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Background: Intravenous (IV) infliximab (IFX) monotherapy is associated with significant loss of response. Therapeutic drug monitoring shows an association with low serum trough drug levels and development of anti-IFX antibodies. Combination therapy with immunomodulators is not always possible, and IFX dose escalation leads to higher drug costs and time pressure on infusion units. Both approaches have raised heightened patient safety concerns due to the Covid-19 pandemic. Subcutaneous (SC) IFX pharmacokinetics lead to improved drug trough levels, which could lead to better clinical outcomes. Method(s): The NHS Greater Glasgow and Clyde biologics database was used to identify selected patients currently treated with IV IFX for IBD for suitability for SC switch. Patients were contacted to allow informed choice to opt in or out of switch. Baseline clinical data was collected, and patients were reviewed at week 8 and week 24 for assessment of clinical disease activity scores, IFX trough levels/anti-drug antibody levels, and faecal calprotectin. Patient experience outcomes were assessed using a quality of life questionnaire (CUCQ-8). Result(s): 31 patients consented to switch;F:M = 17:14. The majority of patients (16) had Crohn's disease, with 13 with UC and 2 IBDU. Mean duration of disease was 9.1 years and duration of prior IV therapy was 3.3 years. 28 patients were reviewed at week 8 and 24 at week 24. At week 24, 71% of patients were in clinical remission (Harvey-Bradshaw index score <5 or partial Mayo score <2), 96% had CRP <5 mg/Land 87% had FCP <250mug/g. 21% of patients had subtherapeutic IFX trough levels at baseline, all had increased by week 8 and there were no subtherapeutic levels measured by week 24. One patient had detectable antibodies at week 24, compared with 9 patients at baseline. Three patients required oral steroid therapy during the 24-week follow up period. There were no hospital admissions, significant infections or adverse reactions within the cohort. 15 patients submitted CUCQ-8 scores, of these 7 patients' scores had worsened at week 8 but by week 24 13/15 were stable or improved compared to baseline. Conclusion(s): Switching from IV to SC infliximab is welcomed by most patients. The efficacy, tolerability, increased drug level and safety which has previously been demonstrated is reproduced in our cohort. This study is the first to explore patient experience outcomes. The finding of initial worsening of the CUCQ-8 score, but overall improvement by week 24 opens further opportunity for engaging patient involvement in switch programmes.
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Background: Ustekinumab (UST) is a fully human IgG1k monoclonal antibody to human IL-12/23p40 approved in several jurisdictions for the treatment of adult patients with moderately to severely active Crohn's disease (CD). UST's impact on induction and maintenance of mucosal healing, fistula healing and extraintestinal manifestations were not fully elucidated in the registration trial program. Method(s): In this prospective, multicenter study (EudraCT number: 2017-005151-83) across all care levels in Germany, we evaluated the real-world effectiveness of UST prescribed within its German label to achieve the primary endpoint of combined clinical (Harvey Bradshaw Index (HBI) score reduction >= 3 points from baseline) and endoscopic (50% reduction of the simple Endoscopic Score for Crohn Disease (SES-CD) from baseline) response in week 52 and a variety of secondary endpoints including mucosal healing defined as the complete absence of mucosal ulcerations in any ileocolonic segment and endoscopic remission defined as an SES-CD score of 0 - 2. Result(s): We recruited 52 CD patients (female n=28, bionaive n=13, bioexposed n=39). See Table 1 for baseline demographics and pertinent history details. At week 52, 50% (n=12/24) of patients achieved the primary endpoint [50% (n=3/6) in the bionaive, 45.5% (n=5/11) bioexposed to one and 57.1% (n=4/7) bioexposed to multiple biologics cohorts, respectively], 58.3% (n=14/24) of patients achieved endoscopic response [50% (n=3/6) in the bionaive, 54.5% (n=6/11) bioexposed to one and 71.4% (n=5/7) bioexposed to multiple biologics cohorts, respectively], 33.3% (n=8/24) of patients achieved endoscopic remission [50% (n=3/6) in the bionaive, 27.3% (n=3/11) bioexposed to one and 28.6% (n=2/7) bioexposed to multiple biologics cohorts, respectively], 45.8% (n=11/24) of patients achieved mucosal healing [50% (n=3/6) in the bionaive, 36.4% (n=4/11) bioexposed to one and 57.1% (n=4/7) bioexposed to multiple biologics cohorts, respectively]. 36 patients (69.2%) experienced >= 1 treatment emergent adverse event (TEAE), in 8 (15.4%) cases rated as severe and in 5 (9.6%) leading to discontinuation of UST, but no very severe events or deaths (Table 2). Conclusion(s): UST reliably induces endoscopic response and mucosal clinical practice. The limited samples size is a direct result from the Covid-19 pandemic. No new safety signals were recorded.
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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).
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Background: Recently, a subcutaneous formulation of biosimilar infliximab (CT-P13) (SC-IFX) has been approved for inflammatory bowel disease (IBD). The aims of this study were to evaluate efficacy, safety, pharmacokinetics and patient experience following a switching to SC-IFX in patients who are in clinical remission on IV-IFX maintenance treatment. Method(s): Multicentre, descriptive, and observational study including Crohn's disease (CD) and ulcerative colitis (UC) patients who were going to be changed from IV-IFX to SC-IFX on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD-GETECCU). All patients were on clinical and biological remission at least 24 weeks before changing. Demographic and disease data, clinical activity (Harvey-Bradshaw index for CD and mayo index for UC), analytical data (C reactive protein (CRP) and fecal calprotectin (FC), as well as trough levels were collected at baseline, at 12 and 24 weeks. Result(s): One hundred and fifty-five patients were included: 54 UC (35%) and 91 (65%) CD;44% women and 56% men;age 45.5 years (32-55). IV-IFX was mainly administered due to active disease (72%) and perianal disease (7%) and during 32 months [range 14-56]. Preswitch, 78 (50.3%) were on 8-weekly dosing of IV-IFX, 77 (49.7%) were with intensification dose and the half (50.3%) were on concomitant immunomodulatory therapy. SC-IFX was mainly switching by COVID-19 pandemic (60%), to increase through levels (15%) or patient request (25%). The majority of patients (140, 90%) remained with standard dose, 8 (5%) required dose intensification (120 mg weekly in 4 and 240 mg every 2 weeks in 4) and 7 (4.5%) had successful de-escalation (120 mg every 3 weeks in 4 and 120 mg every 4 weeks in 3). Clinical indices, CRP levels and FC remained unchanged (Figure). Median SC-IFX levels significantly increased from baseline of 4.5 mug/ dl [range 2.6-9.2] to 14 mug/dl [range 9.5-16.2] at week 12 and 13.2 mug/ dl [range 10.4-19.7] at week 24. No factors (immunossupresor, body mass index, disease location) were associated with the increase of IFX trough levels. During 24 weeks of follow-up, 16 of the 78 patients (20.5%) stopped immunosuppressant treatment. The adverse events were recorded in 9 patients (5.8%), 4 (2.6%) were hospitalized and 4 (2.6%) had surgery (one of them for perianal disease). Nine patients (5.8%) stopped SC-IFX (1 primary failure, 2 loss of response, 4 adverse events, 1 voluntarily, and 1 surgery). Conclusion(s): The switch from IV to SC IFX maintains clinical remission safely in IBD patients, offers higher drug levels and a good patient acceptance. However, the significance of higher drug levels with SC-IFX requires further exploration.
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Objectives: Care for many chronic conditions was altered during the COVID-19 pandemic. For patients with Inflammatory Bowel Disease (IBD), routine maintenance including endoscopies were postponed. The effects of delaying endoscopies on IBD outcomes are currently unknown. This study aimed to evaluate effects of delays of maintenance endoscopies on patients with IBD during the COVID-19 pandemic. Methods: This was a retrospective review of all IBD patients scheduled for routine endoscopy at Northwestern Memorial Hospital March 13, 2020 through May 31, 2020. All endoscopic examination were canceled in this period due to COVID-19. Patients were divided between those whose endoscopies were rescheduled promptly (on-time) or postponed (delayed) after August 31, 2020. Patient outcomes were examined one year after cancellation. Primary outcomes included hospital and emergency room admissions. Secondary outcomes included need for surgery and medication changes. Results: 100 patients were included in the delayed group and 150 in the on-time group, with a mean age of 47.5 and 42.8 years respectively. 59.2% had Crohn's disease (CD), 39.2% had Ulcerative Colitis (UC) and 1.2% had indeterminate colitis. Both groups had a similar initial severity scores as measured by the Harvey-Bradshaw Index in CD and the Simple Clinical Colitis Activity Index in UC. On average, the on-time group endoscopy was re-scheduled 2.8 months after closure compared to 9.1 months for the delayed group. There was no difference in the number of emergency room visits or hospital admissions during the delay. At one-year post-endoscopy, there was no difference in the number of emergency room visits between the on-time group (n=10, 6.7%) and the delayed group (n= 3, 3%), p= 0.17. One-year post-endoscopy there were significantly more hospitalizations in the on-time group (n=14, 9.3%) compared to the delayed group (n=3, 3%), p=0.03. There was one malignancy in the on-time group and two in the delayed group which did not reach statistical significance. Although clinical severity scores were similar at 1 year, there were more IBD related surgeries in the on-time group (16) compared to the delayed group (4), p=0.03. Discussion: Patients with delayed endoscopies due to COVID-19 did not experience worse outcomes compared to patients whose endoscopies remained on-time. There was a trend towards increased malignancies in the delayed group, but higher number of admissions and operations in the on-time group despite similar degree of inflammation on endoscopy. Retrospective nature of this review did not allow us to evaluate all the factors that may have influenced the decision for admission and surgery. Conclusions: Controlled delay in colonoscopies in patients with IBD with closely monitored re-scheduling efforts is safe and can be utilized in times of emergencies without compromising patient outcomes.
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OBJECTIVES: Care for many chronic conditions was altered during the COVID-19 pandemic. For patients with Inflammatory Bowel Disease (IBD), routine maintenance including endoscopies were postponed. The effects of delaying endoscopies on IBD outcomes are currently unknown. This study aimed to evaluate effects of delays of maintenance endoscopies on patients with IBD during the COVID-19 pandemic. METHODS: This was a retrospective review of all IBD patients scheduled for routine endoscopy at Northwestern Memorial Hospital March 13, 2020 through May 31, 2020. All endoscopic examinations were canceled in this period due to COVID-19. Patients were divided between those whose endoscopies were rescheduled promptly (ontime) or postponed (delayed) after August 31, 2020. Patient outcomes were examined one year after cancellation. Primary outcomes included hospital and emergency room admissions. Secondary outcomes included need for surgery and medication changes. RESULTS: 100 patients were included in the delayed group and 150 in the on-time group, with a mean age of 47.5 and 42.8 years respectively. 59.2% had Crohn's disease (CD), 39.2% had Ulcerative Colitis (UC) and 1.2% had indeterminate colitis. Both groups had similar initial severity scores as measured by the Harvey-Bradshaw Index in CD and the Simple Clinical Colitis Activity Index in UC. On average, the on-time group endoscopy was rescheduled 2.8 months after closure compared to 9.1 months for the delayed group. There was no difference in the number of emergency room visits or hospital admissions during the delay. At one-year post-endoscopy, there was no difference in the number of emergency room visits between the on-time group (n=10, 6.7%) and the delayed group (n=3, 3%), p= 0.17. One-year post-endoscopy there were significantly more hospitalizations in the on-time group (n=14, 9.3%) compared to the delayed group (n=3, 3%), p=0.03. There was one malignancy in the on-time group and two in the delayed group which did not reach statistical significance. Although clinical severity scores were similar at 1 year, there were more IBD related surgeries in the ontime group (16) compared to the delayed group (4), p=0.03. DISCUSSION: Patients with delayed endoscopies due to COVID-19 did not experience worse outcomes compared to patients whose endoscopies remained on-time. There was a trend towards increased malignancies in the delayed group, but higher number of admissions and operations in the on-time group despite similar degree of inflammation on endoscopy. Retrospective nature of this review did not allow us to evaluate all factors that may have influenced the decision for admission and surgery. CONCLUSIONS: Controlled delay in endoscopies in patients with IBD with closely monitored re-scheduling efforts is safe and can be utilized in times of emergencies without compromising patient outcomes.
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Background: Inflammatory bowel disease (IBD) patients undergoing treatments that act on the inmune system and present an increased risk of infections. For this reason, we could consider that these patients may have an increased risk of severe SARS-CoV-2 infection, however, it remains unclear. We aimed to analyze the cumulative incidence, the severity of the infection and its influence on the natural history of IBD in patients under biological treatment and also evaluating the possible differences with another group without these therapy. Methods: Retrospective observational study about our IBD patients followed from March 2020 to January 2021 divided into two groups: patients on treatment with biological drugs (anti-TNF, vedolizumab, ustekinumab and tofacitinib) and patients without biological drugs (thiopurines or 5-ASA). We evaluated: the cumulative incidence in 10 months for COVID-19 in the 2 cohorts;clinical variables considered risk factors for the infection, the infection severity and influence on the course of IBD employing Harvey-Bradshaw index in Crohn's disease and Mayo partial index in ulcerative colitis before and after infection. Results: It collected 755 IBD patients. 89 were infected by SARSCOV-2, 43 in the biological group and 46 in non biological group. The cumulative incidence in 10 months was 10.85% in the first group (figure 1) and 12.81% in the second group with no significant differences. We verified comparability of the groups discarded the existence of statistical differences in all of the risk factors (sex, age, hypertension, diabetes, dyslipidemia, cardiovascular disease and BMI). In most cases, the infection was mild (94.4%) and the required treatment was symptomatic in 86.4% of the total (Figure 2), without significant differences between groups. Pneumonia was diagnosed in 5 patients, whose required hospital admission (3 belonged to the biological group and 2 to the other). The maximum respiratory support required was FIO2 36%, no patient required admission to ICU and there were no deaths. Additionally, the course of IBD was not affected because of COVID-19, considering no significant differences were observed in clinical scores in each group before and after infection, even taking into account 14 patients discontinued biological therapy temporarily during infection. Conclusion: Our study suggests that IBD patients under biological therapy do not have an increased incidence of SARS-COV-2 infection and also do not have a higher risk of severe disease than IBD patients without this therapy. Furthermore, COVID-19 does not affect the natural history of IBD. These data go in the same direction as those published to date, however, we need multicentre registries with a larger sample size in the future.
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Background: The risk of COVID-19 in patients with IBD is considered comparable to general population. However, it has been hypothesized that patients on immunosuppressive therapy could be more susceptible to SARS-CoV-2, mainly due to well-known association of immunosuppressive therapy and increased risk of viral infections. Our aim was to examine the frequency of COVID-19 infection among tertiary center IBD patients treated with biological therapy. Methods: These are descriptive data including IBD patients on biological therapy which are regularly followed in Croatian referral IBD center at the University Hospital Centre Zagreb, Croatia. Patients on adalimumab were excluded since they are not regularly followed and are receiving therapy at home. SARS-CoV-2 infection was identified as RNA positive nasopharyngeal swab. Disease activity was measured using Harvey-Bradshaw Index (HBI) in CD, partial Mayo score (pMayo) in UC, and CRP. COVID-19 was defined as mild as any of the symptoms consistent with COVID-19 without shortness of breath, dyspnea, abnormal chest imaging and room SpO2>=97%. Results: Out of total 234 patients on infliximab 15 (6.4%) had COVID-19, which was the case for 3 out of 48 (6.2%) patients on vedolizumab. We have not documented COVID-19 among 67 patients on ustekinumab and 10 on golimumab. Among infected there were 9 patients with CD, 8 UC and 1 IBD unclassified, 61.1% were male and average age was 37 (SD 12). All patients had mild clinical picture with symptoms lasting around 3 days. Overall, 3 UC patients on infliximab had worsening of IBD symptoms (bloody stools and diarrhea) in approximate time to and after COVID infection (increase of pMayo by >=2 points) with only 1 patient requiring glucocorticoid therapy. One male patient had prolonged post-COVID syndrome in terms of fatigue and mild dyspnea over 4 months, but suffered from bronchial asthma. There was no difference in HB index, pMayo or CRP before and after COVID-19 infection (p>0.05). Loss of smell and taste was present 3 patients. Conclusion: Our analysis was limited to IBD patients scheduled to receive a visit;hence it could not represent general IBD population. However, according to the results of other studies, we did not gain the impression of increased risk of infection or poorer clinical outcome in IBD patients on biological therapy. In addition, study from Singh AK et al. reported worse outcomes of COVID-19 IBD patients in UC, but not on biological therapy, which is also in line with our observation (1).
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Background: Vitamin D, a key regulator of immune response, is known to be lower in Inflammatory Bowel Disease (IBD) patients than the general population. Disparity in the incidence of deficiency between ethnic groups has previously been demonstrated. We measured vitamin D in a unique multi-ethnic inception cohort to correlate this with traditional IBD scores and patient reported outcome measures including the 'IBD Disk'. Methods: Data regarding demographics, ethnicity, faecal calprotectin (FCAL) and baseline blood results including Vitamin D was collected prospectively from January-October 2021, from adults presenting with suspected IBD. Montreal classification, Harvey-Bradshaw Index or Partial Mayo score, endoscopic disease severity indices and IBD Disk score were documented in those with confirmed diagnosis at endoscopy. Vitamin D deficiency was defined as <50nmol/l. Results: 179 patients had a Vitamin D level recorded;58 Ulcerative colitis (UC), 58 Crohn's disease (CD), 53 non-IBD controls and 10 still awaiting diagnosis. 44(76%) CD, 32(55%) UC and 28(53%) non-IBD control patients were Vitamin D deficient at first presentation. Median levels were lowest in CD, with a significant difference between CD and non-IBD (median 35nmol/l;IQR 24.05 vs. median 48.9nmol/l;IQR 49.1;p=0.004). Regression analysis demonstrated patients with Crohn's disease were four times more likely to have Vitamin D deficiency compared to UC (OR 4.08;95% CI 1.35-12.36) at diagnosis. No correlation was seen between absolute vitamin D levels or vitamin deficiency state and faecal calprotectin when controlled for various factors regardless of the IBD subtype. The cohort distributions are demonstrated in Figure 1. Within the IBD cohort, Vitamin D levels were significantly lower in Black or Asian patients vs White patients (median 28.5;IQR 20.85 vs median 43.3;IQR 33.95;p=0.004). Figure 2 provides an overview of the cohort distributions. Vitamin D levels at presentation, as demonstrated in Table 1, did not correlate with Disease activity markers (DAMS) whereas baseline haemoglobin did, albeit weakly. Interestingly, Vitamin D and Haemoglobin correlated without reaching statistical significance (Spearman's rho 0.149;p=0.08). Conclusion: Our inception dataset demonstrates high rates of Vitamin D deficiency comparable to prior studies in IBD patients. Both CD and Black or Asian ethnicity were strongly associated with Vitamin D deficiency. Baseline Vitamin D did not correlate with disease activity markers whereas anaemia showed consistent weak association. Our study demonstrates the problem of hypovitaminosis D and the importance of measurement and supplementation, particularly in Black and Asian CD patients, from diagnosis.
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Background: Whether the disease activity of ulcerative colitis (UC) and Crohn's disease (CD) is correlated with the severity of coronavirus disease 2019 (COVID-19) remains poorly investigated with only few selected cohort studies having addressed this in the past. Methods: We conducted a population-based study investigating the outcomes of COVID-19 among patients with UC and CD in Denmark. The Danish COVID-19 IBD Database is an extensive population-based database which prospectively monitors the disease course of laboratory-confirmed COVID-19 among patients with UC and CD. Severe COVID-19 was defined as COVID-19 necessitating intensive care unit admission, ventilator use, or death, while adverse COVID-19 was defined as requirement of COVID-19 related hospitalization. Clinical disease activity was measured by simple clinical colitis index and Harvey-Bradshaw Index in UC and CD, respectively. The biochemical activity was defined as C-reactive protein higher than 5 mg/L or fecal calprotectin higher than 250 μg/g. The endoscopic activity was defined as Mayo Endoscopic Subscore of at least 2 in UC, or Simple Endoscopic Score Crohn's Disease of at least 3 for CD. Sequelae following COVID-19 were defined as symptoms that (i) developed during or after an infection consistent with COVID-19, (ii) and were present for more than 12 weeks, (iii) and were not attributable to alternative diagnoses. Results: During the inclusion period between January 28th, 2020, to April 1st, 2021, the study included 319 patients with UC and 197 patients with CD who developed laboratory confirmed COVID-19. Of these, data on clinical, biochemical, and endoscopic activity were available among 265/319 (83.1%), 319/319 (100.0%), and 66/319 (20.7%) of patients with UC, respectively, and 140/197 (71.1%), 131/197 (66.5%), and 42/197 (21.3%) of patients with CD. Figures 1-2 outlines the outcomes of COVID-19 according to the degree of clinical, biochemical and endoscopic disease activity. In both UC and CD, clinical, biochemical, and endoscopic activity were not associated with adverse or severe COVID-19, nor long-term outcomes, in unadjusted nor adjusted analysis (Table 1). Conclusion: In this population-based study, we found no association between disease activity of UC or CD and severity of COVID-19. These findings have implications for the risk stratification of patients with IBD acquiring COVID-19.