Dataset Information

Immunomodulators and risk for breakthrough infection after third COVID-19 mRNA vaccine among patients with rheumatoid arthritis: A cohort study.

ABSTRACT:

Objectives

To investigate COVID-19 breakthrough infection after third mRNA vaccine dose among patients with RA by immunomodulator drug class, and we hypothesized that CD20 inhibitors (CD20i) would have higher risk for breakthrough COVID-19 vs. TNF inhibitors (TNFi).

Methods

We performed a retrospective cohort study investigating breakthrough COVID-19 among RA patients at Mass General Brigham in Boston, MA, USA. Patients were followed from the date of 3rd vaccine dose until breakthrough COVID-19, death, or end of follow-up (18/Jan/2023). Covariates included demographics, lifestyle, comorbidities, and prior COVID-19. We used Cox proportional hazards models to estimate breakthrough COVID-19 risk by immunomodulator drug class. We used propensity score (PS) overlap-weighting to compare users of CD20i vs. TNFi.

Results

We analyzed 5781 patients with RA that received 3 mRNA vaccine doses (78.8% female, mean age 64.2 years). During mean follow-up of 12.8 months, 1173 (20.2%) had breakthrough COVID_19. Use of CD20i (adjusted HR 1.74, 95%CI 1.30-2.33) and glucocorticoid monotherapy (adjusted HR 1.47, 95%CI 1.09-1.98) were each associated with breakthrough COVID-19 compared to TNFi use. In the PS overlap-weighted analysis, CD20i users also had higher breakthrough COVID-19 risk than TNFi users (HR 1.62, 95%CI 1.02-2.56). A sensitivity analysis excluding patients with cancer or interstitial lung disease yielded similar findings.

Conclusions

We identified CD20i and glucocorticoid monotherapy as risk factors for breakthrough COVID-19 among patients with RA after a 3rd vaccine dose. This contemporary study highlights the real-world impact of blunted immune responses in these subgroups and the need for effective risk mitigation strategies.

SUBMITTER: Schiff AE

PROVIDER: S-EPMC10592996 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Immunomodulators and risk for breakthrough infection after third COVID-19 mRNA vaccine among patients with rheumatoid arthritis: A cohort study.

Schiff Abigail E AE Wang Xiaosong X Patel Naomi J NJ Kawano Yumeko Y Kowalski Emily N EN Cook Claire E CE Vanni Kathleen M M KMM Qian Grace G Bade Katarina J KJ Saavedra Alene A AA Srivatsan Shruthi S Williams Zachary K ZK Venkat Rathnam K RK Wallace Zachary S ZS Sparks Jeffrey A JA

medRxiv : the preprint server for health sciences 20231009

<h4>Objectives</h4>To investigate COVID-19 breakthrough infection after third mRNA vaccine dose among patients with RA by immunomodulator drug class, and we hypothesized that CD20 inhibitors (CD20i) would have higher risk for breakthrough COVID-19 vs. TNF inhibitors (TNFi).<h4>Methods</h4>We performed a retrospective cohort study investigating breakthrough COVID-19 among RA patients at Mass General Brigham in Boston, MA, USA. Patients were followed from the date of 3rd vaccine dose until breakth ...[more]

PMID: 37873462

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Project description:BackgroundThe SARS-CoV-2 mRNA vaccine has been reported to cause various adverse reactions, including the development or exacerbation of autoimmune diseases, but the adverse reactions and the effects of the vaccines on disease activity in patients with rheumatoid arthritis (RA) remain unknown. We therefore investigated the arthritis condition in RA patients after SARS-CoV-2 vaccination.MethodsRA patients who visited our hospital from January to April 2022 completed a questionnaire regarding adverse reactions to the SARS-CoV-2 vaccine. We compared the frequency and duration of post-vaccination arthralgia between RA patients and health care workers in our hospital. For the RA patients who reported post-vaccination arthralgia, we collected medical records for the 6 months after vaccination.ResultsOf the 1198 vaccinated RA patients, 256 (21.4%) had systemic inflammatory symptoms, 18 (1.5%) had allergies including urticaria and asthma, and 37 (3.1%) had arthralgia. A few patients had extra-articular manifestations such as acute exacerbation of interstitial lung disease. Compared with health care workers, RA patients more frequently developed arthralgia, and the arthralgia was longer lasting than that in controls: only 9 (0.8%) of the 1117 health care workers reported arthralgia, and all cases resolved within 3 days. Data from 31 of the 37 RA patients with post-vaccination arthralgia were further analyzed; in these patients, disease activity was highest after 2 months, and 10 patients required additional DMARDs within 6 months. The proportion of concomitant use of PSL at vaccination was higher in these patients. No patients on biological DMARDs or targeted synthetic DMARDs prior to vaccination needed additional DMARDs or a change of regimen.ConclusionRA patients had more frequent and longer-lasting arthralgia after vaccination than healthy subjects, and one-third of patients with post-vaccination arthralgia required additional DMARDs. Although the SARS-CoV-2 mRNA vaccine was administered safely in most RA patients, in some patients RA symptoms may worsen after vaccination.

Project description:ImportanceLittle is known about COVID vaccine breakthrough infections and their risk factors.ObjectiveTo identify risk factors associated with COVID-19 breakthrough infections among vaccinated individuals and to reassess the effectiveness of COVID-19 vaccination against severe outcomes using real-world data.Design setting and participantsWe conducted a series of observational retrospective analyses using the electronic health records (EHRs) of Columbia University Irving Medical Center/New York Presbyterian (CUIMC/NYP) up to September 21, 2021. New York adult residence with PCR test records were included in this analysis.Main outcomes and measuresPoisson regression was used to assess the association between breakthrough infection rate in vaccinated individuals and multiple risk factors - including vaccine brand, demographics, and underlying conditions - while adjusting for calendar month, prior number of visits and observational days. Logistic regression was used to assess the association between vaccine administration and infection rate by comparing a vaccinated cohort to a historically matched cohort in the pre-vaccinated period. Infection incident rate was also compared between vaccinated individuals and longitudinally matched unvaccinated individuals. Cox regression was used to estimate the association of the vaccine and COVID-19 associated severe outcomes by comparing breakthrough cohort and two matched unvaccinated infection cohorts.ResultsIndividuals vaccinated with Pfizer/BNT162b2 (IRR against Moderna/mRNA-1273 [95% CI]: 1.66 [1.17 - 2.35]); were male (1.47 [1.11 - 1.94%]); and had compromised immune systems (1.48 [1.09 - 2.00]) were at the highest risk for breakthrough infections. Vaccinated individuals had a significant lower infection rate among all subgroups. An increased incidence rate was found in both vaccines over the time. Among individuals infected with COVID-19, vaccination significantly reduced the risk of death (adj. HR: 0.20 [0.08 - 0.49]).Conclusion and relevanceWhile we found both mRNA vaccines were effective, Moderna/mRNA-1273 had a lower incidence rate of breakthrough infections. Both vaccines had increased incidence rates over the time. Immunocompromised individuals were among the highest risk groups experiencing breakthrough infections. Given the rapidly changing nature of the SARS-CoV-2, continued monitoring and a generalizable analysis pipeline are warranted to inform quick updates on vaccine effectiveness in real time.Key pointsQuestion: What risk factors contribute to COVID-19 breakthrough infections among mRNA vaccinated individuals? How do clinical outcomes differ between vaccinated but still SARS-CoV-2 infected individuals and non-vaccinated, infected individuals?Findings: This retrospective study uses CUIMC/NYP EHR data up to September 21, 2021. Individuals who were vaccinated with Pfizer/BNT162b2, male, and had compromised immune systems had significantly higher incidence rate ratios of breakthrough infections. Comparing demographically matched pre-vaccinated and unvaccinated individuals, vaccinated individuals had a lower incidence rate of SARS-CoV-2 infection among all subgroups.Meaning: Leveraging real-world EHR data provides insight on who may optimally benefit from a booster COVID-19 vaccination.

Project description:ObjectiveTo assess in rheumatoid arthritis (RA) patients, treated with different immunosuppressive therapies, the induction of SARS-CoV-2-specific immune response after vaccination in terms of anti-region-binding-domain (RBD)-antibody- and T-cell-specific responses against spike, and the vaccine safety in terms of clinical impact on disease activity.MethodsHealth care workers (HCWs) and RA patients, having completed the BNT162b2-mRNA vaccination in the last 2 weeks, were enrolled. Serological response was evaluated by quantifying anti-RBD antibodies, while the cell-mediated response was evaluated by a whole-blood test quantifying the interferon (IFN)-γ-response to spike peptides. FACS analysis was performed to identify the cells responding to spike stimulation. RA disease activity was evaluated by clinical examination through the DAS28crp, and local and/or systemic clinical adverse events were registered. In RA patients, the ongoing therapeutic regimen was modified during the vaccination period according to the American College of Rheumatology indications.ResultsWe prospectively enrolled 167 HCWs and 35 RA patients. Anti-RBD-antibodies were detected in almost all patients (34/35, 97%), although the titer was significantly reduced in patients under CTLA-4-inhibitors (median: 465 BAU/mL, IQR: 103-1189, p<0.001) or IL-6-inhibitors (median: 492 BAU/mL, IQR: 161-1007, p<0.001) compared to HCWs (median: 2351 BAU/mL, IQR: 1389-3748). T-cell-specific response scored positive in most of RA patients [24/35, (69%)] with significantly lower IFN-γ levels in patients under biological therapy such as IL-6-inhibitors (median: 33.2 pg/mL, IQR: 6.1-73.9, p<0.001), CTLA-4-inhibitors (median: 10.9 pg/mL, IQR: 3.7-36.7, p<0.001), and TNF-α-inhibitors (median: 89.6 pg/mL, IQR: 17.8-224, p=0.002) compared to HCWs (median: 343 pg/mL, IQR: 188-756). A significant correlation between the anti-RBD-antibody titer and spike-IFN-γ-specific T-cell response was found in RA patients (rho=0.432, p=0.009). IFN-γ T-cell response was mediated by CD4+ and CD8+ T cells. Finally, no significant increase in disease activity was found in RA patients following vaccination.ConclusionThis study showed for the first time that antibody-specific and whole-blood spike-specific T-cell responses induced by the COVID-19 mRNA-vaccine were present in the majority of RA patients, who underwent a strategy of temporary suspension of immunosuppressive treatment during vaccine administration. However, the magnitude of specific responses was dependent on the immunosuppressive therapy administered. In RA patients, BNT162b2 vaccine was safe and disease activity remained stable.

Project description:PurposePeople living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated.MethodsThis study is a population-scale real-world evaluation of the United Kingdom's third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess the third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population.ResultsThe cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5%, respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Patients with lymphoma had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at an increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01, respectively. p < 0.001 for both).ConclusionsThird dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous and lower than the general population. Many patients with cancer will remain at the increased risk of coronavirus infections even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit the disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.

Dataset Information

Immunomodulators and risk for breakthrough infection after third COVID-19 mRNA vaccine among patients with rheumatoid arthritis: A cohort study.

Objectives

Methods

Results

Conclusions

Publications

Immunomodulators and risk for breakthrough infection after third COVID-19 mRNA vaccine among patients with rheumatoid arthritis: A cohort study.

Similar Datasets

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