Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial.

BACKGROUND AND OBJECTIVES: The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures. METHODS: Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. RESULTS: Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. CONCLUSION: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.

Long-term monitoring of western aspen--lessons learned.

Aspen woodland is an important ecosystem in the western United States. Aspen is currently declining in western mountains; stressors include conifer expansion due to fire suppression, drought, disease, heavy wildlife and livestock use, and human development. Forecasting of tree species distributions under future climate scenarios predicts severe losses of western aspen within the next 50 years. As a result, aspen has been selected as one of 14 vital signs for long-term monitoring by the National Park Service Upper Columbia Basin Network. This article describes the development of a monitoring protocol for aspen including inventory mapping, selection of sampling locations, statistical considerations, a method for accounting for spatial dependence, field sampling strategies, and data management. We emphasize the importance of collecting pilot data for use in statistical power analysis and semi-variogram analysis prior to protocol implementation. Given the spatial and temporal variability within aspen stem size classes, we recommend implementing permanent plots that are distributed spatially within and among stands. Because of our careful statistical design, we were able to detect change between sampling periods with desired confidence and power. Engaging a protocol development and implementation team with necessary and complementary knowledge and skills is critical for success. Besides the project leader, we engaged field sampling personnel, GIS specialists, statisticians, and a data management specialist. We underline the importance of frequent communication with park personnel and network coordinators.