Adverse Events Related to SARS-CoV-2 Vaccine in a Nationwide Cohort of Patients With Inflammatory Bowel Disease.

INTRODUCTION: There are limited data on the safety profile of the severe acute respiratory syndrome coronavirus-2 vaccine among patients taking immunosuppressive medications. Our aim was to evaluate the adverse events related to the vaccines in a nationwide cohort of patients with inflammatory bowel disease on diverse immunosuppressive medications. METHODS: This was a retrospective cohort study using data from the Veterans Health Administration. The primary outcome was any adverse event of special interest (cerebrovascular accident, venous thromboembolism, acute myocardial infarction, Bell palsy) within 90 days of vaccination. RESULTS: A total of 17,201 patients were included, and 12,351 patients (71.8%) received at least 1 vaccine dose. The most common adverse events were acute myocardial infarction and venous thromboembolism. In inverse probability treatment weighting-adjusted logistic regression, full vaccination was not significantly associated with increased adverse events through 90 days, relative to unvaccinated patients. DISCUSSION: Full severe acute respiratory syndrome coronavirus-2 vaccination was not associated with an increased rate of key adverse events relative to unvaccinated individuals among patients with inflammatory bowel disease.

The accelerated waning of immunity and reduced effect of booster in patients treated with bDMARD and tsDMARD after SARS-CoV-2 mRNA vaccination.

Objectives: This study aimed to assess the duration of humoral responses after two doses of SARS-CoV-2 mRNA vaccines in patients with inflammatory joint diseases and IBD and booster vaccination compared with healthy controls. It also aimed to analyze factors influencing the quantity and quality of the immune response. Methods: We enrolled 41 patients with rheumatoid arthritis (RA), 35 with seronegative spondyloarthritis (SpA), and 41 suffering from inflammatory bowel disease (IBD), excluding those receiving B-cell-depleting therapies. We assessed total anti-SARS-CoV-2 spike antibodies (Abs) and neutralizing Ab titers 6 months after two and then after three doses of mRNA vaccines compared with healthy controls. We analyzed the influence of therapies on the humoral response. Results: Patients receiving biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) showed reduced anti-SARS-CoV-2 S Abs and neutralizing Ab titers compared with HC or patients receiving conventional synthetic (cs)DMARDs 6 months after the first two vaccination doses. Anti-SARS-CoV-2 S titers of patients with b/tsDMARDs declined more rapidly, leading to a significant reduction in the duration of vaccination-induced immunity after two doses of SARS-CoV-2 mRNA vaccines. While 23% of HC and 19% of patients receiving csDMARDs were without detectable neutralizing Abs 6 months after the first two vaccination doses, this number was 62% in patients receiving b/tsDMARDs and 52% in patients receiving a combination of csDMARDs and b/tsDMARDs. Booster vaccination led to increased anti-SARS-CoV-2 S Abs in all HC and patients. However, anti-SARS-CoV-2 S Abs after booster vaccination was diminished in patients receiving b/tsDMARDs, either alone or in combination with csDMARDs compared to HC. Conclusion: Patients receiving b/tsDMARDs have significantly reduced Abs and neutralizing Ab titers 6 months after mRNA vaccination against SARS-CoV-2. This was due to a faster decline in Ab levels, indicating a significantly reduced duration of vaccination-induced immunity compared with HC or patients receiving csDMARDs. In addition, they display a reduced response to a booster vaccination, warranting earlier booster vaccination strategies in patients under b/tsDMARD therapy, according to their specific Ab levels.

Tofacitinib in the treatment of ulcerative colitis : A position paper issued by the Inflammatory Bowel Disease Working Group of the Austrian Society of Gastroenterology and Hepatology (ÖGGH).

Ulcerative colitis (UC) is one of the main forms of inflammatory bowel disease (IBD). Despite the widening range of drug treatment options, primary nonresponse, secondary loss of response as well as adverse events call for additional treatment alternatives.Tofacitinib is an oral small-molecule drug of the class of Janus kinase inhibitors which, in the European Union, was approved for the treatment of moderate to severe active UC in August 2018. This position paper, drawn up by the IBD Working Group of the Austrian Society of Gastroenterology and Hepatology, summarizes the mechanism of action, clinical development, marketing authorization status, efficacy and safety of tofacitinib. Also, by providing a synopsis of available data from both pivotal and post-marketing studies, clinical aspects of specific interest are highlighted and discussed.The available body of evidence indicates that tofacitinib is an additional effective medication for the treatment of UC that exhibits a good safety profile. This position paper aims at optimizing the safe and effective use of tofacitinib in daily clinical practice.

Risk of severe and opportunistic infections and the impact of SARS-COV-2 on this risk in a nationwide cohort of patients with inflammatory bowel disease.

BACKGROUND: The Inflammatory Bowel Disease (IBD) patients have adopted lifestyle modifications to prevent infection via SARS COV-2. AIMS: This study aims to examine rate of serious infections and opportunistic infections in the pre-pandemic and pandemic period, and to analyse if the risk associated with medications used to treat IBD were potentially modified by associated change in lifestyle. METHODS: We conducted a retrospective cohort study of patients from the US national Veteran Affairs Healthcare System (VAHS). Patients were stratified into two groups: pre-pandemic (prior to SARS COV-2 pandemic) and pandemic (during SARS COV-2 pandemic) and outcomes were measured in these groups. Primary outcome was occurrence of any serious infection. Secondary outcome was occurrence of any opportunistic infection. RESULTS: There were 17,202 IBD patients in the pre-pandemic era and 15,903 patients in the pandemic era. The pre-pandemic era had a significantly higher proportion of serious infections relative to the pandemic era (5.1% vs. 4.4%, p = 0.002). The proportion of opportunistic infections were similar between pre-pandemic and pandemic eras (0.3% vs. 0.3%, p = 0.82). Relative to 5-ASA, patients taking anti-TNF (HR = 1.50 (1.31-1.72)), anti-TNF+TP (HR = 1.56 (1.24-1.95)) or vedolizumab (HR = 1.81 (1.49-2.20)) had an increased hazard of serious infection (p > 0.001). CONCLUSION: In a nationwide cohort of IBD patients, we found that risk of serious infections could possibly be affected by behavioural modifications due to SARS-COV-2 pandemic.

Efficacy and Safety of Upadacitinib Induction Therapy in Patients With Moderately to Severely Active Crohn’s Disease: Results From a Randomized Phase 3 U-EXCEL Study

Introduction: Eligible patients(N=526) with moderate to severe active Crohn’s Disease(CD), defined as average daily stool frequency(SF)≥4 and/or abdominal pain score(APS)≥2, and a Simple Endoscopic Score for CD(SES-CD) (excluding the narrowing component subscore) ≥6(≥4 for subjects with isolated ileal disease). PBO % [95% CI] h Co-Primary Endpoints Clinical remission, wk 12  Per CDAI a  Per SF/APS b 29.1 [22.4, 35.8] 22.2 [16.0, 28.3] 49.5 [44.2, 54.8] 50.7 [45.5, 56.0] 20.8 [12.7, 28.8]** 28.7 [20.9, 36.4]** Endoscopic response c , wk 12 13.1 [8.1, 18.0] 45.5 [40.3, 50.8] 33.0 [26.2, 39.9]** Key Secondary Endpoints Clinical Remission, wk 4  Per CDAI a  Per SF/APS b 26.7 [20.2, 33.3] 14.8 [9.5, 20.0] 37.1 [32.1, 42.2] 35.7 [30.7, 40.7] 10.8 [2.9, 18.6]* 21.2 [14.3, 28.2]** Corticosteroid-free clinical remission, wk 12  per CDAI d  per SF/APS d (N=64) 15.7 [6.8, 24.7] 12.5 [4.4, 20.6] (N=126) 42.9 [34.2, 51.5] 44.4 [35.8, 53.1] 27.7 [15.7, 39.8]** 32.6 [21.5, 43.7]** Clinical Response CR-100 e  Week 2  Week 12 20.4 [14.4, 26.5] 37.3 [30.1, 44.5] 32.2 [27.3, 37.1] 56.6 [51.4, 61.8] 11.7 [4.2, 19.2]* 19.8 [11.3, 28.4]** Endoscopic remission f , wk 12 7.4 [3.5, 11.3] 28.9 [24.2, 33.7] 21.8 [15.8, 27.8]** Patient randomization was stratified by baseline corticosteroid use, endoscopic disease severity, and the number of previously failed biologics. All patients within this dataset were included here within the ITT population. a Clinical remission per CDAI = per US, CDAI < 150. b Clinical remission per SF/APS = per EU, average daily SF ≤ 2.8 and average daily APS ≤ 1.0 and both not greater than baseline c Endoscopic response = decrease in SES-CD > 50% from baseline (or for subjects with a baseline SES-CD of 4, at least a 2-point reduction from baseline), as scored by a central reviewer. d Corticosteroid-free clinical remission = discontinuation of corticosteroid use and achievement of clinical remission per CDAI or SF/APS at wk 12 among patients on corticosteroids at baseline. e Clinical response-100 = decrease of ≥ 100 points in CDAI from baseline. f Endoscopic remission = SES-CD ≤ 4, at least a 2-point reduction versus baseline and no subscore >1 in any individual variable, as scored by a central reviewer. g Results are based on non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C). h 95% CI for adjusted difference and p-value are calculated according to the Cochran-Mantel-Haenszel (CMH) test adjusted for randomization strata. **P ≤ .0001 or *P ≤ .01 vs PBO;Average daily abdominal pain score, APS;Coronavirus disease 2019, COVID-19;Confidence Interval, CI;Crohn’s Disease Activity Index, CDAI;Simple Endoscopic Score for CD, SES-CD, Placebo, PBO;Once daily, QD;average daily very soft/liquid stool frequency, SF;Upadacitinib, UPA.

Impact of COVID-19 Pandemic on Initiation of Immunosuppressive Treatment in Immune-Mediated Inflammatory Diseases in Austria: A Nationwide Retrospective Study.

OBJECTIVE: Conventional immunosuppressive and advanced targeted therapies, including biological medications and small molecules, are a mainstay in the treatment of immune-mediated inflammatory diseases (IMID). However, the COVID-19 pandemic caused concerns over these drugs' safety regarding the risk and severity of SARS-CoV-2 infection. Thus, we aimed to assess the impact of the COVID-19 pandemic on the initiation of these treatments in 2020. STUDY DESIGN AND SETTING: We conducted a population-based retrospective analysis of real-world data of the Austrian health insurance funds on the initiation of conventional immunosuppressive and advanced targeted therapies. The primary objective was to compare the initiation of these medications in the year 2020 with the period 2017 to 2019. Initiation rates of medication were calculated by comparing a certain unit of time with an average of the previous ones. RESULTS: 95,573 patients were included. During the first lockdown in Austria in April 2020, there was a significant decrease in the initiations of conventional immunosuppressives and advanced targeted therapies compared to previous years (p < 0.0001). From May 2020 onwards, numbers rapidly re-achieved pre-lockdown levels despite higher SARS-CoV-2 infection rates and subsequent lockdown periods at the end of 2020. Independent from the impact of the COVID-19 pandemic, a continuous increase of starts of advanced targeted therapies and a continuous decrease of conventional immunosuppressants during the observation period were observed. CONCLUSIONS: In IMID patients, the COVID-19 pandemic led to a significant decrease of newly started conventional immunosuppressive and advanced targeted therapies only during the first lockdown in Austria.

Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials.

BACKGROUND: There is a great unmet need for advanced therapies that provide rapid, robust, and sustained disease control for patients with ulcerative colitis. We assessed the efficacy and safety of upadacitinib, an oral selective Janus kinase 1 inhibitor, as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. METHODS: This phase 3, multicentre, randomised, double-blind, placebo-controlled clinical programme consisted of two replicate induction studies (U-ACHIEVE induction [UC1] and U-ACCOMPLISH [UC2]) and a single maintenance study (U-ACHIEVE maintenance [UC3]). The studies were conducted across Europe, North and South America, Australasia, Africa, and the Asia-Pacific region at 199 clinical centres in 39 countries (UC1), 204 clinical centres in 40 countries (UC2), and 195 clinical centres in 35 countries (UC3). Patients aged 16-75 years with moderately to severely active ulcerative colitis (Adapted Mayo score 5-9; endoscopic subscore 2 or 3) for at least 90 days were randomly assigned (2:1) to oral upadacitinib 45 mg once daily or placebo for 8 weeks (induction studies). Patients who achieved clinical response following 8-week upadacitinib induction were re-randomly assigned (1:1:1) to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks (maintenance study). All patients were randomly assigned using web-based interactive response technology. The primary endpoints were clinical remission per Adapted Mayo score at week 8 (induction) and week 52 (maintenance). The efficacy analyses in the two induction studies were based on the intent-to-treat population, which included all randomised patients who received at least one dose of treatment. In the maintenance study, the primary efficacy analyses reported in this manuscript were based on the first 450 (planned) clinical responders to 8-week induction therapy with upadacitinib 45 mg once daily. The safety analysis population in the induction studies consisted of all randomised patients who received at least one dose of treatment; in the maintenance study, this population included all patients who received at least one dose of treatment as part of the primary analysis population. These studies are registered at ClinicalTrials.gov, NCT02819635 (U-ACHIEVE) and NCT03653026 (U-ACCOMPLISH). FINDINGS: Between Oct 23, 2018, and Sept 7, 2020, 474 patients were randomly assigned to upadacitinib 45 mg once daily (n=319) or placebo (n=155) in UC1. Between Dec 6, 2018, and Jan 14, 2021, 522 patients were randomly assigned to upadacitinib 45 mg once daily (n=345) or placebo (n=177) in UC2. In UC3, a total of 451 patients (21 from the phase 2b study, 278 from UC1, and 152 from UC2) who achieved a clinical response after 8 weeks of upadacitinib induction treatment were randomly assigned again to upadacitinib 15 mg (n=148), upadacitinib 30 mg (n=154), and placebo (n=149) in the primary analysis population. Statistically significantly more patients achieved clinical remission with upadacitinib 45 mg (83 [26%] of 319 patients in UC1 and 114 [34%] of 341 patients in UC2) than in the placebo group (seven [5%] of 154 patients in UC1 and seven [4%] of 174 patients; p<0·0001; adjusted treatment difference 21·6% [95% CI 15·8-27·4] for UC1 and 29·0% [23·2-34·7] for UC2). In the maintenance study, clinical remission was achieved by statistically significantly more patients receiving upadacitinib (15 mg 63 [42%] of 148; 30 mg 80 [52%] of 154) than those receiving placebo (18 [12%] of 149; p<0·0001; adjusted treatment difference 30·7% [21·7-39·8] for upadacitinib 15 mg vs placebo and 39·0% [29·7-48·2] for upadacitinib 30 mg vs placebo). The most commonly reported adverse events in UC1 were nasopharyngitis (15 [5%] of 319 in the upadacitinib 45 mg group vs six [4%] of 155 in the placebo group), creatine phosphokinase elevation (15 [4%] vs three [2%]), and acne (15 [5%] vs one [1%]). In UC2, the most frequently reported adverse event was acne (24 [7%] of 344 in the upadacitinib 45 mg group vs three [2%] of 177 in the placebo group). In both induction studies, serious adverse events and adverse events leading to discontinuation of treatment were less frequent in the upadacitinib 45 mg group than in the placebo group (serious adverse events eight [3%] vs nine (6%) in UC1 and 11 [3%] vs eight [5%] in UC2; adverse events leading to discontinuation six [2%] vs 14 [9%] in UC1 and six [2%] vs nine [5%] in UC2). In UC3, the most frequently reported adverse events (≥5%) were worsening of ulcerative colitis (19 [13%] of 148 in the upadacitinib 15 mg group vs 11 [7%] of 154 in the upadacitinib 30 mg group vs 45 [30%] of 149 in the placebo group), nasopharyngitis (18 [12%] vs 22 [14%] vs 15 [10%]), creatine phosphokinase elevation (nine [6%] vs 13 [8%] vs three [2%]), arthralgia (nine [6%] vs five [3%] vs 15 [10%]), and upper respiratory tract infection (seven [5%] vs nine [6%] vs six [4%]). The proportion of serious adverse events (ten [7%] vs nine [6%] vs 19 [13%]) and adverse events leading to discontinuation (six [4%] vs ten [6%] vs 17 [11%]) was lower in both upadacitinib groups than in the placebo group. Events of cancer, adjudicated major adverse cardiac events, or venous thromboembolism were reported infrequently. There were no treatment-related deaths. INTERPRETATION: Upadacitinib demonstrated a positive efficacy and safety profile and could be an effective treatment option for patients with moderately to severely active ulcerative colitis. FUNDING: AbbVie.

SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients - A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease.

Background: Individuals with secondary immunodeficiencies belong to the most vulnerable groups to succumb to COVID-19 and thus are prioritized for SARS-CoV-2 vaccination. However, knowledge about the persistence and anamnestic responses following SARS-CoV-2-mRNA vaccinations is limited in these patients. Methods: In a prospective, open-label, phase four trial we analyzed S1-specific IgG, neutralizing antibodies and cytokine responses in previously non-infected patients with cancer or autoimmune disease during primary mRNA vaccination and up to one month after booster. Results: 263 patients with solid tumors (SOT, n=63), multiple myeloma (MM, n=70), inflammatory bowel diseases (IBD, n=130) and 66 controls were analyzed. One month after the two-dose primary vaccination the highest non-responder rate was associated with lower CD19+ B-cell counts and was found in MM patients (17%). S1-specific IgG levels correlated with IL-2 and IFN-γ responses in controls and IBD patients, but not in cancer patients. Six months after the second dose, 18% of patients with MM, 10% with SOT and 4% with IBD became seronegative; no one from the control group became negative. However, in IBD patients treated with TNF-α inhibitors, antibody levels declined more rapidly than in controls. Overall, vaccination with mRNA-1273 led to higher antibody levels than with BNT162b2. Importantly, booster vaccination increased antibody levels >8-fold in seroresponders and induced anamnestic responses even in those with undetectable pre-booster antibody levels. Nevertheless, in IBD patients with TNF-α inhibitors even after booster vaccination, antibody levels were lower than in untreated IBD patients and controls. Conclusion: Immunomonitoring of vaccine-specific antibody and cellular responses seems advisable to identify vaccination failures and consequently establishing personalized vaccination schedules, including shorter booster intervals, and helps to improve vaccine effectiveness in all patients with secondary immunodeficiencies. Trial registration: EudraCT Number: 2021-000291-11.

Course of Fecal Calprotectin after mRNA SARS-CoV-2 Vaccination in Patients with Inflammatory Bowel Diseases.

BACKGROUND: Two years into the pandemic, vaccination remains the most effective option to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Preliminary studies suggest vaccination efficacy in patients with inflammatory bowel diseases (IBD), but little is known about its impact on chronic intestinal inflammation. Here we assessed the mucosal inflammatory activity in patients with IBD before and after immunization with the mRNA-1273 (Moderna) vaccine by measurement of fecal calprotectin (fCP). METHODS: In 42 patients with IBD, the baseline fCP levels obtained prior to the first vaccine were compared with the highest levels measured during and after two doses of vaccination. Patients' sera were collected after the second dose to evaluate anti-SARS-CoV-2 antibodies' titers. RESULTS: We observed a significant fCP elevation in 31% of patients after any dose. Vedolizumab was identified as the only agent associated with an fCP increase (OR 12.4, 95% CI [1.6; 120.2], p = 0.0171). Gastrointestinal adverse events were reported in 9.5% of all subjects and in 75% of cases accompanied by an fCP increase. Anti-SARS-CoV-2 antibodies associated only weakly with the fCP increase after the first dose (p = 0.04). CONCLUSIONS: Our findings support possible collinearity in pathways of SARS-CoV-2 antigen expression and the pathogenesis of IBD.

The Multiple Waves of COVID-19 in Patients With Inflammatory Bowel Disease: A Temporal Trend Analysis.

BACKGROUND: Cases of coronavirus disease 2019 (COVID-19) have emerged in discrete waves. We explored temporal trends in the reporting of COVID-19 in inflammatory bowel disease (IBD) patients. METHODS: The Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is an international registry of IBD patients diagnosed with COVID-19. The average percent changes (APCs) were calculated in weekly reported cases of COVID-19 during the periods of March 22 to September 12, September 13 to December 12, 2020, and December 13 to July 31, 2021. RESULTS: Across 73 countries, 6404 cases of COVID-19 were reported in IBD patients. COVID-19 reporting decreased globally by 4.2% per week (95% CI, -5.3% to -3.0%) from March 22 to September 12, 2020, then climbed by 10.2% per week (95% CI, 8.1%-12.3%) from September 13 to December 12, 2020, and then declined by 6.3% per week (95% CI, -7.8% to -4.7%). In the fall of 2020, weekly reporting climbed in North America (APC, 11.3%; 95% CI, 8.8-13.8) and Europe (APC, 17.7%; 95% CI, 12.1%-23.5%), whereas reporting was stable in Asia (APC, -8.1%; 95% CI, -15.6-0.1). From December 13, 2020, to July 31, 2021, reporting of COVID-19 in those with IBD declined in North America (APC, -8.5%; 95% CI, -10.2 to -6.7) and Europe (APC, -5.4%; 95% CI, -7.2 to -3.6) and was stable in Latin America (APC, -1.5%; 95% CI, -3.5% to 0.6%). CONCLUSIONS: Temporal trends in reporting of COVID-19 in those with IBD are consistent with the epidemiological patterns COVID-19 globally.

Perspectives on Subcutaneous Infliximab for Rheumatic Diseases and Inflammatory Bowel Disease: Before, During, and After the COVID-19 Era.

The coronavirus disease 2019 (COVID-19) pandemic has prompted significant changes in patient care in rheumatology and gastroenterology, with clinical guidance issued to manage ongoing therapy while minimising the risk of nosocomial infection for patients and healthcare professionals (HCPs). Subcutaneous (SC) formulations of biologics enable patients to self-administer treatments at home; however, switching between agents may be undesirable. CT-P13 SC is the first SC formulation of infliximab that received regulatory approval and may be termed a biobetter as it offers significant clinical advantages over intravenous (IV) infliximab, including improved pharmacokinetics and a convenient mode of delivery. Potential benefits in terms of reduced immunogenicity have also been suggested. With a new SC formulation, infliximab provides an additional option for dual formulation, which enables patients to transition from IV to SC administration route without changing agent. Before COVID-19, clinical trials supported the efficacy and safety of switching from IV to SC infliximab for patients with rheumatoid arthritis and inflammatory bowel disease (IBD), and SC infliximab may have been selected on the basis of patient and HCP preferences for SC agents. During the pandemic, patients with rheumatic diseases and IBD have successfully switched from IV to SC infliximab, with some clinical benefits and high levels of patient satisfaction. As patients switched to SC therapeutics, the reduction in resource requirements for IV infusion services may have been particularly welcome given the pandemic, facilitating reorganisation and redeployment in overstretched healthcare systems, alongside pharmacoeconomic benefits and a reduction in exposure to nosocomial infection. Telemedicine and contactless healthcare have been pushed to the forefront during the pandemic, and a lasting shift towards remote patient management and community/home-based drug administration is anticipated. SC infliximab supports the implementation of this paradigm for future improvements of healthcare value delivered. The accumulation of real-world data during the pandemic supports the high level of confidence, with patients, physicians, and healthcare systems benefitting from its uptake.

Characteristics, Comorbidities, and Outcomes of SARS-CoV-2 Infection in Patients With Autoimmune Conditions Treated With Systemic Therapies: A Population-based Study.

OBJECTIVE: To describe characteristics and coronavirus disease 2019 (COVID-19) clinical outcomes of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ulcerative colitis (UC) receiving systemic therapies vs the general population. METHODS: This descriptive retrospective cohort study used data from the United States Optum deidentified COVID-19 electronic health record dataset (2007-2020). Adults with COVID-19 were stratified into 3 disease cohorts (patients with RA, PsA, or UC who had received systemic therapy) and a comparator cohort not meeting these criteria. Incidence proportions of hospitalization and clinical manifestations of interest were calculated. Using logistic regression analyses, risk of endpoints was estimated, adjusting for demographics and demographics plus comorbidities. RESULTS: This analysis (February 1 to December 9, 2020) included 315,101 patients with COVID-19. Adjusting for demographics, COVID-19 patients with RA (n = 2306) had an increased risk of hospitalization (OR 1.54, 95% CI 1.39-1.70) and in-hospital death (OR 1.61, 95% CI 1.30-2.00) compared with the comparator cohort (n = 311,563). The increased risk was also observed when adjusted for demographics plus comorbidities (hospitalization OR 1.25, 95% CI 1.13-1.39 and in-hospital death OR 1.35, 95% CI 1.09-1.68]). The risk of hospitalization was lower in COVID-19 patients with RA receiving tumor necrosis factor inhibitors (TNFi) vs non-TNFi biologics (OR 0.32, 95% CI 0.20-0.53) and the comparator cohort (OR 0.77, 95% CI 0.51-1.17). The risk of hospitalization due to COVID-19 was similar between patients receiving tofacitinib and the comparator cohort. CONCLUSION: Compared with the comparator cohort, patients with RA were at a higher risk of more severe or critical COVID-19 and, except for non-TNFi biologics, systemic therapies did not further increase the risk. (ENCePP; registration no. EU PAS 35384).

Characteristics, Comorbidities, and Outcomes of SARS-CoV-2 Infection in Patients With Conditions Treated With Systemic Immunosuppressive Therapies: A Population-Based Study

Incidence proportions of hospitalization, intensive care unit admission, in-hospital death, all-cause mortality, and clinical manifestations of interest were calculated. Baseline Characteristics and IPs of Clinical Manifestations/Outcomes in the RA, PsA, UC, and Comparator Cohorts. a.At least 1 diagnosis of RA, PsA, or UC, and treatment with IM therapy (JAK inhibitor, TNFi, non-TNFi biologic, or csDMARD) within 2 yrs prior to SARS-CoV-2 diagnosis date;b.Absence of a diagnosis of RA, PsA, or UC, and no treatment with IM therapy within 2 yrs prior to SARS-CoV-2 diagnosis date;c.Baseline was defined as within 6 months prior to SARS-CoV-2 diagnosis date;d.csDMARDs included auranofin, aurothioglucose, azathioprine, chloroquine hydrochloride, chloroquine phosphate, cyclophosphamide, cyclosporine, gold sodium thiomalate, hydroxychloroquine sulfate, leflunomide, mercaptopurine, mesalamine, methotrexate, minocycline hydrochloride, n-acetylpenicillamine, penicillamine, primaquine, sulfasalazine, tacrolimus, and thalidomide;e.Within 90 days prior to SARS-CoV-2 diagnosis date;f.Denominator is the number of pts hospitalized within 30 days of SARS-CoV-2 diagnosis;defined as death during hospitalization;g.Within 90 days of SARS-CoV-2 diagnosis date;h.Within 30 days of SARS-CoV-2 diagnosis date. ARDS, acute respiratory distress syndrome;CI, confidence interval;csDMARD, conventional synthetic disease-modifying antirheumatic drug;ECMO, extracorporeal membrane oxygenation;ICU, intensive care unit;IM, immunomodulatory;IP, incidence proportion;IV, intravenous;JAK, Janus kinase;N, number of pts in the cohort;n, number of pts in the specified category;PsA, psoriatic arthritis;pts, patients;RA, rheumatoid arthritis;TNFi, tumor necrosis factor inhibitor;UC, ulcerative colitis.

Inflammatory Bowel Disease Clinical Activity is Associated with COVID-19 Severity Especially in Younger Patients.

BACKGROUND AND AIMS: Age is a major prognostic factor for COVID-19 outcomes. The effect of inflammatory bowel disease [IBD] activity on COVID-19 is unclear. We examined the relationship between IBD activity and COVID-19 severity according to age. METHODS: We included IBD patients diagnosed with COVID-19, reported to SECURE-IBD between March 13, 2020 and August 3, 2021. Clinical IBD activity was measured by physician global assessment [PGA]. COVID-19-related outcomes were [1] intensive care unit [ICU] admission, ventilation or death, and [2] hospitalization. Using generalized estimating equations, we determined adjusted odds ratios [aOR, 95% confidence interval] for moderate and severe PGA vs clinical remission/mild PGA, controlling for demographics, medications and COVID-19 diagnosis period. We performed stratified analyses by age [≤50 vs >50 years]. RESULTS: Among 6078 patients, adverse COVID-19 outcomes were more common with active IBD: ICU/ventilation/death in 3.6% [175/4898] of remission/mild, 4.9% [45/920] of moderate and 8.8% [23/260] of severe [p < 0.001]; and hospitalization in 13% [649/4898] of remission/mild, 19% [178/920] of moderate and 38% [100/260] of severe [p < 0.001]. Stratified by decade, effect sizes were larger for younger patients. In patients ≤50 years, severe PGA was independently associated with ICU/ventilation/death (aOR 3.27 [1.15-9.30]) and hospitalization (aOR 4.62 [2.83-7.55]). In contrast, severe PGA was not independently associated with COVID-19 outcomes in those older than 50 years. CONCLUSIONS: Clinically active IBD may be a risk factor for severe COVID-19, particularly in younger patients. IBD disease control, including through medication compliance, and strategies to mitigate the risk of COVID-19 infection amongst patients with active IBD [e.g. distancing, immunization] are key to limit adverse COVID-19 outcomes.

Immunologically relevant aspects of the new COVID-19 vaccines-an ÖGAI (Austrian Society for Allergology and Immunology) and AeDA (German Society for Applied Allergology) position paper.

BACKGROUND: The vaccines against the coronavirus disease 2019 (COVID-19) approved in the European Union represent a decisive step in the fight against the pandemic. The application of these available vaccines to patients with pre-existing immunological conditions leads to a multitude of questions regarding efficacy, side effects and the necessary patient information. RESULTS: This review article provides insight into mechanisms of action of the currently available severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and summarises the current state of science as well as expert recommendations regarding tolerability of the vaccines. In addition, the potential to develop protective immune responses is determined. A special focus is given on patients under immunosuppression or in treatment with immunomodulatory drugs. Special groups of the population such as children, pregnant women and the elderly are also considered. CONCLUSION: Despite the need for a patient-specific risk-benefit assessment, the consensus among experts is that patients with immunological diseases in particular benefit from the induced immune protection after COVID-19 vaccination and do not have an increased risk of side effects.

COVID-19 Outcomes Among Racial and Ethnic Minority Individuals With Inflammatory Bowel Disease in the United States.

The coronavirus disease 2019 (COVID-19) has affected more than 29 million people and led to more than 542,000 deaths in the United States.1 Older age, comorbidities, and racial and ethnic minority status are associated with severe COVID-19.2 Among patients with inflammatory bowel disease (IBD), racial and ethnic minorities have worse outcomes, mediated in part by inequitable health care access.3 Racial and ethnic minority patients with IBD and COVID-19 may be an especially vulnerable population. The purpose of this study was to evaluate racial and ethnic disparities in COVID-19 outcomes among IBD patients and the impact of non-IBD comorbidities on observed disparities.