Questions linger about emicizumab use
PRAGUE – Emicizumab appears safe and effective for patients with hemophilia A undergoing surgical procedures, based on experience with a subpopulation of HAVEN 3 trial participants.
Dr. Elena Santagostino
Out of 28 minor procedures performed without preventive factor VIII (FVIII), only 2 were associated with postoperative bleeds requiring treatment, reported lead author Elena Santagostino, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan, and her colleagues.
All events requiring bleeding treatment were associated with dental procedures, highlighting an area where clinicians and dentists may need to exercise caution. Still, overall results supported emicizumab in a surgical setting.
“There were no thrombotic complications or other unexpected events, including inhibitor development,” Dr. Santagostino said at the annual congress of the European Association for Haemophilia and Allied Disorders.
The findings were drawn from 30 patients who underwent 50 surgeries (46 minor, 4 major) during HAVEN 3, a previously reported phase 3 trial investigating the use of emicizumab, a humanized bispecific monoclonal antibody for patients with hemophilia A without inhibitors.
The minor surgeries included dental or orthopedic procedures, esophagogastroduodenoscopy, or colonoscopy. The four major procedures were all orthopedic (knee arthroscopic synovectomy, biceps femoris tear repair, total ankle arthroplasty, and total hip replacement). The investigators analyzed surgery-related bleeds and the nature of FVIII usage.
Preventive FVIII was used in 18 procedures; infusion duration was 24 hours or less in 14 procedures, between 25 hours and 48 hours in 2 procedures, and more than 72 hours in 2 procedures. The median cumulative preventive FVIII dose per procedure was 30 IU/kg.
Of the 46 minor procedures, 28 (61%) were performed without preventive FVIII, and 2 (7.1%) were associated with bleeding requiring treatment, both after dental procedures. Two other participants who received preventive FVIII also needed postoperative bleeding treatment. Of note, these events were also after dental procedures, meaning all four instances of bleeding requiring treatment during the trial were associated with dentistry.
“[I]n this experience, dental procedures were somewhat tricky because the bleeding complications were mainly there,” Dr. Santagostino said.
When asked by an audience member if this trend was unique to mucosal bleeding, Dr. Santagostino said it was too early to draw such a conclusion but offered some insight. “To control and prevent bleeding during a dental procedure is not trivial, because … sometimes if you stop factor VIII treatment quite early, you may have late bleeding, mainly due to local reasons, because … dental procedures are very heterogenous.”
Among three other participants who had postoperative bleeding but did not require treatment, two underwent dental procedures, further supporting this association. Although the study numbers are relatively small, the findings may at least support caution, if not preventive FVIII in the dental setting, Dr. Santagostino said.
The four major procedures – all orthopedic – were knee arthroscopic synovectomy, biceps femoris tear repair, total ankle arthroplasty, and total hip replacement. Along with preoperative preventive FVIII, three of four patients undergoing major surgery received preventive FVIII for 14-18 days postoperatively. Doses ranged from 99-522 IU/kg. No postoperative bleeds occurred in this subgroup.
Study funding was provided by F. Hoffmann–La Roche and Chugai Pharmaceutical. The investigators reported financial relationships with Bayer, Shire, Pfizer, Novo Nordisk, and others.
SOURCE: Santagostino E et al. EAHAD 2019, Abstract OR15.