scholarly journals NUDT15 genotyping during azathioprine treatment in patients with inflammatory bowel disease: implications for a dose-optimization strategy

2020 ◽  
Author(s):  
Ye Xu ◽  
Yu-Qi Qiao ◽  
Han-Yang Li ◽  
Mi Zhou ◽  
Chen-Wen Cai ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Optimization Strategy ◽  
Wild Genotype ◽  
Azathioprine Treatment ◽  
Starting Dose ◽  
Toxicity Analysis ◽  
Inflammatory Bowel ◽  
Dosing Strategy

Abstract Background NUDT15 R139C is an Asian-prevalent genetic variant related to azathioprine (AZA) intolerance in patients with inflammatory bowel disease (IBD). However, it remains unclear how to utilize the genotyping results to improve the step-up dosing strategy with an already low starting dose in Asian practice. Methods Clinical data of eligible IBD patients who received AZA therapy and NUDT15 R139C testing were retrospectively collected. The relationship between NUDT15 genotype, AZA doses, and AZA-induced toxicity and efficacy were comprehensively analysed. Results A total of 159 patients were included for toxicity analysis. Compared with the wild genotype, patients heterozygous for R139C are more prone to developing myelotoxicity and alopecia (P = 0.007; P = 0.042). In particular, they had a 5.4-fold risk of developing myelotoxicity when AZA dosage was increased from 25 mg/d to 50 mg/d (P < 0.001). Regarding efficacy, 115 patients who had received AZA for >4 months and maintained clinical remission on AZA monotherapy were included for further analysis. R139C heterozygotes were finally titrated to a significantly lower dose than the wild genotype [median (interquartile range): 0.83 (0.75–0.96) vs 1.04 (0.89–1.33) mg/kg/d, P = 0.001], whereas the clinical remission rates did not differ between groups (P = 0.88). Conclusions IBD patients with R139C heterozygote are highly susceptible to AZA-induced myelotoxicity at an escalated dose of 50 mg/d. Thus, they may require a smaller dose increase after a starting dose of 25 mg/d. The final target dose of these patients could be set lower than that of the wild genotypes without compromising efficacy.

USTEKINUMAB FOR CHRONIC GRANULOMATOUS DISEASE-ASSOCIATED INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S59-S59
Author(s):  
Sumona Bhattacharya ◽  
Beatriz Marciano ◽  
Harry Malech ◽  
Steven Holland ◽  
Suk See De Ravin ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Chronic Granulomatous Disease ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Colonic Disease ◽  
Cell Transplant ◽  
Granulomatous Disease ◽  
Efficacy And Safety ◽  
Serious Infections ◽  
Inflammatory Bowel

Abstract Introduction Chronic granulomatous disease (CGD) is a rare immunodeficiency caused by mutations in the NADPH oxidase complex. Dysregulated immune function may cause inflammatory bowel disease (IBD). Patients with CGD-associated IBD may not respond to or may develop serious infections as a result of traditional IBD therapies such as vedolizumab and infliximab. Ustekinumab is approved for use in Crohn’s disease and ulcerative colitis however there is scarce data on its efficacy and safety in CGD. Aims To evaluate the efficacy and safety of ustekinumab for CGD-associated IBD. Methods A retrospective chart review was conducted on CGD patients followed at a single center who had consented to participate in a natural history study. Clinical, laboratory, and endoscopic data were extracted in those that had received ustekinumab for IBD. Results Eight patients were found. Four were male and four were female. Five were white, one was Asian, one was black, and one was mixed race. Median age at diagnosis of CGD was 3 years (IQR 8) and of IBD was 15.5 years (IQR 20). Median age at initiation of ustekinumab was 27.5 years (IQR 14) and median duration on ustekinumab was 10 months (IQR 7). Six had colonic disease, two had ileocolonic disease, and six had perianal disease. Six failed other biologics (n=5 for vedolizumab, n=1 for infliximab, n=1 for adalimumab). Six patients symptomatically improved whereas two had no improvement. Changes in hemoglobin and C-reactive protein were equivocal. Three patients had improved endoscopic findings, two had unimproved findings, and three patients lacked this data. Overall, four patients achieved clinical remission. However, none of the five patients with endoscopic reevaluation achieved endoscopic remission. Three patients discontinued therapy due to lack of response: two required surgery and one underwent stem cell transplant. Fungal pneumonia (n=2), otitis media (n=1), oral herpes simplex virus 1 (n=1), and viral gastroenteritis (n=1) were reported. One infusion reaction occurred. Discussion In our cohort of eight patients with CGD-associated IBD receiving ustekinumab, results were mixed with four patients experiencing some degree of clinical or endoscopic improvement including four who achieved clinical remission. Multiple CGD-related variables may account for the mixed laboratory findings. Four of the five patients with endoscopic reevaluation had pre-existing strictures that would be unlikely to reverse with medical therapy alone. Of these, two had otherwise resolved endoscopic inflammation. Only two patients had no endoscopic improvement. Two serious infections occurred however CGD confers increased infectious susceptibility and no infections lead to discontinuation of therapy. Given these promising results, further formalized study of ustekinumab in CGD-associated IBD is needed.

Malnutrition and sarcopenia are prevalent among inflammatory bowel disease patients with clinical remission

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Nalan Gülşen Ünal ◽  
Nevin Oruç ◽  
Okşan Tomey ◽  
Ahmet Ömer Özütemiz
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Inflammatory Bowel

scholarly journals P837 Changes in the intestinal microbiota of patients with inflammatory bowel disease during an 8-week infliximab infusion cycle

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S649-S649
Author(s):  
G Seong ◽  
J H Song ◽  
J Shin ◽  
S M Kong ◽  
E R Kim ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Species Richness ◽  
Maintenance Therapy ◽  
Intestinal Microbiota ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Microbial Composition ◽  
Infliximab Infusion ◽  
Faecal Samples ◽  
Inflammatory Bowel

Abstract Background This study investigated changes in the intestinal microbiota during 8-week infliximab maintenance therapy in inflammatory bowel disease (IBD) patients with clinical remission. Microbial compositional differences were analysed according to the trough level of infliximab (TLI) and mucosal healing (MH) status. Methods 16S rRNA gene-based microbiome profiling was performed on 10 and 74 faecal samples from 10 healthy volunteers and 40 adult IBD patients, respectively. All enrolled IBD patients were in clinical remission during infliximab maintenance therapy. To identify changes in the intestinal microbiota, faecal sampling occurred at 1–2 weeks (1W) and 7–8 weeks (7W) after infliximab infusion. TLI was measured by ELISA at 8 weeks immediately before the subsequent infusion; MH was evaluated by endoscopy within 3 months. Results No significant differences were found in microbial composition, species richness, and diversity indices between 1W and 7W samples or in microbial composition and diversity between healthy volunteer and 1W or 7W samples. However, 7W faecal samples from the patients with TLI≥5 μg/ml showed increased species richness compared with TLI<5 μg/ml, and patients with MH showed increased species diversity compared with non-MH. Beta-diversity analysis showed clustering between samples in the MH and non-MH groups. LefSe analysis identified differential expression of Faecalibacterium prausnitzii group between TLI < 5 μg/ml and TLI ≥ 5 μg/ml and MH and non-MH groups. Conclusion There were no significant changes in the intestinal microbiota during an 8-week infliximab infusion cycle in IBD patients with clinical remission; however, microbial composition, species richness, and diversity were associated with TLI and MH status.

scholarly journals P378 Mucosal healing is achieved in most of the inflammatory bowel disease patients in clinical remission with vedolizumab: a real-life single-centre experience

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S355-S355
Author(s):  
M I Calvo Moya ◽  
I Omella Usieto ◽  
M I Vera Mendoza ◽  
V Matallana Royo ◽  
I Gonzalez Partida ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Practice ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Real Life ◽  
Mucosal Healing ◽  
Surveillance Colonoscopy ◽  
Previously Treated ◽  
Inflammatory Bowel

Abstract Background Current therapeutic goals in inflammatory bowel disease (IBD) include not only the mere absence of symptoms but also the resolution of endoscopic lesions, so-called mucosal healing (MH), which has been related to better outcomes. Data regarding the achievement of MH with vedolizumab (VDZ) in real-life clinical practice is still scarce. Methods Retrospective cohort study was carried out in a tertiary hospital between January 2015 and April 2019 including patients with a basal colonoscopy showing activity and who achieved clinical remission under treatment with VDZ, defined by partial Mayo score <2 for ulcerative colitis (UC) and Harvey–Bradshaw Index score (HBI) <4 for Crohn’s disease (CD). Surveillance colonoscopy was performed along with the follow-up according to clinical practice. In UC patients, MH was defined as Mayo Endoscopic Subscore (MES) = 0; the endoscopic response was defined by a decrease in MES ≥1 point. In CD, MH was defined by achievement SES-CD = 0–3 or Rutgeerts index i0; the endoscopic response was defined by a decrease of SES-CD of 50% or Rutgeerts index <i2 with at least 1 point of decease compared with baseline. Results In total, 118 patients treated with VDZ were analysed, but only 45 met inclusion criteria with a median follow-up of 21 (IQR: 14–19) months. Surveillance colonoscopy was performed after a median time of 12 months (IQR:9–17) of treatment. MH achieved in 33/45 patients (73%): 17/23 CD patients (74%) and 16/22 UC patients (73%). The endoscopic response was achieved in 9 of the remaining 12 patients: 3/6 CD patients and 6/6 UC patients. Only 3 (7%) of patients included showed no endoscopic benefit at the time of surveillance endoscopy. In multivariate analysis, probability of not achieving MH was 75% in patients previously treated with immunosuppressants (ISS) (HR 0.25, 0.11–0.55 IC95; p = 0.001) and 60% in patients previously treated with anti-TNFα (HR 0.40, 0.18–0.90 95% CI; p = 0.026). Type of IBD, concomitant ISS, corticosteroid use at induction, baseline endoscopy score or duration of disease before VDZ treatment were not associated with the achievement of MH. Conclusion In our experience, most of the patients who achieve clinical remission with VDZ also achieve MH. Refractory patients were less likely to achieve MH despite having achieved clinical remission.

scholarly journals P545 Clinical outcomes following a switch from Remicade® to the biosimilar CT-P13 in inflammatory bowel disease patients in clinical remission: preliminary results

2017 ◽  
Vol 11 (suppl_1) ◽  
pp. S357-S358
Author(s):  
L.N. Guerrero Puente ◽  
E. Iglesias Flores ◽  
J.M. Benítez Cantero ◽  
M.J. Cárdenas Aranzana ◽  
R. Medina Medina ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Outcomes ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Preliminary Results ◽  
Inflammatory Bowel
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