Background/Purpose: Adalimumab is an anti–tumor necrosis factor-α (TNF-α) agent indicated for the treatment of immune-mediated diseases. The long-term safety of adalimumab was previously reported in 23,458 patients representing up to 12 years of clinical trial exposure in rheumatoid arthritis (RA), juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis (PsA), plaque psoriasis (Ps), and Crohn’s disease (CD). Here we report an updated analysis examining the long-term safety of adalimumab in adult patients with RA, AS, non-radiographic axial spondyloarthritis (nr-axSpA), peripheral SpA (pSpA), PsA, Ps, hidradenitis suppurativa (HS), CD, ulcerative colitis (UC), and non-infectious uveitis (UV).

Methods: Safety data from 78 clinical trials of adalimumab (RA, 33; AS, 5; nr-axSpA, 2; pSpA, 1; PsA, 3; Ps, 13; HS, 3; CD, 11; UC, 4; UV, 2; other, 1) were included in these analyses, including randomized controlled, open-label, and long-term extension studies conducted in Europe, North America, South America, Asia, Australia, New Zealand, and South Africa through December 31, 2016. Adalimumab postmarketing surveillance data were not included in this analysis. Safety assessments included all adverse events (AEs) and serious AEs (SAEs) that occurred after the first adalimumab study dose and up to 70 days (5 half-lives) after the last study dose.

Results: This analysis included 29,987 patients, representing 56,951 patient-years of exposure (Table 1). The majority of adalimumab exposure was in RA studies. The most frequently reported SAE of interest was infection (highest incidences in CD, RA, UV, and UC). Overall and for most of the adalimumab populations (AS, PsA, Ps, UC, CD, and RA), the observed number of deaths was below what would be expected in an age- and sex‑adjusted population (Table 2). For HS, nr-axSpA, pSpA, and UV studies, the small size of these trials precluded accurate assessment of the standardized mortality ratio, and the 95% CIs all included 1.0.

Conclusion: This analysis of data from clinical trials of adalimumab demonstrated an overall safety profile consistent with previous findings and with the TNF inhibitor class. No new safety signals or tolerability issues with adalimumab treatment were identified and, for most indications, the mortality rate was below what would be expected in an age- and sex‑adjusted population. Efficacy and safety data continue to support the well-established benefits of adalimumab for the approved indications.