Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: The anti-IL6-R antibody tocilizumab (TCZ) is an effective treatment of rheumatoid arthritis (RA). Previous studies showed that TCZ has a positive effect on bone turnover. However the effect of TCZ on bone mineral density (BMD) and regulators of bone remodeling pathways are limited. The objective of this ancillary study was to assess prospectively the TCZ effects on BMD and bone remodeling.
Methods: 103 patients with moderate to severe RA were treated with TCZ 8 mg/kg+ methotrexate (MTX) every 4 weeks in the Torpedo study during 12 months. Total hip and lumbar spine BMD were performed at baseline and after 48 weeks by dual energy X ray absorptiometry (DXA). Pro-collagen serum type I N-terminal propeptide (PINP), a marker of bone formation; serum C-terminal cross-linked telopeptide of type I collagen (CTX-I), a marker of bone resorption, and circulating levels of osteoprotegerin, receptor activator of nuclear factor-kappaB ligand, Wnt signalling pathway inhibitors Dickkopf-1 (Dkk-1) and sclerostin, were assessed at baseline, 12 and 48 weeks. Corticosteroid (CS) use was described using the AUC (Area under the Curve) time weighted of cortisone intake (AUC-CS). Analysis was intent-to-treat. Results were presented in median and tested using the Wilcoxon paired signed-rank test.
Results: 103 patients (75 % women, 52±12 years) with active RA and a mean disease duration of 4 ±3 years were included. BMD was available for 73 patients at baseline and end of study. Serum PINP increased from baseline by 22 % (p≤0.001) and 19% (p≤0.001) at week 12 and week 48, respectively. By contrast CTX-I remained stable over the time which led to an improvement in PINP/CTX-I ratio of 14%, (p≤0.001) and 23 % (p≤0.001) at week 12 and 48, respectively. Serum DKK-1 significantly decreased from baseline by -31 % (p≤0.001) and -25 % (p=0.025) at week 12 and 48, respectively. The evolutions of DKK-1 and P1NP were not correlated. Evolutions of serum OPG and sclerostin were not significant over 48 weeks. There was no change in lumbar spine and hip BMD over 48 weeks. However in patients in the highest quartile of AUC-CS (>7.5mg/d), BMD significantly decrease at trochanter (p=0.016). CS dose was not a determinant of bone remodeling markers changes.
Conclusion: in these patients treated with TCZ in combination with MTX, we did not see the expected bone loss related to inflammation. DKK-1, a key determinant of the bone destructive pattern of RA, decreases in patients treated with TCZ which could participate to a rapid and positive effect on bone balance due to an increase in bone formation. From the results of this small sample of patients, it seems that there is no indication for prevention of CS-induced bone loss in patients receiving TCZ and low doses of corticosteroids.
Disclosure:
K. Briot,
None;
T. Schaeverbeke,
Pfizer, Roche, UCB, BMS,
2,
Pfizer, Roche, Abbott, BMS, UCB ,Schering-Plough,MSD, Novartis ,
5;
F. Etchepare,
Roche-Chugai, Abbott, Esaote, Pfizer,
5;
P. Gaudin,
Abbott, BMS,
5,
Abbott, MSD, Pfizer, Chugai, Roche,
2;
A. Perdriger,
Roche, Chugai,
6;
M. Vray,
Roche-Chugai,
2,
GSK,
5;
S. Rouanet,
Roche Pharmaceuticals,
3;
G. Steinberg,
Roche Pharmaceuticals,
3;
C. Roux,
Roche, Servier, Amgen, MSD, Lilly, Novartis,
5,
Roche, Servier, Amgen, MSD, Lilly, Novartis,
2.
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