Tixagevimab/cilgavimab
Dotaz
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Despite lower virulence, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) still poses a relevant threat for immunocompromised patients. A retrospective multicentric study was conducted to evaluate the efficacy of pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) with a 6-month follow-up for preventing severe COVID-19 in adult patients with hematology malignancy. Among the 606 patients in the cohort, 96 (16%) contracted COVID-19 with a median of 98.5 days after Evusheld administration. A total of 75% of patients had asymptomatic or mild severity of COVID-19, while just 25% of patients with SARS-CoV-2 positivity had to be hospitalized. Two patients (2%) died directly, and one patient (1%) in association with COVID-19. Eight patients (1.3%) of every cohort experienced adverse events related to Evusheld, mostly grade 1 and of reversible character. It was found that complete vaccination status or positive seroconversion was not associated with lower risk of COVID-19 infection. Previous treatment with an anti-CD20 monoclonal antibody was associated with higher rates of COVID-19, while previous treatment with anti-CD38 monoclonal antibody was not, as was the case for recipients of hematopoietic stem cell transplantation or CAR-T cell therapy. Presence of other comorbidities was not associated with more severe COVID-19. The results support the growing evidence for Evusheld's efficacy against severe COVID-19 in patients with hematology malignancies.
- MeSH
- COVID-19 * MeSH
- dospělí MeSH
- hematologické nádory * komplikace farmakoterapie epidemiologie MeSH
- lidé MeSH
- monoklonální protilátky MeSH
- preexpoziční profylaxe * MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: AntiCD20 therapy, such as rituximab, ocrelizumab, or ofatumumab, effectively treats patients with multiple sclerosis (pwMS) or neuromyelitis optica spectrum disorder (pwNMOSD) but negatively affects the humoral immune response to COVID-19 vaccination. One strategy to protect these patients is using tixagevimab/cilgavimab (T/C) as pre-exposure prophylaxis. This study aimed to evaluate the effect of T/C on the incidence of COVID-19 in pwMS and pwNMOSD. METHODS: Data in this observational cohort study were collected in two Czech MS centres through ReMuS registry between March 1, 2020 and December 31, 2022. Adult pwMS and pwNMOSD who were (1) treated with antiCD20 therapy at least six months before T/C administration, or at least from February 1, 2022 in the control group; (2) were already on antiCD20 therapy at the time of vaccination or COVID-19 infection; and (3) were on antiCD20 therapy at least 100 days after T/C, or at least 90 days after August 1, 2022 in the control group, were included. Analysis was performed using frequency-based (propensity score matching) and Bayesian statistical methods (informative and non-informative priors). RESULTS: Using propensity score matching 1:1, 47 patients who received T/C (mean age 45.7 years, median disease duration 12.5 years) were matched with those who did not receive T/C (n = 341; mean age 46.6 years, median disease duration 11.4 years) based on age, MS/NMOSD duration, and number of vaccine doses. None of the T/C patients and three in the control matched group, developed COVID-19 between 10 and 100 days after receiving T/C, August 1, 2022, respectively. The frequency of COVID-19 was not significantly different between groups (p = 0.242). Due to the low number of patients, a Bayesian analysis was also added. Using a non-informative Bayesian prior, the median relative risk of COVID-19 after T/C was 7.6 % (95 % CrI 0.02-115.9 %). The posterior probability of risk difference lower than zero was 96.4 %. Using an informative prior (based on the registration study of Evusheld), the median relative risk of COVID-19 after T/C was 20.2 % (95 % CI 8.4-43.8 %). The posterior probability of the risk difference lower than zero was 100 %. CONCLUSION: This work highlights the possible good efficacy of T/C in antiCD20-treated pwMS and pwNMSOD. Based on Bayesian analysis with an informative prior, the T/C group's risk of COVID-19 infection was approximately 20.2 % of the control group's risk. However, given the low frequency of COVID-19, the results of this pilot analysis must be interpreted with caution.
- MeSH
- COVID-19 * prevence a kontrola komplikace MeSH
- dospělí MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- imunologické faktory MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- neuromyelitis optica * farmakoterapie MeSH
- preexpoziční profylaxe metody MeSH
- roztroušená skleróza * farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Česká republika MeSH
In the post-pandemic COVID-19 period, human activities have returned to normal and COVID-19 cases are usually mild. However, patients with multiple myeloma (MM) present an increased risk for breakthrough infections and severe COVID-19 outcomes, including hospitalization and death. The European Myeloma Network has provided an expert consensus to guide patient management in this era. Vaccination with variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4/5 strains, is essential as novel strains emerge and become dominant in the community. Boosters should be administered every 6-12 months after the last vaccine shot or documented COVID-19 infection (hybrid immunity). Booster shots seem to overcome the negative effect of anti-CD38 monoclonal antibodies on humoral responses; however, anti-BCMA treatment remains an adverse predictive factor for humoral immune response. Evaluation of the immune response after vaccination may identify a particularly vulnerable subset of patients who may need additional boosters, prophylactic therapies and prevention measures. Pre-exposure prophylaxis with tixagevimab/cilgavimab is not effective against the new dominant variants and thus is no longer recommended. Oral antivirals (nirmatrelvir/ritonavir and molnupiravir) and remdesivir are effective against Omicron subvariants BA.2.12.1, BA.4, BA.5, BQ.1.1 and/or XBB.1.5 and should be administered in MM patients at the time of a positive COVID-19 test or within 5 days post symptoms onset. Convalescent plasma seems to have low value in the post-pandemic era. Prevention measures during SARS-CoV-2 outbreaks, including mask wearing and avoiding crowded places, seem prudent to continue for MM patients.
- MeSH
- COVID-19 * epidemiologie MeSH
- konsensus MeSH
- lidé MeSH
- mnohočetný myelom * terapie MeSH
- neutralizující protilátky MeSH
- pandemie MeSH
- SARS-CoV-2 MeSH
- sérologická léčba covidu-19 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
COVID-19 způsobený SARS-CoV-2 představuje již více než dva roky život ohrožující globální pandemické onemocnění, které přispívá k vysoké úmrtnosti. Obzvláště rizikovou skupinou jsou starší jedinci s komorbiditami a imunokompromitovaní nemocní. Úsilí vědeckého výzkumu se proto intenzivně soustředí na vývoj a optimalizaci léčby nemoci COVID-19. Časná léčba SARS-CoV-2-neutralizujícími monoklonálními protilátkami se ukázala in vitro i v klinické praxi jako účinná u pacientů s vysokým rizikem progrese nemoci do těžkého COVID-19. Souhrnná práce shrnuje potenciální klinické přínosy nedávno schválené kombinace monoklonálních protilátek tixagevimab a cilgavimab pro prevenci a léčbu COVID-19.
COVID-19 caused by SARS-CoV-2 is a life-threatening global pandemic disease that has led to high mortality for over two years. Elderly individuals with comorbidities and immunocompromised patients are particularly at risk. Scientifi c research eff orts are therefore intensively focused on the development and optimization of COVID-19 treatment. Early treatment with SARS-CoV-2-neutralizing monoclonal antibodies has been shown to be eff ective both in vitro and in clinical practice in patients at high risk of disease progression to severe COVID-19. This paper summarizes the potential clinical benefi ts of the recently approved monoclonal antibody combination tixagevimab and cilgavimab for COVID-19 prevention and treatment.
- Klíčová slova
- tixagevimab, cilgavimab, imunokompromitovaný hematologický pacient,
- MeSH
- COVID-19 * prevence a kontrola terapie MeSH
- farmakoterapie COVID-19 * metody MeSH
- fixní kombinace léků MeSH
- hematologické nádory MeSH
- lidé MeSH
- monoklonální protilátky farmakologie terapeutické užití MeSH
- preexpoziční profylaxe metody MeSH
- randomizované kontrolované studie jako téma MeSH
- vakcinace metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
