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January 1, 2023
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COVID-19 Vaccine, 2023-2024 Formula (Comirnaty, Spikevax)
By Carol A. Kemper, MD, FACP
Loss of Monoclonal Therapy for COVID-19
This retrospective cohort study performed at the Mayo Clinic in Minnesota from February to June 2022 was the first peer-reviewed publication demonstrating the efficacy of the monoclonal antibody bebtelovimab in the prevention of severe COVID-19 infection compared with nirmatrelvir/ritonavir (Paxlovid).1 A total of 3,607 patients infected with SARS-CoV-2 who were at high risk for progression and who received one or the other agent were assessed for severe outcomes at 30 days post-infection (including hospitalization and death). Approximately 92% of the patients in each group had received at least two COVID-19 vaccines. More patients received bebtelovimab (n = 2,833), and this group was older and a greater number had underlying cardiac, lung, and kidney disease. In addition, 20% of the bebtelovimab group were immunocompromised, including transplant patients, compared with only 2.7% of the Paxlovid group. Despite these significant differences in comorbidities, outcomes at 30 days were similar between the two groups. Progression to severe disease occurred in 1.4% of those receiving bebtelovimab vs. 1.2% of those receiving Paxlovid; and 0.5% of those receiving bebtelovimab required intensive care vs. 0.3% of those receiving Paxlovid. Only six patients died (0.2%), all in the bebtelovimab group.
It is impossible to keep up — and certainly the literature cannot. No sooner had this brief report been published Nov. 15, 2022, when the Food and Drug Administration (FDA) pulled their approval for emergency use of bebtelovimab in the United States on Nov. 30, 2022, for lack of effectiveness against Omicron subvariants BQ.1 and BQ.1.1.1
Over the past two years, the FDA has issued emergency use authorizations for six new monoclonal antibodies in the fight against SARS-CoV-2, none of which are still available. While the monoclonal antibodies sotrovimab and bamlanivimab were used extensively during the winter surge 2021-2022, by March 2022, reports indicated bamlanivimab had lost neutralizing activity against Omicron BA.2, and sotrovimab had lower efficacy against Omicron BA.1 and BA.1.1 and even less effectiveness against BA.2 strains.2 On Feb. 11, 2022, the FDA issued an emergency use authorization for bebtelovimab for use in mild to moderate COVID-19 infection in adults and pediatric patients > 12 years of age at high risk for progression.
By now, we are well past those BA strains mentioned earlier, and their recombinant XE strains, but have moved on to BA.5 and sublineages BQ.1 and BQ.1.1. These latter two subvariants now constitute approximately 57% of the infecting strains in the United States. Data suggest these variants are ~1.5 times as transmissible as earlier BA variants. Other subvariants being closely monitored include BA.2.75, XBB, and BA.2.3.20.
Currently, there are no effective monoclonal antibody therapies available for use against SARS-CoV-2 in the United States. Earlier reports indicated that the antiviral agents remdesivir, molnupiravir, and nirmatrelvir are similarly effective against the Omicron BA.2 strains as against “ancestral strains,” but there are no available data on their efficacy against the current variants.
Information on nomenclature and current variants of concern, and their sublineages, with information on specific genetic mutations, are reviewed in the World Health Organization document.3
- Razonable RR, O’Horo JC, Hanson SN, et al. Comparable outcomes for bebtelovimab and ritonavir-boosted nirmatrelvir treatment in high-risk patients with coronavirus disease-2019 during severe acute respiratory syndrome coronavirus 2 BA.2 Omicron epoch. J Infect Dis 2022;226:1683-1687.
- Takashita E, Kinoshita N, Yamayoshi S, et al. Efficacy of antiviral agents against the SARS-CoV-2 Omicron subvariant BA.2. N Engl J Med 2022;386:1475-1477.
- World Health Organization. Tracking SARS-CoV-2 variants.
Cost-Savings of Outpatient Antimicrobial Therapy
SOURCE: Staples JA, Ho M, Ferris D, et al. Outpatient versus intravenous antimicrobial therapy: A population-based observational cohort study of adverse events and costs. Clin Infect Dis 2022;75:1921-1929.
I am old enough to remember the days when patients were stuck in the hospital for weeks to receive their intravenous (IV) antibiotics for osteomyelitis or other serious infections, many of whom were frustrated and bored. Outpatient programs for the administration of IV antimicrobial therapy took off in the 1990s-2000s and now have become the norm for eligible patients.
Cost-effectiveness studies of outpatient parenteral antimicrobial therapy (OPAT) programs are difficult to perform, in part because of possible selection bias, ascertainment/interpretation of outcomes, and a lack of a comparator group. This Canadian-based matched population study compared the cost and adverse outcomes associated with OPAT vs. inpatient parenteral antimicrobial therapy (IPAT) in British Columbia from 2012-2018. The authors identified a population of 5,928 individuals requiring prolonged IV antimicrobial therapy and created a matched cohort of 921 OPAT and 921 IPAT individuals, based on comorbidities, infection type, and antimicrobial agent. Patients were excluded from the analysis if their total length of stay was less than one day, they left against medical advice, they had prior OPAT therapy within the previous two weeks, or they required hemodialysis within the subsequent two weeks.
Adverse events occurring within 90 days of initiation of therapy included acute kidney injury, venous thromboembolism, Clostridioides difficile infection (CDI), neutropenia, unplanned hospital re-admission, and death. A secondary analysis was performed excluding patients who died within 90 days assuming they were not eligible for OPAT. Notably, allergic reaction, eosinophilia, and rash were not included in this analysis because of difficulty with attribution to antimicrobial therapy.
Infections requiring treatment in this study included osteomyelitis (38.2%), native joint infection (19.1%), prosthetic joint infection (17.6%), endocarditis (11.7%), epidural abscess (1.8%), and pneumococcal meningitis (0.8%). More than two-thirds of patients required peripherally inserted central catheter (PICC) line insertion. The average length of OPAT therapy was 27 days. Adverse events occurred in 35.6% of OPAT patients vs. 39% of IPAT patients (odds ratio [OR], 1.4). OPAT patients were more likely to require unplanned readmission within 90 days compared with IPAT patients (30.5% vs. 23%) and were significantly less likely to develop CDI (1.2% vs. 3.1%) or to die (2% vs. 8.8%). On average, including the index hospitalization and any future hospitalizations, OPAT patients required 32 fewer days of hospitalization compared with IPAT patients.
The estimated cost of treatment was 40% less for OPAT patients ($30,166) compared with IPAT patients ($50,038) (it is not clear whether these were 2018 Canadian dollars).
OPAT can be conducted at outpatient infusion centers or in the home. Either way, OPAT generally requires a team of people who continue to monitor the patient and provide follow-up and advice as needed, including an infectious disease physician, an outpatient infusion company with outpatient infusion nurses and specialized pharmacists, and administrative support. This team provides 24/7 patient care coverage, including weekends and holidays. From my perspective, the most important member of this team is our office nurse, who can respond to patient questions and provide triage for new or recurrent symptoms, medication reactions, or problems with the line — something a medical assistant cannot do.
Interestingly, the physician fees outlined in this study were fairly similar for delivery of either IPAT or OPAT therapy, although I suspect much of the supervision of OPAT care is delivered by phone and free-of-charge. Although a great boon to our patients, OPAT therapy is a time sink for clinic office staff, who can spend hours sorting out how to deal with an ineffectual PICC line or complications of therapy. Importantly, cost-cutting measures are reducing our supply of experienced outpatient nursing staff who can help to manage these problems.
This study does not address the possible disparity in care for elderly Medicare patients, many of whom are forced to receive their IV antimicrobials in a skilled nursing facility because of cost issues. (While Medicare covers the cost of home care visits, PICC line care, and phlebotomy, the cost of the actual antibiotics is not covered — a cost limitation for many elderly patients.) So instead of sitting in the hospital for four to six weeks, older persons with Medicare now have to stay in a facility for four to six weeks, where they are potentially exposed to C. difficile, SARS-CoV-2, and multidrug-resistant organisms. Eligibility criteria for OPAT therapy are outlined by the Infectious Diseases Society of America but make no mention of a lack of Medicare coverage for IV antibiotic therapy.
This study also does not address the cost savings that infectious disease physicians deliver by providing direct OPAT therapy to select patients, thereby avoiding hospitalization altogether — something that requires hours and hours of office time to set up but ultimately is so much more satisfying (and presumably cost effective) to the patient.
Loss of Monoclonal Therapy for COVID-19; Cost-Savings of Outpatient Antimicrobial Therapy
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