. Song ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inadequate Response ◽  
Research Support ◽  
Two Phase ◽  
First Occurrence ◽  
Activity Measures ◽  
Disease Activity Measures

Background:The primary treatment goal for patients (pts) with rheumatoid arthritis (RA) is a state of sustained clinical remission (REM) or low disease activity (LDA).1,2Objectives:To assess the long-term sustainability of responses to upadacitinib (UPA), a JAK inhibitor, with or without background csDMARD(s) in pts with RA.Methods:Data are from two phase 3 randomized, controlled trials of UPA in RA pts with roughly similar baseline disease characteristics: SELECT-NEXT enrolled pts with an inadequate response (IR) to csDMARD(s) on background stable csDMARD(s) receiving UPA 15 mg or 30 mg once daily or placebo for 12 weeks (wks); SELECT-MONOTHERAPY enrolled methotrexate (MTX)-IR pts receiving UPA 15 mg or 30 mg monotherapy or blinded MTX for 14 wks. After 12/14 wks, pts could enter a blinded long-term extension and receive UPA 15 mg or 30 mg for up to 5 years. This post hoc analysis evaluated clinical REM (CDAI ≤2.8; SDAI ≤3.3), LDA (CDAI≤10; SDAI≤11), and DAS28(CRP) <2.6/≤3.2 at first occurrence before Wk 84; additionally, these measures were evaluated at 3, 6, and 12 months after the first occurrence for the total number of pts randomized to UPA 15 mg. Sustainability of response was evaluated by Kaplan-Meier only for those pts who achieved REM/LDA and was defined as time to the earliest date of losing response at two consecutive visits or discontinuation of study drug. The predictive ability of time to clinical REM/LDA was assessed using Harrell’s concordance (c)-index (for reference, an index ~ 0.5, indicates no ability to predict; an index of 1 or -1 would be a perfect prediction). The last follow up dates were 22 March, 2018 (SELECT-NEXT) and 25 May, 2019 (SELECT-MONOTHERAPY), when all pts had reached the Wk 84 visit.Results:Through Wk 84, the percent of treated pts achieving CDAI REM/LDA was 43%/79% for those receiving UPA 15 mg with background csDMARD(s) (SELECT-NEXT) and 37%/76% for those receiving UPA 15 mg without background csDMARD(s) (SELECT-MONOTHERAPY). 35%/25% of pts randomized to UPA 15 mg with background csDMARD(s) and 27%/23% of pts randomized to UPA 15 mg without background csDMARD(s) achieved sustained CDAI REM through 6/12 months after the first occurrence. 64%/56% of pts randomized to UPA 15 mg with background csDMARD(s) and 61%/56% of pts randomized to UPA 15 mg without background csDMARD(s) achieved sustained CDAI LDA through 6/12 months after the first occurrence (Figure 1). Time to initial clinical REM/LDA did not appear to be associated with sustained disease control. The c-indices (95%CI) for CDAI REM in the UPA 15 mg with background csDMARD(s) and UPA 15 mg without background csDMARD(s) groups were 0.541 (0.47, 0.62) and 0.568 (0.49, 0.65) and that of LDA were 0.521 (0.46, 0.58) and 0.498 (0.43, 0.56), respectively. Through last follow-up visit, 55% of pts receiving UPA 15 mg with background csDMARD(s) and 62% of pts receiving UPA 15 mg without background csDMARD(s) remained in CDAI REM while 72% and 70% of pts remained in CDAI LDA, respectively (Figure 2). Similar results were observed across other disease activity measures (SDAI REM/LDA and DAS28(CRP) <2.6/≤3.2).Conclusion:More than a quarter and more than a half of pts with RA and prior IR to csDMARD(s) receiving UPA with or without background csDMARD therapy achieved sustained clinical REM and LDA, respectively, across disease activity measures. Sustainability of responses appeared comparable among pts receiving UPA with or without background csDMARDs through up to 84 wks.References:[1]EULAR: Smolen JS, et al. Ann Rheum Dis 2017;76:960–977.[2]ACR: Singh et al. Arthritis & Rheumatology Vol. 68, No. 1, January 2016, pp 1–26.Disclosure of Interests: :Arthur Kavanaugh Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB – grant/research support, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jessica Suboticki Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB

scholarly journals POS0647 EFFICACY, SAFETY AND CHARACTERISTICS OF IGURATIMOD-BASED THERAPY IN THE TREATMENT OF UA, ERA AND RA PATIENTS FOR 24 WEEKS: A PROSPECTIVE COHORT STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 561.2-562
Author(s):  
X. Liu ◽  
Z. Sun ◽  
W. Guo ◽  
F. Wang ◽  
L. Song ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Adverse Events ◽  
Disease Activity ◽  
Prospective Cohort Study ◽  
Early Rheumatoid Arthritis ◽  
Prospective Cohort ◽  
Combined Treatment ◽  
Serious Adverse Events

Background:Experts emphasize early diagnosis and treatment in RA, but the widely used diagnostic criterias fail to meet the accurate judgment of early rheumatoid arthritis. In 2012, Professor Zhanguo Li took the lead in establishing ERA “Chinese standard”, and its sensitivity and accuracy have been recognized by peers. However, the optimal first-line treatment of patients (pts) with undifferentiated arthritis (UA), early rheumatoid arthritis (ERA), and rheumatoid arthritis (RA) are yet to be established.Objectives:To evaluate the efficacy and safety of Iguratimod-based (IGU-based) Strategy in the above three types of pts, and to explore the characteristics of the effects of IGU monotherapy and combined treatment.Methods:This prospective cohort study (ClinicalTrials.gov Identifier NCT01548001) was conducted in China. In this phase 4 study pts with RA (ACR 1987 criteria[1]), ERA (not match ACR 1987 criteria[1] but match ACR/EULAR 2010 criteria[2] or 2014 ERA criteria[3]), UA (not match classification criteria for ERA and RA but imaging suggests synovitis) were recruited. We applied different treatments according to the patient’s disease activity at baseline, including IGU monotherapy and combination therapies with methotrexate, hydroxychloroquine, and prednisone. Specifically, pts with LDA and fewer poor prognostic factors were entered the IGU monotherapy group (25 mg bid), and pts with high disease activity were assigned to combination groups. A Chi-square test was applied for comparison. The primary outcomes were the proportion of pts in remission (REM)or low disease activity (LDA) that is DAS28-ESR<2.6 or 3.2 at 24 weeks, as well as the proportion of pts, achieved ACR20, Boolean remission, and good or moderate EULAR response (G+M).Results:A total of 313 pts (26 pts with UA, 59 pts with ERA, and 228 pts with RA) were included in this study. Of these, 227/313 (72.5%) pts completed the 24-week follow-up. The results showed that 115/227 (50.7%), 174/227 (76.7%), 77/227 (33.9%), 179/227 (78.9%) pts achieved DAS28-ESR defined REM and LDA, ACR20, Boolean remission, G+M response, respectively. All parameters continued to decrease in all pts after treatment (Fig 1).Compared with baseline, the three highest decline indexes of disease activity at week 24 were SW28, CDAI, and T28, with an average decline rate of 73.8%, 61.4%, 58.7%, respectively. Results were similar in three cohorts.We performed a stratified analysis of which IGU treatment should be used in different cohorts. The study found that the proportion of pts with UA and ERA who used IGU monotherapy were significantly higher than those in the RA cohort. While the proportion of triple and quadruple combined use of IGU in RA pts was significantly higher than that of ERA and UA at baseline and whole-course (Fig 2).A total of 81/313 (25.8%) pts in this study had adverse events (AE) with no serious adverse events. The main adverse events were infection(25/313, 7.99%), gastrointestinal disorders(13/313, 4.15%), liver dysfunction(12/313, 3.83%) which were lower than 259/2666 (9.71%) in the previous Japanese phase IV study[4].The most common reasons of lost follow-up were: 1) discontinued after remission 25/86 (29.1%); 2) lost 22/86 (25.6%); 3) drug ineffective 19/86 (22.1%).Conclusion:Both IGU-based monotherapy and combined therapies are tolerant and effective for treating UA, ERA, and RA, while the decline in joint symptoms was most significant. Overall, IGU combination treatments were most used in RA pts, while monotherapy was predominant in ERA and UA pts.References:[1]Levin RW, et al. Scand J Rheumatol 1996, 25(5):277-281.[2]Kay J, et al. Rheumatology 2012, 51(Suppl 6):vi5-9.[3]Zhao J, et al. Clin Exp Rheumatol 2014, 32(5):667-673.[4]Mimori T, et al. Mod Rheumatol 2019, 29(2):314-323.Disclosure of Interests:None declared

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