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High Immunogenicity to Influenza Vaccination in Crohn's Disease Patients Treated with Ustekinumab.

ABSTRACT: Influenza vaccination can be less effective in patients treated with immunosuppressive therapy. However, little is known about the effects of ustekinumab; an anti-IL-12/23 agent used to treat Crohn's disease (CD), on vaccination response. In this prospective study, we assessed immune responses to seasonal influenza vaccination in CD patients treated with ustekinumab compared to CD patients treated with anti-TNF? therapy (adalimumab) and healthy controls. Humoral responses were assessed with hemagglutinin inhibition (HI) assays. Influenza-specific total CD3+, CD3+CD4+, and CD3+CD8+ T-cell responses were measured with flow cytometry. Fifteen patients treated with ustekinumab; 12 with adalimumab and 20 healthy controls were vaccinated for seasonal influenza in September 2018. Seroprotection rates against all vaccine strains in the ustekinumab group were high and comparable to healthy controls. Seroconversion rates were comparable, and for A/H3N2 highest in the ustekinumab group. HI titers were significantly higher in the ustekinumab group and healthy controls than in the adalimumab group for the B/Victoria strain. Post-vaccination T-cell responses in the ustekinumab group were similar to healthy controls. One-month post-vaccination proliferation of CD3+CD8+ T-cells was highest in the ustekinumab group. In conclusion, ustekinumab does not impair immune responses to inactivated influenza vaccination. Therefore, CD patients treated with ustekinumab can be effectively vaccinated for seasonal influenza.

SUBMITTER: Doornekamp L

PROVIDER: S-EPMC7565576 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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High Immunogenicity to Influenza Vaccination in Crohn's Disease Patients Treated with Ustekinumab.

Doornekamp Laura L Goetgebuer Rogier L RL Schmitz Katharina S KS Goeijenbier Marco M van der Woude C Janneke CJ Fouchier Ron R van Gorp Eric C M ECM de Vries Annemarie C AC

Vaccines 20200814 3

Influenza vaccination can be less effective in patients treated with immunosuppressive therapy. However, little is known about the effects of ustekinumab; an anti-IL-12/23 agent used to treat Crohn's disease (CD), on vaccination response. In this prospective study, we assessed immune responses to seasonal influenza vaccination in CD patients treated with ustekinumab compared to CD patients treated with anti-TNFα therapy (adalimumab) and healthy controls. Humoral responses were assessed with hema ...[more]

PMID: 32824111

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Project description:BackgroundCrohn's disease (CD) is a chronic inflammatory bowel disease characterized by relapsing and remitting inflammation that leads to progressive bowel damage. Despite advances in medical treatment for CD, many patients require surgical intervention. Most studies of surgery rates are from patients treated with anti-tumor necrosis factor alpha (anti-TNFα) treatments, with comparatively little data on the surgery rates of patients treated with vedolizumab and ustekinumab. SOJOURN aimed to estimate the hazard rate and incidence of the first CD-related surgery following initiation of treatment with vedolizumab or ustekinumab in biologic-naïve patients with CD.MethodsSOJOURN was a retrospective, observational cohort study examining administrative claims data from the Optum® Research Database between July 1, 2017 and March 31, 2020. Included participants were adults with a diagnosis of CD and a claim for vedolizumab or ustekinumab (defined as the index treatment) between January 1, 2018 and December 31, 2019, with no claims for a biologic in the 6 months before initiation of this treatment. The variable follow-up started on the day after the index date and continued until whichever came first of discontinuation of the index treatment, surgery event, switching of the index treatment, initiation of combination biologic treatment, disenrollment, or March 31, 2020. The time to the first CD-related surgery on biologic treatment was estimated by Kaplan-Meier analysis. The hazard ratio and incidence rate ratio of CD-related surgery for each treatment cohort was compared using a Cox proportional hazards model and a Poisson regression model, respectively.ResultsOf the 1,122 included patients, 578 received vedolizumab and 544 received ustekinumab. After 1 year of the variable follow-up, 7.7% of patients receiving vedolizumab and 11.6% of patients receiving ustekinumab had undergone a CD-related surgery. Vedolizumab was associated with a 34.2% lower hazard rate of surgery (hazard ratio 0.658, 95% confidence interval [CI] 0.436-0.994, p = 0.047) and a 34.5% lower incidence of surgery (rate ratio 0.655, 95% CI 0.434-0.988, p = 0.044) than ustekinumab.ConclusionsThis real-world analysis of biologic-naïve patients with CD suggests that vedolizumab is associated with greater effectiveness in reducing the rate of CD-related surgery than ustekinumab.

Project description:BackgroundFor cancer patients, rates of influenza-associated hospitalization and death are 4 times greater than that of the general population. Previously, we reported reduced immunogenicity to the standard-dose influenza vaccine in patients with central nervous system malignancy. In other poorly responding populations (eg, elderly patients), high-dose vaccination has improved efficacy and immunogenicity.MethodsA prospective cohort study was designed to evaluate the immunogenicity of the Fluzone® high-dose influenza vaccine in brain tumor patients. Data on diagnosis, active oncologic treatment, and immunologic status (eg, CD4 count, CD8 count, CD4:CD8 ratio) were collected. All patients received the high-dose vaccine (180 µg). Hemagglutination inhibition titers were measured at baseline, day 28, and 3 months following vaccination to determine seroconversion (≥4-fold rise) and seroprotection (titer ≥1:40), which were compared to our prior results.ResultsTwenty-seven patients enrolled. Diagnoses included high-grade glioma (85%), CNS lymphoma (11%), and meningioma (4%). Treatment at enrollment included glucocorticoids (n = 8, 30%), radiation (n = 2, 7%), and chemotherapy (n = 9, 33%). Posttreatment lymphopenia (PTL, CD4 ≤ 200) was observed in 4 patients (15%). High-dose vaccination was well tolerated with no grade III-IV toxicity. Overall, seroconversion rates for the A/H1N1, A/H3N2, and B vaccine strains were significantly higher than in our prior study: 65% vs 37%, 69% vs 23%, and 50% vs 23%, respectively (all P < .04). Seroconversion was universally poor in patients with PTL. While seroprotection at 3 months declined in our prior study, no drop was observed following high-dose vaccination in this cohort.ConclusionsThe immunologic response to HD influenza vaccination was higher in this cohort than standard-dose influenza vaccination in our prior report. These findings mirror those in elderly patients where high-dose vaccination is the standard of care and raise the possibility of an immunosenescence phenotype.

Project description:The fecal microbiota is a rich source of biomarkers that have previously been shown to be predictive of numerous disease states. Less well studied is the effect of immunomodulatory therapy on the microbiota and its role in response to therapy. This study explored associations between the fecal microbiota and therapeutic response of Crohn's disease (CD) patients treated with ustekinumab (UST; Stelara) in the phase 2 CERTIFI study. Using stool samples collected over the course of 22 weeks, the composition of these subjects' fecal bacterial communities was characterized by sequencing the 16S rRNA gene. Subjects in remission could be distinguished from those with active disease 6 weeks after treatment using random forest models trained on subjects' baseline microbiota and clinical data (area under the curve [AUC] of 0.844, specificity of 0.831, sensitivity of 0.774). The most predictive operational taxonomic units (OTUs) that were ubiquitous among subjects were affiliated with Faecalibacterium and Escherichia or Shigella The median baseline community diversity in subjects in remission 6 weeks after treatment was 1.7 times higher than that in treated subjects with active disease (P = 0.020). Their baseline community structures were also significantly different (P = 0.017). Two OTUs affiliated with Faecalibacterium (P = 0.003) and Bacteroides (P = 0.022) were significantly more abundant at baseline in subjects who were in remission 6 weeks after treatment than those with active CD. The microbiota diversity of UST-treated clinical responders increased over the 22 weeks of the study, in contrast to nonresponsive subjects (P = 0.012). The observed baseline differences in fecal microbiota and changes due to therapeutic response support the potential for the microbiota as a response biomarker.IMPORTANCE CD is a global health concern, with increasing incidence and prevalence, causing large economic and health care impacts. Finding prognostic biomarkers that give clinicians the ability to identify patients more likely to respond to CD treatment at diagnosis will reduce the time subjects receive drugs that are unlikely to be beneficial. OTUs associated with remission after treatment induction, especially Faecalibacterium, could be biomarkers for successful UST treatment of anti-tumor necrosis factor alpha (anti-TNF-α) refractory CD patients. More broadly, these results suggest that the fecal microbiota could be a useful noninvasive biomarker for directing or monitoring the treatment of gastrointestinal diseases.

Dataset Information

High Immunogenicity to Influenza Vaccination in Crohn's Disease Patients Treated with Ustekinumab.

Publications

High Immunogenicity to Influenza Vaccination in Crohn's Disease Patients Treated with Ustekinumab.

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