Slide 1: Impact of Glucocorticoid Tapering on Markers of Bone Metabolism in Patients With Rheumatoid Arthritis
844 Impact of Glucocorticoid Tapering on Markers of Bone Metabolism in Patients With Rheumatoid Arthritis Who Achieved Low Disease Activity or Remission on Tocilizumab: Exploratory Analysis From a Randomized Controlled Trial Frank Buttgereit,1* Gerd R. Burmester,1* J. Michael Nebesky,2 Jenny Devenpo
Slide 2: Disclosures
Disclosures • F Buttgereit reports personal fees and grants from Roche • GR Burmester reports consulting and speaker fees from Roche and Sanofi-Genzyme • JM Nebesky and MR John are employees of and own stock in F. Hoffmann-La Roche Ltd • J Devenport is an employee of F. Hoffmann-La Roche Ltd • MY Do
Slide 3: Background
Background GCs can be used to treat inflammatory processes that have a negative effect on bone remodeling1; however, GCs also contribute to bone loss and increased fracture risk1,2 Bone formation Bone resorption GC Osteoblast • Bone loss Osteoclast • Increased P1NP CTX-1 Marker risk for Markers ALP
Slide 4: SEMIRA (Steroid EliMination In RA) RCT: Objectives
SEMIRA (Steroid EliMination In RA) RCT: Objectives PRIMARY OBJECTIVES EXPLORATORY OBJECTIVE To compare GC tapering with GC continuation for To explore variables of maintaining disease control in RA patients receiving TCZ and in at least LDA potential benefit with prednisone tapering, such as bone re
Slide 5: Study Design
Study Design 24-Week TRACK 1 Double-Blind Phase TCZ Experienced Screening Continued prednisone 5 mg/day 4-6 Weeks 5 5 5 5 5 5 226 R TCZ and csDMARDs kept stable for 24 weeks TRACK 2 Tapered prednisone TCZ Naive 24-Week Screening Lead-In Phase 4 3 2 1 0 0 4 Weeks Serum for bone/cartilage • Randomizat
Slide 6: SEMIRA Biomarker Population
SEMIRA Biomarker Population N = 259 Blinded prednisone taper Blinded continued prednisone ITT ITT n = 131 n = 128 n = 114 n = 112 (87% of ITT) (88% of ITT) Completed blinded treatment Completed blinded treatment Number of Patients with Serum Biomarkers for Analysis (BL and Week 24) Biomarker Prednis
Slide 7: Change From BL to Week 24: Other Bone Biomarkers
Change From BL to Week 24: Other Bone Biomarkers There was no difference in the change from BL to week 24 in calcium, phosphorus, or albumin Calcium, mmol/L Phosphorus, mmol/L Albumin-BCG, g/L 0.5 5 0.50 0.25 0.0 0 Value Value Value 0.00 -0.5 -5 -0.25 -0.50 -1.0 -10 Tapered prednisone 126 124 115 11
Slide 8: Change From BL to Week 24 in MMP-3 (cartilage degradation)
Change From BL to Week 24 in MMP-3 (cartilage degradation) MMP-3 (ng/mL)*a 50 • MMP-3 was reduced at week 24 in 25 the tapered versus continued 0 prednisone group, suggestive of reduced cartilage degradation in the -25 tapered group Value -50 -75 -100 Tapered prednisone Continued prednisone 91 91 We
Slide 9: Change From BL to Week 24 in P1NP (bone formation)
Change From BL to Week 24 in P1NP (bone formation) P1NP, µg/mL* • Mean increase in P1NP from BL to 100 week 24 greater with tapered versus continued prednisone 50 • In relative terms – Tapered prednisone: 58.7% Value (95% CI, 41.8% to 75.7%) 0 – Continued prednisone: 8.0% (95% CI, –1.0% to 16.9%) -5
Slide 10: Change From BL to Week 24 in ALP (bone formation)
Change From BL to Week 24 in ALP (bone formation) ALP, U/L* 60 • Mean increase in ALP from BL to week 24 greater with tapered versus continued prednisone 40 • Indicates higher osteoblast activity in the tapered group Value 20 0 -20 Tapered prednisone 92 Continued prednisone 91 Week 24 Analysis Visit
Slide 11: Change From BL to Week 24 in CTX-1 (bone resorption)
Change From BL to Week 24 in CTX-1 (bone resorption) CTX-1, mg/L* • Mean increase in CTX-1 from BL to 0.75 week 24 greater with tapered versus continued prednisone 0.50 • In relative terms – Tapered prednisone: 45.7% Value 0.25 (95% CI, 27.3% to 64.2%) 0.00 – Continued prednisone: 4.8% (95% CI, –5.0
Slide 12: Concept of an Anabolic Window (example: teriparatide)
Concept of an Anabolic Window (example: teriparatide)' Bone formation A B markers Key: Bone formation markers | 100 Bone resorption markers | Bone resorption markers ~ a Pa 3 Bone Turnover (% maximal change) g oO 12 24 0 12 24 36 Parathyroid Hormone, months Parathyroid Hormone, months * During the a
Slide 13: Markers of Bone Turnover (post hoc analysis)
Markers of Bone Turnover (post hoc analysis) 80 Mean (95% CI) Percentage Change to Week 24 60 Small modeling increase over remodeling in tapered group 40 20 0 Tapered Continued Tapered Continued CTX1 P1NP (resorption) (formation) Changes suggest potential for endogenous bone recovery or for reversib
Slide 14: Conclusions
Conclusions • This exploratory biomarker analysis of the SEMIRA trial suggests that GC withdrawal after achievement of LDA resulted in – Increased bone remodeling with a trend toward an anabolic window – Reduced cartilage degradation • It can take a year for the risk for fracture to resolve after pa
Slide 15: Acknowledgments
Acknowledgments The authors thank all the patients, family members, and investigators who participated in the study, and they thank the Independent Data Monitoring Committee for its oversight Switzerland Russia Germany France Serbia Tunisia Italy Note: the entire presentation will be made available