Seronegative Status Is Associated with Less Severe Disease Phenotype in Newly Diagnosed Crohnʼs Disease in the Community

Abstract

Introduction: The prognostic value of seromarkers in inflammatory bowel disease (IBD) has been studied in tertiary referral center populations. We investigated the relationship between seromarker positivity and disease course in newly-diagnosed Crohn's disease (CD) in a community-based cohort. Methods: The Ocean State Crohn's and Colitis Area Registry is a prospective, community-based cohort of patients with newly-diagnosed IBD enrolled from 2008 to 2013. Clinical diagnosis was confirmed by NIDDK IBD Genetics Consortium criteria. Serum was banked at enrollment for subsequent testing. Patients were followed prospectively for a median (interquartile range) of 60.1 (35.7) months for hospitalizations, surgeries, and therapy initiation. Seropositive CD was defined as a clinical diagnosis of CD with two or more positive seromarkers. Seronegative CD was defined as a clinical diagnosis of CD with one or less positive seromarkers. CRP positivity and disease behavior per Montreal Classifications were compared between seropositive and seronegative patients. Time to first hospitalization, surgery, steroid, immunomodulator, or biologic was compared between seropositive and seronegative patients using the Wilcoxon test. Results: Of the 225 newly-diagnosed CD patients, 126 were seropositive and 99 were seronegative. Seronegative patients had lower rates of elevated CRPs than seropositive patients (28.3% vs 61.1%, p < 0.0001). Seronegative patients demonstrated lower rates of stricturing and penetrating disease and higher rates of inflammatory disease behavior when compared with seropositive patients (8.1%, 7.1%, 84.9% vs. 19.8%, 15.1%, 65.1%, p = 0.004). Seronegative patients possessed lower rates of perianal disease compared with seropositive patients (4.0% vs. 11.1%, p = 0.05) (Table 1). At 6, 12, and 24 month follow-up, fewer seronegative patients than seropositive patients experienced disease progression in the form of steroid, immunomodulator, or biologic initiation, hospitalization, or intra-abdominal surgery (Table 2). There was no difference between seronegative and seropositive patients in time to first disease progression event (p= 0.11).Table 1: Baseline Disease Phenotype at Diagnosis in Seronegative and Seropositive Newly Diagnosed Community Crohn's Disease PatientsTable 2: Progression of Disease at 6, 12 and 24 Months in Seronegative and Seropositive Newly-diagnosed Community Crohn's Disease PatientsConclusion: Seropositive CD is associated with higher rates of elevated CRP and more severe disease phenotype. Although we did not detect differences in time to hospitalization, surgery or treatment with advanced therapies, duration of follow-up was limited. Seronegative CD in community-based patients may have a favorable prognosis.