Adam Young

Prevalence of and predictive factors for sustained disease-modifying antirheumatic drug-free remission in rheumatoid arthritis: results from two large early arthritis cohorts.

OBJECTIVE Remission has become an attainable goal of rheumatoid arthritis (RA) treatment, especially since the advent of biologic antirheumatic therapy. Because little is known about patients who achieve disease remission with conventional treatment, we used 2 large independent inception cohorts to study the prevalence of and predictive factors for disease-modifying antirheumatic drug (DMARD)-free sustained remission after treatment with conventional therapy. METHODS Remission of disease was assessed in 454 patients from the Leiden Early Arthritis Clinic (EAC) and in 895 patients from the British Early Rheumatoid Arthritis Study (ERAS) who fulfilled the American College of Rheumatology 1987 revised criteria for the classification of RA and were treated with conventional therapy. Sustained DMARD-free remission was defined as fulfilling the following criteria for at least 1 year: 1) no current DMARD use, 2) no swollen joints, and 3) classification as DMARD-free remission by the patients rheumatologist. Predictive factors were identified by Cox regression analysis. RESULTS Sustained DMARD-free remission was achieved by 68 of 454 patients (15.0%) in the Leiden EAC and by 84 of 895 patients (9.4%) in the ERAS. Six factors were associated with sustained DMARD-free remission in both cohorts: acute onset, short symptom duration before inclusion, not smoking, little radiographic damage at baseline, absence of IgM rheumatoid factor (IgM-RF), and absence of HLA shared epitope alleles. In the ERAS, low disease activity at baseline was also predictive of remission. Multivariate analyses revealed symptom duration and the absence of autoantibodies (anti-cyclic citrullinated peptide 2 and IgM-RF) as independent predictors. CONCLUSION Sustained DMARD-free remission in RA patients treated with conventional therapy is not uncommon. Symptom duration at presentation and the absence of autoantibodies are associated with sustained DMARD-free remission.

Interstitial lung disease has a poor prognosis in rheumatoid arthritis: results from an inception cohort

OBJECTIVES Pulmonary complications of RA are well described. Although some are benign, interstitial lung disease (ILD) has a poor prognosis. Few RA inception cohorts have reported the natural history of ILD related to RA (RA-ILD). We examine its incidence, outcome and prognostic indicators. METHODS Extra-articular features and comorbidity have been recorded yearly in a well-established inception cohort of RA with a 20-year follow-up. Standard clinical, laboratory and radiological measures of RA were recorded at baseline and yearly. Details of deaths were provided by a national central register. RESULTS Out of 1460 patients, 52 developed RA-ILD, half either at baseline or within 3 years of onset. The annualized incidence was 4.1/1000 (95% CI 3.0, 5.4) and the 15-year cumulative incidence 62.9/1000 (95% CI 43.0, 91.7). Incidence of RA-ILD was associated with older age, raised baseline ESR and HAQ. Evidence to implicate any drug effect (e.g. MTX) was lacking. Of these patients, 39 died, attributed to RA-ILD in 28. Median survival following diagnosis of RA-ILD was 3 years. CONCLUSIONS RA-ILD is an important and early feature of RA. It is related to disease activity and has a poor prognosis. Further studies are required to determine whether screening for pulmonary disease would identify these patients at an earlier stage.

Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics—a large multicentre UK study

OBJECTIVES The prevalence of interstitial lung disease (ILD) in RA is ∼5%. Previous work identified increasing age, active articular disease and articular damage as risk factors for RA-associated ILD (RA-ILD). The roles of high-resolution CT (HRCT) and lung function testing in defining the nature and extent of pulmonary involvement have recently been explored. This study is the first to examine predictive and prognostic factors for the development of RA-ILD and to report on the physiological and radiological characteristics of the condition from a large multicentre UK network. METHODS We collected data from centres across the UK on patients with both RA and ILD (proved on HRCT) diagnosed over a 25-year period from 1987 to 2012 using a standard pro forma. Potential predictors of RA-ILD were analysed. Baseline lung function data were recorded and related to HRCT findings. We analysed HRCT for subtype and extent of lung involved and examined the relationship between these and both all-cause and pulmonary mortality. We compared our results with case controls matched for age and gender using computer-generated selection from the RA population from one contributing centre. RESULTS A total of 230 patients were identified from across the UK with proven RA-ILD diagnosed over 25 years. Median age at diagnosis was 64 years and the male:female ratio was 1:1.09. Univariate analysis showed anti-CCP antibody titres to be the single most strongly associated predictor of RA-ILD. Male gender, age at onset, smoking and RF were all independently associated with RA-ILD on multivariate analysis. Vital capacity (VC) was preserved in limited disease but reduced in extensive disease, while gas transfer was reduced in both. Usual interstitial pneumonia (UIP) was the most common subtype on HRCT and both this and extensive disease were associated with increased all-cause mortality. CONCLUSION This is the largest study of RA-ILD in the UK. Anti-CCP antibodies were strongly associated with RA-ILD in both sexes. Smoking was strongly associated with ILD in males, which may explain the higher frequency of RA-ILD in men. The predominant HRCT pattern was UIP and most patients had limited disease at presentation. The presence of UIP and extensive disease are associated with increased mortality. Baseline gas transfer is a useful screening tool for ILD, while the preservation of VC at baseline might predict limited disease on HRCT.

Contemporary patterns of care and disease activity outcome in early rheumatoid arthritis: the ERAN cohort

OBJECTIVES To report from the Early Rheumatoid Arthritis Network (ERAN), time from symptom onset to start of therapy, treatment choices and disease outcome in early RA. METHODS Patients with newly diagnosed RA were prospectively enrolled from 19 centres in the UK and Eire. Standardized information was collected on case report forms at first presentation, 3-6 months, 1 yr and annually thereafter. The choice and intensity of drug treatment was left to the discretion of individual centres. RESULTS A total of 808 patients were recruited between 2002 and 2007, with a mean follow-up of 16 (0-60) months. Of them, 62% fulfilled four or more ACR criteria for RA at first visit. The median time from onset of symptoms to referral to secondary care was 4 months [interquartile range (IQR) 2-9, n = 655] and to start of first DMARD 8 months (IQR 4-13, n = 638). DMARDs were prescribed in 97% of the patients, initially as monotherapy in 91%, and as combination therapy in 9%. The second DMARD (n = 220) was a switch to another as monotherapy in 52% and step-up to combination therapy in 48%. The proportions with a 28-joint disease activity score >5.1 at baseline and 3 yrs were 46 and 19%, >3.2 were 84 and 54% and <2.6 were 6 and 33%, respectively. CONCLUSIONS Patients presenting with RA in ERAN do not receive DMARDs promptly, largely due to delays in referral to secondary care. Contemporary treatment practice is to start with DMARD monotherapy, and to use combination DMARDs as second-line therapy in approximately half of them. Over 3 yrs the proportion of patients continuing to have active disease remains high.

Association of HLA-DRB1 Haplotypes With Rheumatoid Arthritis Severity, Mortality, and Treatment Response

IMPORTANCE Advances have been made in identifying genetic susceptibility loci for autoimmune diseases, but evidence is needed regarding their association with prognosis and treatment response. OBJECTIVE To assess whether specific HLA-DRB1 haplotypes associated with rheumatoid arthritis (RA) susceptibility are also associated with radiological severity, mortality, and response to tumor necrosis factor (TNF) inhibitor drugs. DESIGN, SETTING, AND PARTICIPANTS The Norfolk Arthritis Register (NOAR; 1691 patients and 2811 radiographs; recruitment: 1989-2008; 2008 as final follow-up) was used as a discovery cohort and the Early Rheumatoid Arthritis Study (421 patients and 3758 radiographs; recruitment: 1986-1999; 2005 as final follow-up) as an independent replication cohort for studies of radiographic outcome. Mortality studies were performed in the NOAR cohort (2432 patients; recruitment: 1990-2007; 2011 as final follow-up) and studies of treatment response in the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort (1846 patients enrolled at initiation of TNF inhibitor; recruitment: 2006-2010; 2011 as final follow-up). Longitudinal statistical modeling was performed to integrate multiple radiograph records per patient over time. All patients were from the United Kingdom and had self-reported white ancestry. EXPOSURES Sixteen HLA-DRB1 haplotypes defined by amino acids at positions 11, 71, and 74. MAIN OUTCOMES AND MEASURES Radiological outcome using the Larsen score (range: 0 [none] to 200 [severe joint damage]) and erosions of the hands and feet on radiographs, all-cause mortality, and treatment response measured by change in Disease Activity Score based on 28 joint counts and European League Against Rheumatism (EULAR) response. RESULTS Patients with RA and valine at position 11 of HLA-DRB1 had the strongest association with radiological damage (OR, 1.75 [95% CI, 1.51-2.05], P = 4.6E-13). By year 5, the percentages of patients with erosions of the hands and feet were 48% of noncarriers (150/314) of valine at position 11, 61% of heterozygote carriers (130/213), and 74% of homozygote carriers (43/58). Valine at position 11 also was associated with higher all-cause mortality in patients with inflammatory polyarthritis (hazard ratio, 1.16 [95% CI, 1.03-1.31], P = .01) (noncarriers: 319 deaths in 1398 patients over 17,196 person-years, mortality rate of 1.9% per year; carriers: 324 deaths in 1116 patients in 13,208 person-years, mortality rate of 2.5% per year) and with better EULAR response to TNF inhibitor therapy (OR, 1.14 [95% CI, 1.01-1.30], P = .04) (noncarriers: 78% [439/561 patients] with moderate or good EULAR response; heterozygote carriers: 81% [698/866]; and homozygote carriers: 86% [277/322]). The risk hierarchy defined by HLA-DRB1 haplotypes was correlated between disease susceptibility, severity, and mortality, but inversely correlated with TNF inhibitor treatment response. CONCLUSIONS AND RELEVANCE Among patients with RA, the HLA-DRB1 locus, which is associated with disease susceptibility, was also associated with radiological severity, mortality, and treatment response. Replication of these findings in other cohorts is needed as a next step in evaluating the role of HLA-DRB1 haplotype analysis for management of RA.

2 Can we predict aggressive disease

This chapter will describe the reasons why prognostic factors that predict aggressive disease are helpful and what the problems are in interpreting studies in this field. A summary of cohort studies on prognosis of patients with early rheumatoid arthritis are presented. This is done separately for studies predicting radiographic damage, functional outcome and mortality. The overall conclusions of these studies and the value they have for the clinician are demonstrated.

Hand and foot surgery rates in rheumatoid arthritis have declined from 1986 to 2011, but large-joint replacement rates remain unchanged: results from two UK inception cohorts.

To assess whether there have been any secular changes in orthopedic interventions in patients with rheumatoid arthritis (RA) since 1986, as examined in 2 early rheumatoid arthritis (RA) inception cohorts with up to 25 years of followup.

Predictors of change in bodily pain in early rheumatoid arthritis: An inception cohort study

To investigate possible predictors for lack of pain improvement after 1 year of treatment for early rheumatoid arthritis (RA).

Outcome in rheumatoid arthritis patients with continued conventional therapy for moderate disease activity—the early RA network (ERAN)

OBJECTIVE To report from early RA network (ERAN) on Years 2 and 3 28-joint DAS (DAS-28) and HAQ outcomes in newly diagnosed RA patients treated with DMARD therapies stratified to DAS-28 status after 1 year. METHODS ERAN is a prospective observational cohort of newly diagnosed RA patients, monitored and treated according to local practice. Standardized case report forms are completed at first presentation, 3-6 months, 1 year and annually thereafter. RESULTS A total of 418 newly diagnosed RA patients with 2 years and 302 with 3 years follow-up were identified in 22 ERAN centres from 2002 to 2008. Within their first year from registration, 67% of patients received monotherapy DMARDs, and 26% combination DMARDs including 2% were on anti-TNF therapies. Between Years 1 and 3, 60% received DMARD monotherapy, 34% combination DMARD therapy including 8% on anti-TNF therapies. Seventy-four per cent of patients with Year 1 DAS-28 < 3.2 and 27% with DAS-28 3.2-5.1 achieved a DAS-28 < 3.2 outcome at Year 2 [odds ratio (OR) 7.64; 95% CI 4.6, 12.6], and 71 and 35%, respectively, at Year 3 (OR 4.49; 95% CI 2.5, 7.9). Seventy-nine per cent of patients with a Year 1 DAS-28 < 3.2 and 52% with DAS-28 3.2-5.1 achieved an HAQ < 1.25 at Year 2 (OR 3.47; 95% CI 2.1, 5.6), and 81 and 47%, respectively, at Year 3 (OR 4.92; 95% CI 2.6, 9.0). CONCLUSIONS In RA patients with a DAS-28 3.2-5.1 at 1 year, the likelihood of achieving a target low DAS-28 < 3.2, or a low HAQ, at Years 2 or 3 is poor in a routine care setting using conventional DMARDs according to current practice.

Not 2 old 2 TXT: There is potential to use email and SMS text message healthcare reminders for rheumatology patients up to 65 years old

Short message service (SMS) and email reminders have the potential to improve adherence to appointments and medication taking. Within the UK, information and communication technology (ICT) is widely used with a very high proportion of people having access to the internet and mobile phones. Little is known about ICT use by older adults and those with chronic illness. A feasibility survey was carried out with 112 rheumatology patients in Hertfordshire, UK to determine their current use of the internet, email and SMS and their willingness to receive electronic reminders in the future. A high proportion of patients up to age 65 are successfully using ICT despite older age or functional disability caused by rheumatic disease. Forty-four percent would be willing to receive an electronic appointment reminder and 25% a medication reminder. The results suggest that reminders would be welcomed by some patients and extensive patient training would not be needed before implementation.