Treatment of inflammatory bowel disease: Crohn's disease & ulcerative colitis

The treatment of inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis has improved significantly in recent years. Thanks to new treatment options, many patients can now lead an almost symptom-free life.

However, every disease is different - which is why it is important to tailor treatment to the individual. Dr. Stefan Schlosser, head of the IBD consultation at Vivomed - Gastroenterology and Hepatology Bern, explains what patients should look out for in IBD therapy, which treatment strategies are particularly effective and which mistakes can be avoided.

Whether classic medication, biologics or modern combination therapies - it is crucial that the therapy is tailored to personal needs and the course of the disease. Close support from experienced specialists helps to prevent relapses and improve quality of life in the long term.

Short & sweet: Important tips for inflammatory bowel disease (IBD)

use 5-ASA correctly: In ulcerative colitis, oral 5-ASA therapy should be dosed sufficiently high and - if possible - combined with local (topical) treatment.
Take fatigue seriously: Exhaustion (fatigue) occurs significantly more frequently in IBD patients than in healthy people - actively address this symptom.
Treat iron deficiency: In IBD, intravenous iron administration is preferred over oral supplements.
Surgery is not a failure: An ileocecal resection can be a sensible and effective treatment option.
Antibiotics with caution: Broad-spectrum penicillins can trigger IBD flare-ups and should only be used selectively.

5-ASA for ulcerative colitis - still the proven standard therapy
Mesalazine (5-acetylsalicylic acid, 5-ASA for short) remains the standard treatment for ulcerative colitis. Studies clearly show that a higher dosage can improve efficacy and accelerate the healing process.

One study showed that a double dose of 4.8 g per day led to a better improvement rate (72%) than the standard dose of 2.4 g per day (58%) - after just six weeks. Increasing the dose can therefore be particularly worthwhile during an acute flare-up.

The combination of oral and rectal 5-ASA therapy is even more effective. Response rates of up to 90 % can be achieved within six weeks, compared to around 60 % with rectal use alone and 40 % with oral use alone.

In the case of left-sided ulcerative colitis, the use of 5-ASA clysms or foams is recommended, which act as far as the left colonic flexure. An application time of around 20 minutes is important so that the medication can work optimally.

Biologics for Crohn's disease - modern therapies for a better quality of life
The treatment of Crohn's disease has made enormous progress in recent years. In addition to conventional medications, several biologics are now available that specifically intervene in the inflammatory processes in the intestine and thus enable a lasting remission.

The approved biologics for Crohn's disease include:
Infliximab, Adalimumab, Certolizumab, Risankizumab, Ustekinumab, Vedolizumab and Upadacitinib.

In so-called induction therapy - i.e. at the start of treatment - around 60% of patients respond to these modern active ingredients. Biologics are therefore a central component of today's Crohn's disease therapy.

Risankizumab shows particularly good results
In the Phase IIIb SEQUENCE study, risankizumab was compared directly with ustekinumab.
After 24 weeks, 58.6% of patients on risankizumab achieved clinical remission, compared to 39.5% on ustekinumab.
After 48 weeks, 31.8% of patients in the risankizumab group achieved endoscopic remission - i.e. visible healing of the intestinal mucosa - compared to 16.2% with ustekinumab.

Which biologics work best?
As direct comparative studies between biologics are rare, researchers are increasingly turning to so-called network meta-analyses, in which the results of different studies are compared with each other.

The data show that risankizumab (600 mg) achieved the highest remission rates in biologic-naïve patients (i.e. without previous biologic therapy), followed by infliximab, adalimumab and ustekinumab.
In patients with previous biologic therapy, risankizumab (600 mg) also showed the best results, closely followed by upadacitinib and adalimumab.

Choice of biologics for ulcerative colitis - modern drugs for targeted treatment
The treatment of ulcerative colitis has made great progress in recent years. In addition to conventional therapies, numerous biologics and targeted oral medications are now available that specifically inhibit inflammation in the intestine and can therefore significantly improve quality of life.

The currently approved and frequently used active ingredients include adalimumab (Humira®), golimumab (Simponi®), infliximab (Remicade®), mirikizumab (Omvoh®), risankizumab (Skyrizi®), ustekinumab (Stelara®), vedolizumab (Entyvio®), etrasimod (Velsipity®), ozanimod (Zeposia®), tofacitinib (Xeljanz®) and upadacitinib (Rinvoq®).
These modern drugs enable a sustained remission in many patients and significantly reduce the risk of relapse.

Mirikizumab - focus on quality of life and symptom control
Mirikizumab (Omvoh®) impresses with its special study design: in addition to the classic criteria such as response rates and clinical remission, the urge to defecate was also examined as an additional endpoint in the approval study.
This symptom in particular is a major burden for many sufferers and restricts their everyday lives. The urge to defecate improved significantly with mirikizumab compared to placebo - an important improvement in the quality of life of patients with active ulcerative colitis.

Overview of other modern active substances
In addition to mirikizumab, numerous other effective biologics and small molecules are available:

Anti-TNF antibodies such as adalimumab (Humira®), golimumab (Simponi®) and infliximab (Remicade®) are among the proven standard therapies for moderate to severe ulcerative colitis.
Integrin antibodies such as vedolizumab (Entyvio®) act specifically in the intestine and are characterized by a favourable safety profile.
Interleukin inhibitors such as risankizumab (Skyrizi®), ustekinumab (Stelara®) and mirikizumab (Omvoh®) selectively target the inflammatory pathways and show high remission rates in studies.
S1P receptor modulators such as etrasimod (Velsipity®) and ozanimod (Zeposia®) offer an alternative as oral therapy options for patients who cannot tolerate biologics or do not respond sufficiently to them.
JAK inhibitors such as tofacitinib (Xeljanz®) and upadacitinib (Rinvoq®) also work orally and enable rapid control of inflammation, particularly in more severe or treatment-resistant cases.

Benefits and risks of biologics and small molecules in IBD
The treatment of inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis has developed considerably in recent years. In addition to traditional medications, numerous biologics and small molecules are now available that can specifically inhibit inflammatory processes and significantly improve quality of life.

Local effect increases safety: As a general rule, the more localized the effect of a drug, the safer it is. Among the biologics, those preparations that mainly act in the intestine and therefore do not strongly suppress the immune system are particularly well tolerated. According to experts such as Dr. Stefan Schlosser, these include

Vedolizumab (Entyvio®)
Ustekinumab (Stelara®)
Risankizumab (Skyrizi®)
Mirikizumab (Omvoh®)

These drugs show high efficacy in IBD, while the risk of systemic side effects such as infections is lower.

Complementary oral therapy options:
Small molecules such as ozanimod (Zeposia®), etrasimod (Velsipity®), tofacitinib (Xeljanz®) and upadacitinib (Rinvoq®) work orally and offer an alternative, particularly for patients who do not respond sufficiently to or cannot tolerate classic biologics. They enable rapid control of inflammation, but require regular medical monitoring in order to detect possible risks such as infections or changes in blood values at an early stage.

Risk-benefit assessment and individual therapy
The choice of the right medication always depends on the disease activity, the site of inflammation, previous therapies and individual concomitant diseases. A specialist consultation in the IBD consultation is crucial in order to find the optimal therapy for Crohn's disease or ulcerative colitis and to ensure long-term remission and quality of life.

Surgery for Crohn's disease - a valuable treatment option
In Crohn's disease, bowel resection is often mistakenly seen as the last resort. However, recent studies show that surgery can be a safe and effective treatment option in certain cases.

A population-based real-world study compared two groups of patients over 15 years: one group received an ileocecal resection, the other was treated with TNF inhibitors (tumor necrosis factor antibodies).
The results were remarkable:

The patients who underwent surgery had a 33% lower risk of side effects.
50% of patients who underwent surgery required no further treatment after five years.
These data show that ileocecal resection can be a valid and effective long-term treatment option for patients with localized Crohn's disease. Careful individual assessment together with experienced gastroenterologists is crucial to find the optimal therapy for each patient case.

IBD affects more than just the gut - fatigue and extraintestinal symptoms
Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis do not only affect the gut. Many patients develop extraintestinal symptoms, for example in the eyes, mouth or joints. Fatigue is particularly common and distressing - a pronounced tiredness that can result directly from the systemic inflammation.

Fatigue in IBD - frequent and severe
Data from the SwissCohort Study show: over half of IBD patients report significant fatigue (55%) compared to 35% of healthy controls. In a third of those affected, this fatigue impairs daily activities, while this is only the case in 19.6% of healthy people.

Risk factors for fatigue in IBD are

female gender
younger age at diagnosis
shorter duration of illness
nocturnal diarrhea
low level of education
Symptoms of depression or anxiety

Recognize causes and treat specifically
If patients report extraordinary fatigue, the first thing to look for is active intestinal inflammation. The following factors should also be investigated:

Anemia and iron or vitamin deficiency (e.g. vitamin D, B12, thiamine)
fatigue-promoting therapies such as corticosteroids or thiopurines
post-infectious conditions (e.g. after Epstein-Barr virus or long COVID)
poor quality of sleep, e.g. due to nocturnal diarrhea
relevant concomitant diseases such as coeliac disease, diabetes, hypothyroidism, depression, or heart, kidney, liver and respiratory diseases
Iron deficiency in IBD - intravenous administration preferred

If there is an iron deficiency, it should be supplemented intravenously. Studies show that oral iron can potentially increase inflammatory activity in IBD, while intravenous iron is safer. In addition, meta-analyses show that intravenous iron supplementation is more effective than oral iron supplementation.
The European Crohn's and Colitis Organization (ECCO) therefore recommends intravenous iron as first-line therapy for iron deficiency in IBD patients.

Caution - relapse triggers

It is generally known that non-steroidal anti-inflammatory drugs should be avoided in IBD patients because they can trigger a flare-up. It is probably less well known that antibiotics can also induce flare-ups.

References:

ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment, Hannah Gordon and others
Journal of Crohn's and Colitis, Volume 18, Issue 10, October 2024, Pages 1531-1555, https://doi.org/10.1093/ecco-jcc/jjae091

ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment, Tim Raine and others
Journal of Crohn's and Colitis, Volume 16, Issue 1, January 2022, Pages 2-17, https://doi.org/10.1093/ecco-jcc/jjab178

ECCO Guidelines on Extraintestinal Manifestations in Inflammatory Bowel Disease, Hannah Gordon and others
Journal of Crohn's and Colitis, Volume 18, Issue 1, January 2024, Pages 1-37, https://doi.org/10.1093/ecco-jcc/jjad108