Long-term safety of adalimumab in clinical trials in adult patients with Crohn's disease or ulcerative colitis

Background: Adalimumab is used to treat moderate to severe Crohn's disease (CD) and ulcerative colitis (UC) when conventional therapies fail. Aim: To update long-term adalimumab safety from CD and UC trials; the previous report was CD only, 3160 patients/3402 patient-years (PYs). Methods: Treatment-emergent adverse events (AEs; first dose to 70days after last dose/December 31, 2015) in adults in phase 2/3 and 3/3b trials and open-label extensions were coded using Medical Dictionary for Regulatory Activities (MedDRA-v18.1). Rates were assessed as events/100 (E/100 PYs). Results: The database (16 trials; CD, N=3606; UC, N=1739) represented 4145 and 3397 PYs of exposure, respectively. For CD, incidences of any AEs with adalimumab were 60.8%-65.1%, depending on dose, and 71.5% with placebo; for UC, the incidences were 53.5%-54.8% and 56.1%, respectively. Rates of any AEs (CD, 605 E/100 PYs; UC, 361 E/100 PYs), serious AEs (CD, 36.1 E/100 PYs; UC, 18.9 E/100 PYs), and malignancies (CD, 1.2 E/100 PYs; UC, 1.0 E/100 PYs) were similar between current and prior analyses. Apparent rate of opportunistic infections was lowered to 0.3 and 0.2 E/100 PYs for CD and UC, respectively, by recent MedDRA changes excluding oral candidiasis and tuberculosis. Standardised incidence ratios for malignancies were similar to the general population (CD, 1.45 [95% CI, 0.90-2.22]; UC, 1.36 [95% CI, 0.84-2.07]). Demyelinating disorders were uncommon (CD, 0.1 E/100 PYs; UC, <0.1 E/100 PYs). Conclusions: Patients with moderately to severely active Crohn's disease or ulcerative colitis continued to experience acceptable safety with adalimumab, without new safety signals.