Dataset Information

The Effect of Discontinuing Denosumab in Patients With Rheumatoid Arthritis Treated With Glucocorticoids.

ABSTRACT:

Objective

To evaluate changes in bone turnover and bone mineral density (BMD) in patients with rheumatoid arthritis (RA) receiving glucocorticoids, after discontinuation of denosumab for 12 months.

Methods

We conducted a randomized, double-blind, placebo-controlled, phase II study of RA patients. Patients received placebo, denosumab 60 mg, or denosumab 180 mg every 6 months for 12 months and were followed up for an additional 12 months after discontinuation, during which no bone loss prevention therapy was instituted. Changes from baseline in serum C-terminal telopeptide of type I collagen (CTX), serum procollagen type I N-terminal propeptide (PINP), and lumbar spine and total hip BMD were evaluated.

Results

In this post hoc analysis of patients treated with glucocorticoids at study baseline (n = 82), levels of CTX and PINP decreased significantly from baseline in both denosumab groups. Following denosumab discontinuation, CTX returned to baseline and was not significantly different from the placebo group 6 and 12 months after discontinuation. Median percentage changes from baseline PINP in those treated with denosumab 60 mg were -0.16% and 15.3% at 6 and 12 months, respectively, after discontinuation (P = 0.062 and P = 0.017, versus placebo); corresponding changes with denosumab 180 mg were 9.0% and 75.8%, respectively (P = 0.018 and P = 0.002 versus placebo). Compared to placebo, lumbar spine and total hip BMD increased in patients receiving denosumab and returned to baseline 12 months after discontinuation. No osteoporotic fractures were reported during treatment or in the off-treatment period.

Conclusion

In this analysis of short-term denosumab use in RA patients receiving glucocorticoids, denosumab discontinuation resulted in a gradual increase in bone turnover, which was associated with a return to baseline lumbar spine and total hip BMD.

SUBMITTER: Saag KG

PROVIDER: S-EPMC9305881 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background:Patients with rheumatoid arthritis (RA) are at increased risk for infection after arthroplasty, yet risks of specific biologic medications are unknown. Objective:To compare risk for postoperative infection among biologics and to evaluate the risk associated with glucocorticoids. Design:Retrospective cohort study. Setting:Medicare and Truven MarketScan administrative data from January 2006 through September 2015. Patients:Adults with RA who were having elective inpatient total knee or hip arthroplasty, either primary or revision, and had a recent infusion of or prescription for abatacept, adalimumab, etanercept, infliximab, rituximab, or tocilizumab before surgery. Measurements:Propensity-adjusted analyses using inverse probability weights evaluated comparative risks for hospitalized infection within 30 days and prosthetic joint infection (PJI) within 1 year after surgery between biologics or with different dosages of glucocorticoids. Secondary analyses evaluated non-urinary tract hospitalized infections and 30-day readmissions. Results:Among 9911 patients treated with biologics, 10 923 surgical procedures were identified. Outcomes were similar in patients who received different biologics. Compared with an 8.16% risk for hospitalized infection with abatacept, predicted risk from propensity-weighted models ranged from 6.87% (95% CI, 5.30% to 8.90%) with adalimumab to 8.90% (CI, 5.70% to 13.52%) with rituximab. Compared with a 2.14% 1-year cumulative incidence of PJI with abatacept, predicted incidence ranged from 0.35% (CI, 0.11% to 1.12%) with rituximab to 3.67% (CI, 1.69% to 7.88%) with tocilizumab. Glucocorticoids were associated with a dose-dependent increase in postoperative risk for all outcomes. Propensity-weighted models showed that use of more than 10 mg of glucocorticoids per day (vs. no glucocorticoid use) resulted in a predicted risk for hospitalized infection of 13.25% (CI, 9.72% to 17.81%) (vs. 6.78%) and a predicted 1-year cumulative incidence of PJI of 3.83% (CI, 2.13% to 6.87%) (vs. 2.09%). Limitation:Residual confounding is possible, and sample sizes for rituximab and tocilizumab were small. Conclusion:Risks for hospitalized infection, PJI, and readmission after arthroplasty were similar across biologics. In contrast, glucocorticoid use, especially with dosages above 10 mg/d, was associated with greater risk for adverse outcomes. Primary Funding Source:Rheumatology Research Foundation, National Institutes of Health, and Bristol-Myers Squibb.

Project description:BackgroundLow-dose glucocorticoids are frequently used for the management of rheumatoid arthritis (RA) and other chronic conditions, but the safety of long-term use remains uncertain.ObjectiveTo quantify the risk for hospitalized infection with long-term use of low-dose glucocorticoids in patients with RA receiving stable disease-modifying antirheumatic drug (DMARD) therapy.DesignRetrospective cohort study.SettingMedicare claims data and Optum's deidentified Clinformatics Data Mart database from 2006 to 2015.PatientsAdults with RA receiving a stable DMARD regimen for more than 6 months.MeasurementsAssociations between glucocorticoid dose (none, ≤5 mg/d, >5 to 10 mg/d, and >10 mg/d) and hospitalized infection were evaluated using inverse probability-weighted analyses, with 1-year cumulative incidence predicted from weighted models.Results247 297 observations were identified among 172 041 patients in Medicare and 58 279 observations among 44 118 patients in Optum. After 6 months of stable DMARD use, 47.1% of Medicare patients and 39.5% of Optum patients were receiving glucocorticoids. The 1-year cumulative incidence of hospitalized infection in Medicare patients not receiving glucocorticoids was 8.6% versus 11.0% (95% CI, 10.6% to 11.5%) for glucocorticoid dose of 5 mg or less per day, 14.4% (CI, 13.8% to 15.1%) for greater than 5 to 10 mg/d, and 17.7% (CI, 16.5% to 19.1%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids). The 1-year cumulative incidence of hospitalized infection in Optum patients not receiving glucocorticoids was 4.0% versus 5.2% (CI, 4.7% to 5.8%) for glucocorticoid dose of 5 mg or less per day, 8.1% (CI, 7.0% to 9.3%) for greater than 5 to 10 mg/d, and 10.6% (CI, 8.5% to 13.2%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids).LimitationPotential for residual confounding and misclassification of glucocorticoid dose.ConclusionIn patients with RA receiving stable DMARD therapy, glucocorticoids were associated with a dose-dependent increase in the risk for serious infection, with small but significant risks even at doses of 5 mg or less per day. Clinicians should balance the benefits of low-dose glucocorticoids with this potential risk.Primary funding sourceNational Institute of Arthritis and Musculoskeletal and Skin Diseases.