Publications by authors named "Ricardo J O Ferreira"

34 Publications

Suitability for e-health of non-pharmacological interventions in connective tissue diseases: scoping review with a descriptive analysis.

RMD Open 2021 Jul;7(2)

Section for Outcomes Research, Medical University of Vienna, Vienna, Austria

Objective: Non-pharmacological interventions support patients with connective tissue diseases to better cope with and self-manage their diseases. This study aimed to map existing evidence on non-pharmacological interventions in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and mixed connective tissue diseases regarding content, feasibility and potential suitability in an e-health setting.

Methods: A literature search was performed in eight different databases in July 2020. The intervention's content was extracted using the 'Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide'. A Sankey diagram and descriptive statistics were used to analyse the data and illustrate the relationships between the interventions.

Results: Of 8198 identified records, 119 papers were eligible. One hundred and four of them (87.4%) were conducted between 2000 and 2020, mainly in the USA (SLE n=24 (21.2%), SSc n=16 (14.2%)), Brazil (SLE n=8 (7.1%), SSc n=5 (4.4%)) and Italy (SLE n=0 (0%), SSc n=12 (10.6%)). Fifty-two studies (SLE n=24 (21.2%), SSc n=28 (24.8%)) used multicomponent interventions. The single interventions were physical exercises (SLE n=16 (14.2%), SSc n=17 (15.0%)), coaching/counselling (SLE n=11 (18.0%), SSc n=0 (0%)) and education (SLE n=2 (1.8%), SSc n=3 (2.7%)). Primary outcomes focused on physical function (SLE n=1 (0.9%), SSc n=15 (13.3%)), mouth opening in SSc (n=4 (5.9%)) and physical capacity (SLE n=2 (1.8%), SSc n=1 (0.9%)). No interventions for mixed connective tissue disease were found.

Conclusion: There was a great variety in the intervention's content due to differences in body structure, activity limitations and participation restrictions in SLE and SSc. These results highlight the need for personalised, multicomponent, non-pharmacological interventions, which could be delivered as e-health interventions.
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http://dx.doi.org/10.1136/rmdopen-2021-001710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323400PMC
July 2021

Health Care Workers not in the frontline are more frequently carriers of Coronavirus Disease 2019: The Experience of a Tertiary Portuguese Hospital.

Infect Prev Pract 2020 Dec 1;2(4):100099. Epub 2020 Nov 1.

Nursing Research Centre, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

Background: Health care workers (HCWs) have a high risk of infection with coronavirus disease 2019 (COVID-19), especially those treating patients with confirmed or suspected diagnosis (front-line).

Aim: To evaluate the incidence and prevalence of the COVID-19 infection among HCWs and to analyse the risk factors and the clinical characteristics among infected ones.

Methods: Observational, retrospective, single-center study (Centro Hospitalar e Universitário de Coimbra, Portugal). Data were collected from March 1 to June 30, 2020.

Findings: Overall, 211 (2.63%) out of 8037 HCWs were diagnosed with COVID-19. Most of the infections occurred during the early stage of disease outbreak. Among the infected HCWs, only 20.9% (n=44) were from the front-line. Both front-line and non-front-line HCWs were exposed primarily to patients (48.6% in both groups), but the non-front-line were (presumably) more infected by colleagues (10.8% vs 24.8%, =0.04). Front-line HCWs performed more family isolation than non-front-line (88.9% vs 82.5%, >0.05) and presumably less family members were infected in the former group (19.4% vs 26.3%, >0.05). The proportion of HCWs with asymptomatic infection was statistically significantly lower in the front-line group (2.4% vs 19.9%, =0.05).

Conclusion: The prevention and control actions implemented were effective in mitigating the COVID-19 outbreak; HCW infections occurred mainly in the early stages. Non-front -line HCWs were at a higher risk, warranting specific attention and interventions targeting this group.
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http://dx.doi.org/10.1016/j.infpip.2020.100099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603952PMC
December 2020

Considerations and priorities for incorporating the patient perspective on remission in rheumatoid arthritis: An OMERACT 2020 special interest group report.

Semin Arthritis Rheum 2021 Jul 11. Epub 2021 Jul 11.

Department of Epidemiology & Data Science; and Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, the Netherlands.

Objective: To determine how best to incorporate the patient perspective into rheumatoid arthritis remission criteria.

Methods: At OMERACT 2020, several studies, including a longitudinal multi-centre study testing the validity of adding patient-valued domains to the ACR/EULAR criteria, were presented and discussed by the virtual Special Interest Group.

Results: Overall consensus was that there is insufficient evidence to change the remission criteria at this point. Future work should focus on measurement of the new domain of independence, clarifying the value of the patient global assessment, and optimizing the input of domains that patients value in the criteria.

Conclusion: Incorporating the patient perspective into remission criteria should be further explored.
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http://dx.doi.org/10.1016/j.semarthrit.2021.07.010DOI Listing
July 2021

High patient global assessment scores in patients with rheumatoid arthritis otherwise in remission do not reflect subclinical inflammation.

Joint Bone Spine 2021 Jun 21;88(6):105242. Epub 2021 Jun 21.

Rheumatology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (i.CIBR), University of Coimbra, Coimbra, Portugal. Electronic address:

Objectives: To assess whether high patient global assessment (PGA) scores by patients with rheumatoid arthritis (RA) otherwise in remission reflect subclinical inflammation.

Methods: Cross-sectional, single-center study, including consecutive RA patients. Remission states were defined based on the ACR/EULAR Boolean definition: 4V-remission (tender and swollen 28-joint counts (TJC28/SJC28), C-reactive protein (CRP), and PGA all≤1), PGA-near-remission (the same, except PGA>1), and non-remission (any of TJC28, SJC28, CRP>1). A blinded expert musculoskeletal ultrasonographer scanned 44 joints, 38 tendon sheaths, 4 bursae on the same day of the clinical evaluation. Each structure was assessed for the presence of Grey Scale synovial hypertrophy (GS) and Power Doppler (PD), both scored using a semi-quantitative scale (0-3 points). The Global OMERACT-EULAR Synovitis Score (GLOESS, 0-132, primary outcome), and a global tenosynovitis/bursitis score (GTBS) were compared between remission states, using non-parametric tests. Different sensitivity analyses comparing GS and PD subscores were performed.

Results: In total, 130 patients (mean age 63 years, 86% female, average disease duration 14 years) were included 40 being in 4V-remission, 40 in PGA-near-remission, 50 in non-remission. 4v-remission and PGA-near-remission presented similar median (IQR) GLOESS, [6 (5-11) and 4 (1-7), P>0.05, respectively] and GTBS [0 (0-1) and 0 (0-2), P>0.05, respectively]. The same was observed in GS, PD scores, and in global synovitis score considering only the 16 joints not included in 28-joint counts. These observations were confirmed in patients with≤5 years disease duration.

Conclusions: Subclinical inflammation is not present among persons with elevated PGA who are otherwise in remission. PGA-near-remission patients would be exposed to the risk of overtreatment if current treatment recommendations were strictly followed. This study supports the need to reconsider the role of PGA in definitions used to target immunosuppressive therapy and to provide a separate and enhanced focus to the patient's experience of the disease.
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http://dx.doi.org/10.1016/j.jbspin.2021.105242DOI Listing
June 2021

Definition of Treatment Targets in Rheumatoid Arthritis: Is It Time for Reappraisal?

J Rheumatol 2021 Jun 1. Epub 2021 Jun 1.

R.J. Ferreira, RN, PhD, Nursing Specialist in Chronic Diseases, Invited Professor, Rheumatology Department, Centro Hospitalar e Universitário de Coimbra, and Health Sciences Research Unit: Nursing (UICiSA:E), Nursing School of Coimbra (ESEnfC), Coimbra, Portugal; R.B. Landewé, MD, PhD, Rheumatologist, Full Professor of Rheumatology, Rheumatology, Zuyderland Medical Center, Heerlen, and Amsterdam Rheumatology Center, AMC, Amsterdam, the Netherlands; J.A. da Silva, MD, PhD, Rheumatologist, Full Professor of Rheumatology, Head of Department, Rheumatology Department, Centro Hospitalar e Universitário de Coimbra, and Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal. The authors have no conflicts of interest. Photo for RJF courtesy of the European Alliance of Associations for Rheumatology (EULAR). Address correspondence to Dr. R.J. Ferreira, Serviço de Reumatologia, Consulta Externa, Piso 7, Centro Hospitalar e Universitário de Coimbra, EPE. Avenida Dr. Bissaya Barreto, 3000-075 Coimbra. Portugal. Email:

In the current issue of , Kremer and colleagues compare the Clinical Disease Activity Index (CDAI) with a slightly modified Corrona Routine Assessment of Patient Index Data 3 (cRAPID3) in terms of correlation and disease activity categorization, using 2 large US registries of patients with rheumatoid arthritis (RA). Overall, a low concordance between these 2 composite indices (κ = 0.29) was found in terms of disease activity categories, despite a moderate correlation between their numerical global scores (r = 0.58 and 0.72, for the BRASS and CORRONA registries, respectively).
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http://dx.doi.org/10.3899/jrheum.210050DOI Listing
June 2021

2021 EULAR recommendations for the implementation of self-management strategies in patients with inflammatory arthritis.

Ann Rheum Dis 2021 Oct 7;80(10):1278-1285. Epub 2021 May 7.

National Rheumatoid Arthritis Society, Littlewick Green, UK.

Background: An important but often insufficient aspect of care in people with inflammatory arthritis (IA) is empowering patients to acquire a good understanding of their disease and building their ability to deal effectively with the practical, physical and psychological impacts of it. Self-management skills can be helpful in this regard.

Objectives: To develop recommendations for the implementation of self-management strategies in IA.

Methods: A multidisciplinary taskforce of 18 members from 11 European countries was convened. A systematic review and other supportive information (survey of healthcare professionals (HCPs) and patient organisations) were used to formulate the recommendations.

Results: Three overarching principles and nine recommendations were formulated. These focused on empowering patients to become active partners of the team and to take a more proactive role. The importance of patient education and key self-management interventions such as problem solving, goal setting and cognitive behavioural therapy were highlighted. Role of patient organisations and HCPs in promoting and signposting patients to available resources has been highlighted through the promotion of physical activity, lifestyle advice, support with mental health aspects and ability to remain at work. Digital healthcare is essential in supporting and optimising self-management and the HCPs need to be aware of available resources to signpost patients.

Conclusion: These recommendations support the inclusion of self-management advice and resources in the routine management of people with IA and aim to empower and support patients and encourage a more holistic, patient-centred approach to care which could result in improved patient experience of care and outcomes.
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http://dx.doi.org/10.1136/annrheumdis-2021-220249DOI Listing
October 2021

Portuguese multidisciplinary recommendations for non-pharmacological and non-surgical interventions in patients with rheumatoid arthritis.

Acta Reumatol Port 2021 Jan-Mar;46(1):40-54

Background: Patients with rheumatoid arthritis (RA) report significant levels of disease impact, which are improved, but not fully abrogated by immunosuppressive therapy, even when remission is achieved. This imposes the need for adjuvant interventions targeting the uncontrolled domains of disease impact. Non-pharmacological interventions are widely used for this purpose, but they have not been the object of professional recommendations or guidelines.

Objective: To propose multidisciplinary recommendations to inform clinical care providers regarding the employment of non-pharmacological and non-surgical interventions in the management of patients with RA.

Methods: The EULAR standardized operating procedures for the development of recommendations were followed. First, a systematic literature review was performed. Then, a multidisciplinary Technical Expert Panel (TEP) met to develop and discuss the recommendations and research agenda. For each developed recommendation i) the level of evidence and grade of recommendation were determined, and ii) the level of agreement among TEP members was set. A recommendation was adopted if approved by ≥75% of the TEP members, and the level of agreement was considered high when ≥8. All relevant national societies were included in this construction process to attain their endorsement.

Results: Based on evidence and expert opinion, the TEP developed and agreed on five overarching principles and 12 recommendations for non-pharmacological and non-surgical interventions in patients with RA. The mean level of agreement between the TEP members ranged between 8.5 and 9.9. The recommendations include a broad spectrum of intervention areas, such as exercise, hydrokinesiotherapy, psychological interventions, orthoses, education, general management of comorbidities, among others; and they set the requirements for their application.

Conclusions: These recommendations are based on the consensus judgment of clinical experts from a wide range of disciplines and patients' representatives from Portugal. Given the evidence for effectiveness, feasibility and safety, non-pharmacological and non-surgical interventions should be an integral part of standard care for people with RA. It is hoped that these recommendations should be widely implemented in clinical practice. The target audience for these recommendations includes all health professionals involved in the care of patients with RA. The target patient population includes adult Portuguese people with RA.
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April 2021

The methodological quality is insufficient in clinical practice guidelines in the context of COVID-19: systematic review.

J Clin Epidemiol 2021 07 7;135:125-135. Epub 2021 Mar 7.

Cochrane Austria, Department for Evidence-based Medicine and Evaluation, Danube University Krems, Krems an der Donau, Austria; RTI International, Research Triangle Park, NC, USA.

Objectives: The number of published clinical practice guidelines related to COVID-19 has rapidly increased. This study explored if basic methodological standards of guideline development have been met in the published clinical practice guidelines related to COVID-19.

Study Design And Setting: Rapid systematic review from February 1 until April 27, 2020 using MEDLINE [PubMed], CINAHL [Ebsco], Trip and manual search, including all types of healthcare workers providing any kind of healthcare to any patient population in any setting.

Results: There were 1342 titles screened and 188 guidelines included. The highest average AGREE II domain score was 89% for scope and purpose, the lowest for rigor of development (25%). Only eight guidelines (4%) were based on a systematic literature search and a structured consensus process by representative experts (classified as the highest methodological quality). The majority (156; 83%) was solely built on an informal expert consensus. A process for regular updates was described in 27 guidelines (14%). Patients were included in the development of only one guideline.

Conclusion: Despite clear scope, most publications fell short of basic methodological standards of guideline development. Clinicians should use guidelines that include up-to-date information, were informed by stakeholder involvement, and employed rigorous methodologies.
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http://dx.doi.org/10.1016/j.jclinepi.2021.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937325PMC
July 2021

Validity and reliability of the EULAR instrument RAID.7 as a tool to assess individual domains of impact of disease in rheumatoid arthritis: a cross-sectional study of 671 patients.

RMD Open 2021 02;7(1)

INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, Sorbonne Université, Paris, France.

Objective: The rheumatoid arthritis impact of disease (RAID) questionnaire comprises seven patient-important domains of disease impact (pain, function, fatigue, sleep disturbance, emotional well-being, physical well-being, coping). RAID was validated as a pooled-weighted score. Its seven individual items separately could provide a valuable tool in clinical practice to guide interventions targeting the patient's experience of the disease. The aim was to separately assess the psychometric properties of each of the seven numeric rating scale (NRS) of the RAID (RAID.7).

Material And Methods: Post hoc analyses of data from the cross-sectional RAID study and from the Rainbow study, an open-label 12-week trial of etanercept in patients with RA. Construct validity of each NRS was assessed cross-sectionally in the RAID data set by Spearman's correlation with the respective external instrument of reference. Using the rainbow data set, we assessed reliability through intraclass correlation coefficient between the screening and the baseline visits and responsiveness (sensitivity to change) by standardised response mean between baseline and 12 weeks.

Results: A total of 671 patients with RA with features of established disease were analysed, 563 and 108 from RAID and Rainbow, respectively. The NRS correlated moderately to strongly with the respective external instrument of reference (r=0.62-0.81). Reliability ranged from 0.64 (0.51-0.74) (pain) to 0.83 (0.76-0.88) (sleep disturbance) and responsiveness from 0.93 (0.73-1.13) (sleep disturbance) to 1.34 (1.01-1.64) (pain).

Conclusion: The separate use of the individual NRS of RAID (RAID.7) is valid, feasible, reliable and sensitive to change, representing an opportunity to improve the assessment and treatment of disease impact with minimal questionnaire burden.

Trial Registration Number: NCT00768053.
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http://dx.doi.org/10.1136/rmdopen-2020-001539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871340PMC
February 2021

EULAR recommendations for the reporting of ultrasound studies in rheumatic and musculoskeletal diseases (RMDs).

Ann Rheum Dis 2021 07 22;80(7):840-847. Epub 2021 Jan 22.

UVSQ, Inserm U1173, Infection et inflammation, Laboratory of Excellence INFLAMEX, Université Paris-Saclay, Montigny-le-Bretonneux, France

Objective: To produce European League Against Rheumatism (EULAR) recommendations for the reporting of ultrasound studies in rheumatic and musculoskeletal diseases (RMDs).

Methods: Based on the literature reviews and expert opinion (through Delphi surveys), a taskforce of 23 members (12 experts in ultrasound in RMDs, 9 in methodology and biostatistics together with a patient research partner and a health professional in rheumatology) developed a checklist of items to be reported in every RMD study using ultrasound. This checklist was further refined by involving a panel of 79 external experts (musculoskeletal imaging experts, methodologists, journal editors), who evaluated its comprehensibility, feasibility and comprehensiveness. Agreement on each proposed item was assessed with an 11-point Likert scale, grading from 0 (total disagreement) to 10 (full agreement).

Results: Two face-to-face meetings, as well as two Delphi rounds of voting, resulted in a final checklist of 23 items, including a glossary of terminology. Twenty-one of these were considered 'mandatory' items to be reported in every study (such as blinding, development of scoring systems, definition of target pathologies) and 2 'optional' to be reported only if applicable, such as possible confounding factors (ie, ambient conditions) or experience of the sonographers.

Conclusion: An EULAR taskforce developed a checklist to ensure transparent and comprehensive reporting of aspects concerning research and procedures that need to be presented in studies using ultrasound in RMDs. This checklist, if widely adopted by authors and editors, will greatly improve the interpretability of study development and results, including the assessment of validity, generalisability and applicability.
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http://dx.doi.org/10.1136/annrheumdis-2020-219816DOI Listing
July 2021

Evolving the comprehensive management of rheumatoid arthritis: identification of unmet needs and development of practical and educational tools.

Clin Exp Rheumatol 2020 Nov-Dec;38(6):1056-1067. Epub 2020 Nov 17.

University of Twente, Faculty of Behavioural, Management and Social Sciences, Enschede, The Netherlands.

Objectives: Despite availability of efficacious treatments, unmet needs still exist, preventing optimal and comprehensive management of rheumatoid arthritis (RA). Evolving the management of RA (eRA) is a European-wide educational initiative aiming to support improved patient care through practical and educational tools addressing specific unmet needs.

Methods: A multidisciplinary Steering Committee (17 members, 12 countries) identified unmet needs within the management of RA and prioritised those with the greatest impact on patient outcomes. Practical educational tools addressing priority needs were then developed for dissemination and implementation by the rheumatology community across Europe.

Results: Five areas of priority need were identified: increasing early recognition of RA and treatment initiation; treating RA to target; optimal, holistic approach to selection of treatment strategy, including shared decision-making; improving identification and management of comorbidities; and non-pharmacological patient management. A suite of 14 eRA tools included educational slides, best-practice guidance, self‑assessment questionnaires, clinical checklists, a multidisciplinary team training exercise, an interactive patient infographic, and case scenarios. By April 2020, rheumatology professionals in 17 countries had been actively engaged in the eRA programme; in 11 countries, eRA tools were selected by national leaders in rheumatology and translated for local dissemination. A web platform, with country-specific pages, was developed to support access to the translated tools (https://www.evolvingthemanagementofra.com/).

Conclusions: The eRA programme supports comprehensive management of RA across Europe through development and dissemination of practical educational tools. The eRA tools address priority needs and are available free of charge to the rheumatology community.
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December 2020

Revisiting the use of remission criteria for rheumatoid arthritis by excluding patient global assessment: an individual meta-analysis of 5792 patients.

Ann Rheum Dis 2020 Oct 6. Epub 2020 Oct 6.

Rheumatology, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal

Objectives: To determine the impact of excluding patient global assessment (PGA) from the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean remission criteria, on prediction of radiographic and functional outcome of rheumatoid arthritis (RA).

Methods: Meta-analyses using individual patient data from randomised controlled trials testing the efficacy of biological agents on radiographic and functional outcomes at ≥2 years. Remission states were defined by 4 variants of the ACR/EULAR Boolean definition: (i) tender and swollen 28-joint counts (TJC28/SJC28), C reactive protein (CRP, mg/dL) and PGA (0-10=worst) all ≤1 (4V-remission); (ii) the same, except PGA >1 (4V-near-remission); (iii) 3V-remission (i and ii combined; similar to 4V, but without PGA); (iv) non-remission (TJC28 >1 and/or SJC28 >1 and/or CRP >1). The most stringent class achieved at 6 or 12 months was considered. Good radiographic (GRO) and functional outcome (GFO) were defined as no worsening (ie, change in modified total Sharp score (ΔmTSS) ≤0.5 units and ≤0.0 Health Assessment Questionnaire-Disability Index points, respectively, during the second year). The pooled probabilities of GRO and GFO for the different definitions of remission were estimated and compared.

Results: Individual patient data (n=5792) from 11 trials were analysed. 4V-remission was achieved by 23% of patients and 4V-near-remission by 19%. The probability of GRO in the 4V-near-remission group was numerically, but non-significantly, lower than that in the 4V-remission (78 vs 81%) and significantly higher than that for non-remission (72%; difference=6%, 95% CI 2% to 10%). Applying 3V-remission could have prevented therapy escalation in 19% of all participants, at the cost of an additional 6.1%, 4.0% and 0.7% of patients having ΔmTSS >0.0, >0.5 and >5 units over 2 years, respectively. The probability of GFO (assessed in 8 trials) in 4V-near-remission (67%, 95% CI 63% to 71%) was significantly lower than in 4V-remission (78%, 74% to 81%) and similar to non-remission (69%, 66% to 72%).

Conclusion: 4V-near-remission and 3V-remission have similar validity as the original 4V-remission definition in predicting GRO, despite expected worse prediction of GFO, while potentially reducing the risk of overtreatment. This supports further exploration of 3V-remission as the target for immunosuppressive therapy complemented by patient-oriented targets.
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http://dx.doi.org/10.1136/annrheumdis-2020-217171DOI Listing
October 2020

Comment on: 'It can't be zero!' difficulties in completing patient global assessment in rheumatoid arthritis: a mixed methods study: reply.

Rheumatology (Oxford) 2021 01;60(1):e30-e31

Department of Nursing and Midwifery, University of the West of England, Bristol, UK.

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http://dx.doi.org/10.1093/rheumatology/keaa488DOI Listing
January 2021

The patient global assessment in RA precludes the majority of patients otherwise in remission to reach this status in clinical practice. Should we continue to ignore this?

Semin Arthritis Rheum 2020 08 19;50(4):583-585. Epub 2020 May 19.

Rheumatology department, Centro Hospitalar e Universitário de Coimbra EPE, Praceta Professor Mota Pinto, Coimbra, 3000-075, Portugal; Clínica Universitária de Reumatologia, Faculdade de Medicina da, Universidade de Coimbra, Coimbra, Portugal. Electronic address:

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http://dx.doi.org/10.1016/j.semarthrit.2020.03.014DOI Listing
August 2020

Patient Global Assessment of Disease Activity and Radiographic Progression in Early Arthritis: Three-Year Results From the ESPOIR Cohort.

Arthritis Care Res (Hoboken) 2021 09 26;73(9):1300-1305. Epub 2021 Jul 26.

Institut Pierre Louis d'Epidémiologie et de Santé Publique INSERM, Sorbonne Université, and AP-HP Pitié Salpêtrière Hospital, Paris, France.

Objective: To determine whether patient global assessment of disease activity (PtGA) over the first year of disease course, as part of a Boolean-based definition of remission and considered individually, had a significant relationship with structural progression over 3 years in patients with early arthritis.

Methods: We conducted a prospective, observational study using ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes) cohort data. Remission states were defined as 1) 4-variable remission, which included a tender joint count in 28 joints, a swollen joint count in 28 joints (SJC28), a C-reactive protein (CRP; mg/dl) level, and PtGA (scored 0-10, all scores of ≤1); 2) PtGA near remission, which included the same parameters as 4-variable remission with only PtGA >1 (of a maximum possible score of 10); 3) 3-variable remission (sum of the proportion of patients in 4-variable remission and the proportion of patients in PtGA near remission); or 4) nonremission. The strictest status satisfied both at 6 and 12 months was considered. Radiographic progression was determined as a change of ≥5 points in the total Sharp/van der Heijde score (ΔSHS) from baseline to 3 years. The predictive capacities for radiographic damage of different remission definitions were assessed by odds ratio (OR). The association between each individual component of remission with ΔSHS was tested through multivariate linear regression analyses.

Results: Among 520 patients, 7% achieved 4-variable remission and 12% achieved PtGA near remission. Radiographic progression was observed in 29% of patients who achieved 4-variable remission (OR versus nonremission; OR 0.32 [95% confidence interval (95% CI) 0.15, 0.68]) and in 45% of patients with PtGA near remission (OR 0.65 [95% CI 0.38, 1.11]); the comparison was not statistically different (OR 0.49 [95% CI 0.20, 1.18]). In 3-variable remission, radiographic progression was observed in 39%. Of the individual components, only the SJC28 and CRP level were associated with radiographic progression.

Conclusion: All definitions of remission led to low structural degradation in early arthritis, and 4-variable remission led to less radiographic progression than PtGA near remission, but without a statistically significant difference. Both 4-variable remission and 3-variable remission appear to be useful targets when aiming for structural nonprogression.
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http://dx.doi.org/10.1002/acr.24237DOI Listing
September 2021

'It can't be zero!' Difficulties in completing patient global assessment in rheumatoid arthritis: a mixed methods study.

Rheumatology (Oxford) 2020 05;59(5):1137-1147

Department of Nursing and Midwifery, University of the West of England, Bristol, UK.

Objectives: Patient global assessment (PGA) is purported to add the patient's perspective in the composite measures of RA. However, PGA is not standardized and it is not known whether patients' interpretation of the measure is consistent with its intended purpose. This study aimed to explore difficulties experienced by patients with RA in completing PGA, and to assess the impact of a structured explanation in improving its validity and reliability.

Methods: This was a mixed methods study, using interviews, focus groups and PGA data. During interviews, patients (convenience sample, n = 33) completed three often-used PGA formulations. Then a nurse provided structured explanation about what PGA is and why it is used. After further discussion, patients completed one PGA version again. Interviews were recorded, transcribed and analysed using inductive thematic analysis. We compared PGA scores pre- and post-explanation (Wilcoxon signed-ranks) and the proportion of patients achieving RA remission with PGA ⩽1 (McNemar's tests).

Results: Three themes emerged: understanding the meaning of PGA, the purpose of PGA and measurement difficulties. The difficulties caused systematic errors in PGA completion such as marking higher when feeling well, marking near the centre or away from zero. The structured explanation was helpful. Following the explanation, the median PGA score decreased from 3.0 to 2.1 cm, and the proportion of non-remission solely due to PGA >1 from 52% to 41%; none of these changes was statistically significant.

Conclusion: Many patients have difficulties in completing PGA. Standardization of PGA and a structured explanation may improve its clarity, validity and reliability.
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http://dx.doi.org/10.1093/rheumatology/kez467DOI Listing
May 2020

The impact of fatigue in rheumatoid arthritis and the challenges of its assessment.

Rheumatology (Oxford) 2019 11;58(Suppl 5):v3-v9

Rheumatology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra.

Fatigue is one of the most important symptoms for patients with RA, and imposes a great burden on patients' lives, being associated with significantly reduced health-related quality of life. Although being recognized by the rheumatology community as a major gap in the current management of the disease, fatigue has not been easy to measure and conceptualize. Part of the problem seems to reside in the multidimensional causality of this phenomenon, which may warrant dedicated measures and interventions. Although there are several instruments available to measure it, no consensus has yet been reached to recommend a 'gold-standard'. This review aims at synthesizing the role of fatigue in the global impact of RA; describing validated instruments and their psychometric properties as measures of fatigue among patients with RA; and finally proposing a clinically meaningful, valid and feasible process to measure fatigue in clinical practice.
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http://dx.doi.org/10.1093/rheumatology/kez351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827262PMC
November 2019

Depression, disability and sleep disturbance are the main explanatory factors of fatigue in rheumatoid arthritis: a path analysis model.

Clin Exp Rheumatol 2020 Mar-Apr;38(2):314-321. Epub 2019 Jul 19.

Rheumatology Department, Centro Hospitalar e Universitário de Coimbra EPE, and Coimbra Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal.

Objectives: Fatigue is one of the most prevalent and disabling symptoms among patients with rheumatoid arthritis (RA), however, it is frequently neglected by health professionals. This study aimed to develop a multidimensional explanatory model of fatigue in patients with RA as a basis for better understanding and intervention.

Methods: This was an ancillary analysis of an observational, cross-sectional, single centre study. Patients completed a questionnaire including demographic data and measures of pain, sleep, disability, anxiety, depression, and personality. Fatigue was assessed by the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F). Disease activity and haemoglobin levels were assessed. Path analysis was performed to test and improve a hypothesised model for fatigue.

Results: This analysis included 142 patients, with a mean (SD) age of 61.1 (11.7) years. The final path analysis model presented acceptable fit and explained 60.0% of the variance of fatigue. The predominant direct explanatory factors identified were disability (46.5%) and depression (41.2%), the latter having an additional indirect influence of 19% through disability. Age (-16.2%) and sleep disturbance (15.7%) were also directly linked to fatigue. Personality trait extroversion (-22.4%), pain (20.0%), and disease activity (14.9%) are only indirectly related to fatigue.

Conclusions: Depression, disability and sleep disturbance appear to be the main factors explaining fatigue in patients with RA. Disease activity, pain, and personality seem to play only a secondary role, extroversion being the only personality trait associated with fatigue. These findings foster a shift in the paradigm of care towards a more holistic management of fatigue, integrating adjunctive therapies beyond measures targeted solely at disease remission.
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April 2020

Educational needs in people with ankylosing spondylitis and psoriatic arthritis: a cross-sectional study.

Clin Exp Rheumatol 2020 Mar-Apr;38(2):282-288. Epub 2019 Jul 22.

Department of Nursing and Midwifery, University of the West of England, Bristol; and Academic Rheumatology Unit, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.

Objectives: To assess the educational needs of people with ankylosing spondylitis (AS) and psoriatic arthritis (PsA), test differences across patient subgroups and identify factors independently associated with their educational needs.

Methods: This was a cross-sectional analytic study. Patients with AS and PsA completed the Portuguese version of the Educational Needs Assessment Tool (PortENAT). Data were Rasch-transformed before descriptive and inferential analyses were undertaken. Univariable and multivariable analyses were used to determine differences between patient subgroups and factors independently associated with their educational needs.

Results: The study included 121 patients with AS and 132 with PsA. The level of educational needs varied by diagnostic group, but higher needs for both subgroups were reported regarding the "Disease process", "Feelings" and "Managing pain" domains. Overall, patients with AS had a higher level of educational needs than those with PsA. In both diagnostic groups, female gender was independently associated with higher educational needs. In the PsA group, a shorter disease duration was independently associated with higher educational needs in the following domains: "Managing pain", "Movement" and "Feelings".

Conclusions: Educational needs vary by diagnostic group, gender and disease duration. These differences merit consideration in the design of patient education interventions.
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April 2020

2018 update of the EULAR recommendations for the role of the nurse in the management of chronic inflammatory arthritis.

Ann Rheum Dis 2020 01 12;79(1):61-68. Epub 2019 Jul 12.

Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, The Netherlands.

To update the European League Against Rheumatism (EULAR) recommendations for the role of the nurse in the management of chronic inflammatory arthritis (CIA) using the most up to date evidence. The EULAR standardised operating procedures were followed. A task force of rheumatologists, health professionals and patients, representing 17 European countries updated the recommendations, based on a systematic literature review and expert consensus. Higher level of evidence and new insights into nursing care for patients with CIA were added to the recommendation. Level of agreement was obtained by email voting. The search identified 2609 records, of which 51 (41 papers, 10 abstracts), mostly on rheumatoid arthritis, were included. Based on consensus, the task force formulated three overarching principles and eight recommendations. One recommendation remained unchanged, six were reworded, two were merged and one was reformulated as an overarching principle. Two additional overarching principles were formulated. The overarching principles emphasise the nurse's role as part of a healthcare team, describe the importance of providing evidence-based care and endorse shared decision-making in the nursing consultation with the patient. The recommendations cover the contribution of rheumatology nursing in needs-based patient education, satisfaction with care, timely access to care, disease management, efficiency of care, psychosocial support and the promotion of self-management. The level of agreement among task force members was high (mean 9.7, range 9.6-10.0). The updated recommendations encompass three overarching principles and eight evidence-based and expert opinion-based recommendations for the role of the nurse in the management of CIA.
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http://dx.doi.org/10.1136/annrheumdis-2019-215458DOI Listing
January 2020

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

J Rheumatol 2020 01 1;47(1):20-27. Epub 2019 May 1.

From the Rheumatology Department, Centro Hospitalar Universitário do Algarve, Faro; Lisbon Academic Medical Center, Lisbon; Algarve Biomedical Center, Faro; Health Sciences Research Unit: Nursing (UICiSA:E), Escola Superior de Enfermagem de Coimbra, Coimbra; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra; Rheumatology Department, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal; Amsterdam Rheumatology Center, Amsterdam University Medical Center (UMC); Zuyderland Medical Center, Heerlen, the Netherlands; Hospital Universitario "Dr. José Eleuterio González"/Universidad Autónoma de Nuevo León, Monterrey, Mexico; University of Massachusetts Medical School, Rheumatology Center, Worcester, Massachusetts, USA; Dublin Academic Medical Centre, Dublin, Ireland; Centre for Rheumatic Diseases, Pune, India; Centre for Rheumatology Research, and Medical Research Council (MRC) Centre for Neuromuscular Diseases, University College London, London; Rheumatology Department, Northwick Park Hospital, London North West University Healthcare National Health Service (NHS) Trust, London, UK.

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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http://dx.doi.org/10.3899/jrheum.181286DOI Listing
January 2020

Impact of Patient's Global Assessment on Achieving Remission in Patients With Rheumatoid Arthritis: A Multinational Study Using the METEOR Database.

Arthritis Care Res (Hoboken) 2019 10;71(10):1317-1325

Centro Hospitalar e Universitário de Coimbra, Coimbra Institute for Clinical and Biomedical Research, and University of Coimbra, Coimbra, Portugal.

Objective: There is an ongoing debate about excluding patient's global assessment (PtGA) from composite and Boolean-based definitions of rheumatoid arthritis (RA) remission. This study aimed at determining the influence of PtGA on RA disease states, exploring differences across countries, and understanding the association between PtGA, measures of disease impact (symptoms), and markers of disease activity (inflammation).

Methods: Cross-sectional data from the Measurement of Efficacy of Treatment in the Era of Outcome in Rheumatology international database were used. We calculated the proportion of patients failing American College of Rheumatology/European League Against Rheumatism Boolean-based remission (4-variable remission) solely due to PtGA (PtGA-near-remission) in the overall sample and in the most representative countries (i.e., those with >3,000 patients in the database). Multivariable linear regression models were used to identify the main determinants of PtGA, grouped in predominantly inflammatory impact factors (28 tender joint counts, 28 swollen joint counts, and C-reactive protein level) and disease impact factors (pain and function).

Results: This study included 27,768 patients. Excluding PtGA from the Boolean-based definition (3-variable remission) increased the remission rate from 5.8% to 15.8%. The rate of PtGA-near-remission varied considerably between countries, from 1.7% in India to 17.9% in Portugal. One-third of the patients in PtGA-near-remission group scored PtGA >4 of 10. Pain and function were the main correlates of PtGA, with inflammation-related variables contributing less to the model (R = 0.57).

Conclusion: PtGA is moderately related to joint inflammation overall, but only weakly so in low levels of disease activity. A considerable proportion of patients otherwise in biologic remission still perceive high PtGA, putting them at risk of excessive immunosuppressive treatment.
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http://dx.doi.org/10.1002/acr.23866DOI Listing
October 2019

The Portuguese Rheumatoid Arthritis Impact of Disease (RAID) score and its measurement equivalence in three countries: validation study using Rasch Models.

Qual Life Res 2018 Nov 1;27(11):2909-2921. Epub 2018 Aug 1.

Department of Nursing and Midwifery, University of the West of England, Bristol, UK.

Purpose: The Rheumatoid Arthritis Impact of Disease (RAID) score assesses seven impact domains of interest for people with RA. This study aimed to test patients' understanding of the Portuguese RAID and evaluate its cross-cultural validity for use in Portugal.

Methods: This was a mixed methods study comprising two phases: (i) cognitive debriefing to determine patient's comprehension of the Portuguese RAID and (ii) cross-cultural validation using Rasch analysis. Construct validity was determined by fit to the model, invariance culture (compared with France and UK datasets) and evidence of convergent and divergent validity.

Results: Patients' input (n = 38) led to minor changes in the phrasing of two items to ensure conceptual equivalence between the Portuguese and the original RAID. In Rasch analysis (n = 288), two items 'Sleep' and 'Physical well-being' in the Portuguese dataset did not adequately fit the model specifications, suggesting multidimensionality (sleep-not necessarily associated with RA) and redundancy (physical well-being overlapping with functional disability). Despite the imperfections, the scale had high internal consistency, evidence of convergent and divergent validity and invariance to culture (compared to France n = 195 and UK n = 205 datasets). The scale was well targeted for patients with different levels of disease impact.

Conclusions: The RAID has been successfully adapted into Portuguese and it can be used with confidence in clinical practice. Further research will be required to ensure it captures the full range of sleep problems in RA. Meanwhile, data across the three countries (Portugal, France and the UK) are comparable except for the two items (sleep and physical well-being).
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http://dx.doi.org/10.1007/s11136-018-1959-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208571PMC
November 2018

Determinants of happiness and quality of life in patients with rheumatoid arthritis: a structural equation modelling approach.

Ann Rheum Dis 2018 08 6;77(8):1118-1124. Epub 2018 Apr 6.

Department of Rheumatology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

Objectives: Besides increasing longevity, the ultimate goal of medical care is to improve patients' enjoyment of life, a concept akin to happiness. This study examined the determinants of happiness and quality of life (QoL) in patients with rheumatoid arthritis (RA).

Methods: In this observational, cross-sectional study, patients were assessed on disease activity, disease impact, personality, QoL and happiness. Structural equation modelling estimation was used to analyse the associations between these dimensions, pursuing three hypotheses: H-disease activity and perceived impact of disease are negatively associated with overall QoL and happiness in patients with RA; H-'positive' personality traits are related to happiness both directly and indirectly through perceived disease impact; H-happiness has a mediating effect in the relation between impact of disease and QoL.

Results: Data from 213 patients were analysed. Results supported all driving hypotheses. Happiness was positively related to 'positive' personality and, to a lesser extent, negatively related to impact of disease. Impact of disease, in turn, was positively related to disease activity and mitigated by 'positive' personality traits. Impact of disease had a much stronger relation with QoL than with happiness. Happiness mitigated the negative effect of disease impact on QoL.

Conclusion: Optimisation of QoL and happiness of people with RA requires effective control of the disease process and also improvement of the disease impact domains. Personality seems to play a pivotal mediating role in these relations.
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http://dx.doi.org/10.1136/annrheumdis-2017-212934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059049PMC
August 2018

The impact of patient global assessment in the definition of remission as a predictor of long-term radiographic damage in patients with rheumatoid arthritis: protocol for an individual patient data meta-analysis.

Acta Reumatol Port 2018 Jan-Mar;43(1):52-60

Centro Hospitalar e Universitário de Coimbra EPE.

Background: Remission is the target for management of rheumatoid arthritis (RA) and intensification of immunosuppressive therapy is recommended for those that do not achieve this status. Patient global assessment (PGA) is the single patient reported outcome considered in the American College of Rheumatology/European League Against Rheumatism remission criteria, but its use as target has been questioned. The primary aim of this study is to assess whether excluding PGA from the definition of disease remission changes the association of disease remission with long-term radiographic damage and physical function in patients with RA.

Methods: Individual Patient Data Meta-analysis using data from randomized controlled trials of biological and targeted synthetic agents, identified through ClinicalTrials.gov and PubMed. Different remission states will be defined: (i) 4v-remission [tender (TJC28) and swollen 28-joint counts (SJC28) both≤1, C-reactive protein (CRP)≤1 (mg/dl), and PGA≤1 (0-10 scale)], (ii) 4v-near-remission (TJC28≤1, SJC28≤1, CRP≤1, and PGA>1), (iii) non-remission (TJC28>1 or SJC28>1 or CRP>1), all mutually exclusive, and (iv) 3v-remission (TJC28≤1, SJC28≤1, CRP≤1). Likelihood ratios will be used to descriptively compare whether meeting the 3v and 4v-remission criteria in a single visit (at 6 or 12 months) predicts good outcome in the second year (1-2y). Differences in the predictive value of PGA in the definition of remission will be assessed by comparing the three mutually exclusive disease states using logistic regression analysis. Good outcome is defined primarily by radiographic damage (no deterioration in radiographic scores, whatever the instrument used in each trial), and secondarily by functional disability (Health Assessment Questionnaire consistently ≤0.5 and no deterioration), and their combination ("overall good outcome"). Additional analyses will consider longer periods over which to (concurrently) define remission status and outcome (between 1-5y and 1-10y), different cut-offs to define good radiographic outcome (change ≤0.5, ≤3 and ≤5 in radiographic score), sustained remission and the influence of treatment and other clinical factors.

Discussion: If 4v-remission and 4v-near-remission are associated with a similar probability of good outcomes, particularly regarding structural damage, the 3v-remission (excluding PGA) could be adopted as the target for immunosuppressive therapy. Patients' perspectives would remain essential, but assessed separately from disease activity, using instruments adequate to guide adjunctive therapies. Systematic review registration: PROSPERO, CRD42017057099.
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January 2019

The controversy of using PGA to define remission in RA.

Nat Rev Rheumatol 2018 03;14(4):245

Rheumatology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

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http://dx.doi.org/10.1038/nrrheum.2018.35DOI Listing
March 2018

Influence of the different "patient global assessment" formulations on disease activity score by different indices in rheumatoid arthritis.

Clin Rheumatol 2018 Jul 10;37(7):1963-1969. Epub 2018 Mar 10.

Rheumatology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

Patient global assessment (PGA) is included in almost all rheumatoid arthritis (RA) composite disease activity indices and definitions of remission. However, different PGA formulations exist and are used interchangeably in research and clinical practice. We investigated how five different PGA formulations used in four disease indices affect the remission rates. This was an ancillary analysis of data from a cross-sectional study in patients with RA. The data comprised the following: 28-joint counts, C-reactive protein, and five PGA formulations. Remission rate variation was assessed using five PGA formulations in each index (ACR/EULAR Boolean, CDAI, SDAI, and DAS28-CRP). PGA agreement was assessed by the following: Pearson's correlation; Bland-Altman plots; paired samples t test; and establishing the proportion of patients who scored (i) all formulations within an interval of 20 mm and (ii) each formulation ≤ 10 mm. This analysis included 191 patients. PGA formulations presented good correlations (≥ 0.65), but Bland-Altman plots showed clinically significant differences, which were statistically confirmed by comparison of means. Just over a half (51.8%) of patients scored all PGA formulations within a 20-mm interval. The proportion of those scoring ≤ 10 mm varied from 11.5 to 16.2%. When different formulations of PGA were used in each index, remission differences of up to 4.7, 4.7, 6.3, and 5.2% were observed. When formulations were used in their respective indices, as validated, the remission rates were similar (13.1, 13.6, 14.1, and 18.3%). Using PGA formulations interchangeably may have implications in the assessment of disease activity and in the attainment of remission, and this can impact upon management decisions.
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http://dx.doi.org/10.1007/s10067-018-4063-9DOI Listing
July 2018

Drivers of patient global assessment in patients with rheumatoid arthritis who are close to remission: an analysis of 1588 patients.

Rheumatology (Oxford) 2017 09;56(9):1573-1578

Faculty of Medicine, UPMC University Paris 06, GRC-UPMC 08 (EEMOIS).

Objectives: ACR/EULAR Boolean remission in RA is frequently not obtained solely due to a patient global assessment (PGA) >1/10 (a condition often designated as near-remission). This study aimed to assess which domains of impact could explain an elevated PGA in near-remission patients.

Methods: We performed an ancillary analysis of data from three cross-sectional studies in patients with established RA. Three disease activity states were defined: remission (tender and swollen joint counts, CRP and PGA all ⩽1), near-remission (tender and swollen joint counts, and CRP are all ≤1 but PGA >1) and non-remission. Physical and psychological domains were assessed using the RA Impact of Disease 0-10 (numeric rating scale) as explanatory factors of PGA. Univariable and multivariable linear regression analyses were performed to explain PGA.

Results: A total of 1588 patients (79.1% females) were analysed. The mean disease duration was 13.0 years (s.d. 9.8) and the 28-joint DAS with four variables was 3.2 (s.d. 1.4). Near-remission [mean PGA 3.6 (s.d. 1.9)] was more frequent (19.1%) than remission (12.3%). Scores of RA Impact of Disease domains were similar in near-remission and non-remission patients. In near-remission, PGA was explained (R2adjusted = 0.55) by pain (β = 0.29), function (β = 0.23), physical well-being (β = 0.19) and fatigue (β = 0.15).

Conclusion: Near-remission was more frequent than remission. These patients, despite having no signs of significant inflammation, report an impact of disease similar to the non-remission patients. PGA in near-remission seems to be driven by physical rather than psychological domains. Selecting the best therapy for these patients requires a better understanding of the meaning of PGA, both globally and in individual patients.
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http://dx.doi.org/10.1093/rheumatology/kex211DOI Listing
September 2017
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