Determinants of health-related quality of life across the spectrum of connective tissue diseases using latent profile analysis: results from the LEAP cohort.

OBJECTIVES: Poor health-related quality of life (HRQoL) is well recognized in patients with CTD. We hypothesized that subgroups of patients across the spectrum of CTD experience different HRQoL patterns and aimed to determine patient-level characteristics associated with these different subgroups. METHODS: Using the eight continuous domains of the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire we performed data-driven clustering to derive latent profiles (LPs) of patients with distinct HRQoL patterns. Multivariable ordinal logistic regression was used to determine patient-level characteristics associated with each HRQoL subgroup identified. RESULTS: A total of 309 CTD patients completed the SF-36 questionnaire. The most impaired SF-36 domains in each disease group were vitality, general health and bodily pain. The physical component of the SF-36 was consistently more impaired compared with the mental component, with similar scores across disease groups. Three LPs were identified with poor [n = 89 (29%)], average [n = 190 (61.4%)] and excellent [n = 30 (9.7%)] HRQoL. LPs were not associated with diagnostic grouping or autoantibody profiles. Black background [odds ratio (OR) 0.22 (95% CI 0.08, 0.63)], Indo-Asian background [OR 0.39 (95% CI 0.19, 0.78)], concomitant fibromyalgia [OR 0.40 (95% CI 0.20, 0.78)], sicca symptoms [OR 0.56 (95% CI 0.32, 0.98)] and multimorbidity [Charlson Comorbidity Index; OR 0.81 (95% CI 0.67, 0.97)] were associated with the 'poor' HRQoL LP. CONCLUSION: Distinct HRQoL subgroups exist that are not primarily driven by a specific diagnosis or autoantibody profiles. We identified a number of key demographic and clinical factors associated with poor HRQoL. These factors need to be addressed across the whole CTD spectrum as part of a holistic management approach aimed at improving overall patient outcomes.

Treatment of Rheumatoid Arthritis with Certolizumab Pegol: Results from PROACTIVE, a Non-Interventional Study in the UK and Ireland.

INTRODUCTION: The objective of this non-interventional study was to investigate the long-term safety and effectiveness of certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) in the UK and Ireland. METHODS: Patients were prescribed CZP at their physicians' discretion and followed during routine clinical practice for up to 88 weeks. DAS28(ESR) response (defined as at least a 1.2-point reduction from baseline) was measured in the full analysis set (FAS) at week 12, and patients were categorized by week 12 responder status in all subsequent analyses. The primary outcome was DAS28(ESR) response at week 78. Secondary outcomes included change from baseline in DAS28(ESR), HAQ-DI, and RADAI scores at week 78, and EULAR response at week 78. Adverse drug reactions (ADRs) were recorded for all patients who received at least one dose of CZP. RESULTS: A total of 149 patients were enrolled, of whom 111 (74.5%) formed the FAS. At week 12, 80 patients (72.1%) were DAS28(ESR) responders and 31 (27.9%) non-responders. Compared to non-responders, a greater proportion of week 12 responders had a DAS28(ESR) response at week 78 (43.8% versus 22.6%). Improvements in DAS28(ESR), HAQ-DI, and RADAI scores were also greater on average among week 12 responders, as was the proportion of patients meeting EULAR criteria. Overall, 9 patients (6.1%) experienced 13 ADRs during the study. CONCLUSION: These data demonstrate the safety and effectiveness of CZP in adult patients with RA treated during routine clinical practice in the UK and Ireland. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01288287. FUNDING: UCB Pharma.

Mortality in established rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with reduced life expectancy. Whether the development of RA initiates this process of premature ageing or is part of it is not clear. The excess mortality is apparent within the first few years of disease and increases with RA disease duration. Most of the excess deaths are attributable to infection, cardiovascular disease (in particular coronary heart disease) and respiratory disease. Deaths due to lung cancer and non-Hodgkin's lymphoma, but not other cancers, are also increased. There is some evidence that effective disease-modifying therapy can improve survival but, overall, survival in RA patients has not improved to the same degree as in the general population over recent decades.

Risk factors for clinical coronary heart disease in systemic lupus erythematosus: the lupus and atherosclerosis evaluation of risk (LASER) study.

OBJECTIVE: Accelerated atherosclerosis and premature coronary heart disease (CHD) are recognized complications of systemic lupus erythematosus (SLE), but the exact etiology remains unclear and is likely to be multifactorial. We hypothesized that SLE patients with CHD have increased exposure to traditional risk factors as well as differing disease phenotype and therapy-related factors compared to SLE patients free of CHD. Our aim was to examine risk factors for development of clinical CHD in SLE in the clinical setting. METHODS: In a UK-wide multicenter retrospective case-control study we recruited 53 SLE patients with verified clinical CHD (myocardial infarction or angina pectoris) and 96 SLE patients without clinical CHD. Controls were recruited from the same center as the case and matched by disease duration. Charts were reviewed up to time of event for cases, or the same "dummy-date" in controls. RESULTS: SLE patients with clinical CHD were older at the time of event [mean (SD) 53 (10) vs 42 (10) yrs; p < 0.001], more likely to be male [11 (20%) vs 3 (7%); p < 0.001], and had more exposure to all classic CHD risk factors compared to SLE patients without clinical CHD. They were also more likely to have been treated with corticosteroids (OR 2.46; 95% CI 1.03, 5.88) and azathioprine (OR 2.33; 95% CI 1.16, 4.67) and to have evidence of damage on the pre-event SLICC damage index (SDI) (OR 2.20; 95% CI 1.09, 4.44). There was no difference between groups with regard to clinical organ involvement or autoantibody profile. CONCLUSION: Our study highlights the need for clinical vigilance to identify modifiable risk factors in the clinical setting and in particular with male patients. The pattern of organ involvement did not differ in SLE patients with CHD events. However, the higher pre-event SDI, azathioprine exposure, and pattern of damage items (disease-related rather than therapy-related) in cases suggests that a persistent active lupus phenotype contributes to CHD risk. In this regard, corticosteroids and azathioprine may not control disease well enough to prevent CHD. Clinical trials are needed to determine whether classic risk factor modification will have a role in primary prevention of CHD in SLE patients and whether new therapies that control disease activity can better reduce CHD risk.

The influence of age at symptom onset and length of followup on mortality in patients with recent-onset inflammatory polyarthritis.

OBJECTIVE: To investigate the influence of age at symptom onset and length of followup on mortality in patients with recent-onset inflammatory polyarthritis (IP), and to examine predictors of mortality in relation to disease duration. METHODS: From 1990 to 1994, patients with recent-onset IP were registered with the Norfolk Arthritis Register (NOAR) and followed up prospectively. Standardized mortality ratios (SMRs) were calculated for all-cause and cardiovascular disease (CVD) mortality and for those who were younger than age 55 years at disease onset and for the first 5 and 10 years of followup. Cox proportional hazards models were developed to assess predictors of early and later mortality. RESULTS: Of 1,098 patients, 224 (20%) had died by the end of 2004. All-cause and CVD mortality were increased in rheumatoid factor (RF)-positive patients and in this subgroup, CVD mortality was increased at both early and later followup (SMR 5-year followup 1.93 [95% confidence interval 1.08-3.19]; SMR 10-year followup 2.00 [95% confidence interval 1.37-2.80]). CVD mortality was highest in seropositive patients<55 years of age at disease onset (SMR 5.58 [95% confidence interval 2.24-11.50]). In multivariate models, age at onset, male sex, RF positivity, Health Assessment Questionnaire score>or=1.5, and nodules were predictors of early and later mortality. CONCLUSION: Patients with IP had higher rates of CVD mortality throughout the followup period studied, and this was highest in seropositive patients who were <55 years of age at symptom onset. This subgroup deserves particular attention in terms of disease and risk factor modification. Nodules were independent predictors of CVD mortality, suggesting that extraarticular/vascular inflammation identifies patients at particularly high CVD risk.