Efficacy of Recombinant Zoster Vaccine in Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Individuals with inflammatory bowel disease (IBD) have an increased risk of herpes zoster (HZ) infection. Although the efficacy of recombinant zoster vaccine (RZV) is high among immunocompetent individuals, little is known about its effect among immunosuppressed individuals with IBD. METHODS: We conducted a retrospective cohort study among individuals in the national Veterans Affairs Healthcare System diagnosed with IBD on or before January 3, 2018, the earliest date of RZV vaccinations. We collected data on 7008 and 26,292 eligible patients with IBD in the 50- to 60-year and >60-year age groups, respectively. We identified veterans who received RZV and compared the incidence of HZ between vaccinated versus unvaccinated individuals. We performed multivariable Cox regression with time varying analysis to determine the risk of HZ among the vaccinated (full dose and single dose separately) versus unvaccinated cohort, stratified by IBD medications. RESULTS: The crude HZ incidence rate after full dose vaccination of RZV when compared with the unvaccinated group was lower in both the 50- to 60-year age group (0.00 vs 3.93 per 1000 person-years) and >60-year age group (1.80 vs 4.57 per 1000 person-years). RZV vaccination was associated with a significantly lower risk of HZ among the 50- to 60-year and >60-year age groups, although this was limited by low HZ event rates. CONCLUSION: RZV vaccination was associated with decreased risk of HZ infection among both the 50- to 60-year and >60-year age groups. Greater efforts should be made to vaccinate all patients with IBD with RZV.

Are Patients With Inflammatory Bowel Disease at an Increased Risk of Developing SARS-CoV-2 than Patients Without Inflammatory Bowel Disease? Results From a Nationwide Veterans' Affairs Cohort Study.

INTRODUCTION: The clinic course of SARS-CoV-2 among patients with inflammatory bowel disease (IBD) has been extensively studied. However, there is a paucity of data on whether patients with IBD have an increased risk of developing SARS-CoV-2 with compared with patients without IBD. METHODS: We conducted a nationwide retrospective cohort study in the US Veterans' Affairs healthcare system from January 1, 2020, to June 30, 2020. We matched each patient with IBD with 2 patients without IBD on age, sex, race, location, and comorbidities. The outcome of interest was development of SARS-CoV-2. RESULTS: Among 38,378 patients with IBD and 67,433 patients without IBD, 87 (0.23%) and 132 (0.20%) patients developed incident SARS-CoV-2 infection, respectively (P = 0.29). DISCUSSION: Patients with IBD are not at a significantly increased risk of developing SARS-CoV-2 infection when compared with patients without IBD.

Incidence of Acute Myeloid Leukemia and Myelodysplastic Syndrome in Patients With Inflammatory Bowel Disease and the Impact of Thiopurines on Their Risk.

INTRODUCTION: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are rare myeloid clonal disorders that commonly affect the elderly population and have poor prognosis. There are limited data on the risk of AML/MDS among patients with inflammatory bowel disease (IBD), especially on the impact of thiopurines (TPs). METHODS: We conducted a retrospective cohort study among patients with IBD from Veteran Affairs data set. The exposure of interest was TP exposure: (i) never exposed to TPs, (ii) past TP use (discontinued >6 months ago), (iii) current TP use with a cumulative exposure of <2 years, and (iv) current TP use with a cumulative exposure of ≥2 years. The outcome of interest was a composite outcome of incident diagnosis of AML and/or MDS. Cox regression was used to estimate the adjusted and unadjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for AML/MDS risk associated with TP use defined as a time-varying exposure. RESULTS: Among 56,314 study patients, 107 developed AML/MDS. The overall incidence of AML/MDS in the IBD population was 18.7 per 100,000 patient-years. The incidences among those never exposed to TPs, past users of TPs, current users of TPs with a cumulative exposure of <2 years, and current users of TPs with a cumulative exposure of ≥2 years were 17.0, 17.7, 30.4, and 30.3 per 100,000 patient-years, respectively. In multivariable Cox regression analysis, compared with never exposed to TPs, current use of TPs was associated with increased risk (adjusted HR 3.05; 95% CI 1.54-6.06, P = 0.0014 for current use of TPs with a cumulative exposure of <2 years and adjusted HR 2.32; 95% CI 1.22-4.41, P = 0.0101 for current use of TPs with a cumulative exposure of ≥2 years), whereas past TP exposure was not. DISCUSSION: Among patients with IBD, current TP use was associated with an increased risk of AML/MDS, which reverts to baseline after discontinuation of TP use.

Repeated Occurrences of Basal Cell Cancer in Patients With Inflammatory Bowel Disease Treated With Immunosuppressive Medications.

INTRODUCTION: There are limited data on repeated basal cell cancer (BCC) occurrences among patients with inflammatory bowel disease (IBD), especially the impact of continuing immunosuppressive medications. METHODS: We conducted a retrospective cohort study of 54,919 patients with IBD followed in the Veterans Affairs Healthcare System. We identified patients who had an incident BCC after their IBD diagnosis. We defined patients' exposure based on their IBD medications use as follows: (i) only aminosalicylate (5-ASA) use, (ii) only active thiopurine (TP) use, (iii) past TP use (discontinued >6 months ago) and no antitumor necrosis factor (TNF) use, (iv) anti-TNF use after previous TP use, (v) only anti-TNF use, and (vi) active anti-TNF and TP use. The outcome of interest was the repeated occurrence of BCC. Adjusted and unadjusted hazard ratios with 95% confidence intervals were used to estimate the risk of repeated BCC occurrence. RESULTS: A total of 518 patients developed BCC after their IBD diagnosis. The numbers of repeated BCC occurrences per 100 person-years were 12.8 (5-ASA use only), 34.5 (active TP use), 19.3 (past TP use and no anti-TNF use), 25.4 (anti-TNF use after previous TP use), 17.8 (only anti-TNF use), and 22.4 (active anti-TNF and TP use). Compared with 5-ASA use alone, only active TP use was associated with an increased risk for repeated BCC occurrence (adjusted hazard ratio 1.65, 95% confidence interval 1.24-2.19; P = 0.0005). However, the increased risk was no longer present for other exposure categories. DISCUSSION: Among IBD patients who developed an incident BCC while taking a TP and continued it, there was an increased risk of repeated BCC occurrences.

Safety of Recombinant Zoster Vaccine in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD] have an increased risk of contracting herpes zoster [HZ] infection. However, vaccination rates for HZ are low among IBD patients. A contributing factor may be fear of an IBD flare associated with vaccination. Our aim here was to evaluate if recombinant zoster vaccine [RZV] is associated with an IBD flare. METHODS: This was a retrospective cohort study using data from the Veterans Affairs Healthcare System [VAHS]. The exposure of interest was receiving RZV. We randomly matched such exposed patients with unexposed individuals. The primary outcome was the first episode of IBD flare within 90 days of the index date. Baseline characteristics were compared between groups using a t-test for continuous variables and Chi-square test for categorical variables. Conditional logistic regression was used to estimate the odds ratio [OR] and 95% confidence interval [CI]. RESULTS: Among the eligible study cohort, 1677 patients received RZV. Thirty-six patients, 20 in the exposed group and 16 in the unexposed group, had a confirmed flare by chart review. The 90-day cumulative incidence of IBD flare was not different between the vaccinated and unvaccinated groups [1.2% among those exposed vs 1.0% among those unexposed, p = 0.503]. The OR for IBD flare associated with RZV vaccination was 1.25 [95% CI: 0.65-2.41]. CONCLUSION: In a nationwide cohort of stable IBD patients, administration of RZV was not associated with the risk of IBD flare within 90 days. These findings should motivate further use of this highly effective vaccine.

The impact of IBD medications on risk of pneumonia and pneumonia-related hospitalisation: a nationwide cohort study of 56 410 IBD patients.

BACKGROUND: There are limited data on the incidence of pneumonia and pneumonia-related hospitalisation in the IBD population, and on any association of IBD medications with such outcomes. AIMS: To evaluate the impact of IBD medications on the risk of pneumonia, pneumonia-related hospitalisations and death. METHODS: We conducted a retrospective cohort study of IBD patients from the nationwide Veteran Affairs (VA) dataset. The exposure of interest was different IBD medication groups. We estimated the incidence rate of pneumonia, pneumonia-related hospitalisation and mortality based on IBD medication subgroups. We used a multivariable Cox regression to estimate the adjusted hazard ratios (AHR) and 95% confidence intervals (CIs) for these outcomes. RESULTS: Out of 56 410 patients with IBD, 3759 developed pneumonia, 1489 were hospitalised, and 248 died within 30 days of their pneumonia diagnosis. The crude incidence rates of pneumonia, pneumonia-related hospitalisation and pneumonia-related mortality were 6.47, 2.52 and 0.43, respectively, per 1000 person-years. In multivariable Cox regression analysis, compared to 5-ASA alone, anti-TNF medication was associated with an increased risk of pneumonia (AHR 1.39; 95% CI 1.22-1.59) and hospitalisation (AHR 1.61; 95% CI 1.31-1.98). Use of prednisone in the prior 30 days was associated with increased risk of pneumonia (AHR 2.14; 95% CI 1.92-2.38) and hospitalisation (AHR 2.44; 95% CI 2.08-2.88). CONCLUSION: Anti-TNF medications and prednisone use may be associated with increased risk of developing pneumonia and pneumonia-related hospitalisation. Physicians should evaluate the risk-benefit ratio of IBD medications, especially in the elderly population.

Efficacy of Vedolizumab in a Nationwide Cohort of Elderly Inflammatory Bowel Disease Patients.

BACKGROUND: The elderly inflammatory bowel disease (IBD) population has historically been under-represented in clinical trials, and data on the efficacy of biologic medications in elderly IBD patients are generally lacking. Our study aims to evaluate the efficacy of vedolizumab (VDZ) among elderly IBD patients and compare it with younger IBD patients in a nationwide population-based cohort of IBD patients. METHODS: We conducted a retrospective cohort study of patients within the US national Veterans Affairs Healthcare System (VAHS). Patients were stratified into 2 groups based on age at the time of starting VDZ (60 years of age and older or younger than 60 years of age) with outcomes compared between the 2 groups. The primary outcome was steroid-free remission during the 6- to 12-month period after starting VDZ therapy among those patients who were on steroids when VDZ was started. RESULTS: There were 568 patients treated with VDZ, of whom 56.7% had Crohn's disease and 43.3% had ulcerative colitis. Among them, 316 patients were on steroids when VDZ was started. The percentage of patients who were on VDZ and off steroids during the 6- to 12-month period after VDZ initiation was 46.8% and 40.1% for the younger and elderly groups, respectively (P = 0.2374). Rates of hospitalization for an IBD-related reason within 1 year of VDZ start among the whole cohort were nearly identical in the younger and elderly groups (11.2% vs 11.3%, P = 0.9737). Rates of surgery for an IBD-related reason within 1 year of VDZ start were also similar between the young and elderly (3.9% vs 3.9%, P = 0.9851). CONCLUSIONS: In a nationwide real-world retrospective cohort study of elderly IBD patients, we found that the efficacy of VDZ was similar among younger and older IBD patients and comparable with the published data in clinical trials.

Incidence of Infections and Malignancy Among Elderly Male Patients with IBD Exposed to Vedolizumab, Prednisone, and 5-ASA Medications: A Nationwide Retrospective Cohort Study.

INTRODUCTION: Vedolizumab (VDZ) is postulated to have a potentially safer side effect profile than other biologic medications owing to its gut-selective mechanism. However, extrapolating these safety data to older patients is challenging because of their underrepresentation in or exclusion from most clinical trials, higher rates of withdrawal, and higher rates of comorbidities. Our aim was to evaluate the absolute risk of infections and malignancies in an elderly group of patients with inflammatory bowel disease (IBD) exposed to VDZ vs. the absolute risks associated with 5-aminosalicyclic acid (5-ASA) medications and chronic steroid use. METHODS: We conducted a retrospective cohort study among the US national Veterans Affairs Healthcare System (VAHS). Our cohort comprised patients who were followed in the VAHS, had a diagnosis of IBD, and were aged 65 years or older. The patients were divided into three cohorts: primary exposure group (elderly patients on VDZ), assumed low-risk group (elderly patients on 5-ASA only), and assumed high-risk group (elderly patients on chronic prednisone). The low-risk and high-risk groups were matched to the VDZ group on race, gender, IBD type, age, and Charlson Comorbidity Index (CCI). Primary outcomes gathered and confirmed via chart review included mild infections, severe infections, malignancies, and non-melanoma skin cancers (NMSC). The results were based on a descriptive analysis. RESULTS: A total of 497 patients were included in our study with 213, 186, and 98 patients in the VDZ, 5-ASA, and steroid groups, respectively. The total patient-years (PYs) of follow up were 405, 656, and 303 in VDZ, 5-ASA, and steroid groups respectively. The incidence of mild infection was the lowest in the VDZ group with 93.1 outcomes per 1000 PYs as compared to the 5-ASA group (114.4 outcomes per 1000 PYs) and 155.1 outcomes per 1000 PYs in the steroid group. In regard to severe infections, the VDZ group had an incidence of 38.5 outcomes per 1000 PYs as compared to 30.6 outcomes per 1000 PYs in the 5-ASA group and 67.4 outcomes per 1000 PYs in the steroids group. Mild infections with the highest incidence in the VDZ group were upper respiratory infection (including pharyngitis and sinusitis) at 20.3 per 1000 PYs, Clostridium difficile (15.1 per 1000 PYs), and cellulitis (10.0 per 1000 PYs). The severe infection with the highest incidence was pneumonia for each group, with incidence rates of 10.0, 14.0, and 48.6 per 1000 PYs for the VDZ, 5-ASA, and steroid groups, respectively. Incidence of malignancies (excluding NMSC) was numerically similar in the VDZ and 5-ASA group (17.6 and 15.6 per 1000 PYs, respectively), while the steroid group showed a higher incidence of 42.6 per 1000 PYs. NMSC incidence was numerically similar in the VDZ and steroid groups (36.3 and 39.0 per 1000 PYs, respectively), with the 5-ASA group showing a much lower NMSC incidence (4.6 per 1000 PYs). CONCLUSION: In a large nationwide cohort of elderly patients, we found the safety profile of VDZ among elderly patients with IBD with respect to the risk of infection and malignancy to be numerically similar to elderly patients with IBD taking 5-ASA, and favorable when compared to the elderly patients with IBD taking chronic steroids.

The Efficacy and Safety of Switching From Originator Infliximab to Single or Double Switch Biosimilar Among a Nationwide Cohort of Inflammatory Bowel Disease Patients.

Background: Data on safety and efficacy of switching to Renflexis (SB2) from originator Infliximab (IFX) (single switch) or from originator IFX to Inflectra (CT-P13) to Renflexis (double switch) are limited. Methods: We conducted a retrospective cohort study in a nationwide cohort of patient with inflammatory bowel disease (IBD) in remission who were switched to SB2. The main exposure was the treatment course of SB2. There are 2 levels in this variable: single switch (IFX to SB2) and double switch (IFX to CT-P13 to SB2). The outcome is SB2 drug discontinuation rate and/or not being in remission after 1 year. Logistic regression was used to estimate the adjusted and unadjusted odds ratios with 95% confidence intervals to study the efficacy difference between single switch and double switch. Results: A total of 271 IBD patients were started on SB2. Among them 52 (19.2%) patients did not achieve remission at 1 year and 14 (5.1%) patients had to discontinue SB2 due to adverse events). In logistic regression analysis after controlling for covariates, there was no statistically significant difference observed in regard to efficacy or safety of the single switch versus double switch to SB2 (adjusted odds ratio for double switch compared to single switch = 1.33 (95% confidence interval 0.74-2.41, P = 0.3432). Conclusions: Among IBD patients in remission, double switch was equally effective as compared to a single switch. This will help reassure the gastroenterologists who have concerns regarding the safety and efficacy of switching between multiple biosimilars for treating IBD.