Table 3.

Risk Information on Eculizumab-Related Meningococcal Disease

Year/Month	Activities of Events
2016 Oct	The marketing authorization holder released safety information and publicized the first death of meningococcal disease in Japan in a patient receiving eculizumab.20
2017 Sep	The marketing authorization holder revised the package insert and added the information that there have been cases of meningococcal disease including fatal cases even among patients immunized with meningococcal vaccine.21 The company also revised the patient safety card and stated that meningococcal disease may not be prevented even when vaccinated, and meningococcal disease may quickly become severe and lead to death, and warned patients to receive immediate treatment when they experience any of the symptoms of meningococcal disease. In the revised card, limb pain was added as one of the symptoms of meningococcal disease. A former version of the doctor’s information stated that if meningococcal disease was suspected, urgent medical attention and antibacterial treatment as needed were required. The revised version states that meningococcal disease can be fatal or fatal without early recognition and treatment with antibiotics, and if meningococcal disease is suspected or cannot be ruled out, start treatment with the appropriate antibiotic immediately.22
2017 Nov	The review report from PMDA stated that there is a limit in risk management of meningococcal disease with emphasis on vaccination only. It also stated that meningococcal disease may occur as sepsis without meningitis.3
2018 Mar	The marketing authorization holder released the safety information 2nd report that contains specific descriptions of two cases of meningococcal disease in Japan and stated that in the fatal case, a patient safety card was not presented to a physician, whereas in the recovered case, the card was presented to a physician and antibiotic treatment was initiated.23
2018 Apr	Japanese Society of Hematology, Japanese Society of Nephrology, and Japanese Society of Neurology issued the warning that meningococcal vaccination may not prevent meningococcal disease, and it is important to promptly perform examination for meningococcal disease and consider antibiotic administration if high fever develops. In particular, invasive meningococcal infection can occur suddenly as bacteremia without meningitis, and immediately after onset show no leukocytosis or CRP elevation, and it is difficult to distinguish it from influenza or a cold. There is an acute fulminant type that can result in death from sepsis within 24 hours.24–26
2018 May	Japanese Pediatric Society also issued a warning.27

Abbreviation: PMDA, Pharmaceuticals and Medical Devices Agency.