ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1899

Osteopontin and Leptin Are Associated with Erosive Disease in an Inception Cohort of Rheumatoid Arthritis Treated-to-Target with Combination Conventional DMARD Therapy

Mihir D. Wechalekar1,2,3, Susan Lester4, Sunil Nagpal5, Suzanne Cole6, Jessica Peters7, Anuk Das8, Pravin Hissaria9, Tania Crotti10, Catherine Hill1,11,12, Sudha Raghunath13, Llew Spargo14, Jennifer G Walker13,14,15, Malcolm D. Smith2 and Susanna Proudman1,10, 1Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia, 2Flinders University, Adelaide, Australia, 3Rheumatology Unit, Repatriation General Hospital, Adelaide, Australia, 4Queen Elizabeth Hospital, Adelaide, Australia, 5Immunology, Janssen Research & Development, Spring House, PA, 6Immunology, Janssen Research and Development, Spring House, PA, 7Janssen Research & Development, Spring House, PA, 8Janssen R&D, Berwyn, PA, 9Immunology, SA Pathology, Adelaide, Australia, 10University of Adelaide, Adelaide, Australia, 11Medicine, The University of Adelaide, Adelaide, Australia, 12The Queen Elizabeth Hospital, Adelaide, Australia, 13Repatriation General Hospital, Adelaide, Australia, 14Rheumatology Unit, Royal Adelaide Hospital, South Australia, Adelaide, Australia, 15Flinders University of South Australia, Adelaide, Australia

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ,

Session Information

Date: Monday, November 6, 2017

Title: Rheumatoid Arthritis – Clinical Aspects III: Obesity and Other Comorbidities

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: We sought to identify biomarkers associated with erosive disease and bone loss in an inception rheumatoid arthritis (RA) cohort receiving treat-to-target combination DMARD therapy without oral corticosteroids. Markers of osteoclast activation (RANKL) and inhibition [osteoprotegerin (OPG)], osteoblast inhibition [Dickkopf-1 (Dkk-1), sclerostin (SOST), osteopontin (OPN)], were serially tested. The degree of inflammation (TNFa, IL6, IL1b, ACTH); adipose tissue activity (leptin, insulin) and markers of bone turnover/damage [osteocalcin (OC), parathyroid hormone (PTH), fibroblast growth factor-23 (FGF23)], were also tested.

Methods: Patients with early RA (< 1 year; fulfilling ACR 1987 and/or 2010 classification criteria) received triple therapy (methotrexate, sulfasalazine, hydroxychloroquine) escalated to achieve DAS28 remission. Serum biomarkers were analysed using human bone panel Luminex kits in patients (n=112) at 0, 6, 12 months, and controls (n=33). Responses to treatment were analysed by mixed model regression. Principal component analysis (PCA) was performed on the within-individual correlations between treatment responses. Erosion and femoral neck bone density (BMD) data were available at 0, 1, 2, 3 years, and were analysed using the biomarker log(mean) as a predictor, adjusted for baseline covariates. Erosion progression was analysed using a zero inflated Poisson regression model.

Results: 53% of the cohort were anti-CCP (cyclic-citrullinated peptide) positive; mean (SD) age was 58(14) years, DAS28 5.5(1.3), 73% females, 60% current/past smokers and 20% had erosive disease. Table 1 summarises results. Nine biomarkers changed following therapy: IL6, TNFa, IL1b, RANKL levels were decreased, whereas leptin, SOST, PTH, OC, OPG were increased. IL6 and TNFa represented two different axes of the treatment response (PCA analysis, Figure 1). Anti-CCP positivity (p = 0.009), higher disease activity (p<0.001), OPN (p<0.001), and lower leptin levels (p=0.002) were associated with higher erosion counts, and older age (p=0.001) and higher TNFa (p = 0.022) were associated with a lower probability of remaining erosion-free. Higher TNFa (p=0.003) and lower leptin (p = 0.029) levels were associated with lower BMD.

Conclusion: Biomarkers from both treatment response axes (Figure 1) are associated with erosive disease and bone loss in RA. Low leptin (Component 1) may be a new biomarker for erosive disease and bone loss in RA, and its improvement with treatment was correlated with suppression of IL-6. OPN, which was invariant to treatment, may be a novel biomarker for active erosive disease.

Disclosure: M. D. Wechalekar, Janssen, 2; S. Lester, None; S. Nagpal, Janssen, 3; S. Cole, Janssen, 3; J. Peters, Janssen, 9; A. Das, Janssen, 3; P. Hissaria, None; T. Crotti, None; C. Hill, None; S. Raghunath, None; L. Spargo, None; J. G. Walker, None; M. D. Smith, Janssen, 5; S. Proudman, Actelion Pharmaceuticals US, 2,GlaxoSmithKline, 2.

To cite this abstract in AMA style:

Wechalekar MD, Lester S, Nagpal S, Cole S, Peters J, Das A, Hissaria P, Crotti T, Hill C, Raghunath S, Spargo L, Walker JG, Smith MD, Proudman S. Osteopontin and Leptin Are Associated with Erosive Disease in an Inception Cohort of Rheumatoid Arthritis Treated-to-Target with Combination Conventional DMARD Therapy [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/osteopontin-and-leptin-are-associated-with-erosive-disease-in-an-inception-cohort-of-rheumatoid-arthritis-treated-to-target-with-combination-conventional-dmard-therapy/. Accessed .

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