P046 - Cumulative review of thrombotic microangiopathy, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome reports with SC interferon beta-1a

Abstract

Background/objectives Rare cases of thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome have been reported with interferon beta products. This was a cumulative review of thrombotic microangiopathy cases recorded in a Global Safety Database for subcutaneous interferon beta-1a. Methods Search criteria were all reported cases, serious and non-serious, from all sources (including non-healthcare professionals and clinical trial reports), regardless of event ranking and causality assessment by reporter or Company; data lock was 03 May 2014. Results Ninety one cases with 105 events were retrieved; 76.9% (70/91) patients were female, consistent with the underlying disease of multiple sclerosis. Time-to-onset varied from 2 months to 14 years; 31.9% events occurred within 2-years of treatment initiation. 7 patients had a fatal outcome (5 were secondary to other causes; 2 had insufficient information). 44 patients recovered, 32 had not recovered at the time of the report and in 8 cases the outcome was not reported/unknown. Treatment was discontinued in 84.6% (77/91). In 67.0% (61/91), a causal association between treatment and the occurrence of thrombotic microangiopathy, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected. Risk factors and/or confounding factors were present in 41/91 cases (45.1%). Early prodromal syndrome or specific patterns were not detected although 55.0% (50/91) contained insufficient information. The overall reporting rate of thrombotic microangiopathy, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was 7.2 per 100,000 patient-years. Reporting rates for human serum albumin-containing versus human serum albumin-free formulations were 5.72 and 7.68 per 100,000 patient-years, respectively. Conclusions No new signal relating specifically to increased frequency of thrombotic microangiopathy, as thrombotic thrombocytopenic purpura and hemolytic uremic syndrome with the human serum albumin-free formulation was detected and no additional risk mitigation measures were required regarding the different formulations. The benefit-risk balance of subcutaneous interferon beta-1a remains positive and routine pharmacovigilance monitoring is appropriate.