Long-Term Outcomes of Treatment With and De-Escalation From a Combination of Vedolizumab and Another Biologic or Tofacitinib for Inflammatory Bowel Disease

Introduction: There are scant data on long-term outcomes of treatment of inflammatory bowel disease (IBD) with a combination of advanced therapies, including after de-escalation. Method(s): We identified patients with IBD at a tertiary center who began therapy with vedolizumab (VDZ) in combination with another advanced therapy (biologic or JAK inhibitor) between 2016 and 2020 and examined their outcomes through 6/1/22. We defined biochemical remission as CRP, 5 mg/L and calprotectin < 150 mcg/g, and endoscopic remission as Mayo endoscopic subscore 0 or simple endoscopic score for Crohn's disease (CD) 0. Short-term outcomes of this cohort were previously reported. Result(s): Fourteen patients with a median of 322 (IQR 251-322) weeks of follow up were identified. 10 had ulcerative colitis, 3 CD, and 1 indeterminate colitis. VDZ was combined with tofacitinib in 9 patients, ustekinumab in 3 and adalimumab in 2. Median time on combination therapy was 94 weeks (IQR 17-133). Eight patients achieved objective remission (3 biochemical, 5 endoscopic), 1 changed combination with subsequent endoscopic remission, 2 had primary non-response, 1 had secondary non-response, 1 stopped within 1 month due to reported adverse effect (paresthesia), and 1 lacked follow-up data. Eight patients de-escalated to a single agent, 4 at physician direction and 4 due to insurance denial. Before de-escalation, 6 had objective remission (2 biochemical, 4 endoscopic). After de-escalation, 3 patients maintained objective remission (2 biochemical, 1 endoscopic), 3 had disease flare, of which 1 required colectomy, and 2 lacked data. All 3 patients with disease flare had de-escalated following an insurance denial. Two patients remained on combination therapy through follow up: 1 has endoscopic remission after changing one drug of their combination and 1 has ongoing moderate endoscopic disease despite combination therapy. There were 2 infections requiring hospitalization (rotavirus, C. difficile), and 8 non-serious infections (5 mild SARS-COV-2, 1 peristomal cellulitis, 1 pneumonia, 1 sinus) while on combination therapy. Conclusion(s): In long-term follow up of this small cohort, there were no new signals on effectiveness or safety of combining advanced agents. De-escalation to a single agent was tolerated in half of patients with follow-up data;all patients who flared following de-escalation had adjusted therapy due to insurance denial. More data is needed to inform de-escalation decisions.

Analisis Del Impacto Del Covid-19 En Pacientes Con Enfermedad Inflamatoria Intestinal Empleando Inteligencia Artificial (Savana Manager)

Introduccion: Estudiamos el impacto del COVID-19 en pacientes con Enfermedad Inflamatoria Intestinal (EII) en Castilla-La Mancha. Metodos: Estudio observacional retrospectivo utilizando inteligencia artificial con capacidad de procesamiento de lenguaje natural, SAVANA manager. Esta herramienta, a pesar de sus sesgos (ej: duplicacion de casos), permite analizar grandes poblaciones. Analizamos datos de 1.808.010 pacientes durante 2020. Resultados: Se identificaron 2.243 pacientes con EII y COVID-19, que en comparacion con los casos de COVID-19 sin EII hubo mas hipertension arterial, diabetes mellitus, dislipemia, obesidad o tabaquismo. A pesar de ello, no se apreciaron diferencias en hospitalizacion (0,8607, 0,7320-1,0121, p = 0,0696), ingreso en UCI (0,4113, 0,1025-1,6508, p = 0,2102) o mortalidad (0,9099, 0,6123-1,3521, p = 0,6402). COVID-19 fue mas frecuente en pacientes con EII (3,6413, 3,4616-3,8303, p < 0,0001). Comparando pacientes con EII y COVID-19 segun sus tratamientos, vedolizumab es el unico con mayor riesgo de COVID-19 (0,3091, 0,0967-0,9886, p = 0,0478), sin embargo, el riesgo de hospitalizacion para vedolizumab es menor (0,3091, 0,0967-0,9886, p = 0,0478). Los inmunomoduladores tambien tienen un menor riesgo de hospitalizacion tanto solos (0,6677, 0,4650-0,9588, p = 0,0287) como combinados con anti-TNF (0,5109, 0,2836-0,9205, p = 0,0254). No se encontraron diferencias para monoterapia anti-TNF, ustekinumab o tofacitinib. La tasa de UCI y la mortalidad no son diferentes entre los tratamientos, salvo para tofacitinib (tasa de UCI 0,00%, mortalidad 10,00%), sin embargo, el pequeno numero de pacientes podrian sesgar este resultado. [Table presented] Conclusiones: COVID-19 en pacientes con EII no es diferente en hospitalizacion, ingreso en UCI o mortalidad en comparacion con la poblacion sin Ell. Los pacientes con Ell expuestos a inmunomoduladores y vedolizumab tienen menor riesgo de hospitalizacion que los no expuestos, no se encontraron diferencias para anti-TNF monoterapia o ustekinumab.Copyright © 2023 Elsevier Espana, S.L.U. Todos los derechos reservados.

Two years of the COVID-19 pandemic in the population of Czech patients with inflammatory bowel disease treated with biological therapy*experience of the tertiary IBD center.

Background: Inflammatory bowel disease (IBD) may be associated with a more severe course of infections and a different response to vaccination, especially in complicated IBD course and in association with immune-modifying IBD treatment. The aim of this study was to describe COVID-19 pandemic during years 2020 2022 in IBD patients with long-Term biological therapy. Method(s): A retrospective analysis of SARS-CoV-2 infection incidence in the population of 1,177 IBD (Crohn s disease or ulcerative colitis) patients with long-Term biological therapy (IBD cohort) was performed. The incidence rate, crude incidence rate and standardized incidence ratio of COVID-19 in the IBD cohort, the odds ratio of infection depending on the type of biologic therapy administered, the dynamics of COVID-19 incidence depending on the predominant SARS-CoV-2 variant in the population and the current vaccination coverage of the IBD cohort were calculated. Result(s): From January 2020 to April 2022, 548 confirmed cases of COVID-19 (46.6%) were reported in the IBD cohort, with 39% share of PCR positivity in vaccinated individuals and with 95% occurrence of infection in unvaccinated part of the IBD cohort. Standardized incidence rate ratio of COVID-19 was 27% higher in the IBD cohort compared to the general Czech population. The dynamics of the development of the number of positive cases of COVID-19 in the IBD cohort was identical to the situation in the entire country. A higher odds ratio of the chances of infection was demonstrated in patients treated with tumor necrosis factor inhibitors, but not in patients treated with anti-integrins or monoclonal antibodies against interleukins. In the IBD cohort, 85.2% of patients were properly vaccinated, which was significantly more than the vaccination rate of the entire Czech population. Discussion and conclusion: During the two pandemic years, the incidence of COVID-19 in patients with severe IBD and long-Term biological treatment was higher compared to the general Czech population, despite the favorable vaccination coverage of this high-risk patients group. A higher risk was associated with tumor necrosis factor inhibitor therapy.Copyright © 2023 Galen s.r.o.. All rights reserved.

Real-world efficacy and safety of vedolizumab in managing ulcerative colitis versus Crohn's disease: results from an Italian multicenter study.

BACKGROUND: Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ. RESEARCH DESIGN AND METHODS: Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints. RESULTS: 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016). CONCLUSION: We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.

Vedolizumab subcutaneous formulation maintenance therapy for patients with IBD: a systematic review and meta-analysis.

Background: The application of vedolizumab (VDZ) subcutaneous (SC) formulation has brought more convenience and hope to patients with moderate-to-severe inflammatory bowel diseases (IBDs) in the coronavirus disease 2019 context. Objective: This study aimed to systematically evaluate all previous studies that used VDZ SC formulation for maintenance therapy in patients with IBD. Design: Systematic review and meta-analysis. Data Sources and Methods: The search was conducted using the subject and free terms related to 'Vedolizumab', 'Subcutaneous', and 'IBD', in Embase, PubMed, Web of Science, Cochrane, and at ClinicalTrials.gov databases between 2008 and 2022. The methodological quality of randomized controlled trials (RCTs) and cohort studies was assessed using the Cochrane Handbook of Systematic Reviews and the Newcastle-Ottawa Scale, respectively. The endpoints included efficacy, safety, and immunogenicity. Results: A total of 60 studies and 2 completed clinical registry trials were retrieved, of which 3 RCTs with high methodological quality, and 3 cohort studies with large heterogeneity were included in the meta-analysis. In the RCT study design, patients with ulcerative colitis (UC) under different conditions after treated with VDZ SC were significantly distinct than those for placebo (PBO) in clinical remission, endoscopic remission, and biochemical remission. In Crohn's disease (CD), the aforementioned parameters were slightly higher than those for PBO, but there was not statistically significant in endoscopic remission and the efficacy of anti-tumor necrosis factor-naive patients. The clinical remission, endoscopic remission, and biochemical remission in patients with UC after VDZ SC treatment were similar to those after intravenous (IV) treatment. The risk ratios in patients experiencing adverse events (AEs) and serious AEs after VDZ SC and PBO treatments were 86% and 89% in UC, and 96% and 80% in CD, respectively. Compared with IV, safety was not statistically different. The risk of developing anti-VDZ antibody after VDZ SC treatment was only 20% of that after PBO in patients with UC, but it was 9.38 times in CD. Conclusion: VDZ SC treatment maintained the clinical efficacy of IV induction in patients with IBD without increasing the safety risk, and the efficacy was more pronounced in patients with UC. Immunogenicity might be a potential factor for the decrease in efficacy rate in patients with IBD. Registration: INPLASY 2022120115.

The impact of COVID-19 on patients with Inflammatory Bowel Disease: A population-based study using artificial intelligence

Background: Coronavirus disease 2019 (COVID-19) has been a pandemic that is still very prevalent. Patients with Inflammatory Bowel Disease (IBD) represent a special population considering their already altered immune system and their exposure to several immunosuppressive therapies. We pretend to study the impact of COVID-19 on IBD patients in our community, Castilla-La Mancha (a region in central Spain). Method(s): Retrospective observational study using an artificial intelligence with natural language processing capability, the SAVANA manager, we analyzed data from 1 808 010 patients with Electronic Medical Records (EMR) within the public health system of Castilla-La Mancha from March 1st 2020 to January 1st 2021. Data on demographic characteristics, hospitalization, ICU admission and mortality were collected. We compared COVID outcomes between IBD and non-IBD patients. We compared COVID outcomes in IBD patients according to their treatment (comparing each treatment group to those IBD patients with no treatment);we considered: Immunomodulators (azathioprine, mercaptopurine, methotrexate), antiTNF alone or combined with immunomodulator, vedolizumab, ustekinumab and tofacitinib;mesalazine and corticosteroids were not analyzed. Result(s): 2 243 patients with IBD suffered COVID-19, compared to COVID-19 cases without IBD there were less females, they suffered more arterial hypertension, diabetes mellitus, dyslipidemia, obesity, or tabacco use (TABLE 1). And yet, despite these being proven risk factors for worse outcomes for COVID-19, no differences were appreciated in hospitalization rate, ICU admission, or mortality between those with or without IBD (TABLE 2). COVID-19 was more frequent in IBD patients (32.59 vs 13.28%). Comparing IBD patients with COVID-19 according to their treatments (TABLE 3), vedolizumab is the only treatment with a higher risk for COVID-19 infection, however the hospitalization risk for vedolizumab is lower than for those without it. Immunomodulators do also have a lower hospitalization risk both alone or in combination with antiTNF, no differences were found for antiTNF monotherapy, ustekinumab or tofacitinib. ICU rate and mortality are no different between treatments, except for tofacitinib (0.00% ICU rate, 10.00% mortality), however the small number of patients using this treatment may bias this result. Conclusion(s): COVID-19 in IBD patients is no different in hospitalization, ICU admission or mortality compared to non-IBD population. IBD patients exposed to immunomodulators and vedolizumab have less hospitalization risk than those not exposed, no differences were found for antiTNF alone or ustekinumab. The impact of tofacitinib in COVID outcomes requires further investigation.

Impact of major medication discontinuation during the first wave of COVID-19 pandemic on the risk of early relapse in patients with inflammatory bowel disease: A French observational retrospective study

Background: The prevalence of nonadherence to major treatments and the subsequent adverse outcomes in IBD patients during the first wave of COVID-19 pandemic remain scarce Aim: To investigate the risk of early disease relapse in a cohort of IBD patients under immunosuppressants and/or biologics who decided themselves to discontinue their IBD-related major treatments without previous medical advice during the first wave of COVID-19 pandemic Methods: All consecutive patients with inactive IBD under immunosuppressants and/or biologics who acknowledged having withdrawn their major therapy for IBD without previous medical advice during the first wave of COVID-19 (from March 2020 to December 2020) were enrolled. The primary endpoint was the survival rate without disease relapse. Kaplan-Meier curves were plotted for time from inclusion to IBD relapse and a logistic regression model with uni- and multivariate analyses was performed to identify predictors of relapse after drug discontinuation Results: During the study period, among the 862 IBD patients followed as outpatients either treated with infliximab or vedolizumab (outpatient clinics n= 368) or treated with oral azathioprine, adalimumab golimumab or ustekinumab alone or in combination (n= 494), 54 patients (6.2 %) (42 CD, 12 UC, 28 F, median age 36 years) who had discontinued themselves their IBD-related major therapy without previous medical advice were included. The median duration of drug withdrawal was 7.0 weeks (range 2-24) and the median time to relapse was 9.0 weeks (range 4-20). The most treatments withdrawn were adalimumab (n=19), ustekinumab (n=19), azathioprine (n= 12), golimumab (n=1) and a lesser degree infliximab (n=7) eand vedolizumab (n=6). During the median follow-up period of 24 weeks (range 5-42), 22 out of 54 patients (40.7 %) who discontinued their IBD treatment experienced a relapse in whom 6 requiring administration of oral steroids, 4 hospitalization and 2 IBD-related surgery By univariate analysis, past IBD related surgery was identified as the only predictor of disease relapse after drug withdrawal (OR=3.3 CI 95 % [1.08-10.38] Conclusion(s): In IBD patients, major treatment discontinuation by the patients themselves without medical advices during the first wave of pandemic Covid-19 including the lockdown was associated with a substantial risk of disease relapse occurring in around 4 out of 10 patients and subsequent further risk of need for steroids, hospitalization and surgery. Strategies targeting the adherence to therapy and patient's informations about the real risks leading to drug discontinuation are of paramount interest, especially during health crisis to minimize such issues.

Neutralising antibody potency against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants in infliximab and vedolizumab treated patients with Inflammatory Bowel Disease after three doses of COVID-19 vaccine: A prospective multicentre cohort study

Background: Anti-tumour necrosis factor drugs such as infliximab are associated with attenuated antibody responses after COVID-19 vaccination It is unknown how infliximab impacts vaccine-induced serological responses against highly transmissible Omicron variants, which possess the ability to evade host immunity and are now the dominating variants causing current waves of infection Methods: In this prospective, multicentre, observational cohort study we investigated neutralising antibody responses against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants after three doses of COVID-19 vaccination in 1288 patients with IBD without prior COVID-19 infection, who were established on either infliximab (n=871) or vedolizumab (n=417). Cox proportional hazards models were constructed to investigate the risk of breakthrough infection in relation to neutralising antibody titres Results: Following three doses of COVID-19 vaccine, neutralising titre NT50 (half-inhibitory neutralising titre) was significantly diminished in patients treated with infliximab as compared to patients treated with vedolizumab, against wild-type, BA.1 and BA.4/5 variants (Fig 1). Patients with Crohn's disease showed lower antibody NT50 compared to patients with ulcerative colitis against wild-type strain and BA.4/5 (Fig 2). Older age and thiopurine were independently associated with lower NT50 against wild-type strain and BA.4/5 (Fig 2). Non-white ethnicity was associated with higher NT50 compared to white ethnicity against wild-type strain, BA.1 and BA.4/5 (Fig 2). Breakthrough infection was significantly more frequent in patients treated with infliximab compared to patients treated with vedolizumab (Fig 3). Cox proportional hazards models of time to breakthrough infection after the third dose showed infliximab treatment to be associated with a higher hazard risk (HR) of 1.71 (95% CI [1.08 to 2.71], p=0.022) compared to vedolizumab (Fig 4). Higher neutralising antibody titres against BA.4/5 were associated with a lower hazard risk and a longer time to breakthrough infection (HR 0.87 [0.79 to 0.95] p=0.0028) (Fig 4) Conclusion(s): Following a third COVID-19 vaccine dose, patients established on infliximab treatment have significantly lower neutralising titres against SARS-CoV-2, which were especially low against Omicron variants. Increased breakthrough infection in infliximab recipients was associated with lower neutralising antibody titres against BA.4/5. These data underline the importance of continued COVID-19 vaccination programs, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy may be reduced.

COVID-19 vaccine-induced neutralising antibody responses against SARS-CoV-2 Omicron BA.4/5 are diminished in patients with inflammatory bowel disease on anti-TNF or JAK-inhibitor therapy

Background: Patients with Inflammatory bowel disease (IBD) receiving anti-TNF or JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the currently dominant Omicron BA.4/5 variants. Method(s): We prospectively recruited 329 adults (68 healthy controls (HC) and 261 IBD) who had received three doses of COVID-19 vaccine at nine UK centres. The IBD population was established (>12 weeks therapy) on either thiopurine (n=60), infliximab (IFX) (n=43), thiopurine and IFX combination (n=46), ustekinumab (n=43), vedolizumab (n=46) or tofacitinib (n=23). Pseudoneutralisation assays were performed and the half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARSCoV-2 neutralising response against wild-type (WT) virus and the BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, ethnicity, vaccine type and age. Result(s): Heterologous (two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both WT SARS-CoV-2 virus and the BA.4/5 variants in HCs and IBD (fig 1). Antibody titres against BA.4/5 were significantly lower than antibodies against WT virus in both groups (Geometric Mean Ratio (GMR) [95% CI], 0.11 [0.09, 0.15], P<0.0001 in healthy participants;GMR 0.07 [0.06, 0.08], P<0.0001 in IBD patients). Multivariable models showed that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in IBD patients on IFX (GMR 0.44 [0.20, 0.97], P=0.042), IFX and thiopurine combination (GMR 0.34 [0.15, 0.77], P=0.0098) or tofacitinib (GMR 0.37 [0.15, 0.92], P=0.032), but not in patients on thiopurine monotherapy, ustekinumab or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against WT and BA.4/5 (P<0.05). Conclusion(s): A third dose of COVID-19 vaccine based on the WT spike glycoprotein boosts neutralising antibody titres in patients with IBD. However, responses are lower against the currently dominant variant BA.4/5, particularly in patients taking anti-TNF or JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed IBD patients may receive additional benefit from bivalent vaccine boosters which target Omicron variants. .

Antibody responses to SARS-CoV-2 vaccination outperform responses induced by natural infection in patients with IBD receiving immunosuppressive medications: A report from the ICARUS-IBD consortium

Background: The effects of immunosuppressive medications on immune responses to COVID-19 vaccination in patients with inflammatory bowel diseases (IBD) have been reported. However there is little data on immune responses in naturally infected SARS-CoV-2 patients compared with vaccination. We compared in a longitudinal study SARS-CoV-2 antibody and T cell responses in naturally-infected vs. vaccinated IBD patients Methods: 110 IBD patients enrolled at the Icahn School of Medicine at Mount Sinai were prospectively followed with serial blood collection between May 2020, and February 2022. Samples were screened by ELISA to determine seropositivity, and stratified by infection, vaccination status, and IBD medications. Subsequently, ELISA-based inhibition assay and pseudotyped SARS-CoV-2 microneutralization assays were used to determine the inhibition and neutralization capacity of the seropositive individuals for wild type (WT) delta variant (Dv) and Omicron. Cellular responses were measured by IFN-gamma ELIspot using nucleocapsid and spike peptide libraries Results: Overall, 64 patients had Crohn's Disease and 46 had Ulcerative Colitis (UC), 69 were naturally infected. Only Anti-TNF (N=52), Ustekinumab (N=16), and Vedolizumab (VDZ) (N=33) treatment groups were considered. Only US-available vaccinations were included. Double-vaccinated IBD patients showed greater neutralizing responses to SARS-CoV-2 WT and Dv than naturally-infected individuals (p=0.0003, p=0.0025). Moreover, double-vaccinated individuals had greater neutralizing reactions against WT than DV (p 0.017) and Omicron (p 0.001) variants. Following natural infection, there were no differences between treatment groups in neutralization response, however those double-vaccinated on anti-TNF had lower neutralization than VDZ (p=0.008). Neutralization responses were maintained for a period of 8 months following natural infection and double vaccination SARS-CoV-2 spike T cell responses were significantly higher in naturally infected (p=0.009) and double vaccinated individuals (p=0.005) with no significant differences between treatment groups (p<0.999) Conclusion(s): After a second vaccine dose, IBD patients showed stronger neutralizing antibody titers than naturally infected patients. Those on anti-TNF exhibited lower neutralizing responses than VDZ. T-cell responses were similar in infected and double-vaccinated subjects after vaccination or infection. These data imply COVID-19 immunization provides additional serological protection over natural infection.

One-Year Comparison of Clinical and Endoscopic Outcomes of Tofacitinib Versus Vedolizumab for Ulcerative Colitis After Anti-Tumor Necrosis Factor Failure: A Real-World Cohort Study in the United States

Background: Tofacitinib (tofa) is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We compared 52 week real-world outcomes of tofa vs vedolizumab (vedo) for UC after anti-TNF failure. Method(s): In this retrospective cohort study, adults initiated tofa or vedo after failure of >=1 anti-TNF between 5/1/18 and 4/1/21 at a large U.S. medical center. Vedo patients were frequency matched to tofa patients 2:1 by age and sex. The primary outcome was steroid-free clinical remission at 12 and 52 (+/- 4) weeks (SFCR 12 and 52, simple clinical colitis activity index [SCCAI] <=2 or provider assessment and no use of oral/IV steroids for >=30 days). The secondary outcome was endoscopic response (ER) within 52 weeks (decrease in Mayo endoscopic subscore [MES] by >=1 point). Other outcomes within 52 weeks: Endoscopic remission (MES=0), biochemical response/remission (improvement by 25%/normalization of C-reactive protein), drug discontinuation for non-response (NR), improvement in arthralgia, UC hospitalization, and adverse events (AEs). Multivariable logistic regression was performed for primary/secondary outcomes adjusting for UC duration, number of prior anti-TNFs, steroid/immunomodulator use, albumin, Montreal disease extent >E1, MES = 3, and UC hospitalization within 12 months. Result(s): 136 vedo patients were matched to 68 tofa patients. Tofa patients had more anti-TNF exposures, higher CRP and SCCAI, and most had prior vedolizumab exposure (Table 1). 54% of tofa vs 46% of vedo patients achieved SFCR 12 and 59% vs 45% achieved SFCR 52. Within 52 weeks, 74% tofa vs 55% vedo had ER, 30% vs 27% had endoscopic remission, 55% vs 50% had improvement in arthralgia, 71% vs 59% had biochemical response, 46% vs 32% had biochemical remission, 5% vs 13% had UC hospitalization, 30% vs 29% discontinued treatment for NR, and 0% vs 2% discontinued treatment due to AEs (vedo group only: Perforated diverticulitis, nausea, and oral pain) (Figure 1). During available follow-up (not limited to 52 weeks), the most common AEs (reported among >1% of total cohort) included rash (0% tofa vs 4% vedo), C. difficileinfection (1% vs 2%), shingles (2% vs 1%), COVID-19 (1% vs 2%), other infection (2% vs 4%), and elevated liver enzymes (1% vs 2%) (Figure 2). After multivariable logistic regression, tofa was associated with a non-significantly higher odds of SFCR 12 (OR 1.66, 95% CI 0.77-3.62) and significantly higher odds of SFCR 52 (OR 2.15, 95% CI 1.01-4.61) and ER within 52 weeks (aOR 3.42, 95% CI 1.08- 10.80) vs vedo. Conclusion(s): Tofa was associated with higher odds of SFCR 52 and ER vs vedo for UC. AEs were consistent with known safety profiles. Due to limited sample sizes, larger cohort studies are needed.

Effectiveness and safety of COVID-19 Vaccine among Patients with Inflammatory Bowel Disease: A medical center hospital-based study in central Taiwan

Background: In 2020, the world faced the unprecedented crisis of coronavirus disease 2019 (COVID-19). COVID-19 infection resulted in many complications for IBD patients. However, the association of IBD patients with COVID-19 who had been vaccinated receiving biologics, immunomodulators, or steroids therapies is lacking in Taiwan. Thus, we hypothesized that the first wave of the COVID-19 pandemic would have some effects on IBD patients who were vaccinated and performed this retrospective study. The aim of this study was to investigate the effectiveness and safety of COVID-19 vaccines in patients with IBD receiving biologics, immunomodulators, or steroids therapies in a medical center hospital in middle Taiwan. Method(s): From January 1980 to October 2022, a total of 286 consecutive patients with IBD (UC: 184 patients;CD: 102 patients) was enrolled into our current study. There were 155 patients had received vaccine for at least one dose. Finally, 51 patients who were vaccinated still suffered from COVID-19 with an infection rate of 32.9%. We analyzed the clinical manifestations of COVID-19-positive in IBD patients. Clinical characteristic, and treatment outcomes of all patients with COVID-19 who had been vaccinated were analyzed. Result(s): The mean diagnostic age of these enrolled patients was 45.1years. Male accounted for the majority of our all patients in the study (76.5%). There were 54.1% patients had received COVID-19 vaccine for at least one dose. The mean dose of COVID-19 vaccine was 2.16. Patients with UC presented significantly higher infection rate of COVID-19 than patients with CD. (Table 1). The most common clinical manifestations were sore throat, followed by fever, cough, runny nose and fatigue. The most common type of biologics used in these patients with IBD was Vedolizumab, followed by Adalimumab and Infliximab. There were no differences in the COVID-19 infection rate in different treatment groups among patients with UC or CD patients(Table 2, 3). Conclusion(s): Our current study showed the risk of COVID-19 in IBD patients is not specifically higher than the general population. Our 51 patients with COVID-19 infection had a good outcome and none one needed hospitalization. Patients with UC presented significantly higher infection rate of COVID-19 than patients with CD. The use of biologics or immunomodulators was not associated with an increased risk of COVID-19 in patients with IBD. The use of steroids was also not associated with an increased risk of COVID-19 in patients with IBD if steroids were held two weeks or decreased dosage before vaccinations. Furthermore, we found that IBD patients under adequate therapy can reduce the severity of COVID-19.

SARS-CoV-2 breakthrough infections after COVID-19 vaccination in patients with Inflammatory Bowel Disease: A systematic review and meta-analysis

Background: Patients with inflammatory bowel disease (IBD) have reduced seroconversion rates to COVID-19 vaccination. It is unclear whether an impaired immune response in vaccinated IBD patients impacts the susceptibility to SARS-CoV-2 infection and occurrence of (severe) COVID-19. We evaluated SARS-CoV-2 breakthrough infection rates and the disease course of COVID-19 in vaccinated IBD patients. Method(s): A systematic literature search was performed for studies which reported SARS-CoV-2 breakthrough infection rates and/or the disease course of COVID-19 in patients with IBD after COVID-19 vaccination. Primary outcome was the rates of breakthrough infection per time period. In meta-analyses, the pooled relative risk was calculated with a random effects model for vaccinated patients compared to vaccinated controls, to partially vaccinated and unvaccinated patients with IBD. Result(s): A total of 16 studies were included in analysis. The study period ranged from January 2020 to October 2021, and a follow-up time ranges from 3 weeks to 6 months. The breakthrough infection rates range from 0 to 37.4% in IBD patients within the study follow-up time. Strikingly, only studies with vaccination prior to December 2021 showed a breakthrough infection rate above 2%. (Figure 1). The disease course of a breakthrough infection is generally mild, with mild constitutional and respiratory symptoms in 85% of infected IBD patients. Hospitalization and mortality rates are low (0-8.7% and 0-4.3% respectively). Meta-analyses showed a significantly lower pooled relative risk of breakthrough infection for vaccinated as compared to unvaccinated IBD patients (RR 0.07, 95% CI 0.03;0.18). No difference was observed in risk of breakthrough infections between IBD patients and non-IBD controls (RR 1.01, 95% CI 0.92;1.10), and no difference between vaccinated and partially vaccinated IBD patients (RR 0.67, 95% CI 0.38;1.18). The impact of immunosuppressive therapy on breakthrough infection rates differs between studies. One study reported higher breakthrough infection rates for patients treated with infliximab in comparison to vedolizumab (P<.05). Other studies showed no impact on the breakthrough infection rates for immunosuppressive treatment vs no treatment, anti-TNF-alpha/corticosteroids vs without anti- TNF-alpha/corticosteroids and other biologics vs anti-TNF-alpha. Conclusion(s): Vaccination is effective to prevent COVID-19 infections in patients with IBD. Breakthrough infections do occur, but the disease course is generally mild. Available data seem to suggest a declining trend of breakthrough infections during calendar time. Data on the impact of IBD medication on the rate of breakthrough infections and disease course require further elucidation. (Figure Presented).

What had the greatest impact on the quality of life of IBD patients on intravenous biological therapy in Montenegro during COVID-19?

Background: COVID-19 has affected the quality of life (QoL) of patients with chronic diseases, including patients with IBD. The aim of this study is to evaluate the QoL of patients with IBD on intravenous biological therapy (IvBT), through the Short Inflammatory Bowel Disease Questionnaire (sIBDQ), and to correlate the results with sociodemographic data of the patients. Method(s): This study was comprised of patients older than 18 years of age, with a pathohistologically confirmed diagnosis of IBD (Ulcerative Colitis (UC), and Crohn's Disease (CD)). The study was conducted on September and October 2020, during one of the highest incidences period of COVID-19 in our country. Patients completed the sIBDQ, and DASS-21 (Depression, Anxiety and Stress Score-21) questionnaire too, assessing their level of depression, anxiety and stress. For significant symptoms (DASS-21), we used at least moderate DASS-21 subscale score: DASS-21 Depression (>= 14), DASS-21 Anxiety (>= 10) and DASS-21 Stress (>=19). The Simple Clinical Colitis Activity Index was used to assess the disease activity of UC;for CD, the Harvey-Bradshaw Index was used. Patients who scored below 50 on the sIBDQ were those labeled with worse QoL. We also examined demographic data, data on IBD characteristics and COVID-19 data and their impact on quality of life. Result(s): Of the total number of patients (94), there were 40 (42.5%) females, 42 (44.6%) with CD. All patients have been receiving IvBTh (anti TNFalpha: Infliximab-originator and biosimilar (59 patients) and anti-integrins: Vedolizumab (35 patients)) for at least 6 months prior. The results indicated worse QoL in 25 (27%) patients. Multivariate analysis showed that the greatest impact on poor QoL during the COVD-19 pandemic were: active disease (p= 0.002), significant symptoms on the DASS21 score (p= 0.013), patients who did not regularly go to work or were not employed (p=0.017), if they had a patient with COVID-19 in their immediate environment (p=0.024) and those who had a higher degree of health concerns about coming to regular admission to biological therapy at the IBD unit. (p=0.046). Conclusion(s): 27% of IBD patients on IvBT had worse QoL during the COVID 19 pandemic. In addition to disease activity and significant psychological disturbances, other reasons for lower QoL were identified during the pandemic and are directly related to it. (Figure Presented).

Vaccine escape, increased breakthrough and reinfection in infliximab-treated patients with IBD during the Omicron wave of the SARS-CoV-2 pandemic.

OBJECTIVE: Antitumour necrosis factor (TNF) drugs impair serological responses following SARS-CoV-2 vaccination. We sought to assess if a third dose of a messenger RNA (mRNA)-based vaccine substantially boosted anti-SARS-CoV-2 antibody responses and protective immunity in infliximab-treated patients with IBD. DESIGN: Third dose vaccine induced anti-SARS-CoV-2 spike (anti-S) receptor-binding domain (RBD) antibody responses, breakthrough SARS-CoV-2 infection, reinfection and persistent oropharyngeal carriage in patients with IBD treated with infliximab were compared with a reference cohort treated with vedolizumab from the impaCt of bioLogic therApy on saRs-cov-2 Infection and immuniTY (CLARITY) IBD study. RESULTS: Geometric mean (SD) anti-S RBD antibody concentrations increased in both groups following a third dose of an mRNA-based vaccine. However, concentrations were lower in patients treated with infliximab than vedolizumab, irrespective of whether their first two primary vaccine doses were ChAdOx1 nCoV-19 (1856 U/mL (5.2) vs 10 728 U/mL (3.1), p<0.0001) or BNT162b2 vaccines (2164 U/mL (4.1) vs 15 116 U/mL (3.4), p<0.0001). However, no differences in anti-S RBD antibody concentrations were seen following third and fourth doses of an mRNA-based vaccine, irrespective of the combination of primary vaccinations received. Post-third dose, anti-S RBD antibody half-life estimates were shorter in infliximab-treated than vedolizumab-treated patients (37.0 days (95% CI 35.6 to 38.6) vs 52.0 days (95% CI 49.0 to 55.4), p<0.0001).Compared with vedolizumab-treated, infliximab-treated patients were more likely to experience SARS-CoV-2 breakthrough infection (HR 2.23 (95% CI 1.46 to 3.38), p=0.00018) and reinfection (HR 2.10 (95% CI 1.31 to 3.35), p=0.0019), but this effect was uncoupled from third vaccine dose anti-S RBD antibody concentrations. Reinfection occurred predominantly during the Omicron wave and were predicted by SARS-CoV-2 antinucleocapsid concentrations after the initial infection. We did not observe persistent oropharyngeal carriage of SARS-CoV-2. Hospitalisations and deaths were uncommon in both groups. CONCLUSIONS: Following a third dose of an mRNA-based vaccine, infliximab was associated with attenuated serological responses and more SARS-CoV-2 breakthrough infection and reinfection which were not predicted by the magnitude of anti-S RBD responses, indicative of vaccine escape by the Omicron variant. TRIAL REGISTRATION NUMBER: ISRCTN45176516.

Superior Effectiveness of Tofacitinib Compared to Vedolizumab in Anti-TNF-experienced Ulcerative Colitis Patients: A Nationwide Dutch Registry Study.

BACKGROUND & AIMS: Clinicians face difficulty in when and in what order to position biologics and Janus kinase inhibitors in patients with anti-tumor necrosis factor-alpha (TNF) refractory ulcerative colitis (UC). We aimed to compare the effectiveness and safety of vedolizumab and tofacitinib in anti-TNF-exposed patients with UC in our prospective nationwide Initiative on Crohn and Colitis Registry. METHODS: Patients with UC who failed anti-TNF treatment and initiated vedolizumab or tofacitinib treatment were identified in the Initiative on Crohn and Colitis Registry in the Netherlands. We selected patients with both clinical as well as biochemical or endoscopic disease activity at initiation of therapy. Patients previously treated with vedolizumab or tofacitinib were excluded. Corticosteroid-free clinical remission (Simple Clinical Colitis Activity Index ≤2), biochemical remission (C-reactive protein ≤5 mg/L or fecal calprotectin ≤250 µg/g), and safety outcomes were compared after 52 weeks of treatment. Inverse propensity score-weighted comparison was used to adjust for confounding and selection bias. RESULTS: Overall, 83 vedolizumab- and 65 tofacitinib-treated patients were included. Propensity score-weighted analysis showed that tofacitinib-treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at weeks 12, 24, and 52 compared with vedolizumab-treated patients (odds ratio [OR], 6.33; 95% confidence interval [CI], 3.81-10.50; P < .01; OR, 3.02; 95% CI, 1.89-4.84; P < .01; and OR, 1.86; 95% CI, 1.15-2.99; P = .01; and OR, 3.27; 95% CI, 1.96-5.45; P < .01; OR, 1.87; 95% CI, 1.14-3.07; P = .01; and OR, 1.81; 95% CI, 1.06-3.09; P = .03, respectively). There was no difference in infection rate or severe adverse events. CONCLUSIONS: Tofacitinib was associated with superior effectiveness outcomes compared with vedolizumab in anti-TNF-experienced patients with UC along with comparable safety outcomes.

Real-World Study on Vedolizumab Serum Concentration, Efficacy, and Safety after the Transition from Intravenous to Subcutaneous Vedolizumab in Inflammatory Bowel Disease Patients: Single-Center Experience.

Little is known about how the change from intravenous to subcutaneous vedolizumab in a real-life setting in inflammatory bowel disease patients on stable maintenance therapy affects clinical outcomes. We compared the data on vedolizumab serum trough concentration, efficacy, and safety prior to and six months after the switch from intravenous to subcutaneous vedolizumab. In total, 24 patients, 13 with ulcerative colitis (UC) and 11 with Crohn's disease (CD), were included. Mean serum trough concentration of intravenous vedolizumab was significantly lower than mean serum trough concentration of subcutaneous vedolizumab (p = 0.002). There was no significant difference between C-reactive protein levels, fecal calprotectin levels or clinical scores (Harvey-Bradshaw index or Partial Mayo score) prior to transition to subcutaneous vedolizumab and after 6 months. In four (16.7%) patients, two CD and two UC, therapy was discontinued during the follow-up period with a median of 5 months (minimum-maximum: 4-6). In all patients, therapy was discontinued due to loss of response. In total, 13 adverse events were reported by 11 patients, and the most common adverse event was COVID-19. No serious adverse events were reported. In conclusion, subcutaneous vedolizumab has shown to be effective and safe in patients on previously established maintenance therapy with intravenous vedolizumab.

Uptake of a Switching Program for Patients Receiving Intravenous Infliximab and Vedolizumab to Subcutaneous Preparations.

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.

Real-world experience of switching from intravenous to subcutaneous vedolizumab maintenance treatment for inflammatory bowel diseases.

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.