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1.
J Clin Med ; 11(19)2022 Sep 26.
Article in English | MEDLINE | ID: covidwho-2066174

ABSTRACT

BACKGROUND: Recent trials support the clinical efficacy and safety of subcutaneous infliximab (IFX) or vedolizumab (VDZ) for Inflammatory Bowel Disease (IBD). We evaluated the uptake and rationale for choosing to switch from intravenous infusions to subcutaneous injections. METHODS: Retrospective analysis of all adult patients receiving standard dosing IFX or VDZ maintenance therapy to investigate uptake of subcutaneous injections and the rationale for switching to subcutaneous injections. RESULTS: Of 232 eligible patients (total = 258: IFX = 190, VDZ = 68, and no longer eligible = 26), 58% of patients on IFX and 59% of patients on VDZ chose to switch to subcutaneous treatment. Age, sex, diagnosis, drug, line of treatment, and duration of treatment were not predictors for willingness to switch. Questionnaire responses (n = 51) demonstrate that the decision to switch was not influenced by COVID-19 exposure risk, impact on wider IBD service provision, impact on patient mental health, financial savings, seeking support following a switch, or a sense of independence managing IBD. Switchers (68%) were more motivated by time savings than non-switchers (25%; p = 0.0042). CONCLUSIONS: Switch uptake rates were 58%, with 90% of patients eligible to switch. Switch decision was influenced by time savings for patients but not by other patient-related factors.

2.
Pharmaceutical Journal ; 306(7948), 2022.
Article in English | EMBASE | ID: covidwho-2064946
3.
Aliment Pharmacol Ther ; 56(6): 1044-1054, 2022 09.
Article in English | MEDLINE | ID: covidwho-2032364

ABSTRACT

BACKGROUND: Subcutaneous (SC) vedolizumab is effective in inflammatory bowel diseases (IBD) when administered after induction with two infusions. AIM: To assess the effectiveness, safety and pharmacokinetics of a switch from intravenous (IV) to SC maintenance vedolizumab in patients with IBD METHODS: In this prospective cohort study, patients with IBD who had ≥4 months IV vedolizumab were switched to SC vedolizumab. We studied the time to discontinuation of SC vedolizumab, adverse events (AEs), changes in clinical and biochemical outcomes and vedolizumab concentrations at baseline, and weeks 12 and 24. RESULTS: We included 82 patients with Crohn's disease (CD) and 53 with ulcerative colitis (UC). Eleven (13.4%) patients with CD and five (9.4%) with UC discontinued SC vedolizumab after a median of 18 (IQR 8-22) and 6 weeks (IQR 5-10), respectively. Four patients with CD switched to a different drug due to loss of response, nine switched back to IV vedolizumab due to adverse events, and three due to needle fear. Common AEs were injection site reactions (n = 15) and headache (n = 6). Median clinical and biochemical disease activity remained stable after the switch. Median serum vedolizumab concentrations increased from 19 µg/ml at the time of the switch to 31 µg/ml 12 weeks after the switch (p < 0.005). CONCLUSIONS: Switching from IV to SC vedolizumab maintenance treatment is effective in patients with CD or UC. However, 9% of patients were switched back to IV vedolizumab due to adverse events or fear of needles.


Subject(s)
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Antibodies, Monoclonal, Humanized , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Crohn Disease/chemically induced , Crohn Disease/drug therapy , Gastrointestinal Agents/therapeutic use , Humans , Inflammatory Bowel Diseases/drug therapy , Phobic Disorders , Prospective Studies , Remission Induction , Treatment Outcome
4.
Journal of the Formosan Medical Association ; 121(9):1617-1621, 2022.
Article in English | Scopus | ID: covidwho-2015654
5.
Annals of the Rheumatic Diseases ; 81:127-128, 2022.
Article in English | EMBASE | ID: covidwho-2008875

ABSTRACT

Background: Patients with immune-mediated infammatory diseases (IMIDs) on immunosuppressive therapy have an inadequate serologic response following two-dose SARS-CoV-2 vaccination, and a standard vaccination strategy of three doses for this patient group is currently under implementation in several countries. However, the serological response and safety of this strategy has not been evaluated. Objectives: To assess serological response and safety of a three-dose vaccination strategy in IMID patients on immunosuppressive therapy as compared to standard two-dose vaccination of healthy controls. Methods: The prospective observational Nor-vaC study (NCT04798625) enrolled adult patients on immunosuppressive therapy for infammatory joint-and bowel diseases. Healthy controls were health care workers from participating hospitals. All participants received standard vaccines according to the national vaccination program with three doses in patients and two doses in controls. The third dose was offered to IMID patients >4 weeks after the second dose. Analyses of antibodies binding the receptor-binding domain of the SARS-CoV-2 Spike protein were performed prior to, and 2-4 weeks after the second and third vaccine doses. Levels were compared across groups by Mann-Whitney U tests and multi-variate linear regression was used to identify predictors of response. Results: Overall, 961 patients (315 rheumatoid arthritis, 156 spondyloarthritis, 171 psoriatic arthritis, 132 ulcerative colitis and182 Crohn's disease) (median age 54 years [IQR 43-64];56 % women) and 227 controls (median age 44 years [IQR 32-55];83 % women) were included in the present analyses. TNFi mon-otherapy was used by 399 patients, 229 used TNFi in combination with other immunomodulators, 189 methotrexate monotherapy, 39 vedolizumab, 32 JAKi and 73 patients used other drugs. Patients on rituximab were not included. Patients were vaccinated with Pfzer BNT162b2 (54% patients, 14% controls), Moderna mRNA-1273 (16% patients, 40% controls) or a combination of vaccines (30% patients, 46% controls). Patients received the third vaccine dose a median of 120 (IQR 102-143) days after the second dose. After two doses, median antiSpike antibody levels were signifcantly lower in patients (861 BAU/ml (IQR 418-4275) than controls (6318 BAU/ml (IQR 2468-9857)), p<0.001 (Figure 1). Following the third dose, patients achieved antibody levels comparable to the two-dose vaccinated controls (median 5480 BAU/ml (IQR 1081-12069), p=0.28) (Figure 1). In the patients anti-Spike antibody levels increased by a median of 2685 BAU/ml (IQR 265-9129) from the second to the third dose. Main factors associated with increased antibody level after the third dose were younger age (β-87.7 (p=0.002)), and vaccine status (mRNA-1273 vaccine (β 5549 (p<0.001)) or a combination of vaccines (β 4367.3 (p<0.001)). Adverse events were reported by 438 (48%) of patients after the third dose as compared to 471 (54%) after the second dose and 193 (78 %) of controls. Disease fares were reported by 42 (5%) and 69 (8%) patients after the second and third dose, respectively. Conclusion: This study suggests that a third vaccine dose for immunosup-pressed patients closes the gap in serological response between patients and the healthy population. Antibody levels following the three-dose regimen in IMID patients were comparable to healthy controls vaccinated twice, and no new safety issues emerged. This fnding was consistent across all diagnoses and treatment groups, supporting the implementation of a three-dose vaccine regimen as standard in the IMID population.

6.
Gut ; 71:A58-A59, 2022.
Article in English | EMBASE | ID: covidwho-2005352

ABSTRACT

Introduction Vedolizumab is an anti-integrin biologic therapy for moderate-severe inflammatory bowel disease (IBD). Traditionally this was delivered by intravenous (IV) infusion. The VISIBLE trial demonstrated that subcutaneous (SC) vedolizumab was effective and safe. This also reduced the need for a hospital visit, reducing risk in the COVID-19 pandemic, with a substantial cost saving. Vedolizumab was switched to SC administration in NHS Tayside in October 2020. This study aimed to demonstrate a real-world experience of the use of SC vedolizumab for IBD. Methods Patients were identified from the IBD biologic database. Caldicott approval was granted for a retrospective analysis of patient data via electronic patient records including patient gender, age, IBD diagnosis and dates for when Vedolizumab was commenced, switched to SC or stopped. Blood markers of inflammation (albumin, platelets, CRP and haemoglobin) 1 month before and 3-6 months after the switch to SC and stool calprotectin were recorded when available. Statistical analysis with Chi Square and Mann Whitney non-parametric tests revealed significance if p<0.05. Results Seventy-one patients on IV vedolizumab in October 2020 were invited to switch to SC, supported by a nurse led clinic consultation. One patient declined due to needle phobia and 70 (98%) accepted. SC administration was well tolerated with no patients reporting injection difficulties. Eight patients (11%) stopped SC vedolizumab within a 6-month period, 5 (62.6%) due to a flare in IBD and 3 (37.5%) due to side effects (skin reactions, paraesthesia). Thirty patients who remained on this treatment with no issues were compared to the 8 patients who stopped SC vedolizumab to explore whether there was patient or disease characteristics to identify those who failed this therapy. There was no statistically significant difference in patient age (42 years versus 44 years, p=0.5124) or disease phenotype (UC versus CD, p=0.155) between the two groups. of those that stopped SC administration, more were female (75% versus 57%, p=0.007). There was no difference in total duration of vedolizumab therapy between the groups;19.6 months for those that continued versus 13.6 months for those that stopped, p=0.841. There was no significant difference in albumin, platelets, and haemoglobin reported before or after the switch between the two groups. There was insufficient recording of CRP and calprotectin to allow analysis. Conclusions SC vedolizumab was accepted, well tolerated and effective in the majority of patients in our centre. There was no blood inflammatory biomarker or demographic signature to identify those who stopped SC therapy due to flare or side effects using standard monitoring.

7.
Digestive and Liver Disease ; 54:S113, 2022.
Article in English | EMBASE | ID: covidwho-1996805

ABSTRACT

Background and aim: Dual Targeted Therapy (DTT) is a novel therapeutic strategy proposed for the management of patients with complex inflammatory bowel disease (IBD). Our aim was to evaluate the safety and effectiveness of this approach in a real-life setting Materials and methods: In this single centre retrospective cohort study, we collected data on IBD patients receiving DTT from 2017 to 2022. Baseline characteristics, clinical activity of intestinal and extraintestinal disease, C-reactive protein (CRP) levels, endoscopic assessment and adverse events (AEs) were recorded. Clinical remission, CRP normalization, endoscopic remission and occurrence of AEs were investigated at baseline and during follow up Results: Sixteen patients were identified;indications for DTT were: uncontrolled IBD (11 patients), uncontrolled extraintestinal manifestations (EIMs) (6 patients: 4 spondyloarthritis, 2 psoriatic disease). Patients received vedolizumab (VDZ, 14, 87.5%), ustekinumab (UST, 8, 50%), anti-TNFα (7, 43.8%), sekukinumab (2, 12.5%), tofacitinib (1, 6.3%). The most common combinations were: VDZ+UST (6 patients, 37.5%) and adalimumab+VDZ (3, 18.8%). At baseline, 15/16 (93.8%) and 4/6 (66.6%) patients had active intestinal and EI symptoms, respectively;14 (87.5%) patients had positive CRP and 5 (31.3%) were receiving oral steroids. Median follow-up duration on DTT was 15 months (IQR 11-22). Clinical intestinal remission was reported by 6/16 (37.5%) and 3/11 (27.3%) patients at 6 and 12 months, respectively. Clinical remission of EIMs was reported by 3/7 (42.9%) at 6 and 5/7 (71.4%) patients at 12 months, respectively. CRP normalization was observed in 3/16 (18.8%) and 6/11 (54.5%) patients at 6 and 12 months, respectively. 80% of patients on steroid therapy at baseline discontinued them within 6 months. Endoscopic assessments were available for 8 patients, with endoscopic remission in 2, endoscopic improvement in 3 and no improvement in 3. Four patients (25%) experienced an AE (1 COVID-19 and reactivation of perianal disease;1 mild pneumonitis and reactivation of perianal disease;1 drug-induced pneumonitis;1 arthralgia and COVID-19). Finally, 1 patient underwent colectomy due to uncontrolled disease. Three patients discontinued DTT: 2 because of treatment failure, 1 because of an AE (drug-induced pneumonitis) Conclusions: DTT can be considered a reasonably safe and effective treatment in complex IBD patients, either with uncontrolled intestinal inflammation or with concomitant EIMs, when other therapeutic options have failed

8.
Hepato-Gastro et Oncologie Digestive ; 29(4):523-529, 2022.
Article in French | EMBASE | ID: covidwho-1978911

ABSTRACT

SARS-CoV-2 is not the only news! In IBD, the year 2021 has been rich in novelties. The SEAVUE study, although negative, appears to show that ustekinumab is as effective as adalimumab as first line treatment in Crohn’s disease. The STARDUST study studying the interest of treat-to-target under ustekinumab is also negative, but above all teaches us that treat-to-target is almost becoming a “standard of care”. Of course, the subcutaneous forms of infliximab and vedolizumab are there and will profoundly change our practice. Ultra-processed foods are definitely not only of no interest, but are also associated with an increased risk of developing IBD! Finally, ultrasound continues to prove, if needed, its value in the diagnosis and monitoring of IBD. And let’s not forget that a first episode of proctitis is an STI until proven otherwise.

9.
Gastroenterology ; 162(7):S-1112, 2022.
Article in English | EMBASE | ID: covidwho-1967410

ABSTRACT

Background: Vedolizumab (VDZ) is effective in inducing and maintaining remission in patients with Inflammatory bowel disease (IBD), but limited data exists in the youngest patients diagnosed <6, known as very early onset (VEO)-IBD. We aimed to evaluate the efficacy and safety of VDZ in this cohort. Methods: This was a retrospective study of patients with VEO-IBD followed at the Children's Hospital of Philadelphia, treated with VDZ for >6 months. Data collected included demographics, disease characteristics, medications, hospitalizations, growth, surgeries, and labs. Disease activity was measured using the Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn Disease Activity Index (PCDAI) at baseline and 6 months. Primary outcome was clinical response defined as a decrease in PUCAI>20 or PCDAI>15 at 6 months. Secondary outcomes included improvement in growth, labs, steroid use and hospitalizations. Continuous variables were analyzed using the Friedman test followed by the Wilcoxon signed-rank test. Nominal data was analyzed using McNemar's test. Results: Thirty-three children with VEO-IBD, 66% male, treated with VDZ were included. Median age of diagnosis was 3.7 years (range 1.2-6 years), with a median baseline disease duration of 3 years (range 0.1-18.5 years). IBDU was classified in 61%, and CD in 39%. Disease location was 70% colonic, 27% ileocolonic and 3% small bowel. Seven patients had prior surgeries, including diverting ileostomies (n=6) and subtotal colectomy (n=1). Nineteen (58%) patients were biologic naïve. VDZ was used as combination therapy in 6 (18%) patients (methotrexate n=4, rapamycin n=1, tacrolimus n=1). Bridge therapy was initiated in 78% of patients, with steroids (n=8) and antibiotics (n=18). Clinical response at 6 months was achieved in 19 patients (58%) with improvement in median PUCAI from 25 to 5 (p<0.01) and median PCDAI from 18.75 to 5 (p<0.05). BMI for age Z-score improved from -0.325 to 0.65 (p<0.001). Steroids and antibiotics were tapered off in 6/8 (75%) and 14/18 (78%, p<0.001) respectively. Hospital length of stay decreased significantly during the 12 months after initiating VDZ compared to 3 months prior to initiation (p<0.05). 2 patients underwent surgery including a subtotal colectomy for colonic stricture and diverting ileostomy within 2 months of starting VDZ. Adverse effects included COVID-19 infection (n=2), influenza (n=2), upper respiratory infection (n=2), pneumonia (n=1), tracheitis (n= 1), cellulitis (n=1), molluscum (n=1), and pityriasis rosea (n=1). Conclusion: VDZ is effective at inducing clinical remission in a subset of children with VEO-IBD primarily with colonic disease. It has a favorable safety profile with minimal reported adverse events observed in this study. This study is limited by small sample size and retrospective design. Larger prospective studies are warranted.

10.
Gastroenterology ; 162(7):S-1008, 2022.
Article in English | EMBASE | ID: covidwho-1967396

ABSTRACT

BACKGROUND: Immune-modulating medications for inflammatory bowel diseases (IBD) have been associated with suboptimal vaccine responses. There is conflicting data with SARS-CoV-2 vaccination. METHODS: We measured SARS-CoV-2 vaccine immunogenicity at 2 weeks post 2nd mRNA vaccine in IBD patients as compared to normal healthy donors (NHD). We measured humoral immune responses to SARS-CoV-2: anti-spike Immunoglobulin G (IgG) and anti-receptor binding domain (RBD) IgG were measured by ELISA, and neutralizing antibody titers were measured using recombinant, reporter SARS-CoV-2. Antigen specific memory B cells were measured using recombinant SARS-CoV-2 proteins. Activation induced marker T cell (AIM) assays were performed using SARS-CoV-2 spike megapools. Immunophenotyping was performed by flow cytometry. RESULTS: We enrolled 29 patients with IBD (19 with Crohn's disease, 10 with ulcerative colitis) on infliximab (IFX) monotherapy (N=9), IFX combination therapy with a thiopurine (N=9), vedolizumab monotherapy (N= 11) as compared to matched NHD (N=12). At 2 weeks post vaccination, all subjects made detectable anti-spike IgG and anti-RBD IgG. There were no differences in anti-spike IgG titers among the different groups. IBD patients on IFX monotherapy, but not IBD patients on IFX combination therapy or vedolizumab monotherapy, had lower anti-RBD and neutralization titers as compared to NHD (p-value: 0.041 and 0.023, respectively) (Fig. 1). There were no significant differences in the percentage of spike-specific or RBD-specific memory B cells in IBD patients as compared to NHD (Fig. 1). There were no differences in the percentage of spike-specific CD4+ or CD8+ T cells in all IBD patients as compared to NHDs (Fig. 2). CONCLUSIONS: We demonstrate overall comparable and perserved cell-mediated immunity to SARS-CoV-2 vaccination in a small cohort of IBD patients treated with a range of different immune-modulating medications as compared to healthy controls. Larger numbers of patients are needed to validate these findings.

11.
Gastroenterology ; 162(7):S-1007, 2022.
Article in English | EMBASE | ID: covidwho-1967395

ABSTRACT

Background: Patients with inflammatory bowel diseases (IBD) are commonly treated with immunosuppressive agents. Following the novel corona virus (SARS-CoV-2) pandemic, these patients received early the currently EMA approved vaccines. Data on efficacy and safety of SARS-CoV-2 vaccination on this population are lacking. Methods: Greek IBD patients, from 10 tertiary referral centres, who had completed the initial vaccination protocol with the available anti-COVID-19 vaccines (BNT162b2, mRNA-1273, Ad26.CoV2.S, ChAdOx1) at least two weeks before enrolment, were prospectively studied. Demographic and safety data were collected and blood samples were drawn for serum Anti-S1 IgG measurement [Euroimmun Anti-SARS-CoV-2 QuantiVac ELISA (IgG)]. Results: In total 403 IBD patients (59% Crohn's disease, median age 45 years, 53% male) and 124 healthy controls (HC) were included (Table 1). Antibody testing was conducted after a median of 31 (IQR, 23-46) days post-vaccination. Following a full vaccination regimen, 98% of IBD patients seroconverted (anti-S1 IgG³11 RU/ml). In total, IBD patients had lower anti-S1 levels than HC (RU/ ml 108 vs 133 RU/ml, P=0.00009) Administration of mRNA vaccines resulted in higher seroconversion rates and higher antibody titers than viral vector ones (98.6% vs 93.6%, P= 0.02 and 111.2 RU/ml vs 76 RU/ml, P<0.0001, respectively). Treatment with vedolizumab monotherapy was associated with higher antibody levels than anti-TNFα or ustekinumab monotherapy (P=0.02 and P=0.03). Longer timing between vaccination and antibody measurement was independently associated with impaired vaccine response. In multivariable analysis, specifically in mRNA-vaccinated cohort, older age, anti-TNFα treatment and treatment with biologics plus IMMs were significantly associated with lower antibody response (P=0.01, P=0.008, and P=0.02 respectively). Patients with prior COVID-19 infection showed numerically higher levels of antibodies. All vaccines were safe in IBD patients. Conclusions: Patients with IBD have high seroconversion rates to anti-SARS-CoV-2 vaccines. However, they demonstrate impaired antibody responses compared to HC. Patients receiving viral vector vaccines, and those on anti-TNFα or combination treatment may have further response impairment and it is important to consider booster vaccination in those low-response groups. (Table Presented)

12.
Gastroenterology ; 162(7):S-1005, 2022.
Article in English | EMBASE | ID: covidwho-1967390

ABSTRACT

Background: Immune responses to the SARS-CoV-2 vaccination may be influenced by immunomodulatory drugs (IMDs). We investigated the immune responses and safety in fully vaccinated Japanese patients with IBD. Subjects and Methods: IBD patients and control subjects at 39 institutes were invited to participate in the study from March to October 2021. Blood sample collections to measure anti-SARS-CoV-2 spike IgG antibody titers were planned pre-1st vaccination, pre-2nd vaccination, and at 4 weeks, 3 months and 6 months post-2nd vaccination. Immune responses were compared between groups, considering baseline characteristics and IMD treatments. (UMIN000043545) The interim analyses presented here include mainly data from the 4-weeks post-2nd vaccination time-point. Results: In total, 679 IBD patients and 203 controls were enrolled (Table 1). The IBD group received the BNT162b2 vaccine (86.2%) and the mRNA-1273 vaccine (12.5%), and the control group received the BNT162b2 vaccine (86.9%) and the mRNA-1273 vaccine (12.1%). Only 4 cases (0.7%) in the IBD group and 2 (1.0%) in the control group were infected with COVID-19. Adverse events of 2nd vaccination occurred in 48.4% of the IBD group and 35.1% of the control group. Comparison between administrated and non-administrated IBD patients for each IMD revealed an attenuated genomic mean titer (GMT [U/mL]) in those taking systemic steroids (18.85 vs 31.24), anti-TNF monotherapy (28.31 vs 42.99), anti- TNF therapy+ immunomodulator (IM) (12.86 vs 35.26), vedolizumab+IM (19.49 vs 30.39), ustekinumab+IM (20.44 vs 30.79), and tofacitinib (9.54 vs 32.08), but not in those taking oral 5-ASA (29.50 vs 32.40), or vedolizumab (41.85 vs 40.20) and ustekinumab (55.56 vs 39.26) monotherapies. Estimated least square means of the GMT by a multiple linear regression model are shown in Table 2. GMTs were significantly influenced by increasing age and allergy (51.2, 95%CI 42.1-62.3;p=0.0293), and tended to be influenced by COVID- 19 infection (139.1, 41.0-472.2;p=0.0572). Sex, smoking, drinking, IBD, and adverse events of 2nd vaccination did not affect the GMT. The GMT was significantly higher for mRNA- 1273 (90.3 [60.8-134.1]) than for BNT162b2 (39.6 [35.2-44.6], p= 0.0001). Systemic steroids (22.9 [13.9-37.7], p=0.0119), IM (24.2 [18.7-31.4], p<0.0001), anti-TNF agents (20.8 [15.3-28.3], p<0.0001), vedolizumab (25.2 [15.0-42.2], p=0.0409), ustekinumab (28.9 [18.5-45.0], p=0.0754), and tofacitinib (5.5 [2.8-10.9], p<0.0001), but not oral 5- ASA (39.1 [31.9-47.9], p=0.3225), attenuated GMTs at 4 weeks post-2nd vaccination (Table 2). Conclusion: Aging and most IMD options attenuated immunogenicity in fully vaccinated IBD patients. Prioritization of a booster vaccination should be considered for IBD patients treated with IMDs. (Table Presented) (Table Presented)

13.
Gastroenterology ; 162(7):S-1004-S-1005, 2022.
Article in English | EMBASE | ID: covidwho-1967389

ABSTRACT

Background: IBD patients on immune-modulatory therapies are considered high-risk for SARS-CoV-2 infection. Direct comparisons of serological responses to SARS-CoV-2 infection in IBD patients across different continents and medications are lacking. We performed SARSCoV- 2 sero-surveillance of IBD patients prior to vaccination at seven large tertiary centres in Asia, Europe, and North America. Methods: Clinical data and sera were collected from 2,241 IBD patients receiving routine care at institutions in Belgium, Canada, Hong Kong, India, Japan, United Kingdom, and the United States between May 2020 and September 2021 (Table 1). Sera were taken prior to vaccination. Clinical data were collected from patient questionnaires and medical records. Antibody reactivity to the SARS-CoV-2 spike protein was assessed using the Roche SARS-CoV-2 anti-spike total antibody and/or Siemens Healthineers COV2T anti-spike total antibody assays, which showed 99.4% concordance. We performed univariate analysis to evaluate association between variables and sero-status. Results: The pre-vaccination seroprevalence of antibodies to SARS-CoV-2 in IBD patient varied widely according to location from 0% in Hong Kong, China, to 57.9% in New Delhi, India. Rates in Europe and North America were similar (range 3.6%-8.9%). Overall, SARSCoV- 2 seroprevalence appears to be equal to or less than local populations (Table 1). Seroprevalence rates were associated with IBD type (Crohn's disease 7.8%, ulcerative colitis 12.4%, IBD-unclassified 15.0%, p<0.001), smoking status (p<0.001), and history of COVID diagnosis (p<0.001) or COVID hospitalization (p=0.001), and any immunomodulator (IMM) (p<0.001) (Table 1). Infection as indicated by seropositivity in the absence of known COVID infection occurred in 7.3% of patients. Whilst there were no significant differences in seroprevalence between patients receiving anti-tumor necrosis factor (anti-TNF) medications, vedolizumab (VDZ), and ustekinumab (UST), antibody levels were attenuated in patients on anti-TNF monotherapy (p=0.002), anti-TNF + IMM combination therapy (p=0.002), and VDZ (p=0.02), compared with no medications (Figure 1). Conclusion: We confirm in diverse populations that exposure to anti-TNFs, vedolizumab and immunomodulators, type of disease, and smoking status are associated with seroprevalence and antibody levels. We show for the first time the dominant influence of geographical location on sero-status in these patients. These observations should be considered as we look towards post-vaccination data to help stratify patients for clinical guidelines on SARS-CoV-2 vaccination. (Table Presented) Table 1. Seroprevalence of total anti-SARS-CoV-2 spike antibodies in IBD patients by ICARUS centre with non-IBD controls noted for New Delhi, India, and publicly reported local seroprevalence and by selected patient characteristics.(Figure Presented) Figure 1. Antibody levels by medication group.

14.
Gastroenterology ; 162(7):S-1004, 2022.
Article in English | EMBASE | ID: covidwho-1967388

ABSTRACT

BACKGROUND: The characteristics of SARS-CoV-2 vaccine-induced immunity in inflammatory bowel disease (IBD) patients on immune modifying agents has not been clearly defined due to their exclusion in vaccine trials. Emerging results suggest infliximab impairs antibody response compared to vedolizumab. However there has not been direct comparison to controls. We evaluated this with both humoral and T cell response in IBD patients. METHODS: Antibody and T cell response were analysed in IBD patients who received BNT162b2 (Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccination from a single Australian centre. The control group were healthcare workers (HCW) without IBD. Blood samples were taken at 4 time points: at baseline V0 (before vaccination);V1 (7- 14 days after vaccine 1);V2 (7-14 days after vaccine 2);V3 (21-42 days after vaccine 2). Antibodies to the S1/2 IgG subunit and receptor-binding protein (RBD) were measured and reported here. RESULTS: 88 (28 ulcerative colitis, 50 Crohn's disease) IBD patients were included and compared to 53 healthy controls (Table 1). IBD patients medications included 6 5ASA (6.8%), 6 immunomodulator monotherapy (6.8%), 14 anti-TNF monotherapy (15.9%), 32 anti-TNF combination therapy with immunomodulator (36%), 16 IL12/23 (18%) and 13 vedolizumab (14%). Pre-vaccine baseline sera showed absence of anti-RBD antibodies in all participants. 84 patients (87%) received BNT162b2 and 4 (4.5%) received ChAdOx1 nCoV-19 vaccines. Geometric mean [SD] anti-S1/2 antibody concentrations at 4 weeks after second vaccination (V3) were significantly lower in IBD TNF treated patients (162.6[1.7]) compared to IBD non TNF treated patients (325.2[1.3]), and healthy controls (325.2[1.3]), p<0.0001 (Figure 1). There was no difference between non-TNF treated patients including those on vedolizumab or IL12/23 compared to controls. Similarly there was a significant difference between anti-RBD IgG titres between TNF and non-TNF IBD patients at V3 but not when compared to controls. There was no difference in RBD IgG and anti-S1/2 antibodies between anti-TNF monotherapy and combination therapy. All healthy controls and most IBD patients seroconverted at V3. 2 patients that failed to seroconvert were on steroid. CONCLUSION: TNF agents influence SARS-CoV-2 vaccine-induced antibody response in IBD patients, with lower anti-S1/2 IgG concentrations compared to non-TNF IBD patients and healthy controls. However, there was no difference in RBD IgG concentrations. It is unclear whether these subtle differences in antibody response in IBD patients on TNF agents is biologically meaningful, as most seroconverted after second dose vaccination. They may translate to differences in antibody longevity, but this is yet to be demonstrated. Neutralising antibody and T cell (CD4+/CD8+/follicular T cell) data from this study to come. (Table Presented) (Figure Presented)

15.
Gastroenterology ; 162(7):S-611-S-612, 2022.
Article in English | EMBASE | ID: covidwho-1967352

ABSTRACT

Introduction Objective evaluation of treatment response is the gold standard in ulcerative colitis (UC). In this setting, intestinal ultrasound (IUS) is a non-invasive alternative to endoscopy. Recent studies showed change in IUS parameters after treatment initiation but studies with an endoscopic reference standard are scarce. The aim of this study was to evaluate early change of IUS parameters and determine cut-off values for endoscopic endpoints in UC patients starting anti-inflammatory treatment. Methods In this longitudinal prospective study consecutive patients with moderate-severe UC (baseline endoscopic Mayo score (EMS)≥2) starting an anti-inflammatory treatment were included. Clinical scores, biochemical parameters and IUS parameters were collected at baseline, after 2 (T1), 6 (T2) and 8-26 weeks (T3) around time of the second sigmoidoscopy/colonoscopy. Bowel wall thickness (BWT), Colour Doppler signal (CDS), haustrations, inflammatory fat and wall layer stratification were measured as previously established1. Endoscopic remission (ER) and mucosal healing (MH) were evaluated in the sigmoid and defined as EMS=0 and EMS≤1, respectively. The ultrasonographist and endoscopist were blinded for the outcomes of endoscopy and IUS, respectively. Results 51 consecutive patients were included (Table 1) of whom 31 underwent a second endoscopy. Two additional patients underwent colectomy and were considered non-responders. 18 patients did not undergo second endoscopy due to the COVID-19 pandemic (n=2), refusal (n=5), loss to follow-up (n=1) or treatment escalation because of clinical deterioration confirmed by IUS and biomarkers before second endoscopy was performed (n=10). BWT was significantly lower from T2 onwards in patients reaching MH (p=0.026) and ER (p=0.002) at T3 (Fig 1). A significant decrease in BWT was already visible at T1 in patients receiving infliximab (median DBWT T0-T1: -26% [-43% - -6%], p=0.001) or tofacitinib (median ∆BWT T0-T1: -33% [-46% - -5%], p=0.001) but not in patients treated with vedolizumab (median ∆BWT T0-T1: -14% [-43% - 5%], p=0.11). Most accurate BWT cut-off values at T3 to determine MH and ER were 3.52 mm (AUROC: 0.95, 95% CI: 0.86-1.00, p<0.0001, sens:91%, spec:91%) and 2.98 mm (AUROC: 0.94, 95% CI: 0.85-1.00, p=0.001, sens:87%, spec:100%), respectively. At T2, BWT per 1 mm increase and CDS were inversely associated with MH (BWT: OR: 0.48 (0.24-0.96, p=0.038);CDS: OR 0.16 (0.03-0.83), p=0.028) and ER (BWT: OR: 0.30 (0.11-0.76), p=0.01). Conclusion BWT and CDS 6 weeks after start of treatment could predict MH and ER. In addition, treatment response at IUS is drug-specific. Furthermore, we have provided accurate BWT cut-off values for endoscopic outcomes. In a point-of-care setting, (early) treatment evaluation with IUS could guide treatment decision in UC in order to optimize treatment response. 1. Bots et al. JCC 2021

16.
Gastroenterology ; 162(7):S-601, 2022.
Article in English | EMBASE | ID: covidwho-1967350

ABSTRACT

Introduction: The International Organization for the Study of Inflammatory Bowel Disease (IBD) has recommended vaccination of all patients with IBD as soon as they are able to receive the vaccine, regardless of immune-modifying therapies or disease activity. Nevertheless, some articles have shown a large percentage of individuals who are unwilling to receive the COVID-19 vaccine with fear of potential adverse events. Moreover, IBD patients were excluded from safety and efficacy phase III vaccine trials, as well as those treated with immunosuppressive therapies. Thus, we performed a monocentric real-life survey to assess the adverse events of COVID-19 vaccination among patients with IBD under biologic therapy. Methods: All adult individuals with IBD undergoing biological treatment and followed at Centro Hospitalar Universitário de São João were included. Each patient answered a telephone questionnaire conducted by a gastroenterologist. Results: A total of 301 patients agreed to participate in the study, the majority females (53.2%), with a median age of 42 years old (IQR 32-54). IBD diagnosis included Crohn's disease (76.7%) and ulcerative colitis (23.3%). The proportions of patients receiving tumor necrosis factor inhibitors, ustekinumab and vedolizumab were 75.4%, 13.0% and 11.6%, respectively. This cohort included 239 vaccinated patients (59.0% Pfizer-BioNTech, 20.5% Moderna, 14.2% Janssen and 6.3% AstraZeneca), 173 (57.5%) of whom had complete vaccination. Of the remaining individuals, only 12 did not intend to be vaccinated. The main reasons were: fear of potential adverse events (50.0%), lack of confidence in the vaccine development process (25.0%) and little information about vaccination in IBD patients (16.6%). Among vaccinated patients, the overall adverse events frequency was 56.8% after dose 1 (D1) and 74.1% after dose 2 (D2). The most common symptoms were localized injection-site reactions and fatigue. The vast majority of adverse events were mild and lasted only a few days. Only 4 (1.7%) patients had IBD exacerbation after the vaccine. No serious adverse events were reported and any patient was hospitalized. The percentage of adverse events was higher among patients younger than 50 years (77.6% vs 62.5% after D1, p=0.011;83.0% vs 58.8% after D2, p=0.002). No significant differences were seen based on sex, vaccine type, biologic drug or disease type. Compared to the general population, a lower percentage of IBD patients suffered from local or systemic reactions during the first week after vaccination (Figure 1). Conclusion: We found a high acceptance rate and a good safety profile of SARS-CoV-2 vaccination in IBD patients treated with biologics drugs. Indeed, adverse events were common but overall mild and transitory. These data support the prioritization and rapid vaccination of these individuals. (Figure Presented) Figure 1 – Adverse reactions occurring within seven days after vaccination in IBD patients compared with the general population.

17.
Gastroenterology ; 162(7):S-601, 2022.
Article in English | EMBASE | ID: covidwho-1967349

ABSTRACT

Introduction Vaccination against SARS COV-2 represents currently the best option to reduce COVID-19 mortality and morbidity. Patients with inflammatory bowel diseases (IBD) including liver transplant recipients (LTR) are in higher risk for severe disease. Despite the proven effect of vaccines, the biologic agents (BA) and concomitant immunosuppression can reduce the development of adequate antibody-mediated immunity. The aim of our study was to evaluate the effect of vaccination in these specific groups of patients. Methods A total of 211 patients with IBD on BA was enrolled, including 11 LTR. Most of them were vaccinated with 2 doses of BNT162b2 (97.1%, n=205). Anti-COVID-19 IgG (anti-C19) levels were monitored before the 1st dose (D1) of the vaccine and at least 10 days after the 2nd dose (D2). Adverse events were monitored using a questionnaire after each dose. Results 90.3% of all IBD patients and 84.5% of LTR on BA were fully vaccinated, 24.6% presented positive levels of anti-C19 before D1 (>9.5kAU/l). The mean anti-C19 levels presented after D2 in vedolizumab-treated patients was higher comparing to anti-TNFa-treated patients (323.3 kAU/l vs. 248.3 kAU/l, p<0.05). The mean anti-C19 levels presented after D2 in intensified regimens of vedolizumab and anti-TNFa agents had no significant difference in the humoral response compared to standard regimens (vedolizumab, 315.8 kAU/l vs. 327.6 kAU/l;anti-TNFa 233.6 kAU/l vs. 263.4 kAU/l). Prednison-treated patients showed dose dependent negative trend of anti-C19 levels after D2 (1mg prednisone = -6.05 kAU/l, CI 95% [-11.58, -0.51], p<0.032). LTR with IBD on BA showed no significant difference in anti-C19 levels after D2 comparing to other IBD patients on BA (271.5 vs. 230.1). Positivity of anti-C19 (>9.5 kAU/l) before D1 is associated with higher antibody levels after D2 (p<0.001, beta=124.66, CI 95% [78.61, 170.70]). The age of the patients is inversely proportional with the anti-C19 levels after D2 and with the rate of adverse events (p=0.007, beta=-2.04, CI 95% [-3.52, -0.56];p=0.004, OR=0.95, CI 95% [0.91, 0.98]). Patients which presented adverse events after D1 showed higher incidence rate of adverse events after D2 (p<0.001, OR=15.14, CI 95% [5.68, 44.14]). Most common adverse events were arm pain (80.4%), fatigue (41.9%), headache (20.6%), swelling of the application site (20.1%), chills (15.0%), joint and muscle pain (15.0%), digestive problems (7.3%). Conclusion Anti-TNFa agents are associated with lower humoral response, early 3rd dose should be considered. Intensified regimens do not cause lower antibody response. LTR with IBD on BA showed no significant difference comparing standard IBD patients on BA. Higher doses of prednisone are associated with lower humoral response. Elderly IBD patients should be recommended for an early 3rd dose. (Figure Presented)

18.
Gastroenterology ; 162(7):S-597, 2022.
Article in English | EMBASE | ID: covidwho-1967342

ABSTRACT

Background: Patients with inflammatory bowel disease (IBD), either Crohn's disease (CD) or ulcerative colitis (UC), treated with immunosuppressants and/or biotherapy might have an altered immune response to SARS-CoV-2 infection. The aim of this study was to evaluate the incidence of COVID-19 in a French cohort of IBD patients treated with infliximab or vedolizumab during the first epidemic wave and to identify factors associated with the risk of infection. Methods: All patients with IBD treated with infliximab or vedolizumab from March to June 2020 in 16 French centres were included and followed for 6 months. At baseline, clinical, demographic, family and socio-professional data were collected. At each of their day hospitalization, patients reported the occurrence of symptoms of COVID-19, and the performance of a diagnostic test, if so. Serum was collected at each visit to detect immunisation by SARS-CoV-2 at the end of follow-up and to measure trough levels. Peripheral blood lymphocytes (PBLs) were frozen at each visit for 50% of patients to further analyse the immunological changes associated with COVID-19. Results: 1079 patients were included (CD n=690, mean age 41.6 years, mean disease duration 13.3 years). Clinical and demographic data at baseline are detailed in Tables 1 and 2, respectively. 143 patients (13.3%) had one or more co-morbidities associated with a risk of severe COVID-19 (hypertension 5.6%, chronic lung disease 5%, diabetes 2.4%, obesity 0.3%). Over the 6 months of followup, 458 patients (42%) had active disease defined by an HBI score >4 or Mayo score >2 and/or treatment optimisation (dose increase, shortening of infusion interval, addition of an immunosuppressant or change of biotherapy). 111 patients (10.2%) received corticosteroids at least occasionally (self-medication was not excluded). 341 patients (32%) were tested for COVID-19 by nasal swab, of whom 23 were positive. Three patients were hospitalized. Regarding serology, in the first 13 centres analysed hitherto (886 patients), 20 patients were seropositive at the end of follow-up before the start of the vaccination campaign (January 2021), i.e. 2.2%, compared to 4.5% in the general population at the same period according to Santé Publique France data. Conclusion: The preliminary analysis of this French cohort confirms that patients with IBD are not at higher risk of severe COVID-19 despite the use of biotherapy and repeated hospital stays. This population was significantly less infected than the general population. Clinical, demographic and immunological factors associated with SARS-CoV-2 infection are being analysed as well as factors associated with a lower incidence of infection compared to the general population. (Table Presented) (Table Presented)

19.
Gastroenterology ; 162(7):S-594-S-595, 2022.
Article in English | EMBASE | ID: covidwho-1967337

ABSTRACT

Background : Robust COVID-19 vaccine-induced antibody (Ab) responses are important for protective anti-viral immunity. Data are urgently needed to determine whether vaccineinduced immunity is impacted by commonly used immunosuppressive drug regimens in IBD. Methods: We prospectively recruited 447 adults (90 healthy controls and 357 IBD) at nine UK centres. The IBD study population was established (>12 weeks therapy) on either thiopurine monotherapy (n=78), infliximab (IFX) monotherapy (n=61), thiopurine & IFX combination therapy (n=70), ustekinumab (uste) monotherapy (n=56), vedolizumab (vedo) monotherapy (n=62) or tofacitinib (tofa) monotherapy (n=30). Participants had two doses of either ChAdOx1 nCoV-19, BNT162b2 or mRNA1273 vaccines. The primary outcome was anti-SARS-CoV-2 spike (S1 RBD) Ab concentrations, measured using the Elecsys anti- SARS-CoV-2 spike (S) Ab assay, 53-92 days after second vaccine dose, in participants without prior infection, adjusted by age & vaccine type. Secondary outcomes included proportions failing to generate protective Ab responses (defined cut-off anti-S concentration 15 U/ml, which correlated with 20% viral neutralization). Results: Geometric mean S Ab concentrations (figure 1) were lower in patients treated with IFX (153U/ml;p<0.0001), IFX and thiopurine combination (109U/mL;p<0.0001), tofa (430U/ml;p<0.0001) and uste (561U/ml;p=0.013) compared to controls (1596U/ml). No differences in S Ab concentrations were found between controls and thiopurine monotherapy-treated patients (1020U/ml;p=0.62), nor between controls and vedo-treated patients (944U/ml;p=0.69). In multivariable modelling (figure 2), lower S Ab concentrations were independently associated with IFX (FC 0.10 [95% CI 0.07-0.14], p<0.0001), tofa (0.36 [95% CI 0.19-0.69], p=0.002) and uste (0.56 [95% CI 0.31-1.00], p=0.049), but not with thiopurine (0.77 [95% CI 0.54-1.11], p=0.17) or vedo (1.01 [95% CI 0.61-1.68], p=0.96). mRNA vaccines (3.67 [95% CI 2.72-4.96], p<0.0001) and older age (0.82 [95% CI 0.73-0.91], p=0.0003) were independently associated with higher & lower S Ab concentrations respectively. Protective Ab responses were generated by all thiopurine monotherapy, vedo, tofa and healthy control participants, but not by 11% of patients on IFX monotherapy, 13% on thiopurine & IFX combination therapy and 4% on uste. Conclusions : COVID-19 vaccine-induced Ab responses are significantly reduced in patients treated with IFX, or tofa, and to a lesser extent with uste. No significant reduction was seen in vedo or thiopurine monotherapy-treated patients. Our data suggest that 3rd primary or booster vaccine doses for IBD patients might be tailored to an individual's immunosuppressive treatment. (Figure Presented) (Figure Presented)

20.
Gastroenterology ; 162(7):S-287, 2022.
Article in English | EMBASE | ID: covidwho-1967277

ABSTRACT

Introduction: The immunogenicity and safety following standard two-dose SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases (IMIDs) are not well characterised, and data on third dose vaccination in this patient group are currently lacking. Methods & Aims: This prospective, observational cohort study included adult patients on immunosuppressive therapy for Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and healthy controls receiving standard two-dose SARS CoV-2 vaccination. Patients with a weak serologic response (<100 AU/ml) were allotted a third vaccine dose. Serum samples were collected prior to, and after vaccination for analyses of antibodies to the receptor-binding domain (RBD) of the SARSCoV- 2 spike protein. The aim of the study was to evaluate the immunogenicity and safety following standard and three dose SARS-CoV-2 vaccination in IMID patients on immunosuppressive therapies. Results: a total of 1641 patients (280 CD, 195 UC, 566 RA, 305 SpA, 295 PsA, median age 52 [IQR 40-63], 899 [55%] women), and 1114 healthy controls (median age 43 [IQR 32-55], 854 [77%] women), were included in the study. After standard SARS-CoV-2 two dose vaccination, 1504 (91%) patients compared to 1096 (98%) healthy controls were responders, p<0,001. Anti-RBD levels were lower in patients (median 619 AU/ml [IQR 192-4191]) than controls (median 3355 AU/ml [IQR 896–7849]), p<0,001. Response was shown in ≤90% of patients receiving methotrexate, tumor necrosis factor inhibitor (TNFi) monotherapy, ustekinumab, tozilizumab and vedolizumab, in 80–90% of patients receiving TNFi combination therapy and secukinumab and in £ 80% for JAK inhibitors (78%), and abatacept (53%) (fig.1). Lower age (OR 0.96 [95% CI 0.95–0.98]) and receiving the mRNA-1273 vaccine (OR 5.4 [95% CI 2.4–11.9]) were predictors of response. Of 153 patients with a weak response receiving a third vaccine dose, 129 (84%) became responders. After standard two dose vaccination, adverse events (AE) were reported in 50% of patients and in 78% of controls, with a comparable safety profile. Following the third dose, 44% of patients reported AEs, without new safety issues emerging. No serious AEs were reported. Conclusion: Response rate as well as anti-RBD levels were lower in IMID patients than healthy controls following standard vaccination. Third dose vaccination in serologically weak responders was safe and resulted in a response in most patients. Our data facilitate identification of patient groups at risk of an attenuated vaccine response eligible for post-vaccination serological monitoring. The data also support a third vaccine dose following standard SARS-CoV-2 vaccination to weak-responding IMID-patients. (Figure Presented) Fig.1 Anti-SARS-CoV-2 IgG antibodies following standard two dose SARS-CoV-2 vaccination according to medication group, compared to healthy controls. Violin plot showing the probability density of the data at different values, smoothed by a kernel density estimator. Each data point is a participant, and the solid orange line show the group median. The last row (CTRL vs) shows p-values for a comparison (Mann-Whitney U test) of anti-SARS-COV 2 antibodies between medication groups and healthy controls. ACE=Angiotensin converting enzyme, FL=full length, CTRL=Controls, TNF=Tumor necrosis factor inhibitor, TNF+= Tumor necrosis factor inhibitor combination therapy, MTX=methotrexate, VDZ=vedolizumab, JAK=Janus kinase inhibitor, TCZ=tocilizumab, UST=ustekinumab, ABA=abatacept, SCK=secukinumab.

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