Early MOnitoring of REsponse (MORE) to Golimumab Therapy: Results of a Multicentre, Prospective Observational Trial.

BACKGROUND: The therapeutic goal of clinical remission in patients with moderate to severe ulcerative colitis (UC) is achieved after biological therapy only in 16-39%. Individualization of therapeutic intervention would benefit from prediction of early response. STUDY OBJECTIVE: The primary objective of our study was to assess golimumab (GLM) trough serum level of ≥2.5 µg/mL in combination with a reduction of faecal calprotectin (FC) of ≥50% at week 6 compared to baseline to predict clinical response at week 26 after regular GLM intake. METHODS: Patients with moderate to severe active UC and planned GLM treatment were recruited for a prospective, multicentre, observational study in Germany. Prediction of clinical response was assessed by FC and GLM trough level. Missing data were imputed as therapy failure according to the last observation carried forward method. RESULTS: Fifty nine patients have been enrolled. 54% of patients were anti-TNF naïve. Clinical response at week 6 was a significant predictor for achieving clinical response at week 26 (odds ratio [OR] 10.97, confidence interval [CI], 2.96-40.68; p < 0.001). Moreover, patients with a GLM trough level of ≥2.5 µg/mL and a ≥50% reduction of FC at week 6 had an OR of 5.33 (95% CI, 0.59-47.84) to achieve clinical response at week 26. CONCLUSION: Clinical response at week 6 is the best predictive marker for achieving clinical response at week 26. Consideration of significant reduction of FC and trough GLM serum levels could improve prediction of response.

Validation of the German Inflammatory Bowel Disease Fatigue (IBD-F) Questionnaire.

INTRODUCTION: Fatigue is a common symptom in patients with inflammatory bowel diseases (IBD). To date, there is no instrument to assess IBD-specific fatigue in German. The aim of this study was to translate the IBD Fatigue (IBD-F) scale and to test its psychometric properties in a German IBD population. METHODS: After completing the translation process, 20 IBD patients participated in a pilot testing phase. For further analyses, 180 IBD patients with fatigue answered the IBD-F (Sections I, II, III) and the IBD Questionnaire (IBDQ-D). Reliability was tested by using Cronbach's alpha and corrected item-total correlation. Exploratory factor analyses (EFA) were carried out. Spearman's correlation was calculated between the IBD-F and IBDQ-D . 78 patients could be included to calculate the test-retest reliability. RESULTS: The German version of the IBD-F shows high face and content validity. Internal consistency was excellent, with a Cronbach's alpha of 0.93-0.98. Corrected item-total correlations ranged from 0.51 to 0.89. The correlation between the IBD-F and the IBDQ-D was statistically significant for Section I (rs=-0.59; p<0.01) and Section II (rs=-0.76; p<0.01) of the IBD-F. The EFA identified one relevant factor for each section. Test-retest reliability was acceptable for Section I (intraclass correlation coefficient (ICC)=0.73) and Section II (ICC=0.84). CONCLUSION: The German version of the IBD-F is a reliable and valid tool to assess fatigue in IBD.

Inflammatory Bowel Disease and COVID-19: How Have Patients Coped So Far?

OBJECTIVE: Knowledge about SARS-CoV2 and coronavirus disease 2019 (COVID-19) is growing fast. Massive changes in the health care system imposed by the COVID-19 pandemic clearly impact the overall quality of medical care. In this survey, we aim to explore experiences and concerns of patients with inflammatory bowel disease (IBD) regarding the current pandemic. METHODS: A 40-item web-based questionnaire on disease-related experiences and concerns during the COVID-19 pandemic was made available to patients with IBD from 28 April 2020 to 31 July 2020. RESULTS: An increased risk of SARS-CoV2 infection was a concern for 56.7% of the 1199 patients (aged 41.3±12.8, women 77%, Crohn's disease 58.8%, ulcerative colitis 38.5%); 61.7% feared an increased risk of severe disease course of COVID-19. Effective preventive measures in either outpatient practices or hospitals were observed by 84.7% of the patients. Appointments with an IBD specialist were canceled in 38.7%, frequently on the patients' initiative. Telecommunication visits were considered an acceptable alternative to personal visits by 71.0%. Medication was reduced or paused in 6.9% because of the pandemic. A swab (SARS-CoV2-PCR) was done in 13.2% of the patients; only 3 patients (0.25%) were tested positive. CONCLUSION: The COVID-19 pandemic is a major concern of patients with IBD. However, the cumulative prevalence in our cohort is low. Patients at risk should be identified and counseled individually. When required because of the local COVID-19 situation, telecommunication visits and liberal prescription policies are advisable to reduce in-person contacts, while ensuring continuous therapy and maintaining communication with patients.

Clinical and surgical factors for successful stoma reversal in patients with Crohn's disease-results of a retrospective cohort study.

PURPOSE: Despite the wide range of medical and interventional therapy options available, some patients with Crohn's disease (CD) need an ileostomy or colostomy. The aim of this study was to identify clinical, surgical and drug-related predictors of successful stoma reversal in CD patients. METHODS: A retrospective medical record analysis of surgical department logs, hospital discharge letters and patient reports from outpatient departments was performed for all CD patients who underwent a first ostomy surgery. RESULTS: Our study analysed a total of 149 patients (76 women, 73 men, median age at first stoma of 34 years after a median CD duration of 9 years), with a median follow-up of 78.4 (IQR 88.6) months after first ostomy surgery. Of these patients, 73 (49%) underwent stoma reversal after a median of 11.7 months (IQR 15.7 months) of whom 17 (23.3%) needed a second stoma. In multivariant analysis, Montreal A1 classification (HR 2.07; 95% confidence interval 1.23-3.47; p = 0.006), a primary laparotomy (HR 2.30; 95% confidence interval 1.20-4.41; p = 0.012) and the absence of perianal/rectal CD activity (HR 3.00; 95% confidence interval 1.86-4.86; p < 0.001) emerged as independent predictors of a shorter time to stoma reversal. Introduction or switch of biological therapy after first stoma was not associated with successful reversal of the stoma (OR 4.6 95% confidence interval 1.45-14.66; p = 0.01). Laboratory parameters had no influence. CONCLUSION: Clinical and surgical features-rather than medication or laboratory findings-were found to be predictors of successful stoma reversal in CD patients. Future studies focusing on the definition of a Standard Operation Procedure for emergency and elective CD surgery are warranted.

Clinical predictors for a complicated course of disease in an inception cohort of patients with ulcerative colitis: results from the prospective, observational EPICOL study.

PURPOSE: The clinical course of ulcerative colitis (UC) is highly heterogeneous, with 20 to 30% of patients experiencing chronic disease activity requiring immunosuppressive or biologic therapies. The aim of this study was to identify predictors for a complicated disease course in an inception cohort of patients with UC. METHODS: EPICOL was a prospective, observational, inception cohort (UC diagnosis, ≤ 6 months) study in 311 patients with UC who were naive to immunosuppressants (IS)/biologics. A complicated course of disease was defined as the need for IS and/or biologic treatment (here therapy with a TNF-α antagonist) and/or UC-related hospitalisation. Patients were followed up for 24 months. RESULTS: Of the 307 out of 311 participants (4 patients did not meet the inclusion criteria "confirmed diagnosis of active UC within the last 6 months" (n = 2) and "immunosuppressive-naïve" (n = 2), analysis population), 209 (68.1%) versus 98 (31.9%) had an uncomplicated versus a complicated disease course, respectively. In a multivariate regression analysis, prior use of corticosteroids and prior anaemia were associated with a significantly increased risk for a complicated disease course (2.3- and 1.9-fold increase, respectively; p < 0.001 and p = 0.002). Based on these parameters, a risk model for patient stratification was developed. CONCLUSION: Our study identifies anaemia and an early need for corticosteroids as predictors for a complicated course of disease in an inception cohort of patients with UC. By determining these parameters in routine clinical practice, our results may support the identification of patients who might benefit from early escalation of therapy.

[Inflammatory bowel disease during the COVID-19 pandemic: manifestations and management]. / Chronisch-entzündliche Darmerkrankungen in der COVID-Pandemie: Manifestationen und Management.

The COVID-19 pandemic is significantly affecting the lives of patients with inflammatory bowel disease (IBD). Those affected and their relatives have numerous questions about the risk of the disease, the course of a possible SARS-CoV-2 infection or the influence of CED-specific therapy on these. Many IBD patients also have additional questions about the safety and effectiveness of a vaccination against SARS-CoV-2. The aim of this review is to summarize the latest findings on COVID-19 and IBD, but also to discuss vaccine response (humoral/cellular), the influence of ongoing therapy on the vaccine response as well as the frequency of side effects and the importance of booster immunizations and to create an evidence-based basis for discussion with patients.

SARS-CoV-2 vaccination does not induce relapses of patients with inflammatory bowel disease.

BACKGROUND: Vaccination against SARS-CoV-2 is a promising strategy to protect immunocompromised IBD patients from a severe course of COVID-19. As these patients were excluded from initial clinical vaccination trials, patients frequently express concerns regarding the safety of these vaccines, especially whether vaccination might trigger IBD flares ("hit-and-run-hypothesis"). METHODS: In order to assess the risk of an IBD flare after vaccination against SARS-CoV-2, an anonymous survey was performed at five German IBD centers and one patient organization (Deutsche Morbus Crohn/Colitis ulcerosa Vereinigung (DCCV) e.V.) in August and October 2021. RESULTS: The questionnaire was answered by 914 patients, 781 of whom reported a previous vaccination against SARS-CoV-2 (85.4%). Vaccination against SARS-CoV-2 was not associated with an increased risk of IBD flares (p=0.319) or unscheduled visits to the IBD physician (p=0.848). Furthermore, typical symptoms of an IBD flare including abdominal pain, increases in stool frequency, or rectal bleeding were not influenced by the vaccination. CONCLUSION: Vaccination against SARS-CoV-2 is safe in IBD patients. These results may help to reduce fears regarding the vaccination in IBD patients. Our results can help to reduce fears in IBD patients regarding the SARS-CoV-2 vaccine. A close communication between patients and physicians before and after the vaccination may be beneficial.

Golimumab improves work productivity in patients suffering from moderate to severe ulcerative colitis: results of a prospective study over 24 months.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with recurrent episodes of debilitating symptoms negatively affecting work productivity and health-related quality of life (HRQoL). The use of biologics in UC treatment improves work and HRQoL but prospective long-term data concerning the treatment with TNFα inhibitor golimumab in UC patients are still rare. Therefore, our study aimed to evaluate the change in work productivity, capacity for daily activities and HRQoL in UC patients treated with golimumab in Germany. METHODS: Using the Work Productivity and Activity Impairment questionnaire, the change in work productivity and in capacity for daily activities after 3 months and over the whole observational period of 24 months were assessed (both primary endpoints). Disease-specific and health-related quality of life (QoL) were analyzed with the Inflammatory Bowel Disease Questionnaire (IBDQ), the Short-Form 12 Health Survey Questionnaire (SF-12), and the Partial Mayo Score (secondary endpoints). Further, disease-related hospitalization rates were assessed. RESULTS: This prospective non-interventional study included 286 patients. Thereof, 212 patients were employed at baseline (modified intention to treat analysis set employed at baseline, mITTe). 61.3% of the mITTe patients had moderate and 17.0% had severe UC. Three months after initiation of golimumab therapy, total work productivity impairment (TWPI) score and activity impairment score improved significantly from baseline with a mean change of - 17.3% (p < 0.0001) and - 14.4% (p < 0.0001), respectively. Results persisted over 24 months (mean change TWPI score: - 24.5%, mean change activity impairment score: - 30.0%). Disease- and health-related QoL also improved significantly under golimumab treatment as indicated by increased IBDQ [mean change: 28.0 (SD: ± 36.1, month 3), 42.1 (SD: ± 39.5, month 24)] and SF-12 scores [PCS-12: 45.9 (SD: ± 8.5), MCS-12: 4.9 (SD: ± 10.6, month 3), PCS-12: 5.9 (SD: ± 9.0), MCS-12: 6.4 (SD: ± 11.1, month 24)]. Disease-related hospitalization rate decreased from 16.0% (BL) to 4.3% at month 24 and the mean number of missed working days due to UC decreased from 8.2 (SD: 17.6, BL) to 0.7 (SD: 2.1) after golimumab induction. CONCLUSIONS: Golimumab leads to notable long-term improvements in work productivity, daily activity, HRQoL, and disease-related hospitalization rates in patients with moderate to severe UC. TRIAL REGISTRATION: PEI (Paul-Ehrlich-Institute, Langen, Germany) Registration Nr: NIS#255 ( https://www.pei.de/SharedDocs/awb/nis-0201-0300/0255.html ).

[Effects of SARS-CoV-2 Infection on Symptoms and Therapy of Inflammatory Bowel Disease]. / Auswirkungen einer SARS-CoV-2-Infektion auf Symptomatik und Therapie chronisch-entzündlicher Darmerkrankungen.

INTRODUCTION: The influence of a SARS-CoV-2 infection on inflammatory bowel disease (IBD) has not yet been well characterized and it is unclear whether this requires an adaptation of the immunosuppressive therapy. METHODS: A national register was established for the retrospective documentation of clinical parameters and changes in immunosuppressive therapy in SARS-CoV-2 infected IBD patients. RESULTS: In total, only 3 of 185 IBD patients (1.6 %) were tested for SARS-CoV-2 infection because of abdominal symptoms. In the course of COVID-19 disease, 43.5 % developed diarrhea, abdominal pain or hematochezia (risk of hospitalization with vs. without abdominal symptoms: 20.0 % vs. 10.6 %, p < 0.01). With active IBD at the time of SARS-CoV-2 detection, there was an increased risk of hospitalization (remission 11.2 %, active IBD 23.3 % p < 0.05). IBD-specific therapy remained unchanged in 115 patients (71.4 %); the most common change was an interruption of systemic therapy (16.2 %). DISCUSSION: New abdominal symptoms often appeared in SARS-CoV-2 infected IBD patients. However, these only rarely led to SARS-CoV-2 testing. A high IBD activity at the time of SARS-CoV-2 detection was associated with an increased risk of hospitalization.

Thumb sucking or nail biting in childhood and adolescence is associated with an increased risk of Crohn's disease: results from a large case-control study.

BACKGROUND: The hygiene hypothesis suggests that a reduction in microbial exposure contributes to an impaired immune response later in life and increases the incidence of immune-mediated diseases such as inflammatory bowel diseases (IBD). Thumb sucking and nail biting are two early habits that modulate the oral microbiota composition and antigen load. OBJECTIVE: We hypothesized a lower risk of Crohn's disease (CD) and ulcerative colitis (UC) in adults with prior thumb sucking and nail biting. METHODS: 918 IBD cases and their 918 siblings without IBD were asked to fill out a survey containing 32 questions on environmental factors in childhood and early adulthood. Prevalence of thumb sucking and/or nail biting at the usually well-remembered time of (1) school enrollment and (2) coming-of-age ceremonies was the predefined combined risk factor of this study. RESULTS: 65% of the patients were female and 57% suffered from CD. About 49% of IBD patients but only 44% of their siblings reported thumb sucking/nail biting at the time of school enrollment or coming-of-age (p = .007). Sensitivity analysis revealed that this difference was observed in patients with CD (50% versus 41%; RR= 1.22; 95% CI 1.09-1.37, p = .001) but not in patients with UC (49% versus 48%; RR= 1.02; 95% CI 0.90-1.17; p = .83). CONCLUSION: Contrary to our expectation and challenging the hygiene hypothesis, we found that common oral habits are not protective against IBD. Instead, nail biting at the time of school enrollment and coming-of-age was a statistically significant risk factor for CD in our cohort. Key summary Evidence available before this study: The hygiene hypothesis suggests that a reduction in microbial exposure due to improved health activities has contributed to an immunological imbalance in the intestine and an increased incidence of allergic and autoimmune diseases. A population-based birth cohort study has demonstrated that thumb-sucking and nail biting in children lead to a reduction of the risk of atopic sensitization, asthma, and hay fever. Added value of this study: Contrary to the hypothesis, thumb sucking and nail biting were not associated with a reduced risk of IBD. Instead, thumb sucking and/or nail biting at the usually well-remembered points in time of school enrollment and of religious or secular coming-of-age ceremonies was associated with a higher risk of Crohn's disease but not of ulcerative colitis. Our data did not support the hygiene hypothesis, one pathogenic concept in the context of IBD.

Predictive parameters for the clinical course of Crohn's disease: development of a simple and reliable risk model.

PURPOSE: The aim of our study was to identify clinical parameters in recently diagnosed Crohn's disease (CD) patients for prediction of their disease course. METHODS: EPIC (Early Predictive parameters of Immunosuppressive therapy in Crohn's disease) is a prospective, observational study in 341 patients with a recent CD diagnosis (≤ 6 months), and naïve to immunosuppressants (IS) and anti-tumor necrosis factor α (TNF) agents. Patient characteristics were documented up to 2 years. In line with national and international guidelines, a complicated disease course was defined as need for immunosuppressants and/or anti-TNF agents, and CD-related hospitalization with or without immunosuppressants and/or anti-TNF agents. RESULTS: A total of 212 CD patients were analyzed of whom 57 (27%) had an uncomplicated disease within 24 months, while 155 (73%) had a complicated disease course: need for IS and/or anti-TNF agents (N = 115), CD-related hospitalization with or without IS/anti-TNF agents (N = 40). Identified risk predictors for a complicated disease were as follows: age at onset < 40 years (OR 2.3; 95% CI 1.2-4.5), anemia (OR 2.1; 95% CI 1.1-4.2), and treatment with systemic corticosteroids at first flare (OR 2.2; 95% CI 1.1-4.7). These three parameters were used to develop a risk model allowing prediction of the future disease course. CONCLUSION: Our three-parameter model enables an assessment of each CD patient's risk to develop a complicated disease course. Due to the easy accessibility of these parameters, this model can be utilized in daily clinical care to assist selecting the initial treatment for each individual patient.

The detection of the cytomegalovirus DNA in the colonic mucosa of patients with ulcerative colitis is associated with increased long-term risk of proctocolectomy: results from an outpatient IBD clinic.

PURPOSE: Cytomegalovirus (CMV) infection has been found to be associated with a reactivation of ulcerative colitis (UC) and with an impaired response to medical therapy. In the past, only limited data were available on the long-term outcome for UC patients with positive tissue CMV-PCR in the colonic mucosa. METHODS: Between January 2010 and April 2015, we performed a qualitative PCR screening for CMV DNA in one biopsy from most actively inflamed rectal mucosa (tCMV-PCR). All tCMV-PCR-positive patients received 900 mg of valganciclovir b.i.d. for at least 15 days. We analyzed the association of the tCMV-PCR status with the time to steroid-free remission (SFR) and with the risk of proctocolectomy during the further course. RESULTS: One hundred eight consecutive patients (50 women, 58 men, median age 41 years, median UC duration 6 years) with active UC not responding to anti-inflammatory medication were analyzed. Eight of the 24 tCMV-PCR-positive patients (33.3%) compared to ten of the 84 tCMV-PCR-negative patients (11.9%) underwent proctocolectomy during a median follow-up of 52 months (p < 0.005). The median time from CMV diagnosis to colectomy was 501 days (median, interquartile range (IQR): 170, 902 days) in tCMV-PCR-positive and 958 days (IQR: 287, 1328 days) in tCMV-PCR-negative patients (p < 0.01). The median time to SFR was 126 days in tCMV-PCR-positive patients vs. 63 days in tCMV-PCR-negative patients (p < 0.01). CONCLUSIONS: The detection of the CMV DNA in the colonic mucosa of patients with active UC is associated with a longer time to steroid-free UC remission and with an increased rate and earlier need of proctocolectomy.

[Advances in the diagnosis and treatment of Clostridioides [Clostridium] difficile infections in inflammatory bowel disease]. / Aktuelle Konzepte zur Diagnostik und Therapie der Clostridioides [Clostridium]-difficile-Infektion bei Patienten mit chronisch-entzündlichen Darmerkrankungen.

Patients with chronic inflammatory bowel disease (IBD) have a significantly increased risk of clinically relevant clostridial infection (CDI). In turn, CDI can increase IBD activity. Therefore, rapid diagnosis and therapy is required. Many diagnostic and treatment studies on patients with CDI without inflammatory bowel disease are not congruent with IBD patients. This overview summarizes the everyday data of recent years and condenses these into four guiding principles. 1) patients with IBD present a risk population for a CDI. A CDI not only worsens the disease activity in the short term, but also causes increased morbidity and mortality in the long term. 2) If a CDI is suspected, glutamate-dehydrogenase (GDH) detection should be carried out quickly. If this is positive, and the disease activity is high, a therapy against C. difficile already may be initiated and-if necessary-terminated in cases of negative confirmation tests. 3) IBD patients with a proven CDI should be treated primarily with vancomycin. 4) In a relapsing CDI, fecal microbiome transfer is an effective therapeutic measure. However, activation of the IBD must be expected in about 15 % of cases. Consistent adherence to these guidelines may help treat a CDI in IBD patients.

Topic infliximab injection for refractory rectal stenosis in Crohn's disease: long-term follow-up in two patients.

PURPOSE: TNF blockers are approved for intravenous or subcutaneous systemic therapy of many chronic inflammatory diseases. As it is not possible to achieve a sufficient local clinical improvement through systemic therapy in every patient, diverse approaches of topical therapy using TNF blockers have been investigated in recent years. METHODS: In this paper, we report on long-term clinical results of originator infliximab (IFX) injections into symptomatic combined scarring and inflammatory stenoses of the rectum in two patients with Crohn's disease. Aiming at high tissue IFX levels, 25 mg of IFX was injected into each quadrant of the stenosis after endoscopic balloon dilatation. This off-label treatment was repeated as necessary, depending on the clinical success. RESULTS: Topic IFX injection after balloon dilation reduced imperative stool pressure, isolated episodes of incontinence and incomplete emptying. Improvement lasted between 4 and 14 weeks in one patient and the treatment was repeated 13 times in the following 6.6 years. In the other patient, the technique was necessary only twice with no symptom recurrence in the subsequent 5.3 years. CONCLUSION: Our experience suggests that topic application of a systemically approved anti-TNF substance may be a successful individualized therapy for refractory stenosis of the rectum in patients with Crohn's disease.

Azathioprine allows glucocorticoid withdrawal - post hoc results of a prospective study in patients with inflammatory bowel diseases.

Background Azathioprine is recommended as first-line immunosuppressant in patients with steroid-dependent inflammatory bowel diseases (IBDs). However, data on steroid withdrawal after induction therapy in IBD patients are sparse. Methods In this post-hoc analysis of a prospective multicenter study, we analyzed the proportion and clinical characteristics of 324 azathioprine-tolerant patients as to whether they could terminate the glucocorticoid therapy after initiation of treatment with azathioprine. Results Systemic steroid therapy was required in 190 patients (58.6 %) at baseline and in 40 patients (12.3 %) at the end of the follow-up period (p < 0.001). The median daily dose was 30 mg at baseline and 10 mg at follow-up. At baseline, only 122 patients (37.2 %) were advised to take at least the lowest recommended dose of 2 mg/kg per day. At follow-up, 221 patients (68.2 %) were prescribed at least the recommended maintenance dosage. Conclusion The majority of patients with thiopurine-naïve IBDs that needed systemic steroids at baseline were able to discontinue steroids after 3 - 6 months of azathioprine therapy. These data support the continued high value of azathioprine in the immunosuppressive therapy of IBD.