Background/Purpose: Glucocorticoids (GCs) directly impact bone metabolism via increased bone resorption and inhibited bone formation¹; hence, systemic fracture risk increases with daily and cumulative GC doses.² However, many patients with established rheumatoid arthritis (RA) receive long-term treatment with GCs to suppress inflammation, which confers some benefit in delaying bone erosion.³ This exploratory analysis of the SEMIRA (Steroid EliMination In RA) study⁴ compared changes in markers of bone and cartilage metabolism in RA with low disease activity (LDA) or remission on tocilizumab (TCZ) + GC ± conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) who received either slow GC tapering (GC-taper) or continuation (5 mg; GC-5mg).

Methods: Patients (diagnosed per revised 1987 ACR criteria) had at least stable LDA (DAS28-ESR ≤3.2) for ≥4 weeks, were receiving a stable prednisone regimen (5 mg/day) + TCZ ± csDMARDs for ≥4 weeks, and received TCZ + GCs (prednisone equivalent 5-15 mg/day) for ≥6 months before randomization. Patients were randomly assigned to GC-5mg (n=128) or GC-taper (n=131; starting at 4 mg/day with 1-mg reduction every 4 weeks to 0 mg/day at weeks 16-24) for 24 weeks, during which TCZ ± csDMARDs remained stable. Change between baseline (BL) and week 24 in serum levels of markers of bone and cartilage metabolism—including N-terminal propeptide of type 1 collagen (P1NP), C-terminal telopeptide of type 1 collagen (CTX1), alkaline phosphatase (ALP), matrix metalloproteinase 3 (MMP3), calcium, phosphorus, and albumin—were exploratory outcomes. Within-group and between-group changes from baseline were evaluated by Wilcoxon paired rank test and Wilcoxon signed rank test, respectively.

Results: Figure 1 shows changes from BL to week 24 in bone and cartilage biomarkers. MMP3 (marker of cartilage degradation) was reduced at week 24 in the GC-taper group compared with GC-5mg. Change from BL at week 24 in P1NP (bone formation) and CTX1 (bone resorption) favored the GC-taper arm, with P1NP increasing relatively more than CTX1 (44% and 24%, respectively, compared with GC-5mg), indicating net anabolism. The increase in ALP from BL to week 24 was greater for the GC-taper arm than for the GC-5mg arm, suggesting neomineralization. There was no difference in the change from BL to week 24 in calcium, phosphorus, or albumin (not shown).

Conclusion: The findings of this biochemical marker analysis suggest that withdrawal from GC after achievement of LDA or remission with TCZ results in increased bone remodeling, with a trend toward an anabolic window and reduced cartilage degradation. Given that it could take a year to recover from increased fracture risk after cessation of GC therapy,⁵ our results offer further insight on the reversible risk of systemic harm to noninflamed bone versus benefits for inflamed joints in the context of LDA or remission.

References: 1. Canalis E, Delany AM. Ann N Y Acad Sci 2002;966:73. 2. Van Staa TP et al. Rheumatology 2000;39:1383. 3. Kavanaugh A, Wells AF. Rheumatology 2014;53:1742. 4. Burmester GR et al. Arthritis Rheumatol 2018;70(suppl 10). 5. Vestergaard P et al. Calcif Tissue Int 2008;82:249.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/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-randomi/