Extended report To minimise the effect of increasing disease duration and determine whether clinical variables influence MTX response it is necessary to study patients early in their disease course. The Norfolk Arthritis Register (NOAR) provides an ideal population for further study as patients are recruited at the time of diagnosis, when data are recorded on disease activity and severity and patients are followed annually. The aim of this analysis was to examine whether clinical factors could be used to predict outcome of treatment with MTX used as the first DMARD in patients with early inflammatory polyarthritis (IP). PATIENTS AND METHODS Subjects Subjects were recruited from NOAR, which is a primary care based inception cohort of patients with early IP. Details of the register have been published elsewhere.10 Briefly, NOAR aims to recruit all new cases of IP from a large defined geographical area of approximately 400 000 adults (age >16 years). Any indivi- dual presenting to their primary care physician with swelling of two or more joints lasting at least 4 weeks should be notified to NOAR. A parallel notification system operates from hospitals within the catchment area. All patients who are referred to secondary care are treated by one of four rheumatologists according to their routine clinical practices. For the purposes of this analysis all patients recruited to NOAR between 1 January 1995 and 31 December 2003 who were commenced on MTX as their first DMARD within 3 months of their baseline visit were eligible for inclusion. Clinical guidelines exist for the manage- ment of patients on MTX, patients are started on a standard dose MTX (7.5–10 mg/week) and monitored in accordance with UK national guidelines, with dose escalation (up to 25 mg/ week) at the discretion of the treating rheumatologist. The study was approved by the local research ethics committee and all patients provided written consent. Patients were included in this analysis if they were treated with MTX as their first DMARD within 3 months of their baseline assessment and had 2 years of follow-up data. Baseline assessment One of a team of trained research nurses performed a structured interview and clinical examination at the baseline and follow-up assessments. Clinical and demographic data recorded included age at symptom onset, gender, symptom duration, tender joint count (TJC, 53 joints) and swollen joint count (SJC, 51 joints). All patients also completed a Health Assessment Questionnaire (HAQ), modified for use in British patients.11 At baseline, blood samples were taken for rheumatoid factor (RF) and C-reactive protein (CRP) measurement and DNA was extracted for SE status. RF was measured using a latex agglutination technique and a titre of >1:40 was considered positive. SE status was examined using the Dynal RELI SSO HLA-DRB1 Typing kit (Dynal, Bromborough, UK). The disease activity score (using 28 joint counts) (DAS28) was calculated for each patient using the 28 SJC, 28 TJC and CRP using the formula (DAS28 = (0.566SQRT(TJC28)+0.286SQRT(SJC28)+0.366ln(- CRP+1))61.10+1.15) (from Flendrie and Fransen http://www. umcn.nl/userfiles/other/dasculators.xls/ accessed 23 September 2008). Follow-up Patients were then followed up annually using a nurse- administered questionnaire and HAQ. This records medication details, including start and stop date of DMARDs and reason for 58 stopping treatment. For this study the patient reported reason for stopping treatment was validated by medical record and laboratory data review. Outcome on MTX was then classified as either: (1) stopped for an adverse event; (2) stopped for inefficacy (physician statement) or had second DMARD added; (3) stopped for other reasons; or (4) remained on treatment. Statistical analysis The baseline characteristics were compared between those who stopped MTX treatment at 1 and at 2 years with those who continued treatment at each time-point. Comparison of continuous data was carried out using the Mann–Whitney U test. For categorical data the x2 test was employed. Logistic regression models were used to assess the relationship between predictor variables and the event of interest (either inefficacy or adverse event) compared with remaining on MTX monotherapy (which was taken as the referent category). An analysis that examined predicting MTX failure (for either inefficacy or adverse events) compared with remaining on MTX monother- apy was also performed. The areas under the resulting Receiver Operating Characteristic curve (AUC ROC, were used to determine how accurate the models were at predicting outcome. All analyses were performed using STATA 8.0 (STATA Corporation, College Station, Texas, USA, 1993). RESULTS There were 309 patients who were eligible to be included in this analysis. During the period of recruitment, 1707 patients were ascertained by NOAR and the derivation of the 309 patients included in this analysis is shown in fig 1. These were a typical population with IP in that 66% were female, and median age at symptom onset was 59.3 (interquartile range 48.3–69 years). As expected there was a range of disease activity at baseline, median DAS28 3.9 (interquartile range 3.0–4.8). At baseline 51% of the cohort fulfilled American Rheumatism Association criteria for RA,12 which increased to 70% at 1 year. Figure 2 shows the outcome of MTX monotherapy at 1 and 2 years, illustrating that treatment survival was good with 75% and 61% of patients remaining on monotherapy at 1 and 2 years respectively. Perhaps not surprisingly, more patients stopped monotherapy because of adverse events in the first year and because of inefficacy in the second. There was a small group of patients who stopped for other reasons (including planning pregnancy and patient choice). This latter group was excluded from further analyses. Predicting inefficacy Cumulatively, 25 patients stopped MTX monotherapy for inefficacy in the first year, and 49 patients had stopped monotherapy at 2 years. Of these 49 patients, 35 had a second DMARD added. Baseline clinical and demographic variables of those stopping MTX monotherapy for inefficacy were similar to those remaining on treatment (table 1). By contrast, possession of the SE was associated with MTX inefficacy at both 1 year (unadjusted OR 5.83 95% CI 1.33 to 25.6, p = 0.02) and 2 years (unadjusted OR 3.04 95% CI 1.27 to 7.27, p = 0.01). Adjusting for age, gender, symptom duration and steroid use did not attenuate this association (table 2). However, using the ROC curve, SE positivity was only moderate in predicting MTX inefficacy at 12 months, AUC ROC 0.64 (95% CI 0.48 to 0.75). By including all other variables that showed some evidence of possible association (table 2) as well as age, gender, symptom duration and steroid use did not Ann Rheum Dis 2009;68:57–62. doi:10.1136/ard.2008.088237