FRI0126 POOR ADHERENCE TO METHOTREXATE IS ASSOCIATED WITH PERSISTENT DISEASE ACTIVITY DURING FOLLOW-UP FOR RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 644.1-645
Author(s):  
J. H. Kang ◽  
S. E. Choi ◽  
H. Xu ◽  
D. J. Park ◽  
S. S. Lee

Objectives:Although methotrexate (MTX) is the cornerstone therapy in patients with rheumatoid arthritis (RA), adherence to MTX in these patients is typically suboptimal. Thus, we investigated the proportion of RA patients who were adherent to MTX and whether non-adherence to MTX affected the clinical outcome in these patients during follow-up.Methods:We enrolled 331 RA patients from a single tertiary center. Data were collected at the time of enrollment and then annually for 4 consecutive years. Adherence was defined by the proportion of days covered at 1 year. Patients were divided into two groups: patients who took more than 80% of MTX and those who did not. Univariate and multivariate analyses were performed to identify the association between drug compliance and clinical outcome.Results:Of the 331 RA patients, 8.7% had taken less than 80% of MTX during the follow-up period. Non-adherent patients had lower EuroQol-5D scores (P=0.013) and higher RAPID3 scores (P=0.004) at baseline than adherent patients. Leflunomide was more commonly prescribed to adherent patients than non-adherent patients (P=0.012). Non-adherent patients had a higher mean Disease Activity Score 28 (DAS28)-erythrocyte sedimentation rate score (P=0.001), higher mean DAS28-C-reactive protein (CRP) score (P=0.001), and higher mean rate of tender and swollen joints (P=0.003 and P=0.002, respectively) than adherent patients. In the multivariate analysis, poor MTX adherence was significantly associated with a higher mean DAS28-CRP score (odds ratio, 0.270; 95% confidence interval, 0.165–0.444; P<0.001).Conclusion:Adherence to MTX can affect disease activity during follow-up in Korean patients with RA. Our results provide a rationale for patient education to maintain good drug adherence in RA patients, to control disease activity.Disclosure of Interests:None declared

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ana María Heredia-P ◽  
Gloria Inés Lafaurie ◽  
Wilson Bautista-Molano ◽  
Tamy Goretty Trujillo ◽  
Philippe Chalem-Choueka ◽  
...  

Abstract Background Rheumatoid arthritis (RA) and periodontal disease are inter-related conditions. However, factors predictive of periodontal disease progression in patients with early rheumatoid arthritis (eRA) are lacking. The aim of this study was to identify factors associated with the progression of clinical attachment loss (CAL) in interproximal dental sites of eRA patients. Methods Twenty-eight eRA patients were evaluated for the progression of CAL at 280 interproximal dental sites at 1 year of follow-up. Markers of RA activity (rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein), a marker of bone resorption (Dickkopf-related protein 1), Disease Activity Score 28 and Simple Disease Activity Index were included as potential systemic predictive factors. Plaque index, gingival index, pocket depth, clinical attachment level and Dickkopf-related protein 1 in crevicular fluid at baseline were included as potential local predictive factors. Data were analysed in a hierarchical structure using generalised linear mixed models for progression at each site (> 2 mm) during follow-up. Results C-reactive protein level was the most important predictive systemic factor for the progression of CAL. The mean CAL and a high degree of gingival inflammation in interproximal sites at baseline were important predictive local factors (p <  0.0001). Patients who received combined treatment with disease-modifying antirheumatic drugs and corticosteroids exhibited less CAL (p <  0.0001). The predictive value of the generalised linear mixed model for progression was 85%. Conclusions Systemic factors, including RA disease activity and baseline periodontal condition, were associated with periodontal progression. Pharmacological treatment may affect periodontal progression in patients with early RA.


2019 ◽  
pp. 3-15

The assessment of disease activity is an essential component in the selection of therapeutic approach for the prevention of disability of patients with RA. The current study was conducted to evaluate the disease activity in patients on csDMARDs and bDMARDs after 6 months to 1-year of treatment and to determine whether the benefits of different therapies were sustained over time. For the purpose of the study were selected 220 patients with a mean age 55.05 ± 10.63 SD years, meeting the 1987 ACR classification criteria for RA. Patients were stratified according to treatment regimens into 2 age-matched treatment groups: 96 on csDMARDs and 124 on bDMARD therapy. Patient‘s assessment of disease related pain, global health and physician assessment of global health was made by visual analogue scale (VAS) – 100 mm. Disease activity was the primary outcome domain. Independent joint assessor evaluated 28 joints on baseline, 6th and 12th month of the follow-up period. C-reactive protein (CRP) was used to measure the infl ammation process. DAS28-CRP, CDAI and SDAI were calculated according to the standard formulas. Comparison was performed by analysis variance ANOVA. On baseline, patients on bDMARDs had a significantly higher mean time-averaged 28-joint disease activity score (5.03 ± 0.84 SD vs. 4.35 ± 1.20 SD, p < 0,001), CDAI (25.06 ± 7.32 SD vs. 20.83 ± 10.53 SD, p < 0.001) and SDAI (28.27 ± 8.74 SD vs. 23.19 ± 11.89 SD, p < 0.001) compared to those on csDMARDs. On the 6th month in both groups (bDMARDS and csDMARDs) we found significant decrease in mean DAS28 (p < 0.001, p < 0.001), although no significant difference in disease activity between the groups was measured by this indicator (3.75 ± 2.49 SD vs 3.90 ± 1.10 SD, p = 0.566). Patients on bDMARDs had significantly lower disease activity compared to those on csDMARDs after 6th and 12th month of treatment assessed by CDAI (13.43 ± 4.98 SD vs 16.81 ± 9.94 SD, p = 0.001; 8.65 ± 4.53 SD vs 15.86 ± 10.02 SD, p < 0.001), and SDAI (14.63 ± 5.42 SD vs 18.38 ± 10.49 SD, p < 0.001; 9.39 ± 4.92 SD vs 16.79 ± 10.5 SD, p < 0.001). Unlike results reported by DAS28-CRP which showed no change between the 6th and 12th month in patients receiving csDMARDs (3.90 ± 1.10 SD, 3.82 ± 1.12 SD, p = 0.156), we observed a statistically significant difference in all three time intervals (0, the 6th, 10th month) of the follow up period regarding to CDAI and SDAI. After a year prospective follow-up, therapy with biologic DMARDs results in sustained suppression – minimal disease activity assessed by DAS28-CRP, CDAI and SDAI, compared to patients receiving DMARDs who had moderate disease activity according to these tools. The therapy with bDMARDs was superior to csDMARDs therapy for suppressing disease activity (assessed by DAS28-CRP, CDAI and SDAI) of rheumatoid arthritis (RA) on the 6th and 12th month of the follow-up period.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 583-583
Author(s):  
C. Garufi ◽  
F. Ceccarelli ◽  
F. R. Spinelli ◽  
S. Mancuso ◽  
C. Pirone ◽  
...  

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


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 900.1-900
Author(s):  
L. Diebold ◽  
T. Wirth ◽  
V. Pradel ◽  
N. Balandraud ◽  
E. Fockens ◽  
...  

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


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1463.2-1464
Author(s):  
S. Bayat ◽  
K. Tascilar ◽  
V. Kaufmann ◽  
A. Kleyer ◽  
D. Simon ◽  
...  

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


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 625.2-626
Author(s):  
H. Gerasimova ◽  
T. Popkova ◽  
I. Kirillova ◽  
M. Cherkasova ◽  
A. Martynova ◽  
...  

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


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 492.2-492
Author(s):  
K. Mandai ◽  
M. Tada ◽  
Y. Yamada ◽  
T. Koike ◽  
T. Okano ◽  
...  

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


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 327.1-328
Author(s):  
A. Kavanaugh ◽  
M. H. Buch ◽  
B. Combe ◽  
L. Bessette ◽  
I. H. Song ◽  
...  

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


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 561.2-562
Author(s):  
X. Liu ◽  
Z. Sun ◽  
W. Guo ◽  
F. Wang ◽  
L. Song ◽  
...  

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


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1392.2-1392
Author(s):  
M. De Oliveira ◽  
P. V. Alabarse ◽  
M. Farinon ◽  
R. Cavalheiro Do Espírito Santo ◽  
R. Xavier

Background:Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased mortality and associated with metabolic disorders. Since the metabolomic profile is known to vary in response to different inflammatory conditions, metabolome analysis could substantially improve diagnosis and prognosis of RA.Objectives:To analyze the urine metabolome profile in RA patients and correlate it with disease activity changes over 12 monthsMethods:Seventy-nine RA patients, according to ACR/EULAR 2010 classification criteria, between 40 and 70 years old, were recruited and followed for 12 months. Metabolome analysis was performed by Nuclear Magnetic Resonance spectroscopy (NMR), resulting in the identification of 93 metabolites in urine collected at the baseline and after 12 months. Frequency analysis, Pearson Correlation and Multivariate data analysis with orthogonal projections to latent structures (OPLS) method were performed and a statistical significance was considered as p<0.05.Results:The study population was characterized by the majority of women (86.7%), mean age of 56 years old, around 80% with positive anti-CCP or Rheumatoid Factor. During the one year of follow-up, there was no substantial variation in the DAS28 measurement (baseline: 3.8, after 12 months: 4.0). There was no significant correlation between the metabolome pattern and DAS28 score (p>0.05) over time. However, multivariate analysis (OPLS-DA) demonstrated an adequate differentiation of the population with 0.92 of accuracy (Q2: 0.72 and R2: 0.89).There was a significant increase of L-cysteine, choline, L-Phenylalanin, creatine, L-histidine, oxalacetic acid and xanthine, and a decrease of L-threonine, taurine, butyric and gluconic acid (p<0.05) during the follow-up, metabolites that are involved in the skeletal muscle metabolism.Conclusion:The observed biomarkers indicate,as expected, that the RA metabolic profile is associated with inflammation injury and skeletal muscle amino acid metabolism. Correlations with disease activity changes was compromised by the stable disease status during the 12 months. More studies evaluating correlations with skeletal muscle function and mass are underway.Acknowledgments:Disclosure of interest: Marianne Oliveira: None declared, Rafaela Santo: None declared, Mirian Farinon: None declared, Ricardo Xavier Consultant of: Abbvie, Pfizer, Novartis, Janssen, Lilly, RocheDisclosure of Interests:Marianne de Oliveira: None declared, Paulo Vinicius Alabarse: None declared, Mirian Farinon: None declared, Rafaela Cavalheiro do Espírito Santo: None declared, Ricardo Xavier Consultant of: AbbVie, Pfizer, Novartis, Janssen, Eli Lilly, Roche


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