Background Traditional markers associated with erosive disease in RA do not reliably predict radiographic progression. There are limited data regarding the role of bone biomarkers in erosive disease in early RA treated with conventional DMARDs and no longitudinal data on osteoclast-associated receptor (OSCAR) with therapy. Objectives To determine whether bone biomarkers associated with osteoclast activation (RANKL, OSCAR and Dkk-1) or inhibition (OPG) are associated with erosion progression over 3 years, independent of disease activity in an inception cohort of RA receiving treat-to-target combination DMARD therapy without oral corticosteroids. Methods Dual RF and anti-CCP positive patients with early RA (<1 year; fulfilling ACR 1987 and/or 2010 classification criteria; n=50) received triple therapy (methotrexate, sulfasalazine and hydroxychloroquine) escalated to achieve DAS28 remission. RANKL, OPG and Dkk-1 were analysed by Luminex kits, OSCAR by ELISA at baseline, 6 and 12 months. For radiographic outcomes annual hand and feet radiographs were scored by the van der Heijde modified Sharp (SvH) method. Changes in bone biomarkers and associations with predictor variables were assessed using a linear multi-response random effects model. Relationships between bone biomarkers in the first year and DAS28 remission and radiographic erosion score outcomes over 3 years were analysed using logistic and negative binomial mixed regression respectively. Results Mean (SD) baseline DAS28ESR was 5.55 (1.14), 76% were females, 70% were current/past smokers and mean duration of symptoms prior to diagnosis was 18 (12) weeks. Median (IQR) total SvH score was 2 (7); 24% had erosive disease. With treatment, there was a reduction in DAS28 at 1 year to 3.14 (1.31), significant reduction in RANKL, slight increase in OPG and no significant change in Dkk-1 and OSCAR. DAS28 remission, assessed over 3 years, was less likely to occur both in the presence of detectable RANKL (p=0.01) and/or in the presence of higher average Dkk-1 levels (p=0.007). Baseline erosion scores were higher in the presence of RANKL (p=0.046) and lower OSCAR (p=0.021). There was a trend towards higher erosion scores in the presence of lower OPG levels (p=0.16). Unexpectedly, those with higher mean OPG over the first 12 months had a higher annual increase in erosion scores over 3 years (p=0.018), which may reflect the dynamic processes of bone inflammation. Conclusions Conventional DMARD treatment results in reduction of RANKL, but not OPG, OSCAR or Dkk-1 levels. Higher RANKL levels, lower OSCAR levels and higher mean OPG were associated with erosions. Failure of bone biomarkers to respond to treatment may warrant escalation of therapy to prevent erosion progression. Bone biomarkers may also provide an explanation for the apparent dissociation between disease activity and bone damage in RA. Disclosure of Interest M. D. Wechalekar: None declared, S. Lester: None declared, S. Nagpal Employee of: Johnson & Johnson, S. Cole Employee of: Johnson & Johnson, A. Das Employee of: Johnson & Johnson, P. Hissaria: None declared, T. Crotti: None declared, L. Spargo: None declared, J. Walker: None declared, M. Smith: None declared, S. Proudman: None declared

AIM:While the introduction of the treat-to-target (T2T) strategy has been an important advance in the management of rheumatoid arthritis (RA), the potential for increased toxicity due to use of concurrent drugs could adversely affect patient reported outcomes (PROs). The objective was to determine whether the cessation of therapy due to toxicity affects long-term improvement in PROs in patients treated according to T2T strategy.METHODS:A total of 149 patients from an inception cohort of early RA were included. The occurrence and severity of toxicity were monitored at each visit over 3 years. PROs studied were function (measured using health assessment questionnaire); pain, fatigue and patient global assessment (PtGA) all assessed using a 100 mm visual analogue scale; helplessness and health-related quality of life (HRQoL). For each PRO, effect of drug withdrawal was measured by comparing mean change in PROs among patients with no/temporary vs. permanent withdrawal. In addition, effects of frequency of drug withdrawals, weeks to withdrawal and number of drugs withdrawn were analysed using linear regression.RESULT:After 3 years, 56 (37.4%) patients ceased at least one drug permanently due to toxicity. Patients with no/temporary withdrawal (n = 93) achieved significantly greater improvement in function (mean change = -0.54 vs. -0.31, p = 0.033), pain (mean change = -39.82 vs. -5.02, p = 0.018), fatigue (mean change = -29.14 vs. -14.76, p = 0.015) and PtGA (mean change = -29.64 vs. -17.00, p = 0.018) compared with their counterparts. Higher frequency of withdrawals was associated with lesser improvements in function, pain, fatigue and PtGA, while the number of drugs withdrawn and the weeks to withdrawal had lesser effects. However, the cessation of the drugs due to their toxicity did not have a significant association with HRQoL and helplessness.CONCLUSION:Improvements in function, pain, fatigue and PtGA at 3 years were diminished for patients who ceased drugs due to toxicity while broader measures of HRQoL were not affected.

ObjectiveDespite better disease suppression with combination disease‐modifying antirheumatic drugs (DMARDs), some patients with rheumatoid arthritis (RA) have progressive erosive disease. The objective of this study was to determine whether hand bone mineral density (BMD) loss in the first 6 months of treatment indicates increased risk of erosions at 12 months.MethodsPatients with DMARD‐naive early RA receiving treat‐to‐target therapy were studied (n = 106). Hand BMD was measured at baseline and 6 months by dual x‐ray absorptiometry. Hand and feet radiographs were performed at baseline and 12 months and scored using the van der Heijde modification of the Sharp method. A K‐means clustering algorithm was used to divide patients into 2 groups: the BMD loss group or the no loss group, according to their absolute change in BMD from baseline to 6 months. Multiple regression analysis (hurdle model) was performed to determine the risk factors for both erosive disease and erosion scores.ResultsHand BMD loss at 6 months was associated with erosion scores at 12 months (P = 0.021). In a multiple regression analysis, hand BMD loss (P = 0.046) and older age at onset (≥50 years; P = 0.014) were associated with erosive disease, whereas baseline erosion scores (P = 0.001) and anti–cyclic citrullinated peptide (P = 0.024) were correlated with erosion severity/progression.ConclusionIn RA patients receiving treat‐to‐target therapy, early hand BMD loss could identify patients who are at risk of developing erosive disease at 12 months, potentially allowing intensification of treatment to prevent erosive damage.