Background: The final top-line results of the long-term safety of ADA assessed in patients (pts) with moderately and severely active Crohn's disease (CD) treated in routine clinical practice and enrolled in the global postmarketing observational registry PYRAMID are presented. The primary objective was to rule out a doubled risk of lymphoma for pts treated with ADA compared with the expected background lymphoma rate.
Methods: Pts who were newly prescribed ADA or currently receiving ADA according to the local product label were enrolled in the registry and followed for up to 6 years. Adverse events (AEs), serious AEs (SAEs), AEs of special interest, and AEs leading to drug discontinuation were collected. Registry treatment-emergent AEs (TEAE; any event with onset on/after first dose of ADA until 70 days after last ADA injection) and observational AEs (any event occurring from first dose of ADA until last contact) were collected. AEs were coded using Medical Dictionary for Regulatory Activities (MedDRA) version 18.1 and reported as events/100 patient-years (PY).
Results: A total of 5025 pts were evaluated in this analysis (57.1% female, mean age 37.8 years at enrollment), representing 16680.4 PYs of ADA exposure over 6 years. The mean (SD) duration of ADA exposure during the registry was 1212.4 (835.4) days. A total of 2852 pts (56.8%) had prior biologic use, 1798 (35.8%) used immunomodulators (IMM), and 1463 (29.1%) used corticosteroids (CS) at registry baseline (BL). Overall, 3478 (69.2%) pts discontinued ADA or the registry. A total of 1853 pts (36.9%) reported 4129 treatment-emergent SAEs (24.8/100 PY) (Table). A total of 556 pts reported 792 treatment-emergent serious infections (SI) (4.7/100 PY). The only treatment-emergent SI reported by ≥1% of pts was perianal abscess (0.7/100 PY). The SI rate was higher for pts with concomitant medication at BL (ADA+CS, ADA+IMM, ADA+CS+IMM) vs ADA monotherapy (6.4, 4.8, 5.0 vs 4.2/100PY, respectively). A total of 116 pts experienced 134 treatment-emergent malignancy events (0.8/100 PY), of which 10 were lymphomas. No non-treatment-emergent lymphoma events were reported. The registry exposure-adjusted rate of lymphoma was 0.060/100 PY. The upper bound of the 1-sided 95% CI of this rate was 0.102/100 PYs and fell below 0.168/100 PYs (double the expected rate of 0.084/100 PYs). TEAEs leading to death were reported in 43 pts (0.3/100 PY).
Conclusions: The registry achieved the goal of ruling out a doubling of lymphoma risk in pts with CD treated with ADA. No new safety signals were identified.