A Balasubramanian1, S W Wade2, R A Adler3, C J F Lin1, M Maricic4, C D O'Malley1, K Saag5, J R Curtis5. 1. Amgen Inc., Thousand Oaks and San Francisco, CA, USA. 2. Wade Outcomes Research and Consulting, 358 South 700 East, Suite B-432, Salt Lake City, UT, USA. sallyw@amgen.com. 3. McGuire Veterans Affairs Medical Center and Virginia Commonwealth University, Richmond, VA, USA. 4. University of Arizona School of Medicine, Tucson, AZ, USA. 5. Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
Abstract
Retrospective claims analysis indicated that high levels of daily and cumulative doses of systemic glucocorticoids were associated with elevated fracture risk in a large cohort of new RA patients under age 65. Heightened risk began to decline within months of discontinuation. Findings were similar among patients age <50 years. INTRODUCTION: We evaluated the impact of systemic glucocorticoid exposure on fracture risk among relatively young patients with new-onset rheumatoid arthritis (RA). METHODS: Using administrative data, we identified 42,127 RA patients diagnosed January 1, 2005-December 31, 2012, age 18-64 years, with benefits coverage for ≥12 months before RA diagnosis. Follow-up extended to clinical fracture, cancer diagnosis, or December 31, 2012. Glucocorticoid users were new to therapy. Fracture incidence rates (IR) were stratified by glucocorticoid exposure expressed as prednisone equivalent doses. Cox's proportional hazards models estimated fracture risk adjusted for demographics and baseline clinical characteristics to assess dose-response relationships with current (daily) and prior (cumulative) dose, and by time since discontinuation. RESULTS: Most patients (85 %) had glucocorticoid exposure. Exposed and unexposed patients were demographically similar (74 % female; mean age 49.7 and 48.8 years); 1 % had prior fracture. Fracture IRs (95 % confidence intervals) were 5 to 9 per 1000 person-years at doses <15 mg/day, 16.0 (11.0, 22.6) at doses ≥15 mg/day, and 13.4 (10.7, 16.7) at cumulative doses ≥5400 mg. Adjusted fracture risk was approximately 2-fold higher at highest dose levels compared with 0 mg/day current daily dose and <675 mg cumulative dose, respectively. Fracture risk was 29 % lower at 60-182 days post-discontinuation compared with ongoing use and was similar to unexposed patients by 12 months. Findings were similar among patients age <50 years. CONCLUSIONS: Among younger, new-onset RA patients, fracture risk was significantly elevated at high levels of daily and cumulative dose, and was similar to unexposed patients by 12 months post-discontinuation.
Retrospective claims analysis indicated that high levels of daily and cumulative doses of systemic glucocorticoids were associated with elevated fracture risk in a large cohort of new RApatients under age 65. Heightened risk began to decline within months of discontinuation. Findings were similar among patients age <50 years. INTRODUCTION: We evaluated the impact of systemic glucocorticoid exposure on fracture risk among relatively young patients with new-onset rheumatoid arthritis (RA). METHODS: Using administrative data, we identified 42,127 RApatients diagnosed January 1, 2005-December 31, 2012, age 18-64 years, with benefits coverage for ≥12 months before RA diagnosis. Follow-up extended to clinical fracture, cancer diagnosis, or December 31, 2012. Glucocorticoid users were new to therapy. Fracture incidence rates (IR) were stratified by glucocorticoid exposure expressed as prednisone equivalent doses. Cox's proportional hazards models estimated fracture risk adjusted for demographics and baseline clinical characteristics to assess dose-response relationships with current (daily) and prior (cumulative) dose, and by time since discontinuation. RESULTS: Most patients (85 %) had glucocorticoid exposure. Exposed and unexposed patients were demographically similar (74 % female; mean age 49.7 and 48.8 years); 1 % had prior fracture. Fracture IRs (95 % confidence intervals) were 5 to 9 per 1000 person-years at doses <15 mg/day, 16.0 (11.0, 22.6) at doses ≥15 mg/day, and 13.4 (10.7, 16.7) at cumulative doses ≥5400 mg. Adjusted fracture risk was approximately 2-fold higher at highest dose levels compared with 0 mg/day current daily dose and <675 mg cumulative dose, respectively. Fracture risk was 29 % lower at 60-182 days post-discontinuation compared with ongoing use and was similar to unexposed patients by 12 months. Findings were similar among patients age <50 years. CONCLUSIONS: Among younger, new-onset RApatients, fracture risk was significantly elevated at high levels of daily and cumulative dose, and was similar to unexposed patients by 12 months post-discontinuation.
Entities:
Keywords:
Fracture; Glucocorticoids; Health services research; Osteoporosis; Rheumatoid arthritis
Authors: L Sinigaglia; A Nervetti; Q Mela; G Bianchi; A Del Puente; O Di Munno; B Frediani; F Cantatore; R Pellerito; S Bartolone; G La Montagna; S Adami Journal: J Rheumatol Date: 2000-11 Impact factor: 4.666
Authors: Emily McKeown; Vivian P Bykerk; Faye De Leon; Ashley Bonner; Carter Thorne; Carol A Hitchon; Gilles Boire; Boulos Haraoui; Diane S Ferland; Edward C Keystone; Janet E Pope Journal: Rheumatology (Oxford) Date: 2012-04-25 Impact factor: 7.580
Authors: Jos N Hoes; Johannes W G Jacobs; Harry M J Hulsmans; Ron N J De Nijs; Willem F Lems; George A W Bruyn; Piet P M M Geusens; Johannes W J Bijlsma Journal: Clin Exp Rheumatol Date: 2010-06-23 Impact factor: 4.473
Authors: Amalia A van Everdingen; Johannes W G Jacobs; Dirk R Siewertsz Van Reesema; Johannes W J Bijlsma Journal: Ann Intern Med Date: 2002-01-01 Impact factor: 25.391
Authors: Jeffrey R Curtis; Amy S Mudano; Daniel H Solomon; Juan Xi; Mary Elkins Melton; Kenneth G Saag Journal: Med Care Date: 2009-01 Impact factor: 2.983
Authors: Beth I Wallace; Paul Lin; Neil Kamdar; Mohamed Noureldin; Rodney Hayward; David A Fox; Jeffrey R Curtis; Kenneth G Saag; Akbar K Waljee Journal: Semin Arthritis Rheum Date: 2019-09-07 Impact factor: 5.532