All Patients | Baseline Cumulative Dose | ||||||
---|---|---|---|---|---|---|---|
With AE, n | 0 mg | > 0–300 mg, OR (99.65% CI) | > 300–800 mg, OR (99.65% CI) | > 800–1800 mg, OR (99.65% CI) | > 1800 mg, OR (99.65% CI) | p2 | |
Any AE | 22,207 | Ref | 1.01 (0.93–1.09) | 0.94 (0.86–1.03) | 1.00 (0.92–1.08) | 1.19 (1.09–1.30) | < 0.001 |
Bone-related AE | 6471 | Ref | 1.03 (0.91–1.17) | 0.97 (0.85–1.12) | 1.24 (1.11–1.40) | 1.53 (1.35–1.73) | < 0.001 |
Osteoporosis | 2681 | Ref | 1.00 (0.83–1.21) | 1.01 (0.81–1.25) | 1.43 (1.20–1.71) | 1.81 (1.50–2.18) | < 0.001 |
Fracture | 4059 | Ref | 1.03 (0.88–1.21) | 0.99 (0.84–1.18) | 1.22 (1.06–1.42) | 1.49 (1.29–1.73) | < 0.001 |
Aseptic necrosis of bone | 199 | Ref | 0.92 (0.45–1.89) | 0.99 (0.45–2.15) | 1.29 (0.68–2.44) | 2.13 (1.19–3.81) | < 0.001 |
Cataract | 13,296 | Ref | 0.99 (0.90–1.08) | 0.90 (0.81–1.00) | 0.88 (0.80–0.97) | 0.90 (0.81–0.99) | 0.002 |
Opportunistic infection3 | 1596 | Ref | 1.03 (0.80–1.34) | 1.08 (0.82–1.42) | 1.28 (1.02–1.60) | 1.89 (1.52–2.34) | < 0.001 |
MI or stroke | 1364 | Ref | 1.09 (0.84–1.42) | 0.93 (0.69–1.26) | 1.14 (0.89–1.46) | 1.38 (1.08–1.76) | < 0.001 |
Type 2 diabetes | 1844 | Ref | 0.92 (0.74–1.15) | 0.92 (0.73–1.18) | 0.89 (0.71–1.11) | 1.20 (0.96–1.50) | 0.016 |
Ulcer or GI bleed | 1375 | Ref | 1.15 (0.90–1.47) | 0.96 (0.72–1.29) | 1.06 (0.82–1.37) | 1.16 (0.88–1.53) | 0.106 |
↵1 Models adjusted for patient age, sex, geographic region, insurance plan type, population density, payer, and baseline measures of: biologic DMARD, nonbiologic DMARD, any AE or AE-related medication, hypothyroidism, ischemic heart disease, cancer, asthma/COPD, Deyo-Charlson Comorbidity Index, no. 3-digit ICD-9-CM diagnosis codes, no. NDC (measures of overall health), healthcare costs.
↵2 p value for comparison of 1800 mg cohort with 0 mg (reference) cohort; p < 0.0035 were considered statistically significant.
↵3 Includes opportunistic infections such as tuberculosis, candidiasis, and herpes zoster (Supplementary Table 1 shows the complete list, available with the online version of this article). AE: adverse event; COPD: chronic obstructive pulmonary disease; DMARD: disease-modifying antirheumatic drug; GI: gastrointestinal; ICD-9-CM: International Classification of Diseases, 9th revision, Clinical Modification; MI: myocardial infarction; NDC: National Drug Codes; OGC: oral glucocorticoids.