AB0328 Factors associated with normalized physical function and clinical remission defined with simplified disease activity index by 1-yaear infliximab treatment in patients with rheumatoid arthritis

Background:Pain control in rheumatoid arthritis (RA) patient is an important matter. When pain remains even disease activity is remission, it causes deterioration of activity in daily living (ADL) in past research. In other words, pain affects ADL independently from disease activity, namely the Health Assessment Questionnaire (HAQ) score, a most popular index of ADL for patient with RA[1]. Thus, burden of remnant pain despite clinical remission in RA is serious and pending subject.Duloxetine, a potent reuptake inhibitor of serotonin and norepinephrine, is developed for the treatment of major depressive disorder [2]. It’s effectiveness for pain relief with osteoarthritis is also widely accepted. This drug should be effective not only for chronic pain due to osteoarthritis, but also due to RA. However, effectiveness of duloxetine for remnant pain relief in patient with RA in clinical remission is still unclear.Objectives:In this study, effectiveness of duloxetine for the remnant pain despite clinical remission in patient with RA was statistically evaluated.Methods:RA patients whose pain score with visual analog scale (PS-VAS) >30mm despite Clinical Disease Activity Score (CDAI) is <2.8, were picked up for the study. These patients were divided into groups whether duloxetine was administrated (a group without duloxetine: G-C; a group with duloxetine: G-D).PS-VAS, C-reactive protein, CDAI and simplified disease activity index (SDAI), modified Health Assessment Questionnaire (mHAQ), and QOL value which is calculated from Euro-QOL 5-Dimensions (EQ-5D) were measured at the initiation of duloxetine in the G-D and at the first CDAI remission attained in the G-C, and at week 12 thereafter. Change of these indices were compared with One sample T-test for each group. Patient’s global assessment (PGA) at baseline compared to the other components of CDAI was evaluated for each group statistically with One-tailed T-test. Differences between the two groups at each moment were statistically evaluated with Mann-Whitney U-test. Statistical significance was set less than 1%. All statistical analyses were performed using StatPlus:mac®(AnalystSoft Inc., Walnut, CA, USA).Results:A total of three hundred and six patients were recruited. G-D counted sixty-eight with 18 males and 50 females, while G-C counted 238 with 57 males and 181 females. Average age were 71.3 and 71.5 for G-D and G-C, respectively, with 53.6 months for time span from baseline to initiation in the G-D. 80.8% of the patients in G-D sustained to administrate duloxetine. PGA was 0.6 and 0.5 for G-D and G-C respectively, while the other component of CDAI were below 0.3 in average for both groups and these values were significantly lower than the PGA score in both groups. PS-VAS was 46.4 and 44.0, and significantly decreased to 26.1 and 36.0 in average for G-D and G-C respectively at week 12 when compared to baseline. Reversely, the CDAI score was significantly elevated significantly from 1.16 and 1.19 to 3.25 and 4.34 for G-D and G-C respectively. PGA also significantly increased to 1.5 and 2.4 for G-D and G-C respectively. CRP and the SDAI score also demonstrated same trend significantly as the CDAI score for both groups. mHAQ decreased significantly from 0.430 and 0.495 to 0.393 and 0.487 for G-D and G-C respectively. QOL value increased from 0.800 and 0.817 to 0.811 and 0.840 for G-D and G-C respectively, however no statistical significance demonstrated in both groups.Conclusion:Duloxetine has been suggested to have effectiveness for the pain relief, for improvement of ADL, and for the contribution to QOL maintenance, however, no effect of disease activity control is expected.References:[1]Yoshii I, Chijiwa T, Sawada N. Influence of pain score measured by a visual analog scale (PS-VAS) on the Health Assessment Questionnaire Disability Index and 28-joint Disease Activity Index with C-reactive protein in rheumatoid arthritis patients. Int J Rheum Dis 2018;21:1955-61.[2]Knadler MP, Lobo E, Chappell J, Bergstrom R. Duloxetine. Clin Pharmacokinet 2011;50:281-94.Disclosure of Interests:None declared

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Validity and Risk of Adopting PGA ≤ 2 As A Remission Criteria of Boolean in Clinical Practice in Patient With Rheumatoid Arthritis

10.21203/rs.3.rs-829138/v1 ◽

2021 ◽

Author(s):

Ichiro Yoshii ◽

Tatsumi Chijiwa ◽

Naoya Sawada

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Practice ◽

Disease Activity ◽

Clinical Remission ◽

Global Assessment ◽

Statistical Difference ◽

Activity Index ◽

Disease Activity Index ◽

Remission Criteria ◽

The Mean

Abstract Validity and risk of setting patient’s global assessment (PGA) ≤ 2 as a Boolean remission criteria substituting PGA ≤ 1 in treating rheumatoid arthritis (RA) was investigatedPatients were recruited from an area cohort, of whom attained Boolean remission (Boolean-1) or near remission with PGA ≤ 2 and the rest components were ≤ 1 (Boolean-2). Simplified disease activity index (SDAI) score was compared according to the criteria variations.A total of 517 patients were studied. Mean SDAI score of patients with Boolean-1 was significantly lower than that of patients with Boolean-2 at acquisition. The trend was evident in the patients who attained Boolean-1 remission. Mean SDAI score at acquisition, 6 months after, and 1 year after of patients who attained Boolean-2 first and then Boolean-1, was significantly inferior to that of patients who attained the remissions at the same time. The mean SDAI score at month 6 in the Boolean-2 was not SDAI remission at all.We concluded that setting PGA ≤ 2 as a remission criteria may not have statistical difference in disease activity from PGA ≤ 1, however, there was an determinant risk to misread that includes patient who losses clinical remission after acquisition.

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Synovitis and Osteitis Are Very Frequent in Rheumatoid Arthritis Clinical Remission: Results from an MRI Study of 294 Patients in Clinical Remission or Low Disease Activity State

The Journal of Rheumatology ◽

10.3899/jrheum.110421 ◽

2011 ◽

Vol 38 (9) ◽

pp. 2039-2044 ◽

Cited By ~ 77

Author(s):

FRÉDÉRIQUE GANDJBAKHCH ◽

PHILIP G. CONAGHAN ◽

BO EJBJERG ◽

ESPEN A. HAAVARDSHOLM ◽

VIOLAINE FOLTZ ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Clinical Remission ◽

Activity Index ◽

Disease Activity Index ◽

Patient Characteristics ◽

Subclinical Inflammation ◽

Low Disease Activity ◽

Structural Progression ◽

Bone Edema

Objective.In rheumatoid arthritis (RA), radiographic progression may occur despite clinical remission. This may be explained by subclinical inflammation. Magnetic resonance imaging (MRI) provides a greater sensitivity than clinical examination and radiography for assessing disease activity. Our objective was to determine the MRI characteristics of RA patients in clinical remission or low disease activity (LDA) state.Methods.Databases from 6 cohorts were collected from 5 international centers. RA patients in clinical remission according to Disease Activity Score28-C-reactive protein (DAS28-CRP < 2.6; n = 213) or LDA-state (2.6 ≤ DAS28-CRP < 3.2; n = 81) with available MRI data were included. MRI were assessed according to the OMERACT RA MRI scoring system (RAMRIS).Results.Patient characteristics: 70% women, median age 55 (interquartile range, IQR 43–63) years, disease duration 2.3 (IQR 0.7–5.1) years, DAS28-CRP 2.2 (IQR 1.8–2.6), Simplified Disease Activity Index, SDAI, 3.9 (IQR 1.9–6.5), Clinical Disease Activity Index, CDAI, 3.1 (IQR 1.5– 5.8), rheumatoid factor/anti-cyclic citrullinated peptide positivity 57%/54%, presence of radiographic erosions: 66%. Wrist and metacarpophalangeal MRI (MCP-MRI) data were available for 287 and 241 patients, respectively. MRI inflammatory activity in wrist and/or MCP joints was observed in the majority [synovitis: 95%, bone edema (osteitis): 35%] of patients. The median (IQR) RAMRIS score was 6 (3–9) for synovitis and 0 (0–2) for osteitis. Synovitis and osteitis were not less frequent in DAS28 clinical remission (synovitis/osteitis 96%/35%) than LDA (91/36). A trend towards lower frequencies of osteitis in patients in SDAI and CDAI remission was observed.Conclusion.Subclinical inflammation was identified by MRI in the majority of RA patients in clinical remission or LDA state. This may explain structural progression in such patients. Further work is required to understand the place of modern imaging in future remission criteria.

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American College of Rheumatology/European League Against Rheumatism Remission Criteria for Rheumatoid Arthritis Maintain Reliable Performance When Evaluated in 44 Joints

The Journal of Rheumatology ◽

10.3899/jrheum.130166 ◽

2013 ◽

Vol 40 (8) ◽

pp. 1254-1258 ◽

Cited By ~ 5

Author(s):

Yuko Kaneko ◽

Harumi Kondo ◽

Tsutomu Takeuchi

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Clinical Remission ◽

Global Assessment ◽

Activity Index ◽

Disease Activity Index ◽

University Hospital ◽

Physician Global Assessment ◽

Remission Criteria ◽

The Mean

Objective.To investigate the performance of the new remission criteria for rheumatoid arthritis (RA) in daily clinical practice and the effect of possible misclassification of remission when 44 joints are assessed.Methods.Disease activity and remission rate were calculated according to the Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and a Boolean-based definition for 1402 patients with RA in Keio University Hospital. Characteristics of patients in remission were investigated, and the number of misclassified patients was determined — those classified as being in remission based on 28-joint count but as nonremission based on a 44-joint count for each definition criterion.Results.Of all patients analyzed, 46.6%, 45.9%, 41.0%, and 31.5% were classified as in remission in the DAS28, SDAI, CDAI, and Boolean definitions, respectively. Patients classified into remission based only on the DAS28 showed relatively low erythrocyte sedimentation rates but greater swollen joint counts than those classified into remission based on the other definitions. In patients classified into remission based only on the Boolean criteria, the mean physician global assessment was greater than the mean patient global assessment. Although 119 patients had ≤ 1 involved joint in the 28-joint count but > 1 in the 44-joint count, only 34 of these 119 (2.4% of all subjects) were found to have been misclassified into remission.Conclusion.In practice, about half of patients with RA can achieve clinical remission within the DAS28, SDAI, and CDAI; and one-third according to the Boolean-based definition. Patients classified in remission based on a 28-joint count may have pain and swelling in the feet, but misclassification of remission was relatively rare and was seen in only 2.4% of patients under a Boolean definition. The 28-joint count can be sufficient for assessing clinical remission based on the new remission criteria.

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Association of 17 Definitions of Remission with Functional Status in a Large Clinical Practice Cohort of Patients with Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.181286 ◽

2019 ◽

Vol 47 (1) ◽

pp. 20-27 ◽

Cited By ~ 2

Author(s):

Pedro D. Carvalho ◽

Ricardo J.O. Ferreira ◽

Robert Landewé ◽

David Vega-Morales ◽

Karen Salomon-Escoto ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Practice ◽

Disease Activity ◽

Functional Status ◽

Physical Function ◽

Activity Index ◽

Health Assessment ◽

Disease Activity Index ◽

Sensitivity Analyses ◽

American College Of Rheumatology

Objective.To compare the association between different remission criteria and physical function in patients with rheumatoid arthritis followed in clinical practice.Methods.Longitudinal data from the METEOR database were used. Seventeen definitions of remission were tested: American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean-based; Simplified/Clinical Disease Activity Index (SDAI/CDAI); and 14 Disease Activity Score (DAS)-based definitions. Health Assessment Questionnaire (HAQ) ≤ 0.5 was defined as good functional status. Associations were investigated using generalized estimating equations. Potential confounders were tested and sensitivity analyses performed.Results.Data from 32,915 patients (157,899 visits) were available. The most stringent definition of remission was the ACR/EULAR Boolean-based definition (1.9%). The proportion of patients with HAQ ≤ 0.5 was higher for the most stringent definitions, although it never reached 100%. However, this also meant that, for the most stringent criteria, many patients in nonremission had HAQ ≤ 0.5. All remission definitions were associated with better function, with the strongest degree of association observed for the SDAI (adjusted OR 3.36, 95% CI 3.01–3.74).Conclusion.The 17 definitions of remission confirmed their validity against physical function in a large international clinical practice setting. Achievement of remission according to any of the indices may be more important than the use of a specific index. A multidimensional approach, targeted at wider goals than disease control, is necessary to help all patients achieve the best possible functional status.

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Serum Markers in Rheumatoid Arthritis: A Longitudinal Study of Patients Undergoing Infliximab Treatment

International Journal of Rheumatology ◽

10.1155/2015/276815 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Oddgeir Selaas ◽

Hilde H. Nordal ◽

Anne-Kristine Halse ◽

Johan G. Brun ◽

Roland Jonsson ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Activity Index ◽

Joint Destruction ◽

Disease Activity Index ◽

Serum Levels ◽

Serum Markers ◽

Matrix Metalloproteases ◽

High Disease Activity ◽

Infliximab Treatment

Objective.The aim of this study was to investigate the clinical effect and serum markers in a cohort of rheumatoid arthritis patients with moderate to high disease activity, participating in an open clinical phase IV study conducted in Norway between 2001 and 2003 receiving infliximab treatment.Method.A total of 39 patients were studied, with a mean age of 54 years and 12-year disease duration. The analyses were performed using serum from patients at four assessment time points: baseline and 3, 6, and 12 months after starting treatment with infliximab. A wide variety of clinical data was collected and disease activity of 28 joints and Simple Disease Activity Index were calculated. The joint erosion was determined by X-ray imaging and the Sharp/van der Heijde score was determined. Serum analysis included multiplex immunoassays for 12 cytokines, 5 matrix metalloproteases, and 2 VEGFs.Results.The majority of the RA patients in this study had initially moderate to high disease activity and the infliximab treatment reduced the disease activity significantly and also reduced any further joint destruction and improved disease status. Most of the serum levels of cytokines and metalloproteases remained unchanged during the course of the study, and we were unable to detect changes in TNF-αin serum. Serum levels of IL-6 and VEGF-A decreased significantly after initiation of infliximab treatment.Conclusion.The serum levels of IL-6 and VEGF-A may be promising disease markers as they vary with disease progression. The clinical significance of these findings is yet to be determined and has to be confirmed in future clinical trials before being applied in the clinics.

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Does Clinical Remission Lead to Normalization of EQ-5D in Patients with Rheumatoid Arthritis and Is Selection of Remission Criteria Important?

The Journal of Rheumatology ◽

10.3899/jrheum.090898 ◽

2010 ◽

Vol 37 (2) ◽

pp. 285-290 ◽

Cited By ~ 27

Author(s):

LOUISE LINDE ◽

JAN SØRENSEN ◽

MIKKEL ØSTERGAARD ◽

KIM HØRSLEV-PETERSEN ◽

MERETE LUND HETLAND

Keyword(s):

Rheumatoid Arthritis ◽

General Population ◽

Disease Activity ◽

Clinical Remission ◽

Activity Index ◽

Disease Activity Index ◽

Linear Regression Models ◽

Remission Criteria ◽

The Difference ◽

Activity Index Score

Objective. To compare health-related quality of life (HRQOL) of patients with rheumatoid arthritis (RA) to that of the general population and to investigate the association with disease activity, focusing on different clinical remission criteria.Methods. EQ-5D data from 3156 patients with RA from 11 Danish centers were compared with Danish EQ-5D population norms (n = 16,136). The Disease Activity Score (DAS28) and the Clinical Disease Activity Index score (CDAI) were used as definitions of disease activity and clinical remission. The score difference (ΔEQ-5D) was calculated in each patient as the difference from the age and sex-matched general population and adjusted for age, marital status, education, body mass index, smoking, exercise habits, disease duration, IgM-rheumatoid factor status, joint surgery, extraarticular features, treatment, and comorbidity in multiple linear regression models.Results. 37% vs 22% fulfilled the DAS28 and CDAI remission criteria, respectively. The ΔEQ-5D values for women/men in clinical remission were DAS28 0.05/0.06 vs CDAI 0.01/0.02; low disease activity: DAS28 0.12/0.13 vs CDAI 0.11/0.14; moderate disease activity: DAS28 0.18/0.20 vs CDAI 0.20/0.23; and high disease activity: DAS28 0.38/0.28 vs CDAI 0.33/0.26. Adjusting for confounders reduced the ΔEQ-5D values between 0 and 0.04 units.Conclusion. Patients with RA had worse EQ-5D scores than the general population, and the difference was strongly associated with disease activity. The EQ-5D score for patients in clinical remission approached that of the general population, suggesting that strict treatment goals are critical in order to achieve near-normal HRQOL in patients with RA.

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Sustained Remission Improves Physical Function in Patients with Established Rheumatoid Arthritis, and Should Be a Treatment Goal: A Prospective Observational Cohort Study from Southern Sweden

The Journal of Rheumatology ◽

10.3899/jrheum.150995 ◽

2016 ◽

Vol 43 (6) ◽

pp. 1017-1023 ◽

Cited By ~ 10

Author(s):

Jon Thorkell Einarsson ◽

Pierre Geborek ◽

Tore Saxne ◽

Lars Erik Kristensen ◽

Meliha C. Kapetanovic

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Physical Function ◽

Activity Index ◽

Health Assessment ◽

Disease Activity Index ◽

Treatment Goal ◽

Sustained Remission ◽

Das28 Remission ◽

Long Time

Objective.It has been proposed that remission should be maintained throughout the course of rheumatoid arthritis (RA); however, the evidence supporting this is limited. Physical function measured by the Health Assessment Questionnaire (HAQ) is a major outcome in RA, and HAQ is shown to be one of the strongest predictors of longterm outcomes. The purpose of this study was to investigate the physical function over a long time in patients with RA who achieved sustained remission (SR) compared with that of patients occasionally achieving remission [non-sustained remission (NSR)].Methods.Patients with RA treated with antitumor necrosis factor and included in the South Swedish Arthritis Treatment Group register were eligible for this study. We identified patients with a Disease Activity Score at 28 joints (DAS28) < 2.6 or Simplified Disease Activity Index (SDAI) ≤ 3.3 at some point and those who achieved SR, i.e., remission during consecutive visits for at least 6 months. The course of functional status was assessed using the HAQ at each visit.Results.Of the 2416 patients, 1177 (48.7%) reached DAS28 remission at some point. SR was achieved by 382 (15.8%) for the DAS28 and 186 (7.7%) for the SDAI criteria. Comparing the SR and NSR groups, HAQ improved during the first 12 months in the DAS28 remission. HAQ continued to improve relatively as long as SR was maintained. A higher proportion of patients in SR reached full physical function.Conclusion.In patients with established RA, physical function measured by the HAQ improves in patients reaching SR compared with patients who only occasionally reach remission. The improvement continues while in remission, which supports that maintaining remission should be a treatment goal.

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Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-219876 ◽

2021 ◽

pp. annrheumdis-2021-219876

Author(s):

Evgeniy Nasonov ◽

Saeed Fatenejad ◽

Eugen Feist ◽

Mariana Ivanova ◽

Elena Korneva ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index ◽

Phase Iii ◽

Double Blind Study ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Double Blind ◽

Acr20 Response

ObjectiveTo evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumatoid arthritis despite treatment with methotrexate (MTX).MethodsIn this 24-week multicentre, placebo-controlled, double-blind study, patients were randomised 1:1:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks, OKZ 64 mg once every 4 weeks, or placebo plus MTX. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. The secondary efficacy endpoints included percentage of subjects achieving Disease Activity Score 28-joint count based on C reactive protein <3.2, Health Assessment Questionnaire Disability Index at week 12, ACR50 response and Clinical Disease Activity Index ≤2.8 at week 24. Safety and immunogenicity were assessed throughout the study.ResultsA total of 428 patients were randomised. ACR20 responses were more frequent with OKZ every 2 weeks (63.6%) and OKZ every 4 weeks (70.4%) than placebo (25.9%) (p<0.0001 for both comparisons). There were significant differences in all secondary efficacy endpoints between OKZ-treated arms and placebo. Treatment-emergent serious adverse events (TESAEs) were reported by more patients in the OKZ groups compared with placebo. Infections were the most common TESAEs. No subjects developed neutralising antidrug antibodies.ConclusionsTreatment with OKZ was associated with significant improvement in signs, symptoms and physical function of rheumatoid arthritis without discernible differences between the two regimens. Safety was as expected for this class of agents. Low immunogenicity was observed.Trial registration numberNCT02760368.

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