Comparative Effectiveness of TNF-α and IL-6 Inhibitors on Bone Health Outcomes and Mortality in Rheumatoid Arthritis Patients: A Retrospective Cohort Study.

Background: Rheumatoid arthritis (RA) significantly impacts bone health, leading to osteoporosis and increased fracture risks. This study aims to compare the effects of TNF-α and IL-6 inhibitors on the incidence of fractures, osteoporosis, and mortality among RA patients.

Methods: We conducted a retrospective cohort study using the TriNetX database, spanning from January 1, 2015, to December 31, 2022. The adult patients diagnosed with Rheumatoid Arthritis (RA) were identified and divided into two groups of new users of TNF-α and IL-6 inhibitors. Patients with prior fractures or who switched treatments post-index were excluded. Patients baseline characteristics were adjusted with propensity score matching (PSM). We compared TNF-α and IL-6 inhibitor cohorts in terms of fracture and osteoporosis incidence, and mortality employing Cox proportional hazards models for risk assessment, adjusting for potential confounders.

Results: The study included 2158 RA patients each in the TNF-α and IL-6 cohorts after PSM. Both cohorts had 71 osteoporosis/fractures during a 1-year follow-up. The adjusted HR (95% CI) was 0.987 (0.711-1.372) comparing TNFi versus IL-6is initiators. Similar results were shown stratified by age, sex, and steroid usage. However, all-cause mortality was significantly lower in the TNF-α cohort with an adjusted HR (95% CI) of 0.247 (0.114-0.536). Subgroup analyses showed the TNF-α cohort was associated with lower all-cause mortality among patients older than 65, male patients, and steroid users.

Conclusions: TNF-α and IL-6 inhibitors exhibit comparable effects on the risk of osteoporosis and fractures among RA patients. Notably, TNF-α inhibitors may offer advantages in reducing all-cause mortality, warranting further investigation.