Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn's disease

Akobeng, Anthony K; Gardener, Elizabeth

doi:10.1002/14651858.cd003715.pub2

Cited by 123 publications

(110 citation statements)

References 31 publications

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“…Their efficacy in the treatment of Crohn's disease has become somewhat more controversial [110,[351][352][353][354]. These agents have a long history of clinical use and have been extensively studied in clinical trials for both ulcerative colitis [355,356] and Crohn's disease [357,358]. Sulfasalazine, the prototype aminosalicylate formulation, was developed with the concept of providing both an antibacterial (sulfapyridine) and antiinflammatory (5-aminosalicylic acid, mesalamine, mesalazine) agent into the connective tissues [359].…”

Section: Aminosalicylatesmentioning

confidence: 99%

“…Although sulfasalazine has been commonly used to prevent relapse for patients with quiescent Crohn's disease, neither the National Cooperative Crohn's Disease Study nor the European Cooperative Crohn's Disease Study demonstrated maintenance benefits at (low) dosages of 1-3 g/day. While one trial utilizing a 3 g/day dosage of sulfasalazine demonstrated efficacy at reducing the likelihood of postoperative clinical recurrence [409] there remains little evidence of a maintenance benefit after medically-induced clinical remissions [358].…”

Section: Aminosalicylates In Crohn's Disease Mild To Moderate Active mentioning

confidence: 99%

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Inflammatory Bowel Disease

Stenson

Hanauer

Cohen

2008

Textbook of Gastroenterology

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In the US, H. pylori vacA shows allelic variation in the signal sequence (which may be type sla, slb or s2) and the mid-region (type ml or m2). Previous PCR-based vacA mid-region typing classified most, but not all, Asian and South American strains tested as ml or m2. We now sought to investigate vacA mid-region diversity further.MotlmodL We studied 13 Japanese, 6 Chinese, 9 Thai, and 8 Peruvian H. pylori isolates. cagA was identified by colony hybridisation (CH), vacA signal sequence was typed by PCR, and vacA mid-region was typed proximally by CH and distally by PCR. Sections of the vacA mid-region from 8 strains were PCR-amplified, sequenced, and compared with known sequences from 8 other strains.Rcuts Of the 36 Asian and South American strains studied, 35 were cagA+ (the cagA-was Peruvian) and 35 were vacA sla (1 cagA + Peruvian was slb). vacA mid-regions from the 13 Japanese strains were not PCR-amplified by ml or m2-specific primers, but hybridised weakly with an ml probe. Sequence analysis of vacA from 1 Japanese strain revealed 91% nucleotide identity with the ml probe but only 71% identity with the m2 probe. The previously equivocal Thai and Peruvian strains also had ml-like mid-region sequences. A Chinese strain was ml in the proximal mid-region and m2 distally, showing a clear crossover site. Final mid-region types were: Japanese, all 13 ml; Chinese, 1 ml, 1 ml/m2, 4 m2; Thai, 3 ml, 6 m2; Peruvian 4 ml, 4 m2. Distal mid-region sequences of 16 strains, compared over 294 bp, clustered into 2 groups, ml and m2. Nucleotide identity between ml and m2 strains ranged from 73-78%. Within groups, m2 strains were less diverse than ml strains (m2 range 94-99.7%, ml 88-99.3%, p<0.001). Sequence analysis of 7 ml and 3 m2 strains over 1.1kb proximally showed maintenance of clustering outside the 294bp region C duions These Asian and South American strains are similar in terms of cagA status and vacA sla genotype, but fall into 2 vacA midregion groups. ml sequences are more diverse than m2, and thus may be phylogenetically older. The vacA sequence of 1 Chinese strain suggests recombination in vivo between ml and m2 alleles. Introduction: H.pylori antimicrobial susceptibility is an important determinant ofthe efficacy of eradication therapies'. The prevalence of antimicrobial resistance varies within the UK and may increase given the increased use of eradication therapy. This multicentre study assesses the prevalence and possible associations ofH.pylon antimicrobial resistance. Methods: H.pylon was isolated from antral biopsies of patients undergoing routine endoscopy and cultured according to standard microbiological methods. Antimicrobial resistance was determined using "E-tests" or disc tests (tinidazole only) with breakpoints defined by previous studies. Results: H.pyloni was isolated from 32% (1222/3823) of patients and antimicrobial susceptibility determined in 90% (1077/1222) Previous case-control studies of IBD have used hospital or community derived controls. There are obvious inherent biases in both metho...

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Section: Aminosalicylatesmentioning

confidence: 99%

Section: Aminosalicylates In Crohn's Disease Mild To Moderate Active mentioning

confidence: 99%

Inflammatory Bowel Disease

Stenson

Hanauer

Cohen

2008

Textbook of Gastroenterology

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“…As obvious from Cochrane reviews and meta-analyses, the benefit of sulfasalazine and 5-aminosalicylic acid (5-ASA) preparations in uncomplicated CD is quite limited [2,3,4]. In a meta-analysis of three double-blind randomized studies on the role of 5-ASA in the treatment of active CD, 4 g/day 5-ASA was superior to placebo in reducing the Crohn's disease activity index (CDAI); however, the clinical effect was not convincing [4,5].…”

Section: What Does ‘Step Up' Mean For Crohn's Disease Therapy?mentioning

confidence: 99%

Top-Down or Step-Up Treatment in Crohn's Disease?

Rogler¹

2013

Dig Dis

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In recent years, a change in the treatment goals for patients with Crohn's disease (CD) has come under intense discussion. Whereas 10 years ago treatment was initiated mainly in reaction to acute flares of the disease aimed to improve clinical symptoms, the focus now has changed to the prevention of damage to the intestinal wall. The prevention of structural damage by achievement of ‘mucosal healing', however, is associated with the more ‘aggressive' treatment and an earlier use of immunosuppressants and biologicals. The use of immunosuppressants and biologicals especially in patients with CD has decreased the rates of surgery and hospitalizations, indicating that there is a group of patients definitely profiting from such an early use of immunosuppressive treatment. In this group of patients, the benefits outweigh the disadvantages of immunosuppression: the increased risk of severe infections. However, it remains questionable whether this improvement can only be achieved by completely reversing established treatment strategies. The dispute has been condensed to the questions whether ‘top-down' (e.g. start with a combination of biological and immunosuppressant and ‘de-escalate' if possible) or ‘step-up' treatment (e.g. start with topical steroids, step up to systemic steroid, go to immunosuppression and biologicals if necessary) may be better. In general, in an upcoming era of individualized and personalized medicine, a ‘one-size-fits-all' approach does not appear to be desirable. CD patients definitely should not be undertreated (which is still frequently the case) or remain on steroid treatment (which is inappropriate); however, overtreatment (putting patients at risk of side effects without benefit) is against a fundamental principle of medicine: nihil nocere (do no harm).

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“…There is a growing body of evidence that shows that 5-aminosalicylic acid derivatives are not effective in CD with the exception of sulfasalazine in colonic CD [11,12], however they are still frequently used as part of “step-up” care. In this treatment approach, corticosteroids are considered the cornerstone of induction therapy for patients with severely active CD.…”

Section: Introductionmentioning

confidence: 99%

Risk Stratification of Patients with Crohn's Disease: A Retrospective Analysis of Clinical Decision Making and Its Impact on Long-Term Outcome

Mosli

Sabbahi

Alyousef

et al. 2017

Dig Dis

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Background and Aims: Complications such as need for bowel resections and hospitalization due to Crohn's disease (CD) occur when disease activity persists due to ineffective therapy. Certain “high-risk” features require an early introduction of anti-tumor necrosis factor-α therapy to prevent such complications. We aim to evaluate the prevalence of “high-risk” features among a cohort of patients with CD and examine the association between discordance of early therapy with baseline risk stratification and disease outcome. Patients and Methods: All adult patients with CD were retrospectively identified and their medical records were reviewed. Clinical, endoscopic, laboratory, and radiological data were collected. Patients were divided into “low” and “high” risk groups according to the presence or absence of penetrating disease, perianal involvement, foregut involvement, extensive disease seen on endoscopy or cross-sectional imaging, young age at the time of diagnosis (<40), persistent cigarette smoking and frequent early requirements for corticosteroid therapy. Initial treatment selection and treatment approach (“step-up” vs. “accelerated step-up” vs. “top-down”) within 6 months of diagnosis were recorded. Rates of CD-related bowel resections and hospitalization within 5 years of diagnosis were calculated. Logistic regression analysis was used to examine the association between “discordance” of early treatment selections and risk stratification categories with outcomes. Results: Eighty-five CD patients were included. The median age and duration of disease were 25 (interquartile range [IQR] 19-32) and 5 (IQR 4-6) years, respectively. Sixty five percent were females and 66% were native Saudis. Smoking was reported in 12% of patients and perianal disease in 18%. “High-risk” features were identified in 43 (51%) patients, of which only 6 (14%) were treated with “top-down” therapy and 7 (16%) with “accelerated step-up” care. The risk of requiring a bowel resection, and hospitalization was higher for “high-risk” patients compared to “low-risk” patients (risk ratio [RR] 13.67, 95% CI 1.88-99.41; p = 0.003, and RR 1.86, 95% CI 0.03-0.43; p = 0.0312, respectively). “Discordance” occurred in 34% of cases. Bowel resection was required in 15/85 (18%) patients and 32/85 (38%) required at least one hospitalization within 5 years of diagnosis. Logistic regression analysis identified a statistically significant association between “discordance” and need for bowel resections (OR 6.50, 95% CI 1.59-26.27, p = 0.009), and hospitalizations (OR 3.01, 95% CI 1.08-8.39, p = 0.035) within 5 years of diagnosis. Conclusions: “Discordance” between patient risk-profile and treatment selection early in the course of CD has a significant impact on disease outcome, specifically need for bowel resection and hospitalization, which are more likely to occur in the presence of “high-risk” features. Early identification of “high-risk” features could help prevent long-term complications.

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Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn's disease

Abstract: We found no evidence in this review to suggest that 5-ASA preparations are superior to placebo for the maintenance of medically-induced remission in patients with Crohn's disease. Therefore it appears that additional randomised trials of this regime are not justified.

Cited by 123 publications

References 31 publications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Top-Down or Step-Up Treatment in Crohn's Disease?

Risk Stratification of Patients with Crohn's Disease: A Retrospective Analysis of Clinical Decision Making and Its Impact on Long-Term Outcome

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