Tocilizumab Reduces Bone Loss in ACPA-Positive Rheumatoid Arthritis

Treatment with tocilizumab (TCZ) for 2 years in patients with anticitrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) was shown to reduce levels of bone resorption markers and increase bone mineral density of the femoral neck, according to the results of a recent prospective study published in PLoS One.

In patients with RA, in whom a high risk for osteoporosis and fracture has been reported, the use of interleukin (IL)-6 inhibitors may suppress osteoclast activation. Although ACPA titers have been shown to be inversely associated with bone mineral density, the differential effect of ACPA on bone turnover marker and bone mineral density changes following IL-6 inhibition remains unclear.

The current study recruited patients with active RA who had experienced an inadequate response to methotrexate or biologic agents. Participants’ bone mineral density was measured both before and after 2 years of TCZ therapy. Serum osteocalcin, N-terminal propeptide of type 1 collagen, and C-terminal cross-linking telopeptide of type 1 collagen (CTX) levels were evaluated at baseline and at the end of treatment.

A total of 76 TCZ-treated patients with RA (89.5% women; age, 57.2±13.3 years) were enrolled in the study. The 28-joint disease activity score was negatively associated with bone mineral density and T-scores of the lumbar spine and bilateral femoral neck in these patients.

Following 2 years of TCZ treatment, CTX levels decreased significantly (0.32±0.21 vs 0.26±0.17; P =.038). Right and left femoral neck bone mineral density increased significantly after 2 years of TCZ therapy (right, 0.74±0.14 vs 0.70±0.51; P =.020; left, 0.71±0.22 vs 0.69±0.55; P =.008). T-scores of the bilateral femoral neck also significantly improved (right, –1.42±1.21 vs –1.59±1.17; P =.007; left, –1.43±1.40 vs –1.54±1.43; P =.018) after 2 years of TCZ. No significant changes in levels of the bone formation marker osteocalcin and N-terminal propeptide of type 1 collagen were observed following TCZ treatment.

Decreased CTX levels and improved bone mineral density were reported only among patients with ACPA-positive RA. Following TCZ therapy, femoral neck bone mineral density increased significantly only in patients who received a glucocorticosteroid dose of ≥5 mg/day.

The investigators concluded that among patients with ACPA-positive RA, tight control of disease activity with either IL-6 inhibition or glucocorticosteroids may have an impact on the long-term effect of inflammation on bone.

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Reference

Chen YM, Chen HH, Huang WN, et al. Tocilizumab potentially prevents bone loss in patients with anticitrullinated protein antibody-positive rheumatoid arthritis. PLoS One. 2017;12(11):e0188454.