The impact of COVID-19 on patients with IBD in a prospective European cohort study.

INTRODUCTION: There are concerns on the potential impact of the COVID-19 outbreak on patients with inflammatory bowel disease (IBD). AIM: To report the impact of the COVID-19 outbreak in a European prospective cohort study of patients with IBD. PATIENTS AND METHODS: We prospectively collected data from 5,457 patients with IBD nested in the ongoing I-CARE project and still followed up in April 2020, with monthly online monitoring of clinical activity, treatment, imaging and endoscopy. Investigators were also contacted to report incidental cases. RESULTS: In total, 233 (4.3%) reported COVID-19 and 12 (0.2%) severe COVID-19, with no COVID-19 deaths. The risk of COVID-19 in patients with IBD was not increased compared to the general population (SIR: 1.18 95%CI [1.03-1.34], p = 0.009), as well as the risk of severe COVID-19 (SIR: 0.69 95%CI [0.35-1.20], p = 0.93). We did not observe any negative impact of the different IBD-related medication on the risk of either COVID-19 or severe COVID-19. In 2020, the COVID-19 outbreak resulted in a drastic decrease in endoscopic and imaging procedures from March to May 2020 compared to 2018 and 2019. No impact on clinical IBD disease activity as well as ongoing treatment were noted. CONCLUSION: No increase in either COVID-19 or severe COVID-19 incidences were observed in patients with IBD. There was no impact of COVID-19 on IBD-related medication and clinical activity. Access to endoscopy and imaging was restricted during the first months of the first COVID-19 outbreak.

SARS-CoV-2 seroprevalence in healthcare workers and risk factors.

BACKGROUND: Exposure of healthcare workers (HCW) to SARS-CoV-2 is a public health concern. Not only are HCWs particularly exposed to SARS-CoV-2, but their contamination can also weaken the healthcare system. METHODS: We analyzed exposure of French University Hospital HCWs to SARS-CoV-2 through history of positive RT-PCR test and SARS-CoV-2 seroprevalence. Potential risk factors, such as age, BMI, having children or not, working in a COVID-19 unit, or smoking were explored. RESULTS: From May to June 2020, among the 8960 employees of the University Hospital of Nancy, a serological test was performed in 4696 HCWs. The average (SD) age was 40.4 (11.4) years, and the sample included 3926 women (83.6%). Of the 4696 HCWs, 1050 were smokers (22.4%). Among them, 2231 HCWs had a history of COVID-19 symptoms and/or flu-like syndrome (47.5%) and 238 were seropositive (5.1%). Neither gender, sex, BMI, nor having children were associated with a history of positive RT-PCR test or seropositive status. Previous work in a COVID-19 unit was associated with a history of positive RT-PCR test (p = 0.045), but not with seroprevalence (p = 0.215). As expected, history of COVID-19 clinical manifestations was more frequent in HCWs with positive serology than in HCWs with negative serology (adjusted OR = 1.9, 95%CI [1.4-2.5], p < 0.001). Less expected, smoking was associated with a reduced risk of seropositivity among HCWs (adjusted OR = 0.6, 95%CI [0.4-0.9], p = 0.019). CONCLUSION: HCW are patently exposed to SARS-CoV-2. Care to COVID-19 patients was not associated with a higher SARS-CoV-2 seroprevalence. Smoking appears here associated to a lower seroprevalence.

Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials.

BACKGROUND: Risankizumab, an interleukin (IL)-23 p19 inhibitor, was evaluated for safety and efficacy as induction therapy in patients with moderately to severely active Crohn's disease. METHODS: ADVANCE and MOTIVATE were randomised, double-masked, placebo-controlled, phase 3 induction studies. Eligible patients aged 16-80 years with moderately to severely active Crohn's disease, previously showing intolerance or inadequate response to one or more approved biologics or conventional therapy (ADVANCE) or to biologics (MOTIVATE), were randomly assigned to receive a single dose of intravenous risankizumab (600 mg or 1200 mg) or placebo (2:2:1 in ADVANCE, 1:1:1 in MOTIVATE) at weeks 0, 4, and 8. We used interactive response technology for random assignment, with stratification by number of previous failed biologics, corticosteroid use at baseline, and Simple Endoscopic Score for Crohn's disease (SES-CD). All patients and study personnel (excluding pharmacists who prepared intravenous solutions) were masked to treatment allocation throughout the study. Coprimary endpoints were clinical remission (defined by Crohn's disease activity index [CDAI] or patient-reported outcome criteria [average daily stool frequency and abdominal pain score]) and endoscopic response at week 12. The intention-to-treat population (all eligible patients who received at least one dose of study drug in the 12-week induction period) was analysed for efficacy outcomes. Safety was assessed in all patients who received at least one dose of study drug. Both trials were registered on ClinicalTrials.gov, NCT03105128 (ADVANCE) and NCT03104413 (MOTIVATE), and are now complete. FINDINGS: Participants were enrolled between May 10, 2017, and Aug 24, 2020 (ADVANCE trial), and Dec 18, 2017 and Sept 9, 2020 (MOTIVATE trial). In ADVANCE, 931 patients were assigned to either risankizumab 600 mg (n=373), risankizumab 1200 mg (n=372), or placebo (n=186). In MOTIVATE, 618 patients were assigned to risankizumab 600 mg (n=206), risankizumab 1200 mg (n=205), or placebo (n=207). The primary analysis population comprised 850 participants in ADVANCE and 569 participants in MOTIVATE. All coprimary endpoints at week 12 were met in both trials with both doses of risankizumab (p values ≤0·0001). In ADVANCE, CDAI clinical remission rate was 45% (adjusted difference 21%, 95% CI 12-29; 152/336) with risankizumab 600 mg and 42% (17%, 8-25; 141/339) with risankizumab 1200 mg versus 25% (43/175) with placebo; stool frequency and abdominal pain score clinical remission rate was 43% (22%, 14-30; 146/336) with risankizumab 600 mg and 41% (19%, 11-27; 139/339) with risankizumab 1200 mg versus 22% (38/175) with placebo; and endoscopic response rate was 40% (28%, 21-35; 135/336) with risankizumab 600 mg and 32% (20%, 14-27; 109/339) with risankizumab 1200 mg versus 12% (21/175) with placebo. In MOTIVATE, CDAI clinical remission rate was 42% (22%, 13-31; 80/191) with risankizumab 600 mg and 40% (21%, 12-29; 77/191) with risankizumab 1200 mg versus 20% (37/187) with placebo; stool frequency and abdominal pain score clinical remission rate was 35% (15%, 6-24; 66/191) with risankizumab 600 mg and 40% (20%, 12-29; 76/191) with risankizumab 1200 mg versus 19% (36/187) with placebo; and endoscopic response rate was 29% (18%, 10-25; 55/191) with risankizumab 600 mg and 34% (23%, 15-31; 65/191) with risankizumab 1200 mg versus 11% (21/187) with placebo. The overall incidence of treatment-emergent adverse events was similar among the treatment groups in both trials. Three deaths occurred during induction (two in the placebo group [ADVANCE] and one in the risankizumab 1200 mg group [MOTIVATE]). The death in the risankizumab-treated patient was deemed unrelated to the study drug. INTERPRETATION: Risankizumab was effective and well tolerated as induction therapy in patients with moderately to severely active Crohn's disease. FUNDING: AbbVie.

Re-Routing Infliximab Therapy: Subcutaneous Infliximab Opens a Path Towards Greater Convenience and Clinical Benefit.

Subcutaneous infliximab recently received approval for the treatment of various immune-mediated inflammatory diseases in Europe, following pivotal clinical trials in patients with rheumatoid arthritis and inflammatory bowel disease. Subcutaneous infliximab demonstrated an improved pharmacokinetic profile compared with intravenous infliximab: the more stable exposure and increased systemic drug concentrations mean it has been cited as a biobetter. Alongside the pharmacokinetic advantages, potential benefits for efficacy, immunogenicity, and health-related quality-of-life outcomes have been suggested with subcutaneous infliximab. During the coronavirus disease 2019 pandemic, the benefits of subcutaneous over intravenous therapies became apparent: switching from intravenous to subcutaneous infliximab reduced the hospital visit-related healthcare resource burden and potential viral transmission. Clinical advantages observed in pivotal trials are also being seen in the real world. Accumulating experience from four European countries (the UK, Spain, France, and Germany) in patients with rheumatic diseases and inflammatory bowel disease supports clinical trial findings that subcutaneous infliximab is well tolerated, increases serum drug concentrations, and offers maintained or improved efficacy outcomes for patients switching from intravenous infliximab. Initial evidence is emerging with subcutaneous infliximab treatment after intravenous infliximab failure. High patient satisfaction and pharmacoeconomic benefits have also been reported with subcutaneous infliximab. Treatments aligned with patient preferences for the flexibility and convenience of at-home subcutaneous administration could boost adherence and treatment outcomes. Altogether, findings suggest that switching from intravenous to subcutaneous infliximab could be advantageous, and healthcare professionals should be prepared to discuss supporting data as part of shared decision making during patient consultations.

The tumor necrosis factor inhibitor infliximab is one treatment option that may be appropriate for patients with immune-mediated inflammatory diseases. Patients may prefer tumor necrosis factor inhibitors administered via the subcutaneous (SC) or intravenous (IV) route, with preferences influencing treatment satisfaction and outcomes. In 2019, CT-P13 SC became the first SC infliximab product to receive regulatory approval in Europe, based on pivotal clinical studies that compared SC infliximab to IV infliximab in patients with rheumatoid arthritis and inflammatory bowel disease. Subcutaneous infliximab is now approved in Europe for the treatment of adults with rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. Patients began to switch from IV to SC infliximab outside clinical trials in March 2020, during the coronavirus disease 2019 pandemic. Switching from IV to SC infliximab allowed patients to self-administer treatment at home rather than attend hospital for infusions, reducing potential hospital-acquired infections and lessening the strain on healthcare systems during the pandemic. Clinical trial evidence and growing real-world experience demonstrate that SC infliximab offers clinical advantages in terms of an improved pharmacokinetic profile and potential efficacy, immunogenicity, and health-related quality-of-life benefits compared with IV infliximab. Patients have also reported increased satisfaction with SC infliximab after switching from IV infliximab. Together with the long-standing flexibility and convenience benefits of SC administration, the clinical advantages of SC infliximab make it a valid therapeutic option for rheumatoid arthritis and inflammatory bowel disease. This warrants discussion with appropriate patients as part of shared treatment decision making.

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.

French experience with telemedicine in inflammatory bowel disease: a patients and physicians survey.

BACKGROUND AND AIMS: The use of telemedicine dramatically increased during the COVID-19 pandemic. We collected patients and physicians experience on telemedicine in the field of inflammatory bowel disease (IBD). METHODS: We conducted a nationwide survey between September 2020 and January 2021. A self-administered questionnaire was sent to participants through mailing lists of the national patients' association and IBD expert groups. RESULTS: Overall, 300 patients and 110 gastroenterologists filled out the survey. On a 10 points scale of satisfaction with telemedicine, 60% of patients noted a score ≥8 and 52.7% of physicians ≥7. Patients and gastroenterologists felt that the duration of teleconsultations appeared to be shorter than in-person visits in 57.5 and 55.1% of cases, respectively. All participants agreed that telemedicine is appropriate in dedicated situations and not for flare-up consultations. For 55.1% of patients, quality of care was the same via telemedicine, whereas 51.4% of gastroenterologists believed they managed less well their patients. Lack of clinical examination being pointed out as the main limitation of telemedicine. Three-quarters of patients and gastroenterologists would agree to use telemedicine more often in the future. CONCLUSION: Patients and gastroenterologists were satisfied with telemedicine and would be willing to use it in the future. However, telemedicine does not replace in-person visits and should be discussed on a case-by-case basis.

Viral infections in inflammatory bowel disease: Tips and tricks for correct management.

Over the past decades, the treatment of inflammatory bowel diseases (IBD) has become more targeted, anticipating the use of immune-modifying therapies at an earlier stage. This top-down approach has been correlated with favorable short and long-term outcomes, but it has also brought with it concerns regarding potential infectious complications. This large IBD population treated with immune-modifying therapies, especially if combined, has an increased risk of severe infections, including opportunistic infections that are sustained by viral, bacterial, parasitic, and fungal agents. Viral infections have emerged as a focal safety concern in patients with IBD, representing a challenge for the clinician: they are often difficult to diagnose and are associated with significant morbidity and mortality. The first step is to improve effective preventive strategies, such as applying vaccination protocols, adopt adequate prophylaxis and educate patients about potential risk factors. Since viral infections in immunosuppressed patients may present atypical signs and symptoms, the challenges for the gastroenterologist are to suspect, recognize and diagnose such complications. Appropriate treatment of common viral infections allows us to minimize their impact on disease outcomes and patients' lives. This practical review supports this standard of care to improve knowledge in this subject area.

IBD goes home: from telemedicine to self-administered advanced therapies.

INTRODUCTION: Major challenges have been posed by the coronavirus disease 2019 pandemic in the routine management of patients with inflammatory bowel disease (IBD). The need for constant monitoring of diseases activity and prompt adjustment of therapy have been balanced with the risk of contagion related to face-to-face consultations. Therefore, digital health initiatives have been pursued for safety reasons as vicarious instruments to avoid overcrowding of the IBD clinics. However, concerns and skepticism about the feasibility of digital health and telemedicine modalities limited their uptake in clinical practice in the pre-pandemic period. AREAS COVERED: We conducted a literature overview on the current state of the art and the potential future benefits deriving from the integration of telemedicine systems, home-based laboratory tests, and self-administered drugs into IBD daily practice. EXPERT OPINION: Digital health and telemedicine approaches at distance have been experimented as effective tools to avoid overcrowding of clinics and reduce risk from SARS-CoV2 exposure. Home-based point of care testing, such as fecal calprotectin and dried blood samples, might represent an effective method of remote monitoring of patients particularly when in-person visits are precluded. High expectations are placed on the use of self-administered advanced therapies, such as new subcutaneous formulation of biologics.

Inflammatory Bowel Disease and COVID-19 Vaccination: A Patients' Survey.

BACKGROUND: Vaccination against COVID-19 is a major public health challenge, including the community of patients with inflammatory bowel disease. Vaccination coverage is suboptimal in inflammatory bowel disease population. It is of paramount importance to ensure an effective and rapid vaccination program with the adherence of the largest number of well-informed patients. AIMS: We assessed the acceptance of COVID-19 vaccination among inflammatory bowel disease patients. METHODS: We performed a survey as part of routine practice, between January 8th and February 22nd, 2021. All consecutive adult patients followed at Nancy University Hospital for inflammatory bowel disease were included. Patients completed a self-administered, structured, paper-based questionnaire. Demographic data, medical history, knowledge, and perceptions of COVID-19 vaccination were collected. RESULTS: Among the 104 patients who responded to the survey, 57 patients (54.8%) had intent to receive the COVID-19 vaccine. Vaccine efficacy, social responsibility, herd immunity, and desire to return to normal life were associated with self-reported willingness to receive a vaccine (20.2%, 20.2%, 11.5%, and 15.4%, respectively). Unknown long-term safety, risk of adverse reaction to vaccine and concern that the vaccine is being developed too quickly were the most commonly reported reasons for non-uptake (27.9%, 15.4%, and 12.5%, respectively). CONCLUSION: Half of the patients with inflammatory bowel disease would like to be vaccinated against SARS-CoV-2. This rate is similar to that reported in the French general population. Despite some concerns, patients with inflammatory bowel disease understood the necessity to be vaccinated against COVID-19.

Patients with Inflammatory Bowel Disease Are Not at Increased Risk of COVID-19: A Large Multinational Cohort Study.

The impact of COVID-19 on inflammatory bowel disease (IBD) patients under pharmacological immunosuppression is still not clearly understood. We investigated the incidence of COVID-19 and the impact of immunosuppression and containment measures on the risk of SARS-CoV-2 infection in a large IBD cohort, from a multicenter cohort from 21st of February to 30th of June, 2020. Ninety-seven patients with IBD (43 UC, 53 CD, one unclassified IBD) and concomitant COVID-19 over a total of 23,879 patients with IBD were enrolled in the study. The cumulative incidence of SARS-CoV-2 infection in patients with IBD vs. the general population was 0.406% and 0.402% cases, respectively. Twenty-three patients (24%) were hospitalized, 21 (22%) had pneumonia, four (4%) were admitted to the Intensive Care Unit, and one patient died. Lethality in our cohort was 1% compared to 9% in the general population. At multivariable analysis, age > 65 years was associated with increased risk of pneumonia and hospitalization (OR 11.6, 95% CI 2.18-62.60; OR 5.1, 95% CI 1.10-23.86, respectively), treatment with corticosteroids increased the risk of hospitalization (OR 7.6, 95% CI 1.48-40.05), whereas monoclonal antibodies were associated with reduced risk of pneumonia and hospitalization (OR 0.1, 95% CI 0.04-0.52; OR 0.3, 95% CI 0.10-0.90, respectively). The risk of COVID-19 in patients with IBD is similar to the general population. National lockdown was effective in preventing infection in our cohort. Advanced age and treatment with corticosteroids impacted negatively on the outcome of COVID-19, whereas monoclonal antibodies did not seem to have a detrimental effect.

Systematic Review on Inflammatory Bowel Disease Patients With Coronavirus Disease 2019: It Is Time to Take Stock.

BACKGROUND & AIMS: Data on the clinical characteristics of patients with inflammatory bowel diseases (IBDs) with coronavirus disease 2019 (COVID-19) are scarce. The aim of our systematic review was to investigate symptoms and diagnostic-therapeutic management of IBD patients with COVID-19. METHODS: We searched PubMed, Embase, Web of Science, and MedRxiv up to July 29, 2020, to identify all studies reporting clinical information on adult and pediatric IBD patients with confirmed COVID-19. RESULTS: Twenty-three studies met our inclusion criteria, including 243,760 IBD patients. COVID-19 was diagnosed in 1028 patients (509 with Crohn's disease [49.5%], 428 with ulcerative colitis [41.6%], 49 with indeterminate colitis [4.8%], and 42 with missing data [4.1%]), accounting for a cumulative prevalence of 0.4%. Viral infection occurred more frequently in males than in females (56.5% vs 39.7%), and the mean age ranged from 14 to 85 years. The most common symptoms were fever (48.3%), cough (46.5%), and diarrhea (20.5%), and a COVID-19 diagnosis was achieved mainly through polymerase chain reaction analysis of nasopharyngeal swabs (94.4%) and chest computed tomography scans (38.9%). Hydroxychloroquine (23.9%), lopinavir/ritonavir (8.2%), steroids (3.2%), and antibiotics (3.1%) were the most used drugs. Overall, approximately a third of patients were hospitalized (30.6%), and 11.4% of them required admission to the intensive care unit. In total, 29 COVID-19-related deaths were reported (3.8%), and increasing age and the presence of comorbidities were recognized as risk factors for COVID-19 and negative outcomes. CONCLUSIONS: Diarrhea occurs more frequently in IBD patients with COVID-19 than in the non-IBD population. Further studies are needed to define the optimal diagnostic-therapeutic approach in IBD patients with COVID-19.