Patient Perspective on Remission in Rheumatoid Arthritis

Absence of disease activity, or remission, is the most important treatment goal for patients with rheumatoid arthritis (RA). Since a new preliminary definition of remission in RA for clinical trials has been proposed, we investigated what determinants of disease activity patients associate with a state of remission and whether dimensions of impact of disease on daily life are involved. Our report summarizes progress of a workshop at OMERACT 10 on the patient perspective on remission in RA, including the results of a short pre-conference survey among patients, the discussions among the participants and a research agenda resulting from these discussions. This initial OMERACT workshop on remission from the patient perspective showed that there is a great interest among patients, physicians, and researchers to study the concept of remission, taking into account measures that patients indicate as important, but that there is a lack of data on appropriate measures, resulting in a considerable research agenda.

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AB0140 A HIGH-CONFIDENCE DEFINITION OF THERAPEUTIC RESPONSE IN RHEUMATOID ARTHRITIS USING A MONTE CARLO SIMULATION APPROACH

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3341 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1097.2-1098

Author(s):

V. Strand ◽

S. Cohen ◽

L. Zhang ◽

T. Mellors ◽

A. Jones ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Monte Carlo ◽

Disease Activity ◽

Health Assessment Questionnaire ◽

Health Assessment ◽

High Confidence ◽

Response Status ◽

Definition Of ◽

Fidelity Score ◽

Assessment Questionnaire

Background:Therapy choice and therapy change depend on the ability to accurately assess patients’ disease activity. The clinical assessments used to evaluate treatment response in rheumatoid arthritis have inherent variability, normally considered as measurement error, intra-observer variability or within subject variability. Each contribute to variability in deriving response status as defined by composite measures such as the ACR or EULAR criteria, particularly when a one-time observed measurement lies near the boundary defining response or non-response. To select an optimal therapeutic strategy in the burgeoning age of precision medicine in rheumatology, achieve the lowest disease activity and maximize long-term health outcomes for each patient, improved treatment response definitions are needed.Objectives:Develop a high-confidence definition of treatment response and non-response in rheumatoid arthritis that exceeds the expected variability of subcomponents in the composite response criteria.Methods:A Monte Carlo simulation approach was used to assess ACR50 and EULAR response outcomes in 100 rheumatoid arthritis patients who had been treated for 6 months with a TNF inhibitor therapy. Monte Carlo simulations were run with 2000 iterations implemented with measurement variability derived for each clinical assessment: tender joint count, swollen joint count, Health Assessment Questionnaire disability index (HAQ-DI), patient pain assessment, patient global assessment, physician global assessment, serum C-reactive protein level (CRP) and disease activity score 28-joint count with CRP.1-3 Each iteration of the Monte Carlo simulation generated one outcome with a value of 0 or 1 indicating non-responder or responder, respectively.Results:A fidelity score, calculated separately for ACR50 and EULAR response, was defined as an aggregated score from 2000 iterations reported as a fraction that ranges from 0 to 1. The fidelity score depicted a spectrum of response covering strong non-responders, inconclusive statuses and strong responders. A fidelity score around 0.5 typified a response status with extreme variability and inconclusive clinical response to treatment. High-fidelity scores were defined as >0.7 or <0.3 for responders and non-responders, respectively, meaning that the simulated clinical response status label among all simulations agreed at least 70% of the time. High-confidence true responders were considered as those patients with high-fidelity outcomes in both ACR50 and EULAR outcomes.Conclusion:A definition of response to treatment should exceed the expected variability of the clinical assessments used in the composite measure of therapeutic response. By defining high-confidence responders and non-responders, the true impact of therapeutic efficacy can be determined, thus forging a path to development of better treatment options and advanced precision medicine tools in rheumatoid arthritis.References:[1]Cheung, P. P., Gossec, L., Mak, A. & March, L. Reliability of joint count assessment in rheumatoid arthritis: a systematic literature review. Semin Arthritis Rheum43, 721-729, doi:10.1016/j.semarthrit.2013.11.003 (2014).[2]Uhlig, T., Kvien, T. K. & Pincus, T. Test-retest reliability of disease activity core set measures and indices in rheumatoid arthritis. Ann Rheum Dis68, 972-975, doi:10.1136/ard.2008.097345 (2009).[3]Maska, L., Anderson, J. & Michaud, K. Measures of functional status and quality of life in rheumatoid arthritis: Health Assessment Questionnaire Disability Index (HAQ), Modified Health Assessment Questionnaire (MHAQ), Multidimensional Health Assessment Questionnaire (MDHAQ), Health Assessment Questionnaire II (HAQ-II), Improved Health Assessment Questionnaire (Improved HAQ), and Rheumatoid Arthritis Quality of Life (RAQoL). Arthritis Care Res (Hoboken) 63 Suppl 11, S4-13, doi:10.1002/acr.20620 (2011).Disclosure of Interests:Vibeke Strand Consultant of: Abbvie, Amgen, Arena, BMS, Boehringer Ingelheim, Celltrion, Galapagos, Genentech/Roche, Gilead, GSK, Ichnos, Inmedix, Janssen, Kiniksa, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Setpoint, UCB, Stanley Cohen: None declared, Lixia Zhang Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Ted Mellors Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Alex Jones Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Johanna Withers Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Viatcheslav Akmaev Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation

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Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 Enhances the Ability of SLE Responder Index to Identify Responders in Clinical Trials

The Journal of Rheumatology ◽

10.3899/jrheum.110550 ◽

2011 ◽

Vol 38 (11) ◽

pp. 2395-2399 ◽

Cited By ~ 31

Author(s):

ZAHI TOUMA ◽

DAFNA D. GLADMAN ◽

DOMINIQUE IBAÑEZ ◽

SHAHRZAD TAGHAVI-ZADEH ◽

MURRAY B. UROWITZ

Keyword(s):

Systemic Lupus Erythematosus ◽

Clinical Trials ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Systemic Lupus ◽

Original Definition ◽

Definition Of

Objective.To evaluate the performance of the Systemic Lupus Erythematosus (SLE) Responder Index (SRI) when the SLE Disease Activity Index 2000 (SLEDAI-2K) is substituted with SLEDAI-2K Responder Index-50 (SRI-50), a valid and reliable index of disease activity improvement. Also, to determine whether the SRI-50 will enhance the ability of SRI in detecting responders.Methods.Our study was conducted on patients who attended the Lupus Clinic from September 2009 to September 2010. SLEDAI-2K, SRI-50, the British Isles Lupus Assessment Group measure, and the Physician’s Global Assessment were determined initially and at followup. SRI was determined at the followup visit according to its original definition using the SLEDAI-2K score and by substituting SLEDAI-2K with SRI-50.Results.A total of 117 patients with SLEDAI-2K ≥ 4 at baseline were studied. Patients had 1 followup visit over a 3-month period. Twenty-nine percent of patients met the original definition of SRI and 35% of patients met the definition of SRI when SLEDAI-2K was substituted with SRI-50. The use of SRI-50 allowed determination of significant improvement in 7 additional patients. This improvement could not be discerned with the use of SLEDAI-2K as a component of SRI. At followup visits that showed improvement, SRI-50 scores decreased to a greater extent than SLEDAI-2K scores (p < 0.0001).Conclusion.SRI-50 enhances the ability of SRI to identify patients with clinically important improvement in disease activity. SRI-50 was superior to SLEDAI-2K in detecting partial clinical improvement, ≥ 50%, between visits. These properties of the SRI-50 enable it to be used as an independent outcome measure of improvement or as a component of SRI in clinical trials.

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Canadian Recommendations for Clinical Trials of Pharmacologic Interventions in Rheumatoid Arthritis: Inclusion Criteria and Study Design: Table 1.

The Journal of Rheumatology ◽

10.3899/jrheum.110188 ◽

2011 ◽

Vol 38 (10) ◽

pp. 2095-2104 ◽

Cited By ~ 8

Author(s):

JACOB KARSH ◽

EDWARD C. KEYSTONE ◽

BOULOS HARAOUI ◽

J. CARTER THORNE ◽

JANET E. POPE ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Trial ◽

Clinical Trials ◽

Disease Activity ◽

Study Design ◽

New Drugs ◽

Nominal Group ◽

Consensus Method ◽

Inclusion Criteria ◽

Design Features

Objective.Current clinical trial designs for pharmacologic interventions in rheumatoid arthritis (RA) do not reflect the innovations in RA diagnosis, treatment, and care in countries where new drugs are most often used. The objective of this project was to recommend revised entry criteria and other study design features for RA clinical trials.Methods.Recommendations were developed using a modified nominal group consensus method. Canadian Rheumatology Research Consortium (CRRC) members were polled to rank the greatest challenges to clinical trial recruitment in their practices. Initial recommendations were developed by an expert panel of rheumatology trialists and other experts. A scoping study methodology was then used to examine the evidence available to support or refute each initial recommendation. The potential influence of CRRC recommendations on primary outcomes in future trials was examined. Recommendations were finalized using a consensus process.Results.Recommendations for clinical trial inclusion criteria addressed measures of disease activity [Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) > 3.2 PLUS ≥ 3 tender joints using 28-joint count (TJC28) PLUS ≥ 3 swollen joint (SJC28) OR C-reactive protein (CRP) or ESR > upper limit of normal PLUS ≥ 3 TJC28 PLUS ≥ 3 SJC28], functional classification, disease classification and duration, and concomitant RA treatments. Additional recommendations regarding study design addressed rescue strategies and longterm extension.Conclusion.There is an urgent need to modify clinical trial inclusion criteria and other study design features to better reflect the current characteristics of people living with RA in the countries where the new drugs will be used.

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Reasons for discordances between ultrasonography and magnetic resonance imaging in the evaluation of the ankle, hindfoot and heel of the patients with rheumatoid arthritis

Medical Ultrasonography ◽

10.11152/mu-2304 ◽

2019 ◽

Vol 21 (4) ◽

pp. 405 ◽

Cited By ~ 2

Author(s):

Oana Șerban ◽

Daniela Fodor ◽

Iulia Papp ◽

Mihaela Cosmina Micu ◽

Dan Gabriel Duma ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Disease Activity ◽

Activity Index ◽

Imaging Techniques ◽

Disease Activity Index ◽

Resonance Imaging ◽

Magnetic Resonance Imaging Mri ◽

Definition Of

Aim: To compare the ultrasonography (US) performance with magnetic resonance imaging (MRI) in identifying pathology in ankles, hindfeet and heels of rheumatoid arthritis (RA) patients and to evaluate the reasons for discordances between the two imaging methods.Material and methods: RA patients were enrolled and evaluated using the Clinical Disease Activity Index (CDAI) and the Disease Activity Score 28 with C-reactive Protein (DAS28-CRP). The ankle (tibiotalar joint, tendons), hindfoot (talonavicular, subtalar joints) and heel of the most symptomatic or dominant foot (for the asymptomatic patient)were evaluated by two pairs of examiners using US and contrast-enhanced MRI.Results: Totally, 105 joints, 245 tendons and 35 heels in 35 patients [mean age 59.2±11.25 years old, median disease duration 36 (16.5-114), mean CDAI 19.87±12.7] were evaluated. The interobserver agreements between the two sonographers, and the two radiologists were good and very good (k=0.624-0.940). The overall agreement between US and MRI was very good for subcalcaneal panniculitis (k=0.928, p<0.001), moderate for synovitis (k=0.463, p<0.001) and tenosynovitis (k=0.514, p<0.001), fair for osteophytes (k=0.260, p=0.004), and poor for erosions (k=0.063, p=0.308) and heel’s structures. MRI found more erosions, synovitis, osteophytes,tenosynovitis and retrocalcaneal bursitis, but US found more enthesophytes and plantar fasciitis. Many of the discordancesbetween the two imaging techniques have explanations related to the technique itself or definition of the pathologic findings.Conclusions: US is comparable to MRI for the evaluation of ankle, hindfoot and heel in RA patients and discordances in theinterpretation of the pathological findings/normal structures must be carefully analyzed.

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Fatigue

Oxford Textbook of Rheumatoid Arthritis ◽

10.1093/med/9780198831433.003.0021 ◽

2020 ◽

pp. 251-258

Author(s):

Emma Dures ◽

Neil Basu

Keyword(s):

Rheumatoid Arthritis ◽

Health Beliefs ◽

Societal Perspective ◽

Work Disability ◽

Research Agenda ◽

Healthcare Costs ◽

Patient Perspective ◽

Pain Disability ◽

Societal Burden

Fatigue in rheumatoid arthritis (RA) is associated with inflammation, pain, disability, sleep, depression, and health beliefs, implying complex, multicausal pathways comprising differing combinations of variables. From a patient perspective, it is a common, overwhelming, and distressing symptom. From a societal perspective, fatigue is a significant predictor of high healthcare costs and the main reason for work disability and loss. This chapter will highlight the role of patients in establishing the importance of the symptom, including the proposal that it should be measured in studies of RA whenever possible. Acknowledgement of fatigue as a patient priority is a relatively recent development, and highlights the value of collaborating with patients in shaping the research agenda. There will be discussion of the scale of fatigue in RA, including data on prevalence and descriptions of its nature and impact. Research has established the unpredictable and unearned nature of RA-related fatigue with its physical, cognitive, and emotional components, and identified the associated individual and societal burden. This will be followed by conceptual models informing our understanding of the biology of rheumatoid arthritis-related fatigue, the role of bioinformatics, and the challenges of unravelling the mechanisms of this multidimensional symptom. Finally, the evidence for interventions and treatments to alleviate fatigue will be presented, with a focus on non-pharmacological approaches to support fatigue self-management.

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Remission in Rheumatoid Arthritis: Working Toward Incorporation of the Patient Perspective at OMERACT 12

The Journal of Rheumatology ◽

10.3899/jrheum.141113 ◽

2015 ◽

Vol 43 (1) ◽

pp. 203-207 ◽

Cited By ~ 11

Author(s):

Lilian H. van Tuyl ◽

Martina Sadlonova ◽

Bev Davis ◽

Caroline Flurey ◽

Niti Goel ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Qualitative Research ◽

Health Professionals ◽

Working Group ◽

Research Agenda ◽

Patient Perspective ◽

Disease Flare ◽

Methodological Challenges ◽

Disease Questionnaire ◽

Selection Of

Objective.The treatment of rheumatoid arthritis (RA) should target patient-relevant outcomes, making patient perspective on remission essential. In 2010, patients, physicians, health professionals, and researchers at the Outcome Measures in Rheumatology (OMERACT) conference developed an ambitious research agenda to study the concept of remission. Qualitative research has since helped us understand the concept of remission from the patient perspective.Methods.During OMERACT 12, the OMERACT working group on patient perspective on remission in RA elaborated on data generated to date and discussed the methodological challenges ahead. Challenges included (1) selection of domains, (2) choice of a patient remission definition or a single domain to add to the current remission definition, and (3) the importance of pain in defining remission from a patient perspective.Results.Focus in the coming years will be on increasing our understanding by identifying the most important domains from the patient perspective regarding remission and investigating how these domains can be measured. Investigation into the Rheumatoid Arthritis Impact of Disease questionnaire, disease flare, as well as the concordance of domains from our ongoing remission survey is appropriate. More data and further discussions are needed to decide on the next steps.Conclusion.Progress summarized over 4 years highlights the main methodological challenges discussed within the working group on patient perspective on remission in RA during OMERACT 12.

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The Influence of the Definition of Patient Global Assessment in Assessment of Disease Activity According to the Disease Activity Score (DAS28) in Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.110487 ◽

2011 ◽

Vol 38 (11) ◽

pp. 2326-2328 ◽

Cited By ~ 12

Author(s):

MAXIME DOUGADOS ◽

MAHAUT RIPERT ◽

PASCAL HILLIQUIN ◽

PATRICE FARDELLONE ◽

OLIVIER BROCQ ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Global Assessment ◽

Disease Activity Score ◽

Patient Global Assessment ◽

Activity Score ◽

Before And After ◽

Definition Of ◽

Very High ◽

Assessment Of Disease Activity

Objective.Patient global assessment (PGA) is one of the 4 items included in the Disease Activity Score (DAS28) for evaluation of activity of rheumatoid arthritis (RA). We studied the influence of the use of 3 different techniques of PGA on the assessment of disease activity.Methods.We evaluated 3 different DAS28 according to the technique of PGA in 108 patients with active RA before and after 12 weeks of etanercept therapy.Results.The reliability (intraclass coefficient of correlation) between screening and baseline was very high and similar for the 3 DAS28. The percentage of patients in the different states of disease (from remission to higher disease activity) and the sensitivity to change across the 3 DAS28 scales were very similar.Conclusion.The different techniques of collection of PGA to be included in the DAS calculation yield similar results. However, an accepted, unequivocal technique should be encouraged in order to reduce heterogeneity in scoring DAS among patients with RA.

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