SAN DIEGO — Treatment with natalizumab significantly reduced the rates of overall hospitalization and disease-specific hospitalization for adults with Crohn's disease, according to data from 1,373 adults presented at the annual Digestive Disease Week.
Hospitalization is one of the greatest expenses associated with Crohn's disease (CD), and preventing hospitalization remains a major goal of treatment, said Dr. Bruce E. Sands, a gastroenterologist at Massachusetts General Hospital and Harvard Medical School, both in Boston.
To investigate the impact of natalizumab on all-cause and CD-specific hospitalizations, Dr. Sands and his colleagues analyzed pooled data from two previous randomized, controlled trials—ENCORE (Evaluation of Nifedipine and Cerivastatin on the Recovery of Endothelial Function) and ENACT-1 (Evaluation of Natalizumab as Continuous Therapy)—which included a total intent-to-treat population of 1,414 persons.
The two patient groups had an average age of 38 years and similar demographic characteristics at baseline. The patients had been randomly assigned to receive an intravenous dose of 300 mg natalizumab or a placebo every 4 weeks for a 12-week induction period. The hospitalization rate was calculated as hospital admissions per 100 courses (per 100 patients). The study involved an additional analysis of a subgroup of 346 patients who had failed prior anti-TNF therapy and had active inflammation, as shown by elevated C-reactive protein levels. “We observed a total of 136 all-cause hospitalizations in the entire cohort, and of these, 109 were Crohn's related,” Dr. Sands said.
In a multivariate analysis, natalizumab was associated with a significant reduction of 35% in the all-cause hospitalization rate. Natalizumab use also was associated with a comparable 30% reduction in the CD-related hospitalization rate, but the difference was not statistically significant.
In the multivariate model, the effect size was even more dramatic for the subset of anti-TNF-resistant patients. The all-cause hospitalization rate in this group was significantly lower for patients who received natalizumab, compared with placebo (9.7/100 patients vs. 20.8/100 patients). The CD-related hospitalization rates also were significantly lower for natalizumab patients vs. placebo patients (6.3/100 patients vs. 12.8/100 patients). “Both anti-TNF experience and elevated C-reactive protein were associated with greater risk of hospitalization,” he added.
In both univariate and multivariate analysis, the other independent predictors of hospitalization were low body mass index, baseline C-reactive protein level, prior anti-TNF experience, and elevation of baseline Crohn's Disease Activity Index (CDAI). Age, gender, and baseline steroid and immunosuppressant use were not associated with risk of hospitalization.
Dr. Sands has received consulting fees, grants, and research support from companies including Abbott Laboratories, Centocor Inc., Genentech Inc., Procter & Gamble Pharmaceuticals Inc., Otsuka America Pharmaceutical Inc., Shire PLC, and UCB BioPharma.