Pharmacovigilance Surveillance of Autoimmune Diseases Induced By Biological Agents: A review of 12013 cases (aeBIOGEAS-SEMI Registry)

RAMOS CASALS MANUEL; ARTEAGA SOFIA; PEREZ ALVAREZ ROBERTO; RETAMOZO SOLEDAD; PEREZ DE LIS MARTA; FLORES-CHAVEZ ALEJANDRA; GALCERÁN-CHAVES CELESTE; KOSTOV, BELCHIN; BRITO ZERON PILAR

San Diego

Congreso; ACR / ARHP ANNUAL MEETING; 2017

American College of Rheumatology

Aims. Biological agents are therapies designed to target a specific molecular component of the immune system, and are currently licensed for use in autoimmune, digestive, dermatological and neoplasic diseases. However, their increasing use has been linked with the paradoxical development of autoimmune processes. The scenario has dramatically change in recent years due to the increased number of biologics used in daily practice and the emerging use of biologics in patients with solid cancers. Methods. In 2006, the Study Group on Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine created the BIOGEAS project, a multicenter study devoted to collecting data on the use and safety of biological agents in adult patients. The aeBIOGEAS Registry (autoimmune events) was designed to collect data on autoimmune diseases secondary to the use of biologic agents, with the aim of formulating a standardized, consensual protocol for these patients, though a systemic and yearly MEDLINE search. The baseline analysis included articles published between January 1990 and December 2007 and identified nearly 200 cases of autoimmune diseases (mainly lupus, vasculitis and sarcoidosis) triggered by biological agents, overwhelmingly anti-TNF. We present the updated results of the aeBIOGEAS Registry (cases collected until May 31, 2017). Results. The aeBIOGEAS Registry currently includes 12013 cases of autoimmune diseases related to the administration of biological agents, including more than 50 different systemic and organ-specific autoimmune processes; the most frequently reported were psoriasis (n=6377), inflammatory bowel disease -IBD- (n=783), demyelinating CNS diseases (n=453), lupus (n=369), interstitial lung diseases -ILD- (n=378), peripheral neuropathies (n=328), vasculitis (n=291) and hypophysitis (n=207). The main biological agents identified consisted of anti-TNF agents in 9220 cases (mainly adalimumab in 4051, infliximab in 3109 and etanercept in 1496), B-cell targeted therapies in 729 (mainly rituximab in 664), immune checkpoint inhibitors in 552 (mainly ipilimumab in 426 and nivolumab in 77) and vascular endothelial growth factor inhibitors in 504 cases (bevacizumab). With respect to the biologic, the main associations were reported for the development of lupus and hepatitis in patients treated with infliximab (44% and 45% of the reported cases of induced lupus and hepatitis, respectively), demyelinating CNS diseases, sarcoidosis, uveitis and IBD in patients treated with etanercept (47%, 41%, 67% and 83%, respectively), psoriasis in patients treated with adalimumab (56%), ILD in patients treated with rituximab (49%) and hypophysitis in patients treated with ipilimumab (96%). With respect to the underlying disease for which the patient received the biological agent, the main associations were reported for the development of lupus, vasculitis and sarcoidosis in patients with RA (68%, 84% and 47% of the reported cases of induced lupus, vasculitis and sarcoidosis, respectively), uveitis and IBD in patients with JIA (60% and 41%, respectively), psoriasis in patients with IBD (33%), hypophysitis in patients with melanoma (90%) and ILD in patients with hematological neoplasia (50%).Conclusion. As the use of biological therapies expands, the number and diversity of induced autoimmune disorders is increasing exponentially (Figure). Paradoxically, for many of these drug-related processes, current treatment indications include the very biological agent producing the adverse event. Management of these biologic-induced autoimmune diseases will be an increasing clinical challenge in the daily practice in the next years.