Initiation of Tumor Necrosis Factor α Antagonists and Risk of Fractures in Patients With Selected Rheumatic and Autoimmune Diseases

Abstract

Objectives We tested the hypothesis that initiation of TNFα antagonists reduced the risk of fractures compared to nonbiologic comparator in patients with autoimmune diseases. Methods Using four large administrative databases, we assembled retrospective cohorts of patients with autoimmune diseases who initiated either a TNFα antagonist or a nonbiologic medication. We identified 3 mutually exclusive disease groups: rheumatoid arthritis (RA); inflammatory bowel disease (IBD); and psoriasis, psoriatic arthritis or ankylosing spondylitis (PsO-PsA-AS). We used baseline covariate data to calculate propensity scores (PS) for each disease group and used Cox regression to calculate hazard ratios (HR) and 95% confidence intervals (95%CI). We compared the risk of combined hip, radius/ulna, humerus, or pelvic fractures between PS-matched cohorts of new users of TNFα antagonists and nonbiologic comparator. Results We identified 9,020, 2,014 and 2,663 new PS matched episodes of TNFα antagonist and nonbiologic comparator use in RA, IBD and PsO-PsA-AS cohorts, respectively. The risk of combined fractures was similar between new users of TNFα antagonists and nonbiologic comparators for each disease (HR: 1.17, 95%CI [0.91, 1.51]; HR: 1.49, 95%CI [0.72, 3.11]; and HR: 0.92, 95%CI [0.47, 1.82] for RA, IBD and PsO-PsA-AS, respectively). In RA, the risk of combined fractures was associated with an average daily dose of prednisone equivalents >10 mg/day at baseline compared with no glucocorticoid (HR: 1.54, 95%CI [1.03, 2.30]). Conclusions The risk of fractures did not differ between initiators of a biologic and a nonbiologic comparator for any disease studied. Among RA patients, use of >10mg/day of prednisone equivalents at baseline increased the fracture risk.

Biological Disease-Modifying Antirheumatic Drugs and Osteoporotic Fracture Risk in Patients with Rheumatoid Arthritis: A Danish Cohort Study

“…Our results of a nonbeneficial effect of bDMARDs on fracture risk in rheumatoid arthritis are mainly in line with the few observational studies in this topic, [10][11][12][13] despite the differences in design and characteristics. These included the use of different databases (administrative or claims databases compared to a nationwide clinical database in our study), difference in follow-up (1-2 years vs >4 years mean follow-up), and not considering vertebral fracture in the studies by Kim et al 11 and Roussy et al 13 The only negative association between TNF inhibitor use and overall risk of all factures (and not for those of the hip and spine) comes from an observational study with a short follow-up time (<1 year), and no appropriate consideration of timing of exposure and outcome, thus prone to several biases.…”

“…This means, control of disease activity in both comparison groups resulted in comparable beneficial effects on bone health and fracture risk, and hence, no reduction in fracture risk among bDMARD users versus no biological treatment. This is an important difference between observational studies (including ours) that reported a neutral effect of bDMARDs on fracture risk, [11][12][13] and those single-arm clinical trials, which reported a beneficial effect on bone mineral density in a quasi-experimental before-after design. 7,9,[29][30][31][32] An important alternative interpretation of our study was that bDMARDs do not increase the fracture risk, in contrary to many other anti-inflammatory or other drugs used in the management of rheumatoid arthritis.…”

Medications associated with fracture risk in patients with rheumatoid arthritis

“…As chronic inflammation is one of the main reasons for the increased risk of OP and fractures in RA, it is thought that effective anti-inflammatory medication might decrease bone loss and consequently fracture risk. However, consistent with our findings, previous studies mostly using administrative data could not demonstrate a reduction in non-vertebral fracture risk either with TNFi or all bDMARDs assessed together compared with non-bDMARDs 23 26 43–45. One study examining vertebral fracture risk with TNFi reported no statistical association even though a risk reduction was found in all site fractures with TNFi monotherapy 43.…”

“…Our study confirms the glucocorticoid-fracture association and also adds to the existing literature about fracture risk with DMARDs 10 23 26 43–45. We assessed TNFi and non-TNFi and vertebral and non-vertebral fractures separately, which had not previously been done comprehensively.…”

Comparative risk of osteoporotic fracture among patients with rheumatoid arthritis receiving TNF inhibitors versus other biologics: a cohort study

“…While treatment with TNFis have stabilized/improved BMD at hips and spines [5] and even decreased vertebral facture risk among RA patients [6], such effect was not observed for hand BMD [5] or non-vertebral fractures [24].…”