Predictive Factors for the Long-Term Clinical Course in Patients with Rheumatoid Arthritis Receiving Second-Line Anti-Rheumatic Drugs in Real-World Practice: An Analysis Using Disease Activity Trajectory-Based Clustering Approach

Abstract Background: The purpose of this study was to stratify patients with rheumatoid arthritis (RA) according to the trend of disease activity by trajectory-based clustering and to identify the predictive factors for treatment response and the switching patterns of biologics according to trajectory groups. Methods: We analysed the data from a nationwide RA cohort from the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Patients treated with second-line disease-modifying anti-rheumatic drugs (DMARDs) were included. Trajectory modeling for clustering was used to group the disease activity trend. The predictive factors and switching patterns of biologics for each trajectory were investigated.Results: The trends in the disease activity of 688 RA patients were clustered into 4 groups: rapid decrease and stable disease activity (group 1, N = 319), rapid decrease followed by an increase (group 2, N = 36), slow and continued decrease (group 3, N = 290), and no decrease in disease activity (group 4, N = 43). In the multivariable analysis for predictive factors, current smoking (OR, 7.845; 95% CI 2.158–28.220), low hemoglobin (OR 0.694; 95% CI, 0.532–0.901), and high initial disease activity score according to the 28-joint assessment (DAS28) (OR, 2.397; 95% CI, 1.638–3.586) were significantly associated with group 4 compared with group 1. Group 1 had a higher proportion of patients who had never had switching (86.5%) and who were initially treated with non-TNF inhibitors (44.2%) compared with groups 2 (52.8% and 25%), 3 (50.3% and 23.4%), and 4 (25.6% and 18.6%).Conclusions: The trajectory-based approach was useful for clustering the disease activity in longitudinal data in patients with RA. Among the four trajectories, the group with sustained high disease activity was associated with current smoking, low hemoglobin, high initial DAS28, and frequent switching of biologics.

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Golimumab in patients with active rheumatoid arthritis despite methotrexate therapy: 52-week results of the GO-FORWARD study

Annals of the Rheumatic Diseases ◽

10.1136/ard.2009.116319 ◽

2010 ◽

Vol 69 (6) ◽

pp. 1129-1135 ◽

Cited By ~ 95

Author(s):

Edward Keystone ◽

Mark C Genovese ◽

Lars Klareskog ◽

Elizabeth C Hsia ◽

Stephen Hall ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Safety Profile ◽

Active Rheumatoid Arthritis ◽

Joint Disease ◽

Serious Adverse Events ◽

American College Of Rheumatology ◽

Group 4 ◽

Increased Risk ◽

Group 1

ObjectiveTo evaluate the efficacy and safety of golimumab to 52 weeks in patients with active rheumatoid arthritis despite methotrexate.MethodsPatients were randomly assigned to receive placebo plus methotrexate (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus methotrexate (group 3) and golimumab 100 mg plus methotrexate (group 4). At week 16, patients in groups 1, 2 and 3 who had less than 20% improvement in tender and swollen joints entered early escape. At week 24, patients in group 1 who had not entered early escape crossed over to 50 mg golimumab plus methotrexate.ResultsAt week 16, 31%, 27% and 17% of patients in groups 1, 2 and 3, respectively, entered early escape. At week 52, 44%, 45%, 64% and 58% of patients in groups 1, 2, 3 and 4, respectively, achieved 20% improvement in the American College of Rheumatology criteria; and 34%, 31%, 42% and 53%, respectively, achieved low disease activity (≤3.2) according to the 28-joint disease activity score. Patients in group 4 appeared to have an increased risk of serious adverse events and serious infections.ConclusionThe results of various outcome measures showed that the response rates achieved by patients receiving golimumab to 24 weeks were sustained to 52 weeks. The safety profile appeared to be consistent with the known safety profile of tumour necrosis factor inhibitors.

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THU0227 CAFFEINE INTAKE MODULATES DISEASE ACTIVITY AND CYTOKINES LEVELS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2100 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 340.2-341

Author(s):

V. Orefice ◽

F. Ceccarelli ◽

C. Barbati ◽

R. Lucchetti ◽

G. Olivieri ◽

...

Keyword(s):

Disease Activity ◽

Lupus Erythematosus ◽

Caffeine Intake ◽

Caffeine Consumption ◽

Group 4 ◽

Group 3 ◽

Group 2 ◽

The Impact ◽

Group 1

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease mainly affecting women of childbearing age. The interplay between genetic and environmental factors may contribute to disease pathogenesis1. At today, no robust data are available about the possible contribute of diet in SLE. Caffeine, one of the most widely consumed products in the world, seems to interact with multiple components of the immune system by acting as a non-specific phosphodiesterase inhibitor2.In vitrodose-dependent treatment with caffeine seems to down-regulate mRNA levels of key inflammation-related genes and similarly reduce levels of different pro-inflammatory cytokines3.Objectives:We evaluated the impact of caffeine consumption on SLE-related disease phenotype and activity, in terms of clinimetric assessment and cytokines levels.Methods:We performed a cross-sectional study, enrolling consecutive patients and reporting their clinical and laboratory data. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2k)4. Caffeine intake was evaluated by a 7-day food frequency questionnaire, including all the main sources of caffeine. As previously reported, patients were divided in four groups according to the daily caffeine intake: <29.1 mg/day (group 1), 29.2-153.7 mg/day (group 2), 153.8-376.5 mg/day (group 3) and >376.6 mg/day (group 4)5. At the end of questionnaire filling, blood samples were collected from each patient to assess cytokines levels. These were assessed by using a panel by Bio-Plex assays to measure the levels of IL-6, IL-10, IL-17, IL-27, IFN-γ, IFN-α and Blys.Results:We enrolled 89 SLE patients (F/M 87/2, median age 46 years, IQR 14; median disease duration 144 months, IQR 150). The median intake of caffeine was 195 mg/day (IQR 160.5). At the time of the enrollment, 8 patients (8.9%) referred a caffeine intake < 29.1 mg/day (group 1), 27 patients (30.3%) between 29.2 and 153.7 mg/day (group 2), 45 patients (51%) between 153.8 and 376.5 mg/day (group 3) and 9 patients (10.1%) >376.6 mg/day (group 4). A negative correlation between the levels of caffeine and disease activity, evaluated with SLEDAI-2K, was observed (p=0.01, r=-0.26). By comparing the four groups, a significant higher prevalence of lupus nephritis, neuropsychiatric involvement, haematological manifestations, hypocomplementemia and anti-dsDNA positivity was observed in patients with less intake of caffeine (figure 1 A-E). Furthermore, patients with less intake of caffeine showed a significant more frequent use of glucocorticoids [group 4: 22.2%,versusgroup 1 (50.0%, p=0.0001), group 2 (55.5%, p=0.0001), group 3 (40.0%, p=0.009)]. Moving on cytokines analysis, a negative correlation between daily caffeine consumption and serum level of IFNγ was found (p=0.03, r=-0.2) (figure 2A); furthermore, patients with more caffeine intake showed significant lower levels of IFNα (p=0.02, figure 2B), IL-17 (p=0.01, figure 2C) and IL-6 (p=0.003, figure 2D).Conclusion:This is the first report demonstrating the impact of caffeine on SLE disease activity status, as demonstrated by the inverse correlation between its intake and both SLEDAI-2k values and cytokines levels. Moreover, in our cohort, patients with less caffeine consumption seems to have a more severe disease phenotype, especially in terms of renal and neuropsychiatric involvement. Our results seem to suggest a possible immunoregulatory dose-dependent effect of caffeine, through the modulation of serum cytokine levels, as already suggested byin vitroanalysis.References:[1]Kaul et alNat. Rev. Dis. Prim.2016; 2. Aronsen et alEurop Joul of Pharm2014; 3. Iris et alClin Immun.2018; 4. Gladman et al J Rheumatol. 2002; 5. Mikuls et alArth Rheum2002Disclosure of Interests:Valeria Orefice: None declared, Fulvia Ceccarelli: None declared, cristiana barbati: None declared, Ramona Lucchetti: None declared, Giulio Olivieri: None declared, enrica cipriano: None declared, Francesco Natalucci: None declared, Carlo Perricone: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi

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POS0563 THE NATURAL COURSE OF RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE FOCUSING ON LUNG PHYSIOLOGY AND DISEASE ACTIVITY: A PROSPECTIVE COHORT STUDY (PART 2)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3084 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 516.1-516

Author(s):

S. H. Chang ◽

J. S. Lee ◽

C. H. Park ◽

M. U. Kim ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Natural Course ◽

Annual Change ◽

Low Disease Activity ◽

Activity Group ◽

Lung Physiology ◽

Group A ◽

Group B ◽

Group D

Background:Interstitial lung disease (ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). However, the effect of RA disease activity on the course of ILD is not yet known.Objectives:To assess the natural course of lung physiology of RA-ILD and the relation between arthritis activity and pulmonary physiology in patients with RA-ILD.Methods:The Korean Rheumatoid Arthritis ILd (KORAIL) cohort is the prospective observational cohort and aims to investigate the natural course of RAILD. Based on either 1987 or 2020 ACR criteria, patients diagnosed with RA and ILD based on CT scan were recruited from six tertiary medical hospitals in Korea since January 2015. RA disease activity was assessed using disease activity (DAS)28-ESR and CRP, annually. Pulmonary function tests (PFT), including FVC and DLCO were conducted annually. According to the transition of DAS28-ESR status, we classified patients into four groups: Group A. persistent remission or low disease activity, Group B. improvement, Group C. worsening, Group D. persistent moderate to high disease activity.Results:We analyzed 143 patients who completed a 2-year follow-up (visit 2) or had died with available PFT results at least twice. Mean duration since RA diagnosis and since ILD diagnosis was 7.6±8.0 and 2.7±3.1 years, respectively. Twenty-four patients were Group A, 33 Group B, 10 Group C and 30 Group D. The mean of FVC (mL) and % of the predicted value in FVC was significantly lower in Group D than in other groups (Table 1). The annual rate of decline in FVC was -42 (95% CI -93~10) mL·year-1 in Group B while -113 (95% CI -206~-21) mL·year-1 in Group C (Figure 1A). The annual decline rate in Group C was further exaggerated in patients with ≥ 80% of FVC predicted (-141, 95% CI -251~-32 mL·year-1). During two years of follow-up, patients ever experienced a relative decline of ≥10% from the enrollment in FVC predicted was 27.3%(n-9/33) in Group B whereas 30.0% (3/10) in Group C. The annual rate of decline in % of DLco predicted value was also the largest in Group C (-4.6 %·year-1, 95%CI -8.5~-0.7), which further exaggerated in patients with ≥ 80% of FVC predicted (-4.9%·year-1, 95 %CI -8.3~-1.5, Figure 1B). Of note, about half of patients with maintained not only low disease activity (Group A) but also moderate to severe disease activity (Group D) improved in DLco at least 10% or more from the enrollment of DLco predicted value (Group A: 54.2%, n=13/24, Group D: 46.7%, n=14/30).Conclusion:RA disease activity is associated with the change of lung physiology in patients with RA-ILD; worsening disease activity associated with a further decrease of annual change in FVC and maintaining low disease activity associated with a further increase of annual change in % of DLco predicted value.Table 1.The analysis of forced vital capacity (FVC) according to disease activity transition group.Group AGroup BGroup CGroup DFVC (mL), mean±SD2810.0±771.12528.8±735.32801.0±952.72048.3±575.7FVC % of predicted, mean±SD87.5±14.586.5±16.693.0±15.677.2±17.3Rate of FVC decline, mL·year-1 (95% CI)-52 (-112,7)-42 (-93,10)-113 (-206, -21)1 (-52, 54)A 10-point decline from V1 in predicted FVC value, n (%)29 (20.3)6 (25.0)6 (18.2)3 (30.0)Relative decline of 10% from the enrollment in predicted FVC value, n (%)35 (24.5)5 (20.8)9 (27.3)3 (30.0)Figure 1.The annual change of pulmonary physiology according to disease activity transition group.Acknowledgements:This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (grant no.HI14C1277).Disclosure of Interests:None declared

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THU0214 Predictive factors for achievement of low disease activity at 52 weeks are different between young and elderly rheumatoid arthritis patients treated with abatacept

10.1136/annrheumdis-2018-eular.3382 ◽

2018 ◽

Author(s):

N. Takahashi ◽

T. Kojima ◽

S. Asai ◽

N. Ishiguro ◽

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Predictive Factors ◽

Low Disease Activity

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Predictive Factors Related to the Efficacy of Golimumab in Patients with Rheumatoid Arthritis

Clinical Medicine Insights Arthritis and Musculoskeletal Disorders ◽

10.4137/cmamd.s22155 ◽

2015 ◽

Vol 8 ◽

pp. CMAMD.S22155 ◽

Cited By ~ 4

Author(s):

Katsuaki Kanbe ◽

Junji Chiba ◽

Yasuo Inoue ◽

Masashi Taguchi ◽

Akiko Yabuki

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Predictive Factors ◽

Disease Duration ◽

Radiographic Progression ◽

Serum Levels ◽

Serum Concentrations ◽

Regression Analyses ◽

Tnf Α ◽

Baseline Characteristics

In order to investigate the predictive factors related to clinical efficacy and radiographic progression at 24 weeks by looking at the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 including baseline characteristics in patients with rheumatoid arthritis (RA) treated with golimumab, serum concentrations of TNF-α and IL-6 were analyzed every 4 weeks up to 24 weeks in 47 patients treated with golimumab. Baseline levels of the Disease Activity Score 28 C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI) scores were also assessed. Radiographic progression using the van der Heijde-modified Sharp (vdH-S) score was assessed in 29 patients. Multiple regression analyses related to the DAS28-CRP score and delta total sharp score at 24 weeks was undertaken using the baseline characteristics of patients and serum concentrations of matrix metalloproteinase (MMP)-3, TNF-α, and IL–6. The DAS28-CRP score and SDAI decreased significantly at 4 weeks up to 24 weeks compared with baseline. Serum levels of TNF-α were not changed significantly up to 24 weeks compared with baseline, but those of IL-6 decreased significantly at 4 weeks up to 8 weeks. Multiple regression analyses showed that disease duration and serum levels of MMP-3 were related significantly to the DAS28-CRP score at 24 weeks. Radiographic progression was related significantly to disease duration with regard to joint space narrowing and bone erosion. However, serum levels of TNF-α and IL-6 were not correlated significantly with the DAS28-CRP score and radiographic progression. These data suggest that decreasing serum levels of IL-6 significantly, MMP-3, and disease duration are predictive factors for RA activity in patients taking golimumab.

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Platelet-To-Lymphocyte Ratio Can Be Used As Marker To Predict Activity And Severity In Moderate And High Disease Activity of Rheumatoid Arthritis: A Retrospective Study

10.21203/rs.3.rs-1077543/v2 ◽

2021 ◽

Author(s):

Bilin Chen ◽

Qing Zhu ◽

Shu Li ◽

Yan Ge ◽

Peijun Wu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Logistic Regression ◽

Disease Activity ◽

Roc Analysis ◽

High Disease Activity ◽

Regression Analyses ◽

Platelet To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Activity Group ◽

Ultrasound Score

Abstract Objective: This study aimed to study and evaluate the value of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) as markers to predict the disease activity and severity in patients with rheumatoid arthritis (RA).Methods: A total of 139 inpatients with RA were divided into two groups: moderate activity group (3.2<DAS28-CRP score<5.1) and high activity group (≥5.1). The correlation of routine hematological indices with DAS28 and joint ultrasound score (gray-scale ultrasound score, GS-US; power Doppler ultrasound score, PD-US; total ultrasound score, T-US) were analyzed by Pearson's correlation and logistic regression analyses. Receiver operating characteristics (ROC) analysis was performed to compare the efficacy of blood indices, ESR, or CRP in reflecting the disease activity and severity of RA.Results: The values of PLR, NLR, PD-US, and T-US were significantly different between moderate and high disease activity groups (p<0.001), and PLR was significantly correlated with PD-US and DAS28. Logistic regression analyses showed that PLR was an independent risk factor for disease activity by DAS 28 and joint damage severity by PD-US and T-US. ROC analysis showed that the efficacy of using PLR alone to evaluate the disease activity and joint severity of RA was similar to that of using combined CRP and ESR. The best cut-off value of PLR for predicting high disease activity and high joint severity was determined as 236.6.Conclusions: PLR can be used as a marker to predict activity and severity in patients with moderate and high RA disease activity.

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Smoking and Methotrexate Inefficacy in Rheumatoid Arthritis: What About Underlying Molecular Mechanisms?

The Journal of Rheumatology ◽

10.3899/jrheum.210217 ◽

2021 ◽

pp. jrheum.210217

Author(s):

Gerrit Jansen ◽

Maurits C.F.J. de Rotte ◽

Robert de Jonge

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Molecular Mechanisms ◽

Disease Activity Score ◽

Current Issue ◽

Early Arthritis ◽

Current Smoking ◽

Negative Effect ◽

Dose Dependent ◽

Over Time

The study by Safy-Khan, et al in the current issue of The Journal of Rheumatology1 reports that in a methotrexate (MTX)-based treatment regimen for patients with early arthritis, current smoking was significantly associated with a smaller reduction of Disease Activity Score in 28 joints (DAS28) over time compared to noncurrent smoking. This negative effect of current smoking on DAS28 was dose-dependent: patients who smoked 10–19 cigarettes per day did worse than patients who smoked 1–9 cigarettes per day.

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Differences in Predictive Factors for Sustained Clinical Remission with Abatacept Between Younger and Elderly Patients with Biologic-naive Rheumatoid Arthritis: Results from the ABROAD Study

The Journal of Rheumatology ◽

10.3899/jrheum.160051 ◽

2016 ◽

Vol 43 (11) ◽

pp. 1974-1983 ◽

Cited By ~ 13

Author(s):

Masahiro Sekiguchi ◽

Takao Fujii ◽

Kiyoshi Matsui ◽

Kosaku Murakami ◽

Satoshi Morita ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Elderly Patients ◽

Disease Activity ◽

Predictive Factors ◽

Clinical Remission ◽

Health Assessment ◽

The Elderly ◽

Joint Disease ◽

Younger Patients ◽

Reactive Protein

Objective.To differentiate predictive factors for sustained clinical remission between elderly and younger patients with rheumatoid arthritis (RA) receiving abatacept (ABA) as an initial biological disease-modifying antirheumatic drug.Methods.The study involved 277 biologic-naive patients with RA with high or moderate disease activity, who were treated with intravenous ABA and evaluated for 48 weeks in 43 Japanese hospitals and rheumatology clinics (the ABatacept Research Outcomes as a First-line Biological Agent in the Real WorlD study: UMIN000004651). Predictive factors associated with sustained clinical remission defined by the 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) during the 24–48–week or 36–48–week periods were determined in elderly (≥ 65 yrs, n = 148) and younger patient groups (< 65 yrs, n = 129) using logistic regression analysis.Results.Clinical remission was achieved at 24 and 48 weeks in 35.1% and 36.5% of patients in the elderly group and 34.9% and 43.4% in the younger group, respectively. In elderly patients, anticitrullinated protein antibody (ACPA) positivity and a lower DAS28-CRP score were significantly associated with sustained clinical remission; however, a lower Health Assessment Questionnaire-Disability Index (HAQ-DI) score was not related to sustained clinical remission. In younger patients, lower DAS28-CRP and HAQ-DI scores were predictive factors for sustained clinical remission, whereas ACPA positivity was not a useful predictive factor for sustained clinical remission.Conclusion.Although the effectiveness of ABA in biologic-naive patients with RA was equally recognized in elderly and younger patients, the baseline clinical characteristics associated with sustained clinical remission were substantially different.

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Association between Serum 25-Hydroxyvitamin D Level and Rheumatoid Arthritis

BioMed Research International ◽

10.1155/2015/913804 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 4

Author(s):

Xiaomin Cen ◽

Yuan Liu ◽

Geng Yin ◽

Min Yang ◽

Qibing Xie

Keyword(s):

Rheumatoid Arthritis ◽

Complete Remission ◽

Disease Activity ◽

Normal Group ◽

High Disease Activity ◽

Low Disease Activity ◽

Hydroxyvitamin D ◽

Activity Group ◽

25 Hydroxyvitamin D ◽

Baseline Characteristics

The objective of this study is to examine and evaluate whether serum 25(OH)D is associated with disease activity in patients with rheumatoid arthritis (RA). Our results suggested that serum 25(OH)D in RA groups has significant lower level (35.99±12.59 nmol/L) than that in the normal groups (54.35±8.20 nmol/L,P<0.05). Based on the DAS28, patients with RA were divided into four subgroups, and no differences were found in the four groups (P>0.05). The 25(OH)D levels in complete remission, low disease activity, middle disease activity, and high disease activity group were32.86±12.26,33.97±13.28,38.41±10.64, and38.94±13.35 nmol/L, respectively. Based on the serum 25(OH)D levels, patients with RA were divided into inadequate group and normal group, and there were no significant differences in baseline characteristics and disease activity in the two groups. Our results showed that serum 25(OH)D levels in the inadequate group are significantly lower than those in the normal group. However, no correlations were found between 25(OH)D levels and disease activity among 116 patients with RA. The present findings will help to understand the association between 25(OH)D and disease activity of RA.

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