Azathioprine in the therapy of paediatric inflammatory bowel disease – part I: treatment indications, dosing and thiopurine-related adverse events

2021 ◽  
Vol 75 (6) ◽  
pp. 500-507
Author(s):  
Kristýna Pospíšilová ◽  
Jiří Bronský
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Bowel Disease ◽  
Maintenance Phase ◽  
Treatment Indications ◽  
Number Of Patients ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Keywords Crohn's Disease ◽  
Available Information

Background: Thiopurines (in Europe mainly azathioprine) are widely used in the treatment of inflammatory bowel diseases in children. Due to a prolonged time until the onset of therapeutic effect, those drugs are aimed to be used in the maintenance phase of the therapy rather than for induction of remission. Thiopurines are sometimes used in combination therapy (with aminosalicylates or biological treatment agents). The adverse events of these drugs occur as often as in 15–40% cases and may lead to treatment cessation in a significant number of patients. Aims: To overview available information on (mainly) children suffering from inflammatory bowel disease. Conclusion: Genetic examination accompanied with laboratory monitoring of blood count parameters (specifically at the beginning of therapy) and biochemistry can help prevent some of the severe adverse events. Keywords Crohn’s disease, ulcerative colitis, pediatrie, merkaptopurin, thiopuriny

scholarly journals INFLAMMATORY BOWEL DISEASE CARE IN BRAZIL: HOW IT IS PERFORMED, OBSTACLES AND DEMANDS FROM THE PHYSICIANS’ PERSPECTIVE

2020 ◽  
Vol 57 (4) ◽  
pp. 416-427
Author(s):  
Eduardo Garcia VILELA ◽  
Henrique Carvalho ROCHA ◽  
Antônio Carlos MORAES ◽  
Genoile Oliveira SANTANA ◽  
José Miguel PARENTE ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Structural Damage ◽  
Federal District ◽  
New Drugs ◽  
Double Balloon Enteroscopy ◽  
The North ◽  
Number Of Patients ◽  
Bowel Diseases ◽  
Inflammatory Bowel

ABSTRACT BACKGROUND: Inflammatory bowel diseases (IBD) are chronic inflammatory affections of recurrent nature whose incidence and prevalence rates have increased, including in Brazil. In long term, they are responsible for structural damage that impacts quality of life, morbidity and mortality of patients. OBJECTIVE: To describe the profile of physicians who treat IBD patients as well as the characteristics of IBD care, unmet demands and difficulties. METHODS: A questionnaire containing 17 items was prepared and sent to 286 physicians from 101 Brazilian cities across 21 states and the Federal District, selected from the register of the State Commission of the “Study Group of Inflammatory Bowel Disease of Brazil” (GEDIIB). RESULTS: The majority of the physicians who answered the questionnaire were gastroenterologists and colorectal surgeons. More than 60% had up to 20 years of experience in the specialty and 53.14% worked at three or more locations. Difficulties in accessing or releasing medicines were evident in this questionnaire, as was referrals to allied healthy professionals working in IBD-related fields. More than 75% of physicians reported difficulties in performing double-balloon enteroscopy and capsule endoscopy, and 67.8% reported difficulties in measuring calprotectin. With regard to the number of patients seen by each physician, it was shown that patients do not concentrate under the responsibility of few doctors. Infliximab and adalimumab were the most commonly used biological medicines and there was a higher prescription of 5-ASA derivatives for ulcerative colitis than for Crohn’s disease. Steroids were prescribed to a smaller proportion of patients in both diseases. The topics “biological therapy failure” and “new drugs” were reported as those with higher priority for discussion in medical congresses. In relation to possible differences among the country’s regions, physicians from the North region reported greater difficulty in accessing complementary exams while those from the Northeast region indicated greater difficulty in accessing or releasing medicines. CONCLUSION: The data obtained through this study demonstrate the profile of specialized medical care in IBD and are a useful tool for the implementation of government policies and for the Brazilian society as a whole.

scholarly journals Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis of Results from Phase 2/3 Studies

2020 ◽  
Author(s):  
William J Sandborn ◽  
Brian G Feagan ◽  
Silvio Danese ◽  
Christopher D O’Brien ◽  
Elyssa Ott ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Bowel Disease ◽  
Safety Profile ◽  
Phase 2 ◽  
Phase 3 ◽  
Number Of Patients ◽  
Serious Infections ◽  
Inflammatory Bowel

Abstract Background Ustekinumab is currently approved globally in Crohn’s disease (CD) and psoriatic diseases. Recent phase 3 data demonstrate safety/efficacy in ulcerative colitis (UC). Crohn’s disease and UC phase 3 programs had similar study designs, facilitating integrated safety analyses. Methods Data from 6 ustekinumab phase 2/3 CD and UC studies were pooled, and safety was evaluated through 1 year. Patients received 1 placebo or ustekinumab (generally 130 mg or ~6 mg/kg) intravenous induction, then subcutaneous (90 mg) maintenance every 8/12 weeks. Analyses incorporated all patients who received ≥1 ustekinumab dose. Safety outcomes are presented as percentages of patients (induction) and as number of patients with events per 100 patient-years of follow-up (through 1 year). For key safety events, 95% confidence intervals (CIs) are provided, as appropriate. Hazard ratios with 95% CIs from time-to-event analyses for serious adverse events and serious infections were also performed. Results Through 1 year, 2574 patients received ustekinumab (1733 patient-years of follow-up). The number of patients with adverse events per 100 patient-years (placebo 165.99 [95% CI, 155.81–176.67] vs ustekinumab 118.32 [95% CI, 113.25–123.55]), serious AEs (27.50 [95% CI, 23.45–32.04] vs 21.23 [95% CI, 19.12–23.51]), infections (80.31 [95% CI, 73.28–87.84] vs 64.32 [95% CI, 60.60–68.21]), serious infections (5.53 [95% CI, 3.81–7.77] vs 5.02 [95% CI, 4.02–6.19]), and malignancies excluding nonmelanoma skin cancer (0.17 [95% CI, 0.00–0.93] vs 0.40 [95% CI, 0.16–0.83]) were similar between placebo and ustekinumab. Conclusions The safety profile of ustekinumab across the pooled inflammatory bowel disease population through 1 year was favorable and generally comparable to placebo. These data are consistent with the established safety profile of ustekinumab across indications. ClinicalTrials.gov numbers NCT00265122; NCT00771667; NCT01369329; NCT01369342; NCT01369355; NCT02407236.

scholarly journals Risk of Infections of Biological Therapies with Accent on Inflammatory Bowel Disease

2014 ◽  
Vol 17 (4) ◽  
pp. 485 ◽  
Author(s):  
Radu M Nanau ◽  
Lawrence E Cohen ◽  
Manuela G Neuman
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Bowel Disease ◽  
De Novo ◽  
Current Knowledge ◽  
Certolizumab Pegol ◽  
Biological Therapies ◽  
Number Of Patients ◽  
Inflammatory Bowel ◽  
Integrin Antagonists

Background: Biological therapies using anti-tumor necrosis factor (TNF)-α agents have an important impact in the treatment of inflammatory bowel disease, rheumatoid arthritis, psoriasis, and other inflammatory conditions. However, a significant number of patients lose their response to these medications over time. Clinical trials have demonstrated that antibodies against anti-TNF agents may impact treatment response and increase the risk of infusion reactions. Of concern is also the possibility of developing adverse events induced by anti-TNF agents. The purpose of the present systematic review is to describe the current knowledge on the risk of infections associated with anti-TNF agents antagonists, as well as integrin antagonists. We also intend to describe case reports of these adverse events in inflammatory bowel disease patients. Methods: Currently approved anti-TNF biologicals in IBD include the monoclonal antibodies infliximab, adalimumab, certolizumab pegol and golimumab. Integrin antagonists include natalizumab, etrolizumab and vedolizumab. Results: The most frequently-reported adverse events of these biologicals were infections, and these are described in detail in this study. Discussion: Most adverse events are due to the failure of host immunological control, which involves de novo infection, or reactivation of latent bacterial or viral infection, often with a different expression of disease. Conclusion: Risk assessment in individuals undergoing treatment with biologicals represents a step towards achieving treatment personalization to identify those patients that will safely benefit from this therapeutic approach. Patients and physicians must be alert for anti-TNF agents and anti-integrin medication as potential causes of drug-induced infections and monitor the therapies. Personalizing therapeutic vigilance promises to optimize benefits while minimizing infections.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Localization and Activity of Inflammatory Bowel Disease Using 111ln Leukocyte Imaging

1988 ◽  
Vol 27 (03) ◽  
pp. 83-86 ◽  
Author(s):  
B. Briele ◽  
F. Wolf ◽  
H. J. Biersack ◽  
F. F. Knapp ◽  
A. Hotze
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Cell Uptake ◽  
Disease Extent ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Leukocyte Imaging

A prospective study was initiated to compare the clinically proven results concerning localization/extent and activity of inflammatory bowel diseases with those of 111ln-oxine leukocyte imaging. All patients studied were completely examined with barium enema x-ray, clinical and laboratory investigations, and endoscopy with histopathology. A total of 31 leukocyte scans were performed in 15 patients (12 with Crohn’s disease, 3 with ulcerative colitis). The scans were graded by comparing the cell uptake of a lesion (when present) and a bone marrow area providing a count ratio (CR). The inflammatory lesions were correctly localized on 26 leukocyte scans, and in 21 scans the scintigraphically estimated extent of disease was identical to endoscopy. In 5 cases the disease extent was underestimated, 4 scans in patients with relapse of Crohn’s disease were falsely negative, and in one patient with remission truly negative. The scintigraphically assessed disease activity was also in a good agreement with clinical disease activity based on histopathology in all cases. We conclude that leukocyte imaging provides valuable information about localization and activity of inflammatory bowel disease.

scholarly journals Different renal manifestations associated with very early onset pediatric inflammatory bowel disease: case report and review of literature

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
A. Angeletti ◽  
S. Arrigo ◽  
A. Madeo ◽  
M. Molteni ◽  
E. Vietti ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Interstitial Nephritis ◽  
Inflammatory Bowel Diseases ◽  
Bowel Disease ◽  
Early Onset ◽  
Renal Involvement ◽  
Granulomatous Interstitial Nephritis ◽  
Disease Case ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Background Inflammatory bowel diseases are characterized by chronic inflammation of the gastrointestinal tract. In particular, Crohn disease and ulcerative colitis represent the two most common types of clinical manifestations. Extraintestinal manifestations of inflammatory bowel diseases represent a common complications, probably reflecting the systemic inflammation. Renal involvement is reported in 4–23% of cases. However, available data are limited to few case series and retrospective analysis, therefore the real impact of renal involvement is not well defined. Case presentation We report the case of a 10-years old male affected by very early onset unclassified-Inflammatory bowel diseases since he was 1-year old, presenting with a flare of inflammatory bowel diseases associated with acute kidney injury due to granulomatous interstitial nephritis. Of interest, at 7-year-old, he was treated for IgA nephropathy. To our knowledge, no previous reports have described a relapse of renal manifestation in inflammatory bowel diseases, characterized by two different clinical and histological phenotypes. Conclusions The link between the onset of kidney injuries with flares of intestinal inflammation suggest that nephritis maybe considered an extra-intestinal manifestation correlated with active inflammatory bowel disease. However, if granulomatous interstitial nephritis represents a cell-mediated hypersensitivity reaction than a true extraintestinal manifestation of inflammatory bowel diseases is still not clarified. We suggest as these renal manifestations here described may be interpreted as extraintestinal disorder and also considered as systemic signal of under treatment of the intestinal disease.

Expanding Contributions of Monogenic Very Early Onset Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Jodie Ouahed
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Current Issue ◽  
Epithelial Barrier ◽  
Mevalonate Kinase Deficiency ◽  
Bowel Diseases ◽  
Life Threatening ◽  
Mucosal Homeostasis ◽  
Inflammatory Bowel

Abstract Currently over 70 genes known to be causative in very early onset inflammatory bowel disease (VEOIBD) have been identified. In the current issue of Inflammatory Bowel Diseases, 2 articles describing monogenetic forms of VEOIBD are highlighted. One describes a patient with life-threatening VEOIBD and a mutation in ITGA6, illustrating the importance of the epithelial barrier in maintaining mucosal homeostasis. The other describes the presentation and management of 10 patients with VEOIBD secondary to damaging mutations in MVK, resulting in mevalonate kinase deficiency. Though most monogenic causes of VEOIBD remain “private,” understanding the different categories of pathways affected in children with VEOIBD is critical and has already resulted in invaluable insight in the management of patients with VEOIBD and may hold strong implications for the care of IBD overall.

The SPOSIB SB2 Sicilian Cohort: Safety and Effectiveness of Infliximab Biosimilar SB2 in Inflammatory Bowel Diseases, Including Multiple Switches

2020 ◽  
Author(s):  
Fabio Salvatore Macaluso ◽  
Walter Fries ◽  
Anna Viola ◽  
Andrea Centritto ◽  
Maria Cappello ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Tumor Necrosis ◽  
Prospective Observational Study ◽  
Cumulative Number ◽  
Serious Adverse Events ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Necrosis Factor

Abstract Background No data on the recently introduced infliximab (IFX) biosimilar SB2 in inflammatory bowel disease (IBD) are available. Methods The Sicilian Prospective Observational Study of Patients With IBD Treated With Infliximab Biosimilar SB2 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease. All consecutive IBD patients starting the IFX biosimilar SB2 from its introduction in Sicily (March 2018) to September 2019 (18 months) were enrolled. Results Two hundred seventy-six patients (Crohn disease: 49.3%, ulcerative colitis: 50.7%) were included: 127 (46.0%) were naïve to IFX and naïve to anti-tumor necrosis factor medications (anti-TNFs), 65 (23.5%) were naïve to IFX and previously exposed to anti-TNFs, 17 (6.2%) were switched from an IFX originator to SB2, 43 (15.6%) were switched from the biosimilar CT-P13 to SB2, and 24 (8.7%) were multiply switched (from IFX originator to CT-P13 to SB2). The cumulative number of infusions of SB2 was 1798, and the total follow-up time was 182.7 patient-years. Sixty-seven serious adverse events occurred in 57 patients (20.7%; incidence rate: 36.7 per 100 patient-year), and 31 of these events caused the withdrawal of the drug. The effectiveness after 8 weeks of treatment was evaluated in patients naïve to IFX (n = 192): 110 patients (57.3%) had steroid-free remission, while 56 patients had no response (29.2%). At the end of follow-up, 72 patients (26.1%) interrupted the treatment, without significant differences in treatment persistency estimations between the five groups (log-rank P = 0.15). Conclusions The safety and effectiveness of SB2 seem to be overall similar to those reported for the IFX originator and CT-P13.

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