AB0479 BARICITINIB AND UPADACITINIB AFFECT THE LEVELS OF BONE DESTRUCTION MARKERS AND BONE FORMATION INDICATORS IN PATIENTS WITH RHEUMATOID ARTHRITIS

• Published in: Annals of the rheumatic diseases Vol. 82; no. Suppl 1; p. 1433
• Main Authors: Felis-Giemza, A, Kurowska, W, Marecka-Kuzdub, M, Kuca-Warnawin, E, Massalska, M, Maśliński, W
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2023
• Subjects: Bone growth; Bone resorption; Bone turnover; Collagen (type I); Immunomodulation; Inflammatory diseases; Janus kinase; Kinases; Osteocalcin; Osteogenesis; Osteoprotegerin; Peripheral blood; Rheumatoid arthritis; TRANCE protein
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2023-eular.4464

BackgroundJanus kinase inhibitors (JAKis) baricitinib and upadacitinib inhibit the radiographic progression of joint damage in patients with rheumatoid arthritis (RA) [1-3]. Recent findings indicate that treatment with JAKi can lead to the repair of arthritic bone erosions [4]. However, although the immunomodulatory effects of JAKis have been extensively studied in inflammatory diseases, the effects of JAKis on bone metabolism in patients with RA are not fully understood.ObjectivesTo investigate the effect of baricitinib and upadacitinib on the levels of bone destruction markers and bone formation indicators in the peripheral blood of patients with RA.MethodsThe study included 14 patients with RA (all women, aged 23–65 years, mean age 47.7 ± 12.4 years) with high disease activity at baseline (median DAS 28-ESR 5.625, range: 5.11–7.17); median ESR 11.50 mm/h (range 5.00–60.00 mm/h); median CRP 12.15 mg/ml (range 1.00–40.00 mg/ml). Peripheral blood plasma samples were collected from patients prior to JAKi treatment, and during therapy with baricitinib 4 mg once daily (n=9) or upadacitinib 15 mg once daily (n=5).Concentrations of C-telopeptide fragments of type I collagen (CTX-I), osteocalcin, Receptor Activator for Nuclear Factor κ B Ligand (RANKL), and osteoprotegerin (OPG) were measured in plasma by the enzyme-linked immunosorbent assays.Changes in the variables were assessed using paired Student t-test or Wilcoxon matched-pair signed rank test (depending on the type of data distribution). P-values <0,05 were considered significant.ResultsThe median duration of treatment with JAKi was 12 months (range 7–18 months). Eleven (78.6%) patients were treated for more than 12 months. The effects of JAKis were analyzed in two-time intervals: after 5-8 months of therapy and after 12 months of therapy. The median DAS 28-ESR decreased to 2.83 (range 1.13–7.56, p=0,014), after 5-8 months of therapy, and to 2.53 (range 0.75–7.34, p=0.002) after 12 months of therapy.The concentration of bone turnover marker CTX-I decreased gradually during JAKi treatment from a median pre-treatment level of 247.1 ng/ml (range 50.0–1228.0 ng/ml) to 186.0 ng/ml (range 0.0–394.0 ng/ml) after 5-8 months of therapy, and 78.0 ng/ml (range 0.0–481.0; p=0.031) after 12 months of therapy.Conversely, treatment with JAKi resulted in a gradual increase in the median osteocalcin concentration from a pre-treatment level of 17.0 ng/ml (5.0–37.0 ng/ml) to 24.0 ng/ml (6–92 ng/ml) and 28.6 ng/ml (11.0–43.0 ng/ml) after 5-8 months and 12 months of therapy (p=0.027), respectively.In a subgroup of 6 patients (2 treated with upadacitinib and 4 treated with baricitinib), a decrease in RANKL/OPG concentration ratios were observed after 5-8 months or/and after 12 months of therapy (from pre-treatment median ratio of 0.23, range: 0.09–1.26 to 0.11, range: 0.00–0.87 after therapy; p=0.03). In 5 patients, the RANKL/OPG ratio did not change during treatment with baricitinib or upadacitinib.ConclusionThe decrease in the concentration of CTX-I, a marker of bone destruction, with a simultaneous increase in the concentration of osteocalcin, a marker of bone formation, and a decrease (at least in a subgroup of patients) in the concentration of RANKL, a stimulator of bone resorption, in relation to its receptor-decoy OPG, suggests that treatment with baricitinib and upadacitinib may promote bone anabolic processes in patients with RA.References[1]van der Heijde D, et al. RMD Open, 2018. doi: 10.1136/rmdopen-2018-000662.[2]Taylor PC, et al. N Engl J Med, 2017. doi: 10.1056/NEJMoa1608345.[3]Fleischmann R, et al. Arthritis Rheumatol, 2019. doi: 10.1002/art.41032.[4]Adam S, et al. Transl Med, 2020. doi: 10.1126/scitranslmed.aay4447.Acknowledgements:NIL.Disclosure of InterestsNone Declared.