Radiographic progression in clinical trials in rheumatoid arthritis: a systemic literature review of trials performed by industry.

OBJECTIVES: To summarise radiographic data in randomised controlled trials (RCTs) as part of the radiographic inhibition claim of disease-modifying antirheumatic drugs (DMARDs) approved for patients with rheumatoid arthritis (RA). METHODS: A systemic literature review was performed using the Medline database from 1994 to February 2020. The results were grouped based on the scoring methods (Sharp, Genant modification, van der Heijde modification) and RA patient populations. RESULTS: One hundred sixty-eight publications were selected. After detailed assessment, 52 RCTs (7 methotrexate (MTX)-naive, 23 MTX inadequate response (IR), 9 DMARDs IR and 3 tumour necrosis factor-alpha inhibitors (TNFi) IR studies) were finally included. Information on patient population, scoring method used, reader reliability, statistical analyses and detailed radiographic data on baseline and change scores over multiple follow-up periods are presented. CONCLUSION: The data gathered in this review serve as a repository for the design of future trials with radiographic damage as an outcome.

Vasodilators and low-dose acetylsalicylic acid are associated with a lower incidence of distinct primary myocardial disease manifestations in systemic sclerosis: results of the DeSScipher inception cohort study.

OBJECTIVES: To investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) <55%, and/or congestive heart failure and sudden cardiac death) in systemic sclerosis (SSc). METHODS: 601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5-4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed. RESULTS: During 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF <55% and/or CHF and cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.05). CONCLUSIONS: The present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.

Association of the different types of radiographic damage with physical function in patients with rheumatoid arthritis: analysis of the RAPID trials.

OBJECTIVES: To evaluate the separate effects of erosions (E) (bone damage), joint space narrowing (JSN) (cartilage loss) and (sub)luxation (SLUX) (soft tissue damage) in four different joint groups on physical disability in rheumatoid arthritis (RA). METHODS: 3-year follow-up data from the Rheumatoid Arthritis PreventIon of structural Damage (RAPID) 1 and 2 trials were used. These randomised controlled trials compared certolizumab plus methotrexate (MTX) versus MTX in patients with RA. Physical function was measured by Health Assessment Questionnaire (HAQ). Radiographic damage was measured by the van der Heijde-modified Sharp score; separate scores for E, JSN and SLUX were available. Generalised estimating equations were performed to assess the relationship between HAQ and E, JSN and SLUX scores, separately and in all joint groups. RESULTS: In separate models for each type of damage and after adjusting for age, gender, baseline disease activity and treatment group, E and JSN were more strongly associated with HAQ than with SLUX. In combined models, JSN was the only type of lesion associated with HAQ when all joints were included together. When separate joint groups were analysed, E in the wrist and JSN in the metacarpophalangeal joints (MCPs) were most strongly associated with function. CONCLUSIONS: Among RA-related joint damage, cartilage loss quantified by JSN is an important determinant of physical function. However, when analysing joint groups separately, erosive damage in the wrist and JSN in the MCPs had the most important influence on disability. These data indicate that the comprehensive assessment of joint damage is needed to reliably reflect disease-related damage.

Digital ulcers predict a worse disease course in patients with systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is a systemic autoimmune disease with high morbidity and significant mortality. There is a great need of predictors that would allow risk stratification of patients with SSc and ultimately initiation of treatment early enough to ensure optimal clinical results. In this study, we evaluated whether a history of digital ulcers (HDU) at presentation may be a predictor of vascular outcomes and of overall clinical worsening and death in patients with SSc. METHODS: Patients from the EULAR Scleroderma Trials and Research (EUSTAR) database, satisfying at inclusion the 1980 American College of Rheumatology classification criteria for SSc, who had a follow-up of at least 3 years since baseline or who have died, were included in the analysis. HDU at presentation as a predictor of disease worsening or death was evaluated by Cox proportional hazards regression analysis. RESULTS: 3196 patients matched the inclusion criteria (male sex 13.2%, 33.4% diffuse subset). At presentation, 1092/3196 patients had an HDU (34.1%). In multivariable analysis adjusting for age, gender and all parameters considered potentially significant, HDU was predictive for the presence of active digital ulcers (DUs) at prospective visits (HR (95% CI)): 2.41 (1.91 to 3.03), p<0.001, for an elevated systolic pulmonary arterial pressure on heart ultrasound (US-PAPs):1.36 (1.03 to 1.80), p=0.032, for any cardiovascular event (new DUs, elevated US-PAPs or LV failure): 3.56 (2.26 to 5.62), p<0.001, and for death (1.53 (1.16 to 2.02), p=0.003). CONCLUSIONS: In patients with SSc, HDU at presentation predicts the occurrence of DUs at follow-up and is associated with cardiovascular worsening and decreased survival.

Cardiovascular and selected comorbidities in early arthritis and early spondyloarthritis, a comparative study: results from the ESPOIR and DESIR cohorts.

OBJECTIVES: To investigate the prevalence of comorbidities in early rheumatoid arthritis (ERA) and early axial spondyloarthritis (ESpA) versus the general population. METHODS: Baseline data of 689 patients with ERA from the Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort (age 48.2±12.1 years, symptoms duration 14.2±14.5 weeks) and 645 patients with ESpA from Devenir des Spondylarthropathies Indifférenciées Récentes (DESIR; age 32.8±8.4 years, axial symptoms duration 79.0±45.7 weeks) were analysed. Metabolic and cardiovascular diseases (CVD), infections and neoplasia were determined in each cohort. The prevalence (95% CI) of several comorbidities was compared with that in the French general population. For patients without CVD, the 10-year risk of developing CVD was calculated using the Framingham and SCORE equations. The heart age was calculated using the 2008 Framingham points system. RESULTS: 42% of patients with ERA and 20.3% of patients with ESpA had at least 1 comorbidity; the most common were arterial hypertension (AHT) and dyslipidaemia. AHT prevalence (95% CI) in ERA (18.2% (15.5% to 21.3%)), but not in ESpA (5.08% (3.57% to 7.14%)), was significantly increased (p<0.05) compared with the general population (7.58%). Prevalence of tuberculosis history was higher in ERA (4.7% (3.3% to 6.6%)), and ESpA (0.99% (0.4% to 2.3%)) than in the general population (0.02%; both p<0.05). No differences were observed in malignancies, coronary heart disease or diabetes. In ERA, among patients without a history of CVD, an intermediate to high CVD risk was found. The heart age exceeded the real age by 4.1±9.6 years in ERA and by 2.1±7.0 years in ESpA (p<0.001). CONCLUSIONS: We found an increased prevalence of AHT and tuberculosis history in ERA and ESpA, and an increased CVD risk. These results should prompt rheumatologists to check these comorbidities early in the disease.

A Romanian version of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument.

OBJECTIVES: UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) Instrument is a comprehensive, self-administered survey for the assessment of gastrointestinal involvement in scleroderma patients, developed and validated in English. Our objective was to translate and validate a Romanian version of UCLA SCTC GIT 2.0. METHODS: Translation from English into Romanian has been made using the forward-backward method. Sixty-four patients, attending a referral centre as part of an extensively studied cohort, were approached in a consecutive manner over a period of two years for administration of the questionnaire. We evaluated the reproducibility, internal consistency, construct validity and discriminative capacity of the translation (Romanian GIT). RESULTS: Fifty-four patients returned completed questionnaires. Internal consistency was demonstrated by Cronbach's alpha coefficient (0.931). Construct validity is supported by moderate, but significant correlations of Romanian GIT total score with the Mental Component Summary (MCS) of SF-36 (r=0.541, Spearman correlation) and among subscales, by significant correlations with SHAQ total score (r=0.559, Spearman correlation) and by strong correlations with gastrointestinal subscale of SHAQ (SHAQ GI) (r=0.726, Spearman correlation). Reproducibility was good as well. Divergent validity was supported by significant differences between patients with or without a clinical diagnosis of gastrointestinal disease. Other differences in the Romanian GIT total score were tested among subgroups of patients. CONCLUSIONS: The Romanian GIT has acceptable reliability and validity. This questionnaire can be used for the assessment of gastrointestinal involvement in scleroderma patients.

Relationship between disease activity indices and their individual components and radiographic progression in RA: a systematic literature review.

OBJECTIVE: The aim of this study was to investigate the relationship between different disease activity indices (DAIs) and their individual components and radiographic progression in patients with RA. METHODS: A systematic literature review until July 2013 was performed by two independent reviewers using the Medline and Embase databases. Longitudinal studies assessing the relationship between DAIs and single instruments and radiographic progression were included. The results were grouped based on the means of measurement (baseline vs time integrated) and analysis (univariable or multivariable). RESULTS: Fifty-seven studies from 1232 hits were included. All published studies that assessed the relationship between any time-integrated DAI including joint count and radiographic progression reached a statistically significant association. Among the single instruments, only swollen joint count and ESR were associated with radiographic progression, while no significant association was found for tender joint count. Data with respect to CRP are conflicting. Data on patient's global health, pain assessment and evaluator's global assessment are limited and do not support a positive association with progression of joint damage. CONCLUSION: Published data indicate that all DAIs that include swollen joints are related to radiographic progression while, of the individual components, only swollen joints and acute phase reactants are associated. Therefore composite DAIs are the optimal tool to monitor disease activity in patients with RA.

Concepts of functioning and health important to people with systemic sclerosis: a qualitative study in four European countries.

OBJECTIVE: To describe the experiences of people with systemic sclerosis (SSc) in different European countries of functioning and health and to link these experiences to the WHO International Classification of Functioning, Disability and Health (ICF) to develop a common understanding from a bio-psycho-social perspective. METHOD: A qualitative multicentre study with focus-group interviews was performed in four European countries: Austria, Romania, Sweden and Switzerland. The qualitative data analysis followed a modified form of 'meaning condensation' and the concepts that emerged in the analysis were linked to the ICF. RESULTS: 63 people with SSc participated in 13 focus groups. In total, 86 concepts were identified. 32 (37%) of these were linked to the ICF component body functions and structures, 21 (24%) to activities and participation, 26 (30%) to environmental factors, 6 (7%) to personal factors and 1 (1%) to the health condition itself. 19 concepts (22%) were identified in all four countries and included impaired hand function, household activities, paid work, drugs, climate and coldness, support from others and experiences with healthcare institutions, non-pharmacological treatment, social security and benefits. CONCLUSION: Concepts identified in all four countries could be used for guiding clinical assessment, as well as interdisciplinary team care and rheumatological rehabilitation for patients with SSc. For a full understanding of the aspects of the disease that were most relevant to people with SSc, people with SSc from multiple countries needed to be involved.