Patients with paroxysmal nocturnal hemoglobinuria (PNH) who are receiving complement inhibitors are at an increased risk of infection, and there are questions surrounding the timing and effectiveness of vaccines. New data regarding the frequency of these infections and the response to vaccines in patients with PNH were presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition.

Following these proceedings, featured expert Ronald S. Go, MD, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD. Dr Go’s clinical perspectives on these findings are presented here.

The risk of infection with encapsulated bacteria is much higher in patients with PNH who receive anticomplement therapy compared with the general population. An interesting study presented at ASH 2023 evaluated the competency of the immune system to mount a spike-specific IgG antibody response after a series of 4 doses of the SARS-CoV-2 vaccine in patients with PNH and/or aplastic anemia and in healthy volunteers (abstract 2712). Some patients, especially those with PNH, were receiving complement inhibitors. After the first dose, 42.6% of patients with PNH and aplastic anemia did not mount a spike-specific IgG antibody response compared with 5% of healthy volunteers. The IgG titers of patients with PNH and aplastic anemia caught up to those of healthy volunteers after the third dose. I think that this reinforces the need for patients with PNH to receive an adequate series of vaccinations, including boosters.

The current mitigation strategy for preventing infection in adults who are on anticomplement therapy is to give vaccines against encapsulated bacteria before starting the therapy and then start antibiotic therapy during the first 2 weeks of complement inhibitor therapy until the vaccines work. The question is whether you should give the vaccine before starting anticomplement therapy or after starting anticomplement therapy. Some experts suggest giving the vaccine after the patient gets the first dose of anticomplement therapy and under antibiotic coverage. That way, complement is already suppressed, so it is less likely to be amplified and there is a lower risk of worsening hemolysis if vaccines are administered. In my opinion, both approaches are quite effective, and, with the current strategy of oral antibiotics for the first 2 weeks of complement inhibitor therapy, I have not personally seen anyone have serious infections. We understand that the risk of infection with encapsulated bacteria, including Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type b, is still much higher, but the incidence is low (abstract 575). So, I would say that the current mitigation strategy works well.

There is guidance from the Centers for Disease Control and Prevention (CDC) that patients receiving complement inhibitors should be revaccinated against meningococcal disease every 2 to 5 years, depending on the vaccine. This is just one example of the role that boosters can play in these patients. Thus, these vaccines are not “one and done,” and that is something that the clinician should remember because, after years of treatment and no infections happening, it is easy to forget that patients receiving complement inhibitors need boosters when nonimmunocompromised patients and those who are not on this therapy may not need boosters.

Although C3 inhibitors are newer on the market, and long-term data are therefore not there, I do not see a big difference at the practice level in terms of infectious complications with these agents compared with C5 inhibitors. In my practice, I see 10 times more patients with atypical hemolytic uremic syndrome than with PNH, and I have used the C5 inhibitors 10 times more often, although many of these patients do not need more than 6 months of therapy. But I think that the infectious safety, at least for the first year, is similar between C3 and C5 inhibitors.