Of 2 patient fatalities in the analysis, one was unvaccinated and treated with nonconventional therapies for COVID-19 and the other had a history of deep venous thrombosis and was complicated by pulmonary embolism.
New data from a post-hoc analysis showed a low incidence rate of 0.024 in COVID-19 infections in patients with neuromyelitis optica spectrum disorder (NMOSD) receiving inebilizumab (Uplizna; Horizon Therapeutics), an anti-CD19, B-cell depleting monoclonal antibody.1
Data from the N-MOmentum trial (NCT02200770) trial showed that over a 28-month period,17 COVID-19 infections were reported and confirmed among 182 inebilizumab-treated patients with NMOSD (women, n = 15, unknown, n = 2) between March 2020 and July 2022. Two of these reported infestions were observed between March and November 2020, prior to the availability of vaccines, while the remainder were reported as of July 31, 2022.
Findings were presented as an abstract poster at the 2023 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum held February 23-25, in San Diego, California, by lead author Bruce Cree, MD, PhD, MAS, FAAN, professor of clinical neurology, University of California, San Francisco (USCF) Weill Institute for Neurosciences, and clinical research director, UCSF Multiple Sclerosis and Neuroinflammation Center. In this analysis, investigators explored the risk and outcomes of COVID-19 infection in patients receiving inebilizumab.
“This raises a very important question, is COVID vaccination effective in patients who are treated with B cell depleting therapies? I think this is another area of investigation, which really is very important. We've never seen COVID before you've seen other coronaviruses but they're very different. Unlike influenza, where we have all these layers of immunity against influenza, we need those layers of immunity if you're on a B cell depleting therapy. At least the humoral component of immunity, which is the antibody portion of it is abrogated by treatment with inebilizumab and other B cell depleting antibodies,” Cree told NeurologyLive®.
Reports of adverse reactions because of COVID-19 infections were analyzed in patients treated with inebilizumab in the N-MOmentum clinical trial during the COVID-19 pandemic, period overlapped between March 2020 and November 2020 and a post-approval safety database where the cutoff for data was July 31, 2022. The median age of infected patients was 57 (range, 32-68) years (n = 15). The median treatment exposure to inebilizumab for patients was 123 days (range, 10-2379 days, n = 11) from the first infusion to COVID-19 diagnosis.
Among the total 17 adverse events, 10 were reported as serious and 5 reported having pneumonia. Of 10 patients with known outcomes, 6 reported “recovered/resolved,” 2 reported not recovered/resolved at the same time of reporting, and 2 patients died. The 1 patient, a 62-year-old from Peru, died May 2020 before vaccines became available. Reasons for the death included the possibly because of COVID pneumonia, possible renal failure, received antibiotics, hydroxychloroquine and ivermectin. The other patient, 32 years from the US, died Feb 2021, with reasons possibly because of vaccinated partially, a history of obesity, deep vein thromboembolism, sickle cell trait, treated for possible COVID pneumonia complicated by pulmonary embolis with acute cor pulmonale. Treatment with inebilizumab was reported as not changed in 3 of the patients, discontinued in 1 patient, and action unknown in the rest of the patients.
“We need to understand the T-cell function there a bit better and we also need to develop strategies for if we want to see a strong and robust humoral response, what to do with inebilizumab patients or for that matter anti-CD20 treated patients?,” Cree added.
Limitations of the analysis include that milder COVID cases were possibly under-reported, as well as that COVID-19 vaccination status was not known in the patients. Investigators noted that vaccination status and comorbidities of these patients are being further investigated.
Another post hoc analysis on N-MOmentum trial in February 2022, suggested that inebilizumab was effective in reducing the severity of attacks for patients with NMOSD.2 These findings, presented at the 48th Annual Meeting of the North American Neuro-Ophthalmology Society (NANOS 2022), Feb 12-17, in Austin, Texas, showed that 89% of the 161 patients treated with inebilizumab were attack-free vs 58% of the 52 patients who received placebo during the placebo-controlled period.