Cumulative Review of Thrombotic Microangiopathy, Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome Reports with Subcutaneous Interferon β-1a (P3.270)

OBJECTIVE: To review cases of thrombotic microangiopathy (TMA) recorded in a Global Safety Database for subcutaneous (sc) interferon β-1a. BACKGROUND: Rare cases of TMA, manifested as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS) have been reported with interferon β products. DESIGN/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: A total of 91 cases with 105 events were retrieved; 76.9[percnt] (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[percnt] events occurred within 2-years of treatment initiation. Seven patients had a fatal outcome (5 were secondary to other causes; 2 haali-frederic.bend insufficient information). Forty-four 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[percnt] (77/91). In 67.0[percnt] (61/91), a causal association between treatment and the occurrence of TMA, TTP-HUS was suspected. Risk factors and/or confounding factors were present in 41/91 cases (45.1[percnt]). Early prodromal syndrome or specific patterns were not detected although 55.0[percnt] (50/91) contained insufficient information. The overall reporting rate of TMA, TTP-HUS was 7.2 per 100,000 patient-years. Reporting rates for human serum albumin (HSA)-containing versus HSA-free formulations were 5.72 and 7.68 per 100,000 patient-years, respectively. CONCLUSIONS: No new signal relating specifically to increased frequency of TMA as TTP and HUS with the HSA-free formulation was detected and no additional risk mitigation measures were required regarding the different formulations. The benefit-risk balance of sc interferon β-1a remains positive and routine pharmacovigilance monitoring is appropriate. Study Supported by: Merck Serono SA Aubonne, Switzerland, a subsidiary of Merck KGaA, Darmstadt, Germany.