Rheumatoid arthritis patients on persistent moderate disease activity on biologics have adverse 5-year outcome compared to persistent low-remission status and represent a heterogeneous group

Abstract Background The long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity. Methods We included longitudinally monitored RA patients from the Hellenic Registry of Biologic Therapies with persistent (cumulative time ≥ 50% of a 5-year period) moderate (pMDA, 3.2 < DAS28 ≤ 5.1) or remission/low (pRLDA, DAS28 ≤ 3.2) disease activity. The former was further classified into persistent lower-moderate (plMDA, DAS28 < 4.2) and higher-moderate (phMDA, DAS28 ≥ 4.2) subgroups. Five-year trajectories of functionality (HAQ) were the primary outcome in comparing pRLDA versus pMDA and assessing heterogeneity within the pMDA subgroups through multivariable mixed-effect regression. We further compared serious adverse events (SAEs) occurrence between the two groups. Results We identified 295 patients with pMDA and 90 patients with pRLDA, the former group comprising of plMDA (n = 133, 45%) and phMDA (n = 162, 55%). pMDA was associated with worse 5-year functionality trajectory than pRLDA (+ 0.27 HAQ units, CI 95% + 0.22 to + 0.33; p < 0.0001), while the phMDA subgroup had worse 5-year functionality than plMDA (+ 0.26 HAQ units, CI 95% 0.18 to 0.36; p < 0.0001). Importantly, higher persistent disease activity was associated with more SAEs [pRLDA: 0.2 ± 0.48 vs pMDA: 0.5 ± 0.96, p = 0.006; plMDA: 0.32 ± 0.6 vs phMDA: 0.64 ± 1.16, p = 0.038]. Male gender (p = 0.017), lower baseline DAS28 (p < 0.001), HAQ improvement > 0.22 (p = 0.029), and lower average DAS28 during the first trimester since treatment initiation (p = 0.001) independently predicted grouping into pRLDA. Conclusions In clinical practice, RA patients with pMDA while on bDMARDs have adverse long-term outcomes compared to lower disease activity status, while heterogeneity exists within the pMDA group in terms of 5-year functionality and SAEs. Targeted studies to better characterize pMDA subgroups are needed, in order to assist clinicians in tailoring treatments.

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Rheumatoid arthritis patients on persistent moderate disease activity on biologics have adverse 5-years outcome compared to persistent low-remission status and represent a heterogeneous group.

10.21203/rs.3.rs-41068/v2 ◽

2020 ◽

Author(s):

Irini Genitsaridi ◽

Irini Flouri ◽

Dimitris Plexousakis ◽

Konstantinos Marias ◽

Kyriaki Boki ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Practice ◽

Disease Activity ◽

Serious Adverse Events ◽

Term Outcome ◽

Mixed Effect ◽

Long Term Outcome ◽

Moderate Disease ◽

Moderate Disease Activity

Abstract Background The long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity. Methods We included longitudinally-monitored RA patients from the Hellenic Registry of Biologic Therapies with persistent (cumulative time ≥50% of a 5-year period) moderate (pMDA, 3.2<DAS28≤5.1) or remission/low (pRLDA, DAS28≤3.2) disease activity. The former was further classified into persistent lower-moderate (plMDA, DAS28<4.2) and higher-moderate (phMDA, DAS28≥4.2) subgroups. Five-year trajectories of functionality (HAQ) was the primary outcome in comparing pRLDA versus pMDA and assessing heterogeneity within the pMDA subgroups through multivariable mixed-effect regression. We further compared serious adverse events (SAEs) occurrence between the two groups.Results We identified 295 patients with pMDA and 90 patients with pRLDA, the former group comprising of plMDA (n=133, 45%) and phMDA (n=162, 55%). pMDA was associated with worse 5-year functionality trajectory than pRLDA (+0.27 HAQ units, CI 95% +0.22 to +0.33; p<0.0001), while the phMDA subgroup had worse 5-year functionality than plMDA (+0.26 HAQ units, CI 95% 0.18 to 0.36; p<0.0001). Importantly, higher persistent disease activity was associated with more SAEs [pRLDA: 0.2±0.48 vs pMDA: 0.5±0.96, p=0.006; plMDA: 0.32 ±0.6 vs phMDA: 0.64 ±1.16, p=0.038)]. Male gender (p=0.017), lower baseline DAS28 (p<0.001), HAQ improvement >0.22 (p=0.029) and lower average DAS28 during the first trimester since treatment initiation (p=0.001), independently predicted grouping into pRLDA. Conclusions In clinical practice, RA patients with pMDA while on bDMARDs have adverse long-term outcomes compared to lower disease activity status, while heterogeneity exists within the pMDA group in terms of 5-year functionality and SAEs. Targeted studies to better characterize pMDA subgroups are needed, in order to assist clinicians in tailoring treatments.

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Rheumatoid Arthritis Patients On Persistent Moderate Disease Activity On Biologics Have Adverse 5-years Outcome Compared To Persistent Low-remission Status Yet They Represent A Heterogeneous Group: Lower-moderate Has Better Functionality And Fewer Serious Adverse Events Than Higher-moderate Subgroup

10.21203/rs.3.rs-41068/v1 ◽

2020 ◽

Author(s):

Irini Genitsaridi ◽

Irini Flouri ◽

Dimitris Plexousakis ◽

Konstantinos Marias ◽

Kyriaki Boki ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Practice ◽

Adverse Events ◽

Disease Activity ◽

Serious Adverse Events ◽

Term Outcome ◽

Long Term Outcome ◽

Moderate Disease ◽

Moderate Disease Activity

Abstract Background The long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice, exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity. Methods We included longitudinally-monitored RA patients from the Hellenic Registry of Biologic Therapies with persistent (cumulative time ≥50% of a 5-year period) moderate (pMDA, 3.2<DAS28≤5.1) or remission/low (pRLDA, DAS28≤3.2) disease activity. The former was further classified into persistent lower-moderate (plMDA, DAS28<4.2) and higher-moderate (phMDA, DAS28≥4.2) subgroups. Five-year trajectories of functionality (HAQ) was the primary outcome in comparing pRLDA versus pMDA and assessing heterogeneity within the pMDA subgroups through multivariable mixed-effect regression. Results We identified 295 patients with pMDA and 90 patients with pRLDA, the former group comprising of plMDA (n=133, 45%) and phMDA (n=162, 55%). pMDA was associated with worse 5-year functionality trajectory than pRLDA (+0.27 HAQ units, CI 95% +0.22 to +0.33; p<0.0001), while the phMDA subgroup had worse 5-year functionality than plMDA (+0.26 HAQ units, CI 95% 0.18 to 0.36; p<0.0001). Importantly, higher persistent disease activity was associated with more serious adverse events (SAEs) [pRLDA: 0.2±0.48 vs pMDA: 0.5±0.96, p=0.006; plMDA: 0.32 ±0.6 vs phMDA: 0.64 ±1.16, p=0.038). Male gender (p=0.017), lower baseline DAS28 (p<0.001), HAQ improvement >0.22 (p=0.029) and lower average DAS28 during the first trimester since treatment initiation (p=0.001), independently predicted grouping into pRLDA. Conclusions In clinical practice, RA patients with pMDA while on bDMARDs have adverse long-term outcome compared to lower disease activity status, while heterogeneity exists within the pMDA group in terms of 5-year functionality and SAEs. Targeted studies to better characterize pMDA subgroups are needed, in order to assist clinicians in tailoring treatments.

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Comparison of the long-term outcome for patients with rheumatoid arthritis with persistent moderate disease activity or disease remission during the first year after diagnosis: data from the ESPOIR cohort

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2013-204178 ◽

2014 ◽

Vol 74 (4) ◽

pp. 724-729 ◽

Cited By ~ 35

Author(s):

B Combe ◽

I Logeart ◽

M C Belkacemi ◽

S Dadoun ◽

T Schaeverbeke ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

First Year ◽

Term Outcome ◽

Long Term Outcome ◽

Disease Remission ◽

Moderate Disease ◽

Moderate Disease Activity

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AB0272 CAN NONSTEROIDAL ANTI-INFLAMMATORY DRUGS CONTROL THE SYMPTOMS OF MODERATE RHEUMATOID ARTHRITIS?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2901 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1162.2-1162

Author(s):

E. Pogozheva ◽

A. Karateev ◽

V. Amirdzhanova ◽

E. Filatova

Keyword(s):

Rheumatoid Arthritis ◽

Global Health ◽

Disease Activity ◽

Biological Agents ◽

Das 28 ◽

Moderate Disease ◽

Inflammatory Drugs ◽

Moderate Disease Activity

Objectives:to evaluate the efficacy of long-term pain therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA) with an initially moderate disease activity (DAS 28 <5,1).Methods:the study included 404 RA patients, disease duration was more than 1 year, mean DAS 28 3.7±1.6, mean age 58.6±10.0 years, 69% women, 76,7% RF “+”, 81,5% ACPA “+”. 91,2% of the patients received conventional DMARDs (methotrexate), 8,8% - biological agents. All patients received NSAIDs (aceclofenac) to control their symptoms. Тhe follow-up period was 6 months. We evaluated the dynamics of the DAS 28 index, the level of pain and patient global health on a 100- mm visual analog scale (VAS).Results:the level of pain (VAS) decreased from 63,1 ± 15,4 to 46,3± 8,3 (p=0,001) by 3 months of follow-up and up to 39,5± 11,2 (p= 0,001) by 6 months of follow-up. The patient global health (VAS) also improved from 58,2 ± 13,4 at baseline to 40,3 ± 11,2 (p=0,001) at 3 months and to 35,5 ± 9,7 (p=0,001) at 6 months of follow up. The mean DAS 28 remained within the moderate disease activity and decreased from 3,7±1,5 to 3,4 ±1,1 (p=0,01) after 3 months, and to 3,1± 0,9 (p=0,01) after 6 months.Conclusion:long-term NSAID therapy allows to control the disease activity in patients with moderate RA. This should be taken into account when planning therapy, including deciding whether to “switch” DMARDs and prescribing biological agents.Disclosure of Interests:None declared

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P127 Treating rheumatoid arthritis patients with moderate disease activity: an analysis of the upadacitinib SELECT Phase III randomised studies

Rheumatology ◽

10.1093/rheumatology/keab247.122 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Phillip G Conaghan ◽

Karel Pavelka ◽

Song-Chou Hsieh ◽

Terri-Leigh Bonnington ◽

Toby C Kent ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Phase Iii ◽

Integrated Analysis ◽

Inadequate Response ◽

Mixed Effect ◽

Advisory Boards ◽

Moderate Disease ◽

Patient Reported ◽

Moderate Disease Activity

Abstract Background/Aims Some health systems restrict use of advanced therapies for rheumatoid arthritis (RA) to patients with high disease activity (DAS28>5.1). Upadacitinib (UPA), a selective JAK inhibitor, has demonstrated significant improvement in patients with moderate-to-severe RA. We aimed to explore the efficacy and safety of UPA in RA patients with moderate disease activity. Methods This was a post-hoc, subgroup analysis from three phase 3 registrational trials evaluating once daily UPA 15mg versus placebo (PBO) in patients with moderate (DAS28(CRP)>3.2, ≤5.1) and high (DAS28(CRP)>5.1) disease activity. Patients had prior inadequate response to csDMARDs (SELECT-COMPARE and SELECT-NEXT integrated analysis) or bDMARDs (SELECT-BEYOND). Clinical and functional outcomes were analysed at the studies primary endpoint (Week12). Missing data were handled using non-responder imputation for binary endpoints and mixed-effect model repeat measurement for continuous variables. Results Across all three studies mean baseline DAS28(CRP) was ∼4.5 and ∼6.2 in moderate and severe patients, respectively. At Week 12 significantly greater proportions of csDMARD-inadequate responder (IR) and bDMARD-IR patients receiving UPA 15 mg achieved ACR20, low disease activity (DAS28(CRP)≤3.2) and remission (DAS28(CRP)<2.6) compared to PBO in both disease severity subgroups (Table 1). Improvement in physical function assessed by Health Assessment Questionnaire for Rheumatoid Arthritis (HAQ-DI) and pain visual analogue scale (VAS) were significantly greater with UPA 15mg vs PBO for severe csDMARDs-IR and bDMARD-IR populations and numerically greater in moderate bDMARD-IR patients. Across all IR populations higher proportions of patients with moderate disease treated with UPA 15mg achieved DAS28(CRP)≤3.2 and DAS28(CRP)<2.6 compared to those with severe disease. The safety profile of UPA in moderate and severe patients was comparable and consistent with previously published data. Conclusion UPA 15mg was effective in improving clinical, functional, and patient reported outcomes in patients with either moderate or severe RA. P127 Table 1:Baseline characteristics and efficacy endpoints at week 12 from SELECT-NEXT, -COMPARE and -BEYONDTimepointKey EndpointscsDMARD IR (SELECT COMPARE and SELECT NEXT integrated)ModerateSevereUPA 15mg (n = 209)PBO (n = 195)UPA 15mg (n = 649)PBO (n = 671)BaselineAge (yrs; Mean ± SD)53.7 ± 12.654.5 ± 12.454.9 ± 11.654.1 ± 12.3Duration since diagnosis (yrs; Mean ± SD)7.5 ± 7.47.3 ± 6.78.0 ± 7.98.2 ± 8.2DAS28(CRP) (Mean ± SD)4.6 ± 0.44.6 ± 0.46.2 ± 0.76.1 ± 0.7HAQ-DI (Mean ± SD)1.2 ± 0.61.2 ± 0.61.7 ± 0.61.7 ± 0.6Pain VAS (0-100) (Mean ± SD)52.5 ± 21.448.4 ± 21.669.8 ± 18.268.9 ± 17.9Week 12ACR20 (% response, 95% CI)63.6 (57.1, 70.2)***33.8 (27.2, 40.5)71.2 (67.7, 74.7)***37.0 (33.3, 40.6)DAS28 (CRP) ≤3.2, (% response, 95% CI)61.7 (55.1, 68.3)***28.7 (22.4, 35.1)40.7 (36.9, 44.5)***10.3 (8.0, 12.6)DAS28 (CRP) ≤2.6, (% response, 95% CI)41.4 (34.5, 47.8)***14.9 (9.9, 19.9)25.1 (21.8, 28.5)***4.6 (3.0, 6.2)ΔHAQ-DI (mean, 95% CI)-0.43 (-0.51, -0.35)***-0.23 (-0.32, -0.15)-0.67 (-0.72, -0.61)***-0.31 (-0.36, -0.25)Δ Pain VAS (0-100) (% response, 95% CI)-25.0 (-28.6, -21.4)***-7.0, (-10.6, -3.2)-32.8 (-35.1, -30.5)***-16.1 (-18.4, -13.8)TimepointKey EndpointsbDMARD IR (SELECT-BEYOND)ModerateSevereUPA 15mg (n = 39)PBO (n = 38)UPA 15mg (n = 124)PBO (n = 128)BaselineAge (yrs; Mean ± SD)56.1 ± 11.157.7 ± 13.456.4 ± 11.557.6 ± 10.9Duration since diagnosis (yrs; Mean ± SD)13.6 ± 10.014.7 ± 9.411.9 ± 9.214.6 ± 9.3DAS28(CRP) (Mean ± SD)4.7 ± 0.34.4 ± 0.56.2 ± 0.86.2 ± 0.7HAQ-DI (Mean ± SD)1.4 ± 0.71.1 ± 0.51.8 ± 0.61.7 ± 0.6Pain VAS (0-100) (Mean ± SD)58.1 ± 22.449.8 ± 22.271.3 ±74.5 ±Week 12ACR20 (% response, 95% CI)61.5 (46.3, 76.8)*36.8 (21.5, 52.2)66.1 (57.8, 74.5)***26.6 (18.9, 34.2)DAS28 (CRP) ≤3.2, (% response, 95% CI)64.1 (49.0, 79.2)**28.9 (14.5, 43.4)36.3 (27.8, 44.8)***9.4 (4.3, 14.4)DAS28 (CRP) ≤2.6, (% response, 95% CI)43.6 (28.0, 59.2)*21.1 (8.1, 34.0)24.2 (16.7, 31.7)***6.3 (2.1, 10.4)ΔHAQ-DI (mean, 95% CI)-0.24 (-0.41, -0.07)-0.12 (-0.30, 0.05)-0.47 (-0.56, -0.37)***-0.18 (-0.28, -0.08)Δ Pain VAS (0-100) (% response, 95% CI)-16.8 (-25.4, -8.1)-5.4 (-14.3, 3.4)-28.7 (-33.5, -24.0)***-12.2 (-17.0, -7.3)*p ≤ 0.05;**p ≤ 0.01;***p ≤ 0.001 for comparison of UPA versus PBO. Disclosure P.G. Conaghan: Other; P.C. has been a consultant or speaker for AbbVie, BMS, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer. K. Pavelka: Other; K.P. has received honoraria for consultations and lectures from AbbVie, Roche, Pfizer, MSD, Sanofi, UCB and Amgen. S. Hsieh: None. T. Bonnington: Other; T.B. is an employee at AbbVie Limited. T.C. Kent: Other; T.C. is an employee at AbbVie Limited. C.J. Edwards: Other; C.E. has received honoraria, advisory boards, speakers bureau, research support from AbbVie, BMS, Biogen, Fresenius, Gilead Janssen, Lilly, Pfizer, MSD, Novartis, Roche, Samsung, Sanofi, UCB.

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LONG-TERM OUTCOME OF TREATING RHEUMATOID ARTHRITIS: RESULTS AFTER 20 YEARS

The Lancet ◽

10.1016/s0140-6736(87)91672-2 ◽

1987 ◽

Vol 329 (8542) ◽

pp. 1108-1111 ◽

Cited By ~ 329

Author(s):

D.L. Scott ◽

B.L. Coulton ◽

D.P.M. Symmons ◽

A.J. Popert

Keyword(s):

Rheumatoid Arthritis ◽

Term Outcome ◽

Long Term Outcome

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CORRELATION STUDY OF DISEASE ACTIVITY SCORE AND SERUM CARTILAGE OLIGOMERIC MATRIX PROTEINLEVELS OF RHEUMATOID ARTHRITIS PATIENTS IN BANDUNG, INDONESIA

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i1.15251 ◽

2016 ◽

Vol 10 (1) ◽

pp. 290

Author(s):

Nyi Mekar Saptarini ◽

Dainar Eka Pratiwi ◽

Ellin Febrina ◽

Marlia Singgih Wibowo ◽

Tutus Gusdinar

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Matrix Protein ◽

Disease Activity Score ◽

Correlation Study ◽

Activity Score ◽

Rheumatology Clinic ◽

Das 28 ◽

Moderate Disease ◽

Moderate Disease Activity

ABSTRACTObjective: This study was designed to determine the correlation between Disease Activity Score (DAS 28) and the serum Cartilage Oligomeric MatrixProtein (COMP) levels in Indonesian Rheumatoid Arthritis (RA) patients. Methods: The subjects were patients who visit the rheumatology clinic at one governmental hospital in Bandung, Indonesia. DAS was determinedby the QxMD Software based on erythrocyte sedimentation rate, and serum COMP levels were determined by enzyme-linked immunosorbent assay.Statistical analysis was conducted with IBM SPSS Statistics 23. Results: DAS 28 value was 3.36 ± 0.16 which indicates the moderate disease activity. Serum COMP levels were 843.80 ± 35.79 ng/ml in RA patientsand 830.00 ± 48.92 ng/ml in normal controls. Conclusion: There is no correlation between DAS 28 and serum COMP levels in RA patients (p = 0.496 and rho = 0.129). Keywords: Autoimmune disease, Rheumatoid arthritis monitoring, Cartilage oligomeric matrix protein, Disease activity score 28

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