Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. Patients on prophylaxis were administered one dose of 50 IU/kg of N8-GP every fourth day. Bleeds were treated with doses of 20-75 IU/kg. Total exposure to N8-GP in the trial was 14,114 exposure days (159 patient-years). For the prophylaxis arm (n=175), the median annualised bleeding rate (ABR) was 1.33 (interquartile range, 0.00-4.61), the mean ABR was 3.70 (95 % confidence interval 2.94-4.66) and 70 (40 %) patients had no bleeds during the trial. Across treatment arms, 83.6 % of bleeds resolved with one injection and 95.5 % with up to two injections. N8-GP had a favourable safety profile and was well tolerated. The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units [BU]) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients.

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BackgroundTocilizumab, an interleukin-6 (IL-6) receptor antagonist, has been used in patients with coronavirus disease 2019 as an anti-cytokine agent. IL-6 also plays a complex role in hemostasis and thrombosis. We observed a transient elevation of D-dimer in our patients who received tocilizumab, which triggered this study. MethodsA retrospective hospital-based cohort analysis of patients with confirmed COVID-19 who received tocilizumab during the study period of March 15, 2020, to May 20, 2020, was conducted. We retrieved demographic, clinical, and laboratory data, and patients who were receiving therapeutic anticoagulation therapy prior to tocilizumab administration were excluded. Descriptive analysis was performed, and the cause of death and trends of D-dimer and inflammatory markers were studied. ResultsOut of the 436 confirmed COVID-19 patients admitted during the study period, 24 met the inclusion criteria. Their median age was 47.5 years. They were 18 males and 6 females; 15 patients survived and nine expired. Of the group that survived, 12 received therapeutic anticoagulation. Of the seven patients who did not receive therapeutic anticoagulation, four expired (one from sepsis and three probably from thromboembolic complications) compared to five deaths in the 17 patients who received therapeutic anticoagulation (four from sepsis and one possibly from thromboembolic complications). ConclusionsThe interplay between IL-6, IL-6 receptor antagonist, and venous thromboembolism is complex. We observed a transient elevation of D-dimer in COVID-19 patients who received tocilizumab, and a trend toward increased death secondary to thromboembolism. This observation is novel and highlights the potential thrombophilic side effects of tocilizumab.

Acute kidney injury is commonly observed in patients with multiple myeloma and other plasma cell dyscrasias. The pathophysiologic causes, however, are varied. We report a case of a severe 'drug reaction with eosinophilia and systemic symptoms' syndrome associated with acute interstitial nephritis in a patient with multiple myeloma likely related to the administration of lenalidomide. This disease entity requires prompt recognition and cessation of the offending drug and often treatment with high-dose corticosteroids.