Optimising care and dealing with complications in IBD patients

How to optimise care for inflammatory bowel disease (IBD) patients, from management to complications, was the focus of a dedicated two-speaker session during the 2024 Irish Society of Gastroenterology (ISG) Winter Meeting. The expert session, which took place in the Fitzpatrick Castle Hotel, Killiney, Co Dublin, on 21 November, was sponsored by Tillotts Pharma.

UC management

Prof Johan Burisch, Consultant Gastroenterologist, Copenhagen University Hospital, Hvidovre, Denmark, gave a detailed presentation on the management of ulcerative colitis (UC) flare in mild-to-moderate patients.

During his talk at the ISG Winter Meeting, Prof Burisch emphasised the need to “get the most out of established treatments for UC before we move on to newer therapies”, focusing on the use of 5-ASA (aminosalicylates) therapy specifically.

He outlined evidence-based strategies to consider for optimisation of 5-ASA therapy in UC patients, with key elements including individual dosing, treatment duration, adherence, and topical therapy.¹

Dosing optimisation

“Of course the first thing is to choose the right dose for the right patient,” Prof Burisch said, citing an American Gastroenterological Association (AGA) technical review (2019) of data on different induction doses of 5-ASA (≥2g vs <2g) and the induction of remission.²

“What it shows basically is if you choose any dose above 2g, this is better than choosing low-dose mesalazine. It is also what is summarised in most guidelines around the world.”

Furthermore, doses over 3g have also been shown to be superior efficacy-wise compared to low doses (<2g), Prof Burisch noted, citing further data from the review,² which showed mesalazine doses over 3g/day (RR, 0.81 [0.71-0.92]) and 2-3g/day (RR, 0.88 [0.79-0.99])
were superior to under 2g/day of mesalazine for induction of remission, with low heterogeneity.*

He then cited data from the ASCEND II³ and ASCEND III⁴ trials (randomised, double-blind, controlled trials which assessed the efficacy of 4.8g/day vs 2.4g/day of mesalazine in adults with active UC) confirming the efficacy of higher doses in different subgroups, including those who had tried other treatments.

As well as optimising the initiation dosage, the right maintenance dose is also very important in 5-ASA treatment for UC, Prof Burisch reminded delegates at the ISG Winter Meeting. The standard optimum dose for maintaining remission is between 2-3g/day of mesalazine, he said, quoting a systemic review and meta-analysis of trial data supporting this approach.⁵

He also quoted a Japanese study looking at 527 patients with UC who achieved remission on 4.8g/d 5-ASA treatment and what happened when they were switched to maintenance dosing (>3g/d vs <3g/d).⁶

“This is again something we need to consider when dealing with our patients. If it was difficult to get them into remission and we used higher doses, maybe we should keep them on higher doses for a longer time before going down in dosage,” he said, highlighting the importance of stratifying patients appropriately.

He quoted another study, which showed a reduction in the risk of flares with high-dose mesalazine compared to low-dose mesalazine in UC patients with low adherence, “which is something we should consider in clinical practice when dealing with patients with low adherence”.⁷

Topical therapy

Prof Burisch next discussed the role of topical therapy for induction of remission in UC⁸ and for prevention of relapse.⁹

“Combination of topical and oral mesalazine for maintenance of remission is better than low-dose oral mesalazine, as has been shown in several studies,” he said, summarising the findings.

Adherence

Medication adherence is a key issue to ensuring the best outcomes for UC patients on 5-ASA therapy, Prof Burisch emphasised.

Research has shown non-adherent patients have up to five times higher risk of relapse than those who take their medicine regularly, he said.¹⁰

Prof Burisch cited data which showed an overall 79 per cent rate of non-adherence with any 5-ASA after one year, with a substantial decrease in 5-ASA therapy adherence after just 30 days and after 90 days.¹¹ “This is something all of us who see these patients are familiar with,”
he remarked.

If patients are not taking their medication as prescribed, then drug effectiveness will obviously be impacted and the clinician may think it is not working for them and switch to another treatment unnecessarily, Prof Burisch stressed.

“We really need to address this issue. If you don’t address it and you do not have a good enough relationship with your patient where they feel comfortable enough to admit that they are not taking their medication, it makes it difficult to make the right decisions. You might move on [to a different medication] for the wrong reasons,” Prof Burisch told the Medical Independent.

In this regard, research also confirms the importance of consulting with patients about drug formulation and dosage frequency preferences to try to maximise adherence, he said.¹²

“Trial data shows that those patients who have a good understanding of their disease and a good relationship with their physician have better adherence,” Prof Burisch stated.¹³

Clostridioides difficile infection (CDI) and IBD

The second speaker in this session was Dr Tee Keat Teoh, Consultant Microbiologist, Public Health Laboratory and St James’s Hospital, Dublin, who addressed the risk of CDI in IBD.

He reminded the meeting that CDI is the leading cause of hospital-acquired infectious diarrhoea in adults, and is associated with significant morbidity, mortality, and costs.^15,16 CDI can lead to complications like severe colitis, toxic megacolon, and death.¹⁴

CDI normally develops in people who are already vulnerable, with key risk factors including previous antibiotic exposure, older age, a weakened immune system, recent hospital or nursing home admission, and previous history of CDI, Dr Teoh outlined.¹⁷

The literature shows that IBD patients have a five times increased risk of CDI compared to the general population, tend to do worse, and recurrent CDI risk is also significantly increased, especially in those aged below 50, he noted.¹⁸

Specifically, there is an increased incidence of CDI in UC, compared to Crohn’s disease.¹⁸ Colonic dysbiosis from colitis impairs resistance to bacterial colonisation, and immunosuppression may impair immune response to CDI, Dr Teoh explained, adding that about 8 per cent of IBD patients have asymptomatic toxigenic C.difficile.

Diagnosis of CDI in IBD patients is difficult, largely due to the symptom overlap of both conditions,¹⁸ and they also present differently (younger age, more often community onset, antibiotic exposure less likely),²⁰ Dr Teoh said.

Furthermore, CDI in IBD patients can lead to subsequent IBD flares, escalation of treatment, and poorer patient outcomes.²⁰

Currently, there is no international consensus guidance for specifically managing IBD patients with CDI, Dr Teoh pointed out.

General European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidance on managing CDI recommends fidaxomicin for first-line use in all patients with CDI, he noted.²¹ Metronidazole is no longer recommended as a first-line agent for CDI treatment by the aforementioned bodies in their latest guidance.

Dr Teoh also discussed the use of other treatments for CDI in IBD patients including faecal microbiota transplant, which while shown to be safe and effective is not yet easily accessible in Ireland.²²

In relation to prescribing IBD immunosuppressives during CDI diagnosis, Dr Teoh noted that the literature is sparse, but an AGA practice review says the decision should be individualised, but is positive towards continuation in uncomplicated CDI.²⁰

Concluding his talk, Dr Teoh recommended using a detailed algorithm for the diagnosis and treatment of CDI in IBD, published in Curr Opin Gastroenterol.¹⁸

*Not all mesalazine preparations are licensed for doses >3g/day for inducing remission. Please check individual product SmPCs.