Introduction

Crohn’s disease (CD) is a type of inflammatory bowel disease. CD that can cause bowel damage and disability over time.^1,2 The exact cause of CD remains unknown; however, it is believed that genetic and environmental factors impact its development.³ CD mainly affects adults between the ages of 18 and 35 years old; however, there is an increase in paediatric cases.^1,2 Approximately 25% of CD patients are children and teenagers.² The rate of children and adults being diagnosed with CD is increasing and varies globally. Research shows that CD in children varies globally. In Europe, about 2 to 7 children per 100,000 develop CD each year. In North America, the rate is slightly higher at 6-8 children per 100,000. In Asia and the Middle East, the rates are much lower, at less than 2 per 100,000; however, rates are still increasing and remain a cause for concern.⁴ Therefore, CD is becoming a worldwide problem in areas that previously did not have many cases. The increase in CD cases in children may be caused by pollution, lifestyle, and dietary changes.¹  

Paediatric cases present with a set of unique challenges, including a child’s development, growth, and nutrition, which can be affected by treatment. As a result, paediatric cases of CD are typically associated with poor growth. Furthermore, children can be impacted emotionally and psychologically ²  

Despite these challenges, treatments have improved in recent years. Biologic therapies are crucial for treatment outcomes and target specific parts of the immune system involved in the inflammation seen in CD; this helps prevent symptoms and achieve remission.^1,5  This article will explore what biologic therapies are, how they work, and what they mean for children living with CD.

What causes paediatric crohn’s disease?

The exact cause of CD is unknown. However, it is believed to be caused by a combination of genetic, environmental, immune, and gut microbiome factors. CD develops when the body’s immune system, which usually protects us from harmful bacteria, overreacts to bacteria and other substances in the gut. The immune system is constantly activated, which causes chronic inflammation.^1,6

In children, many factors contribute to developing CD:

• Genetics: Inheriting specific genetic mutations can make children more susceptible to developing CD. For instance, mutations in genes involved in the immune system, including NOD2, can dysregulate the immune system and thus increase your risk of developing CD. Interestingly, there are over 260 genes associated with CD¹ 
• Immune system dysregulation: Immune cells in the gut, such as T cells (TH1 and TH17), become overly active and release chemical messengers called cytokines, including tumour necrosis factor (TNF), IL-12, and IL-23. These chemical messengers increase T cell numbers and inflammation, leading to an excessive, unbalanced response that sustains a chronic inflammatory loop^6,7
• Gut bacteria and microbiome imbalance: Children with CD often have fewer beneficial bacteria and more harmful bacteria in their intestines; this imbalance triggers the immune system to attack and damage the gut beyond repair^1,6,8
• Gut barrier: The lining of the intestine is supposed to act like a strong wall. The barrier lets the good things, such as nutrients, in and keeps harmful bacteria out. In CD, the gut barrier is damaged and leaky, allowing bacteria to get into the body and trigger inflammation^1,8,9

The chronic inflammation in CD can cause irreversible intestinal damage over time.⁶ Furthermore, paediatric CD cases are often different to adults, with paediatric CD being more aggressive. In paediatric CD, inflammation occurs simultaneously in various areas of the digestive tract, including the small intestine, colon, and stomach or oesophagus; this is less common in adults, where inflammation is mainly restricted to the small intestine or colon. More than 50% of children require surgery if CD continues for many years. As a result, paediatric CD presents an added challenge because it causes abdominal pain, diarrhoea, and affects nutrition, growth, and puberty, as the body is still developing. Therefore, early diagnosis and treatment are essential in children.⁸ 

Standard treatment approaches before biologics

The goal of treating children with CD is to achieve remission, which means controlling and preventing inflammation and associated symptoms. Additionally, treatment aims to maintain long-term remission and to focus on the child’s growth and development. Controlling CD is important so the child can achieve development milestones linked to height, weight, and puberty and improve their quality of life.¹⁰ Standard treatment involves corticosteroids, anti-inflammatory medications used to reduce inflammation and initiate remission.^7,10 They should not be used in the long-term to maintain remission because they are associated with side effects, including high blood pressure, cataracts, and being more prone to infections. Corticosteroids are effective for short-term treatment. Additionally, immunomodulators are another treatment choice that work by suppressing the immune system to reduce inflammation. Azathioprine and 6-mercaptopurine are the most commonly used CD treatment today.¹⁰ However, long-term use of immunomodulators carries the risk of liver toxicity and disease, nausea, and pancreatitis; therefore, they are also only used as short-term treatments.²  

Another therapeutic approach is nutritional therapy. One type of nutritional therapy is exclusive enteral nutrition (EEN), in which people with CDs receive a liquid diet for up to 3 months.⁸ EEN reduces the time of surgery and post-surgical complications. It is more effective than corticosteroids for children in reducing gut inflammation.^1,8 

Biologic therapy has revolutionised the management of CD for children. Biologic therapy is used in moderate and severe paediatric cases for those who do not respond well to EEN or steroids.⁸ Biologic therapy reduces inflammation and brings relief from symptoms, targets the long-term damage, heals the gut, and prevents relapse in paediatric cases.^1,11 

Biologic therapies and evolving strategies in paediatric crohn’s disease

TNF inhibitors were the first biologics used in children and remain the most commonly used in paediatric CD. Infliximab, the first biologic drug approved for CD, and adalimumab can be given as subcutaneous injections (under the skin). Both are very effective in children with moderate to severe disease or when standard treatments, such as steroids, are not working.^2,7 Many children feel better within weeks, and these treatments can help with complications, such as fistulas, and reduce the chance of CD coming back after surgery.⁷ 

One of the big questions doctors face is when to start biologic treatment. In the past, they were used only when other treatments failed, a “step-up” approach. However, new research shows that starting biologic therapies earlier – sometimes within months of diagnosis – can lead to better outcomes. Children treated this way are more likely to reach remission, heal the gut lining, and avoid repeated flare-ups.^11,13 One study found that early use of infliximab combined with another immunosuppressive drug healed the gut in nearly 74% of children, compared with 42% when biologics were introduced later.¹³  

Sometimes, biologics are combined with other treatments, such as azathioprine or methotrexate. The combined treatments can improve the effectiveness of biologics and prevent the body from developing antibodies that block their action. However, combining treatments can increase the risk of infections; therefore, doctors weigh the advantages and disadvantages carefully for each child.¹³   

Other biologics are now becoming options for children who don’t respond to anti-TNF treatments. Vedolizumab is a gut-specific treatment that tends to have fewer systemic effects, while ustekinumab targets different parts of the immune system and shows promise in teenagers. In complicated cases, doctors have tried using two biologics at the same time, for example, infliximab plus vedolizumab. Early reports show that this can help some children who have run out of other options, though close monitoring is required to monitor for side effects, including infections.¹⁴

Biologic therapies are strong treatments; therefore, safety and monitoring are very important. Doctors may check blood drug levels to ensure they’re working well and not being blocked by antibodies. Additionally, families need to be aware of infection risks, the importance of staying up to date with vaccines, and the need for long-term monitoring. For children, extra attention is given to their mental health, puberty, and growth because CD and its treatments can affect all of these areas.^2,7,13     

For future therapeutics, biosimilars – similar products to existing biologics – are becoming available and are cheaper than biologic therapies, allowing more children to access treatment.¹⁵ Additionally, researchers are studying new combinations, such as biologics with special diets or microbiome-based approaches with personalisation that could help doctors pick the right therapy from the start and find one that is more beneficial for a child with CD.^16,17 Moreover, new types of medicines, including JAK inhibitors such as upadacitinib, are being studied in young people where anti-TNF biologics are not effective.¹⁸

Summary 

Paediatric Crohn’s disease is a complex, more aggressive condition than the adult variant, affecting growth and quality of life. Biologic therapies have transformed care by controlling inflammation, healing the gut, and reducing complications. With emerging options, including biosimilars and personalised approaches, future treatments promise safer, more accessible, and tailored care.