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THU0070 RANKL, OPG and OSCAR but Not Dkk-1 Predict Radiographic Progression in An Inception Cohort of Seropositive Rheumatoid Arthritis (RA) Treated-To-Target with Combination Conventional DMARD Therapy
  1. M.D. Wechalekar1,2,
  2. S. Lester3,
  3. S. Nagpal4,
  4. S. Cole4,
  5. A. Das4,
  6. P. Hissaria5,
  7. T. Crotti6,
  8. L. Spargo5,
  9. J.G. Walker1,2,
  10. M.D. Smith2,
  11. S.M. Proudman5,6
  1. 1Repatriation General Hospital
  2. 2Flinders University
  3. 3The Queen Elizabeth Hospital, Adelaide, Australia
  4. 4Janssen Research, Spring House, United States
  5. 5Royal Adelaide Hospital
  6. 6University of Adelaide, Adelaide, Australia

Abstract

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

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