Rheumatoid Arthritis

Denosumab Plus csDMARD Shows Promise for Reducing Joint Destruction in RA

Caleb Rans, PharmD
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It is unclear whether disease control prevents RA-related bone loss, but data suggest it does in patients with early RA and high disease activity.1 Two systemic analyses of RA studies concluded that biologic DMARDs reduce generalized and localized bone loss.2,19 However, few studies were phase 3 trials, and most measured markers of bone turnover.2,19 High-quality trials that measure BMD change or fracture risk are needed. Bisphosphonates, denosumab, and parathyroid hormone are agents approved for osteoporosis and glucocorticoid-induced osteoporosis. Bisphosphonates and denosumab appear to have similar efficacy at preserving BMD.1 In some RA studies, denosumab also prevented and repaired erosions.2 The ACR guidelines for glucocorticoid-induced osteoporosis categorize patients as having low, moderate, or high fracture risk.18 They recommend calcium (1000 to 1200 mg/d) and vitamin D (600 to 800 IU/d) supplements for all patients, plus an osteoporosis agent (preferably an oral bisphosphonate) for patients with moderate to high fracture risk.

It is unclear whether disease control prevents RA-related bone loss, but data suggest it does in patients with early RA and high disease activity.1 Two systemic analyses of RA studies concluded that biologic DMARDs reduce generalized and localized bone loss.2,19 However, few studies were phase 3 trials, and most measured markers of bone turnover.2,19 High-quality trials that measure BMD change or fracture risk are needed. Bisphosphonates, denosumab, and parathyroid hormone are agents approved for osteoporosis and glucocorticoid-induced osteoporosis. Bisphosphonates and denosumab appear to have similar efficacy at preserving BMD.1 In some RA studies, denosumab also prevented and repaired erosions.2

The ACR guidelines for glucocorticoid-induced osteoporosis categorize patients as having low, moderate, or high fracture risk.18 They recommend calcium (1000 to 1200 mg/d) and vitamin D (600 to 800 IU/d) supplements for all patients, plus an osteoporosis agent (preferably an oral bisphosphonate) for patients with moderate to high fracture risk.

In Japan, researchers found data from a large phase 3 study that showed combined conventional synthetic disease-modifying antirheumatic drugs and denosumab therapy was found to significantly inhibit the progression of joint destruction in patients with rheumatoid arthritis.

The concurrent use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and denosumab was found to significantly suppress the progression of joint destruction in patients with RA, according to study results published in the Annals of the Rheumatic Diseases.

Researchers conducted a double-blind placebo-controlled randomized study of 654 patients with rheumatoid arthritis (RA) receiving csDMARD therapy. Study participants were randomly assigned in a 1:1:1 manner to receive a single 60 mg-dose of denosumab or placebo every 6 months or every 3 months. The primary study outcome was the difference in the modified total Sharp score (mTSS) from start of therapy to 12 months.

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After analysis, the researchers found that the mean changes in the mTss at 12 months were 1.49 (95% CI, 0.99-1.99), 0.72 (95% CI, 0.41-1.03), and 0.99 (95% CI, 0.49-1.49) in the placebo, 3-month, and 6-month groups, respectively. Overall, they reported that patients in the denosumab arms showed significantly reduced progression of joint destruction.

With respect to safety, no major differences were noted between the groups.

One key limitation of the study was the short duration of follow-up.

“Denosumab inhibits the progression of joint destruction, increases bone mineral density and is well tolerated in patients with RA taking csDMARD,” the investigators concluded.

Reference

Takeuchi T, Tanaka Y, Soen S, et al. Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial [published online April 29, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2018-214827

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