Pharmacovigilance Surveillance of Autoimmune Diseases Induced By Biological Agents: A review of 16123 cases (aeBIOGEAS-SEMI Registry)

RETAMOZO SOLEDAD; SISO ALMIRALL ANTONI; BRITO ZERON PILAR; RAMOS CASALS MANUEL; KOSTOV, BELCHIN; PEREZ ALVAREZ ROBERTO; FLORES-CHAVEZ ALEJANDRA; PEREZ DE LIS MARTA

Amsterdam

Congreso; EUROPEAN LEAGUE AGAINST RHEUMATISM (EULAR); 2018

EULAR

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 Dec 31, 2017). Results. The aeBIOGEAS Registry currently includes 16123 cases of more than 50 different systemic and organ-specific triggered autoimmune diseases related to the administration of 46 different biological molecules in patients with inflammatory/neoplasic underlying diseases. Underlying diseases consisted on inflammatory diseases in 9907 (61%) cases, overwhelmingly rheumatic diseases (n=8639), and cancer in the remaining 6216 (39%) cases, overwhelmingly solid neoplasia (n=5955). The main biological agents identified consisted of anti-TNF agents in 9514 cases (mainly adalimumab in 4147, infliximab in 3028 and etanercept in 1648), checkpoint inhibitors in 5264 (overwhelmingly the CTL4 inhibitor ipilimumab in 4980 cases), thyrosine kinase inhibitors in 952 (mainly imatinib in 377 cases) and B-cell targeted therapies in 298 cases. Organ-specific classification of triggered autoimmune diseases included cutaneous (n=7140), digestive (n=2323), endocrine (n=1701), pulmonary (n=1683), systemic/rheumatic (n=1230), neurological (n=1172), ocular (n=349), cardiac (n=322), hematological (n=106) and renal (n=96). The most frequently reported induced autoimmune diseases were psoriasis (n=6401), enterocolitis (n=1947), interstitial lung diseases (n=1680), thyroiditis (n=1076), hypophysitis (n=492), demyelinating CNS diseases (n=452), peripheral neuropathies (n=431), lupus (n=371), vasculitis (n=339), uveitis (n=298), vitiligo (n=256) and sarcoidosis (n=185). Conclusion. The number and diversity of induced autoimmune disorders is increasing exponentially in parallel with the increased use of biological therapies in neoplasic diseases, which are currently representing 40% of reported cases. Management of these biologic-induced autoimmune diseases will be an increasing multidisciplinary clinical challenge in the daily practice in the next years.