Dr. Richard Colletti – Network Director for ImproveCareNow – announced today that an ImproveCareNow study has been accepted for oral presentation at Digestive Diseases Week in May. This is a highly innovative study done in collaboration with the Department of Biostatistics and Epidemiology of the University of Pennsylvania. It is a replication of the REACH study, and the first pediatric comparative effectiveness study of anti-TNF drugs.
Congratulations to Mike Kappelman, Wallace Crandall and the research team. And congratulations and thank you to all of the centers whose data made this study possible. More comparative effectiveness studies are planned.
Here is the abstract:
Kappelman MD, Bailey LC, Crandall WV, Zhang P, King E, Joffe M, Colletti RB, Forrest CB and the ImproveCareNow Network
Real-World Clinical and Comparative Effectiveness of Infliximab in Pediatric Crohn’s Disease
Background and Aims: Clinical trials in pediatric Crohn’s disease (CD) are difficult to recruit for, enroll highly selected subjects, and utilize standardized protocols. Thus, efficacy data from trials may not be generalizable to clinical practice. Studies of real-world clinical effectiveness are needed to fully evaluate evolving therapeutic options. We sought to use data from a multicenter clinical registry (the ImproveCareNow Network, ICN) to evaluate the clinical and comparative effectiveness of anti-TNFα biological therapy in children with moderate to severe CD.
Methods: ICN maintains a registry of medication use and clinical and laboratory data collected during pediatric gastroenterology outpatient IBD encounters (33 centers in this analysis). We identified a cohort of new users of infliximab and adalimumab with characteristics (selection criteria) similar to subjects enrolled in the REACH clinical trial. To evaluate clinical effectiveness, Pediatric Crohn’s Disease Activity Index (PCDAI) scores and corticosteroid use were evaluated at the visit closest to 10 weeks following induction. Missing data were estimated by multiple imputation. Response (PCDAI <30 and decrease by ≥ 15 points), remission (PCDAI < 10), and steroid-free status were determined. To evaluate comparative effectiveness, we performed a trial simulation comparing 6 month outcomes of remission and steroid-free remission, adjusting for disease severity and medication use for the 6 months before the start of the trial, among biologic initiators and non-biologic users, using Cox proportional hazards models and generalized estimating equations.
Results: 192 biologic initiators (53% male, mean age 14.9 years, mean PCDAI 39.7) were included in the analysis. Overall, 80% experienced response, 39% remission, and 33% steroid free status at week 10. Among those on concomitant immunomodulators, 82% experienced response and 48% experienced remission (REACH clinical trial 88% and 59% respectively). In the trial simulation, 198 biologic trials were compared with 1157 non-biologic trials. Biologics were associated with increased remission (hazard ratio 1.5, 95% CI 1.1-2.0) and steroid free remission (hazard ratio 2.0, 95% CI 1.5-2.7), with corresponding number needed to treat (NNT) of 7.8 and 5.3.
Discussion: The real-world clinical effectiveness of anti-TNFα biological therapy observed in a multi-center pediatric IBD network is similar to the efficacy estimates from the REACH clinical trial. Concomitant immunomodulator use is associated with increased effectiveness. Compared with conventional care, biological therapy is more effective at achieving remission, particularly steroid-free remission. The NNT can be used to guide clinical decision making regarding risks and benefits. These findings support the use of the ICN registry for comparative effectiveness research.