scholarly journals Anti-Mycobacterial Antibiotic Therapy Induces Remission in Active Paediatric Crohn’s Disease

2020 ◽  
Vol 8 (8) ◽  
pp. 1112 ◽  
Author(s):  
Gaurav Agrawal ◽  
Harrison Hamblin ◽  
Annabel Clancy ◽  
Thomas Borody
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Antibiotic Therapy ◽  
Clinical Remission ◽  
Activity Index ◽  
Disease Activity Index ◽  
Mucosal Healing ◽  
Paediatric Patients ◽  
Endoscopic Remission ◽  
Paediatric Crohn’S Disease

Crohn’s disease is increasing in incidence and prevalence in younger people and is of a particularly aggressive nature. One emerging treatment targets Mycobacterium avium paratuberculosis (MAP), an organism implicated in the causation of Crohn’s disease. This study reviewed a cohort of paediatric patients with active Crohn’s disease treated with Anti-Mycobacterial Antibiotic Therapy (AMAT). Sixteen paediatric patients, the majority of whom had failed conventional immunosuppressive therapy, were treated with AMAT. Endoscopic remission was scored using the Simple Endoscopic Score for Crohn’s Disease and clinical remission was assessed using the Weighted Paediatric Crohn’s Disease Activity Index (wPCDAI). Inflammatory blood markers were also routinely recorded. Patients were followed up clinically and endoscopically during treatment after an average of two months (range 1–6) and 17 months (range 2–49), respectively. A significant reduction in both scores assessing clinical improvement (p < 0.001) and mucosal healing (p < 0.0078) was observed at these timepoints; 47% of patients had achieved clinical remission and 63% endoscopic remission. Haemoglobin and serum inflammatory markers normalised for more than 50% of the cohort by six months of treatment. No adverse effects were reported throughout treatment. This is the first report of Anti-Mycobacterial Antibiotic Therapy offering a safe and efficacious therapy for paediatric patients with Crohn’s disease. Further larger randomised studies are required in order to validate these findings.

Outcomes of Passable and Non-passable Strictures in Clinical Trials of Crohn’s Disease: A Post-hoc Analysis

2021 ◽  
Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Parambir S Dulai ◽  
John K Marshall ◽  
Jean-Frederic Colombel ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Symptom Improvement ◽  
Logistic Regression Models ◽  
Post Hoc Analysis ◽  
Endoscopic Remission ◽  
Post Hoc ◽  
The Impact

Abstract Background and Aims There is paucity of evidence on the reversibility of Crohn’s disease [CD]-related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures. Methods This was a post-hoc analysis of three large CD clinical trial programmes examining outcomes with infliximab, ustekinumab, and azathioprine, which included data on 576 patients including 105 with non-passable strictures and 45 with passable strictures, as measured using the Simple Endoscopic Score for Crohn’s Disease [SES-CD]. The impact of non-passable strictures on achieving clinical remission [CR] and endoscopic remission [ER] was assessed using multivariate logistic regression models. CR was defined as a Crohn’s Disease Activity Index [CDAI] &lt;150, clinical response as a CDAI reduction of ≥100 points, and ER as SES-CD score &lt;3. Results After 1 year of treatment, patients with non-passable strictures demonstrated the ability to achieve passable or no strictures in 62.5% of cases, with 52.4% and 37.5% attaining CR and ER, respectively. However, patients with non-passable strictures at baseline were less likely to demonstrate symptom improvement compared with those with passable or no strictures, with reduced odds of 1-year CR (adjusted odds ratio [aOR] 0.17, 95% CI 0.03–0.99, p = 0.048). No significant differences were observed between patients with non-passable strictures at baseline and those with passable or no strictures in rates of ER [aOR 0.82, 95% CI 0.23–2.85, p = 0.751] at 1 year. Conclusions Patients with non-passable strictures can achieve symptomatic and endoscopic remission when receiving therapies used to treat CD, although they are less likely to obtain CR compared with patients without non-passable strictures. These findings support the importance of balancing the presence of non-passable strictures in trial arms.

P089 REAL-WORLD EXPERIENCE: CLINICAL AND ENDOSCOPIC EFFECTIVENESS OF STANDARD VEDOLIZUMAB DOSING AND MODIFIED MAINTENANCE DOSING IN PATIENTS WITH MODERATE-SEVERE CROHN’S DISEASE

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S75-S75
Author(s):  
Scott D Lee ◽  
Anand Singla ◽  
Caitlin Kerwin ◽  
Kindra Clark-Snustad
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Real World ◽  
Clinical Remission ◽  
Mucosal Healing ◽  
Clinical Disease ◽  
Endoscopic Remission ◽  
Starting Dose

Abstract Background Vedolizumab (VDZ) is an effective treatment for Crohn’s disease (CD); however, inadequate and loss of response is common. Pivotal VDZ trials evaluated alternative dosing intervals, demonstrating numeric but not statistical superiority in efficacy as compared to FDA-approved dosing. The safety and effectiveness of FDA-approved and modified-dosing schedules in a real-world population are unknown. We aimed to evaluate clinical and endoscopic effectiveness & safety of standard and modified maintenance VDZ dosing in a real world cohort. Methods We retrospectively reviewed CD patients (pts) treated with &gt;3 months VDZ, assessing Harvey Bradshaw Index (HBI), Simple Endoscopic Score for Crohn’s disease (SESCD), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), C-reactive protein (CRP), albumin and hematocrit prior to and following standard VDZ dosing, and prior to and following modified VDZ maintenance dosing. We measured duration on therapy and adverse events. Results We identified 226 eligible pts, mean age 41.5 years, 55.3% female, median disease duration 10 years, 88.9% with prior biologic exposure. Mean duration on VDZ was 28.3 months. Standard VDZ dosing: 61.5% of pts with active clinical disease and adequate follow up data achieved clinical response after 3–12 months; 41.0% had clinical remission. 51.9% of pts with active endoscopic disease and adequate follow up data achieved mucosal improvement; 42.3% had endoscopic remission; 26.0% had mucosal healing after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized CRP after 3–12 months. Modified maintenance dosing: 72 non-remitters to standard VDZ dosing received modified VDZ maintenance dosing. 51.5% of pts with active clinical disease prior to starting dose modification and adequate follow up data achieved clinical response after 3–12 months of modified maintenance dosing; 42.4% had clinical remission. 22.2% of pts with SESCD ≥3 prior to starting dose modification achieved mucosal improvement after 3–24 months; 22.2% had mucosal healing. 26.7% of pts with SESCD ≥4 prior to starting modified dosing had endoscopic remission after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized their CRP after 3–12 months. Safety: 82.7% of pts reported ≥1 adverse events, most commonly infection and worsening CD symptoms. Discussion Standard VDZ dosing resulted in clinical and endoscopic improvement in pts with moderate-severe CD, with prior exposure to multiple advanced therapies. For non-remitters to standard dosing, modified VDZ maintenance dosing improved clinical disease activity in ∼50% of pts and improved endoscopic disease activity in ∼20% of pts, suggesting that for pts who did not achieve remission with standard VDZ dosing, modified VDZ dosing may result in clinical and endoscopic improvement.

scholarly journals OP02 Ustekinumab versus adalimumab for induction and maintenance therapy in Moderate-to-Severe Crohn’s Disease: The SEAVUE study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S001-S002
Author(s):  
P M Irving ◽  
B E Sands ◽  
T Hoops ◽  
J L Izanec ◽  
L L Gao ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Activity Index ◽  
Study Drug ◽  
Controlled Study ◽  
Serious Adverse Events ◽  
Endoscopic Remission ◽  
Secondary Endpoints ◽  
Dose Modifications

Abstract Background We studied the efficacy and safety of ustekinumab (UST) vs adalimumab (ADA) through 1 year in biologic-naïve patients (pts) with moderate-to-severe Crohn’s disease. Methods SEAVUE was a multicenter, randomized, blinded, parallel-group, active-controlled study in adults with CD Activity Index (CDAI) scores ≥220/≤450. Biologic-naïve pts failing/intolerant to conventional therapy with any size ulcer on baseline (BL) ileocolonoscopy were eligible. Pts were randomized 1:1 to UST (⁓6mg/kg IV at BL then 90mg SC every 8 weeks [Ws]) or ADA (160/80mg SC at BL/W2, then 40mg SC every 2 Ws) per US-approved regimens (no dose modifications). Primary endpoint was clinical remission at W52 (CDAI &lt;150). Major secondary endpoints were corticosteroid-free remission, clinical response (≥100-point CDAI decrease from BL), remission in pt-reported CDAI components (PRO-2 symptom remission: abdominal pain mean daily score ≤1 and stool frequency mean daily score ≤3), and endoscopic remission (SES-CD score ≤3/0 for pts with BL score=3) at W52 and clinical remission at W16. Results 386 pts were randomized to UST or ADA. BL demographics and disease characteristics were balanced between groups and indicative of pts with early, moderate-to-severe CD (median CD duration, 2.58 years; CDAI, 289.5; SES-CD, 8.0). At W52, 65% of UST-treated and 61% of ADA-treated pts achieved clinical remission (Δ=4.0%; 95% CI, -5.5%, 13.5%; p=0.417). Major secondary endpoints, including endoscopic remission, were similar between groups (Table 1), as were remission rates at assessment points through W52. Some other secondary endpoints showed numerical (not statistical) differences between UST and ADA (Table 1). Key safety events are summarized in Table 2. Among UST-treated and ADA-treated pts, 34.0% and 40.5% had infections, 2.6% and 7.2% had serious adverse events (AEs) of worsening CD, and 6.3% and 11.3% had AEs that led to discontinuation (DC) of study drug, respectively. One ADA-treated pt had active pulmonary TB. Injection-site reactions associated with active treatment occurred in 1.0% of UST-treated and 10.3% of ADA-treated pts. Overall, 15.2% of UST-treated and 23.6% of ADA-treated pts DC before W52. Reasons for DC were primarily lack of efficacy (UST, 2.1% vs ADA, 5.1%), AEs (UST, 5.7% vs ADA, 10.7%), and withdrawal of consent (UST, 5.8% vs ADA, 5.1%). Time to treatment DC was longer with UST vs ADA (post hoc analysis). Conclusion Both UST and ADA were highly effective in this population of biologic-naïve pts. Rates of clinical remission at W52 were not statistically significantly different between treatment groups. DC rates were numerically lower for UST. Safety results were consistent with prior experience for both treatments.

scholarly journals Exclusive Enteral Nutrition versus Infliximab in Inducing Therapy of Pediatric Crohn’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Youyou Luo ◽  
Jindan Yu ◽  
Jingan Lou ◽  
Youhong Fang ◽  
Jie Chen
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Effects ◽  
Enteral Nutrition ◽  
Clinical Symptoms ◽  
Activity Index ◽  
Group Versus ◽  
Disease Activity Index ◽  
Mucosal Healing ◽  
Exclusive Enteral Nutrition

Aim. To compare the effectiveness of exclusive enteral nutrition (EEN) and infliximab (IFX) therapy in pediatric Crohn’s disease (CD). Methods. In a prospective study of children initiating EEN or infliximab therapy for CD, we compared clinical outcomes using the pediatric Crohn’s disease activity index (PCDAI), growth improvement, endoscopic mucosal healing, and adverse effects. Data were measured at baseline and after 8 weeks of therapy. Results. We enrolled 26 children with CD; of whom, 13 were treated with infliximab, 13 with EEN. Clinical response (PCDAI) reduction ≥ 15 or final PCDAI ≤ 10 was achieved by 83.3% in the EEN group and 90.9% in the IFX group. Body mass index for age (BMIFA) z-scores were significantly increased in both groups (P<0.05). No significant differences were observed in PCDAI, height for age (HFA), or BMI recovery between two groups. Adverse effects were detected in 30.7% on infliximab and 0% on EEN. Mucosal healing was achieved in 71.4% cases in the EEN group versus 85.7% in the IFX group. Conclusion. EEN provided similar improvements as IFX in clinical symptoms, mucosal healing, and BMI. EEN therapy has less adverse effects when compared with IFX. This trial is registered with the Clinical Registration Number: ChiCTR-OON-17010834.

scholarly journals Bovine lactoferrin and Crohn’s disease: a case study

2017 ◽  
Vol 95 (1) ◽  
pp. 133-141 ◽  
Author(s):  
David B. Alexander ◽  
Masaaki Iigo ◽  
Mohamed Abdelgied ◽  
Keiji Ozeki ◽  
Satoshi Tanida ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Disease Recurrence ◽  
Mucosal Healing ◽  
University Hospital ◽  
Bovine Lactoferrin ◽  
Colonoscopic Examination

A 22-year-old male suffering from abdominal pain, repeated diarrhea, and weight loss visited the Digestive Disease Department of Nagoya City University Hospital on 19 December 2011. He was hospitalized and diagnosed with Crohn’s colitis. His Crohn’s Disease Activity Index (CDAI) was 415. Treatment by granulocyte apheresis, mesalazine, and adalimumab was started. His CDAI was 314 on 30 December and 215 on 5 January. A colonoscopic examination on 19 January showed almost complete remission in the transverse colon and marked remission in the rectum. Mesalazine therapy was stopped on 28 February, and the patient was instructed to self-inject 40 mg of adalimumab every other week. His CDAI was 50 on 10 April, indicating clinical remission. His last self-injection of adalimumab was on 24 April 2012, and he started taking 1 g of bovine lactoferrin (bLF) daily. His CDAI was 35 on 8 January 2013. He continued taking 1 g of bLF daily without any other treatment for Crohn’s disease. Laboratory blood tests on 7 September 2015 showed no sign of disease recurrence, and a colonoscopic examination on 23 October 2015 showed almost complete mucosal healing. This case indicates that ingestion of bLF to maintain Crohn’s disease in a remissive state should be further explored.

scholarly journals The Association Between Genetic Variants, Pharmacokinetics, and Infliximab Efficacy in Pediatric Patients With Crohn's Disease in China

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenhui Hu ◽  
Yan Feng ◽  
Ziqing Ye ◽  
Zifei Tang ◽  
Lai Qian ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Genetic Variants ◽  
Pediatric Patients ◽  
Activity Index ◽  
Area Under The Curve ◽  
Disease Activity Index ◽  
Threshold Level ◽  
Mucosal Healing ◽  
Nucleotide Polymorphisms

Background: Infliximab is an effective therapy for Crohn's disease (CD). Early non-invasive predictors of disease remission allow for modification of treatments. The aim of this study was to investigate the associations between genetic variants, pharmacokinetics, and infliximab efficacy in pediatric patients with CD.Methods: This retrospective observational study included CD patients under infliximab therapy between August 2015 and December 2020. Information on demographics, laboratory tests, medication data, and disease activity index was collected. The trough levels of infliximab (TLI) and antibodies to infliximab (ATI) were measured at week 14, and reactive drug monitoring was performed during follow-up. Ten single-nucleotide polymorphisms involved in the NF-κB-mediated inflammatory response, pharmacokinetics, and therapeutic response to infliximab were genotyped.Results: A total of 62 pediatric CD patients were enrolled. The clinical remission (CR) rate was 69.4 and 63.2% at week 14 and week 30, respectively. TLI at week 14 was significantly independently associated with CR at week 14 and mucosal healing (MH) at week 30 (p = 0.007 and p = 0.025, respectively). The optimal TLI threshold level capable of distinguishing between the CR and non-CR groups was 2.62 μg/ml (p &lt; 0.001, area under the curve = 0.79, sensitivity = 69.2%, specificity = 78.9%), while that capable of distinguishing between the MH and non-MH groups was 3.34 μg/ml (p &lt; 0.001, area under the curve = 0.85, sensitivity = 78.6%, specificity = 79.4%). Rs3397 in TNFRSF1B was associated with time to ATI production in CD patients (p &lt; 0.001).Conclusions: Higher TLI contributed to achieving MH. Genotyping rs3397 in TNFRSF1B may identify patients who are prone to generating immunogenicity to drugs.

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