Inflammatory bowel disease​ (IBD): Further reading and references for health professionals

Reference

Summary

Gastroenterological Society of Australia (GESA)

Clinical Update for General Practitioners and Physicians, Inflammatory Bowel Disease (Updated 2018)

Provides a general guide to appropriate  diagnosis and management of IBD.  

Primarily intended  for Australian clinicians, this update complements recent consensus statements published by the European Crohn's and Colitis Organisation (ECCO), the British Society of Gastroenterology and other international organisations. 

European Crohn’s and Colitis Organisation (ECCO)

ECCO guidelines on therapeutics in Crohn’s disease: Medical treatment 

International recommendations for the management of Crohn’s disease.

European Crohn’s and Colitis Organisation (ECCO)

Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: Current management 

International recommendations for the management of ulcerative colitis.

Reference

Summary

Gastroenterological Society of Australia (GESA)

Clinical update for general practitioners and physicians, inflammatory bowel disease (updated 2018)

Section  4.3.1.1 5-ASA Therapy:  Mesalazine  preparations.

5-ASA can be given orally and rectally.  A combination of both  can achieve remission more quickly than oral therapy alone. For the treatment of distal disease, rectal 5-ASA therapy is  at least as effective as rectal steroids. 

Marshall et al, 2010

Rectal 5-aminosalicylic acid for induction of remission in ulcerative colitis

A systematic review including 38 randomised trials, evaluated the efficacy of rectal 5-ASA for treating active distal UC. Rectal 5-ASA was superior to placebo for  inducing:   

• symptomatic  remission;  pooled odds ratio [OR]: 8.3 (8 trials, 95% confidence interval [CI] 4.28 to 16.12; p < 0.00001), 
• endoscopic  remission;  OR:5.3 (7 trials, 95% CI 3.15 to 8.92; p < 0.00001), and 
• histological improvement and remission; OR:6.3 (5 trials, 95% CI 2.74 to 14.40; p < 0.0001).   

Rectal 5-ASA was superior to rectal corticosteroids for symptomatic improvement and remission.   

Authors’ conclusions: rectal 5-ASA should be considered a first-line therapy for patients with mild to moderately active distal UC.   

Marteau et al, 2005

Combined oral and enema treatment with  Pentasa  (mesalazine) is superior to oral therapy alone in patients with extensive mild/moderate active ulcerative colitis: a randomised, double blind,  placebo controlled  study

A randomised  double blind  study in 127 patients with extensive mild/moderate active UC.   

Combination of oral and rectal  mesalazine  was more effective in achieving remission  at 8 weeks (64% (95% CI 50% to 76%)) than oral  mesalazine  alone  (43% (95% CI 28% to 58%;  p = 0.03) 

Reference

Summary

Lemaitre et al, 2017

Association Between between use of thiopurines or  tumor  necrosis factor antagonists alone or in combination and risk of lymphoma in patients  with  inflammatory bowel disease

Cohort study of over 189,000 patients with IBD to assess the risk of lymphoma associated with thiopurines and anti-TNF agents.   

Compared with unexposed patients, the risk of lymphoma was higher among those exposed to:

• thiopurine monotherapy (adjusted hazard ratio [aHR] 2.60; 95% CI 1.96 to 3.44; p < .001),
• anti-TNF monotherapy (aHR 2.41; 95% CI 1.60 to 3.64; p < .001), or
• combination therapy (aHR 6.11; 95% CI 3.46 to 10.8; p < .001).   

The risk of lymphoma was higher for patients exposed to combination therapy vs those exposed to thiopurine monotherapy (aHR 2.35; 95% CI 1.31 to 4.22; p < .001) or anti-TNF monotherapy (aHR 2.53; 95% CI 1.35 to 4.77; p < .001).

Reference

Summary

Nielsen et al, 2020

Efficacy and safety of methotrexate in the management of inflammatory bowel disease: A systematic review and meta-analysis of randomized, controlled trials

Systematic review and  meta-analysis  of 10 randomised control trials (n = 767) of methotrexate (MTX) for induction and maintenance of remission in IBD.  Authors concluded that:

• Parenteral MTX is efficacious for maintenance of remission in Crohn disease.
• MTX monotherapy is not effective for induction of remission in Crohn disease.
• In ulcerative colitis, MTX is not shown to be effective for induction or maintenance of remission.

Reference

Summary

Gastroenterological Society of Australia (GESA)

Clinical update for general practitioners and physicians, inflammatory bowel disease (updated 2018)

Section 5.1.3 Faecal Calprotectin in Established IBD

Faecal calprotectin is a non-invasive biomarker of disease activity in IBD. Data support its utility in monitoring for sub-clinical disease activity and relapse.

Reference

Summary

Gastroenterological Society of Australia (GESA)

Clinical update for general practitioners and physicians, inflammatory bowel disease (updated 2018)

Section  4.9.1 Thiopurine Metabolite Testing 

Thiopurine metabolite testing can be used to optimise thiopurine dosing and identify ‘shunters’ who might benefit from the addition of allopurinol in combination with a reduced dose of thiopurine. This testing can also be used to identify non-adherence and to minimise the risk of hepatotoxicity. 

Reference

Summary

Mitrev et al, 2017

Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases

Evidence-based consensus statements from a committee of 25 Australian and international experts.

For anti-TNF agents, therapeutic drug monitoring (TDM) should be performed:

• upon treatment failure,
• following successful induction,
• when contemplating a drug holiday and
• periodically in clinical remission only when results would change management.   

Further data are required prior to recommending TDM for non-anti-TNF biological agents. 

Reference

Summary

Jorgensen et al, 2017

Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial

Non-inferiority, double-blind trial including 482 patients on stable treatment with infliximab originator. Patients were randomised in a 1:1 ratio to continue infliximab originator or switch to biosimilar infliximab treatment, with unchanged dosing regimen. Patients were being treated for a range of conditions – 55 (32%) had Crohn disease, 93 (19%) had ulcerative colitis, 91 (19%) had spondyloarthritis, 77 (16%) had rheumatoid arthritis, 30 (6%) had psoriatic arthritis, and 35 (7%) had chronic plaque psoriasis.

• Over 52 weeks, disease worsening occurred in 53 (26%) patients in the infliximab originator group and 61 (30%) patients in the biosimilar infliximab group.
• The frequency of adverse events was similar between groups (for serious adverse events, 24 (10%) for infliximab originator vs 21(9%) for biosimilar infliximab; for overall adverse events, 168 (70%) vs 164 (68%); and for adverse events leading to discontinuation, 9 (4%) vs 8 (3%), respectively.

Haifer et al, 2021

Switching Australian patients with moderate to severe inflammatory bowel disease from originator to biosimilar infliximab: a multicentre, parallel cohort study

Prospective, open label, multicentre, parallel cohort, non-inferiority study in 7 Australian hospitals  over 48 weeks. Examining  non-medical switching of originator and biosimilar infliximab in 345 patients with IBD (232 with CD)

• Deterioration of clinical condition was experienced by similar numbers of patients in the originator (7%) and biosimilar (8%) groups.
• Switching clinically stable patients with IBD from originator to biosimilar infliximab was safe and clinically non-inferior to continuing treatment with originator infliximab.
• Serious adverse events leading to infliximab discontinuation were infrequent in both the switch (6, 3%) and control (6, 4%) groups.  Infliximab treatment persistence over 48 weeks was similar for the 2 groups.

Reference

Summary

Gastroenterological Society of Australia (GESA)

Clinical update for general practitioners and physicians, inflammatory bowel disease (updated 2018)

Section  4.3.1.2 Corticosteroids

Corticosteroids are used for moderate-to-severe active IBD. They suppress  inflammation and  provide  rapid relief of symptoms. However, significant side-effects should exclude recurrent or long-term use. Corticosteroids are not effective for maintenance therapy.