Session Information
Date: Sunday, November 13, 2016
Title: Osteoporosis and Metabolic Bone Disease – Clinical Aspects and Pathogenesis - Poster
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Patients with autoimmune diseases are at increased risk of early onset osteoporosis due to multiple reasons including prolonged exposure to corticosteroids and the disease process itself in RA patients. Same patients are more likely to be on TNF inhibitors or other biologics, which causes them to be at an increased risk of infections. Denosumab, an anti-RANK ligand inhibitor used to treat osteoporosis, is associated with increased infection risk as Receptor activator of nuclear factor kappa-B ligand (RANKL) is also expressed on activated T and B lymphocytes(1). It is unknown if there is an added risk of infections when TNF inhibitors/biologic agents and denosumab are used concomitantly.
Methods: Data was collected and analyzed on 40 patients in the rheumatology clinic who had been on denosumab and TNF inhibitor/ other biologic for 5 years at the Keck Medical Center of USC.
Results: The mean age of the population was 70 ± 9.8 SD years, among which 98% were females. 75% had RA, 10% SLE, 2.5% SLE and Sjogren’s, 2.5% SLE with Antiphospholipid Syndrome(APLS), 2.5% RA and SLE, 2.5 % Microscopic Polyangiitis, 2.5% Psoriatic arthritis, and 2.5% Neurologic Behcet’s disease. We noted a 17.5% cumulative infection rate before denosumab over 2 years, which is 8.75 cases per 100 person-years. 9% hospitalization rate for infections was noted prior to denosumab. Importantly no infections developed within the first year of initiating denosumab. After 5 years of denosumab with TNF/other biologics, cumulative infection rate was 62.5 % and incidence rate was 12.5 cases per 100 person-years. In the FREEDOM Trial at 3 years, cumulative incidence rate of infections was 52.9%. In our study, 70% patients were on TNF inhibitors and 30% were on other biologics. At 5 years, Cumulative Infection rate was 71.4% among the TNF group and was 50% in the other biologics group. Urinary tract infection (UTI) accounted for the most common infection (17.5%). Other common infections: Pulmonary(15%), skin and soft tissue(12.5%), GI(5%), Tinea(5%)Herpes zoster(2.5%), HSVII(2.5%), sialadenitis(2.5%) . No opportunistic infections, and no reactivation of latent TB found in our patients.
Conclusion: No infections developed within the first year, suggesting a cumulative effect of increased infection risk, if any. We cannot attribute the overall infection rate solely to the combination of denosumab and biologics as patients who developed infections either had Diabetes Mellitus, urinary incontinence, recent surgery, underlying pulmonary disease. Whether prophylactic antibiotics are indicated in patients with recurrent infections PRIOR to denosumab is uncertain, but may be a consideration in certain patients. References: 1. Cummings SR, San Martin J, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–765. doi: 10.1056/NEJMoa0809493
To cite this abstract in AMA style:
Chhibar P, Ehresmann G. Increased Infection Risk with Concomitant Use of RANK Ligand-Inhibitor, Denosumab and TNF-Inhibitors or Other Biologics: Reality or Illusion? Long Term Experience at the University of Southern California [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/increased-infection-risk-with-concomitant-use-of-rank-ligand-inhibitor-denosumab-and-tnf-inhibitors-or-other-biologics-reality-or-illusion-long-term-experience-at-the-university-of-southern-califor/. Accessed .« Back to 2016 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-infection-risk-with-concomitant-use-of-rank-ligand-inhibitor-denosumab-and-tnf-inhibitors-or-other-biologics-reality-or-illusion-long-term-experience-at-the-university-of-southern-califor/