Long-term Prognosis of Nonceliac Enteropathies and a Score to Identify Patients With Poor Outcomes: A 30-year Multicenter Longitudinal Study.

Introduction: Long-term prognosis of nonceliac enteropathies (NCEs) is poorly understood. We aimed to evaluate long-term outcomes and develop a prognostic score for NCEs.

Methods: NCEs patients from an international multicenter cohort (4 Italian centers, 1 United Kingdom, 1 French, 1 Norwegian, 1 United States, 1 Indian) followed-up over 30 years were enrolled. Complications and mortality were analyzed with Kaplan-Meier curves, standardized mortality ratios (SMR), and multivariate Cox regression. A clinical score to identify patients at risk of poor outcomes was developed.

Results: Two hundred sixty-one patients were enrolled (144 female, mean age at diagnosis 49 ± 18 years, median follow-up 70 months, interquartile range 24-109). The most common etiologies were idiopathic villous atrophy (39%), drug related (17%), common variable immune deficiency (15%), infectious (10%), and autoimmune enteropathy (9%). Five-year and 10-year complication-free survival were 89% and 77%, respectively, whereas 5-year and 10-year overall survival were 88% and 74%, respectively. Causes of death included sepsis/major infections (22%), lymphoproliferative disorders (22%), solid-organ malignancies (12%), cardiovascular/metabolic disease (10%), and was unknown in 33%. Mortality was increased in NCEs compared with the general population (SMR 3.17, 95% confidence interval [CI] 2.24-4.34). Older age at diagnosis ( P < 0.001), anemia (hazard ratio [HR] 2.53, 95% CI 1.33-4.80, P < 0.01), and lack of clinical (HR 3.21, 95% CI 1.68-6.18, P < 0.01) and histological response (HR 2.14, 95% CI 1.08-4.23, P = 0.04) were independent predictors of mortality at Cox regression. A 5-point score was developed to identify high-risk patients: very low risk (0 pts), low risk (1-2 pts), intermediate risk (3 pts), and high risk (4-5 pts), with 10-year survival rates of 100%, 87%, 62%, and 16%, respectively.

Discussion: Mortality in NCEs is increased because of complications and lack of response to current therapies. We developed a clinical score to personalize follow-up. Targeted treatments are needed to improve outcomes.