Su1159 Risk of Infections With Natalizumab Therapy Among Patients With Crohn's Disease: An Analysis of the Food and Drug Administration Adverse Event Reporting System

Abstract

Background: Natalizumab is a humanized monoclonal antibody to alpha-4 integrin that is approved by the Food and Drug Administration (FDA) for the induction of remission and maintenance of moderate to severe Crohn's disease (CD). Progressive Multifocal Leukoencephalopathy (PML) secondary to an opportunistic infection with John Cunningham virus has been reported with natalizumab usage in CD. We sought to clarify the risk of other opportunistic infections in CD patients treated with natalizumab by analyzing reports to Adverse Event Reporting System (AERS) since its approval. Methods: The AERS is a publicly available database of voluntary reports for post marketing surveillance of all FDA approved drugs. 2,053,106 files between January 2008 and June 2011 were downloaded and analyzed using SPSS 20 (IBM Co. Armonk, NY, USA). They were queried for Primary Suspect (PS) reports of adverse events where natalizumab (or its trade names) was used for the treatment of Crohn's disease. Control drugs (5-aminosalicylic acid and sulphasalazine, including trade names) served as a basis of comparison. Further queries for outcomes of viral, bacterial, fungal and parasitic infection as well as control reactions (syncope, hernia, deafness and vertigopredefined to have no association with natalizumab or control drugs) were performed using reactions terms from the Medical Dictionary for Regulatory Activities. Each report also had concomitant medications analyzed. Any patients reported who used a concomitant biologic medication (including a tumor necrosis factor α inhibitors) were excluded from analysis. Use of immunomodulators (methotrexate, azathioprine, and mercaptopurine) or systemic corticosteroids was noted. Odds ratios for the risk of opportunistic infections with natalizumab were calculated using the Fischer's exact test. Results: 141 PS reports of infections were identified with natalizumab among CD patients, with a majority having a bacterial origin (115 reports, 82%). The reports demonstrated a female predominance (64.54%) with a mean age of 41 ±14 years. Similar usage of corticosteroids was seen among natalizumab cases and controls (14.18% versus 25.93%, p = 0.27) while a higher usage of immunomodulators was seen among control cases (0.71% versus 14.82%, p = 0.004). Significant odds of developing infections with natalizumab were seen only in the subcategory of bacterial infections (table 1). The majority of bacterial infections (figure 1) occurred in the respiratory system (33 reports, 29%) followed by 22 reports (19%) of disseminated infections. Conclusion: Risk of infections in patients receiving natalizumab for CD appears to be restricted to bacterial infections, with a female predominance and mainly affecting the respiratory system. Using this method, significant risk of other opportunistic infections was not found. Table 1: Reported risk of various infections in Crohn's disease patients treated with Natalizumab