One step away from fighting intestinal diseases in minors

Cramps, diarrhea, bloody diarrhea, an urgent need to go to the toilet, fatigue or weight loss are some of the symptoms experienced by people with inflammatory bowel disease (IBD), a chronic condition that includes Crohn’s disease and ulcerative colitis.

In Mario’s case, the name is fictitious as he asks not to reveal his identity, and he has Crohn’s disease which causes him to have painful fistulas. He is only 16 years old and “they’ve operated on me nine times already,” he says. “The worst thing is the flare-ups. They make it difficult for me to walk, I have trouble sitting because of the pain… I’m a little fed up with it, but it is what it is,” he says, who retired after years of bouts of illness since He was diagnosed at age nine.

“I’ve already had nine surgeries. The worst thing is the exacerbations. I’m fed up, but it is what it is.”

Like him, more than 400,000 people in Spain suffer from IBD. These chronic pathologies lead to a significant reduction in the quality of life of most patients if they are not controlled, which happens to half of the patients.

The problem is that these conditions usually debut in young people, between the ages of 20 and 30, and their incidence is increasing: almost every fourth case is diagnosed in minors.

“That’s why It is important to predict which treatment will work best for them and in the years to come.“for pediatric patients,” explains Dr. Luis Andrés López Fernández, head of the Pharmacogenetics Laboratory of the Pharmaceutical Service of the General Hospital of the Gregorio Marañón University in Madrid.

The aim of treatment is to control the disease and reduce complications, as well as maintain good nutritional status to achieve the least possible impact on the child’s growth. Now, as with adults, it is not so easy to control.

These are chronic pathologies without radical treatment. That is, for which there is no cure. However, its development may vary depending on the treatment.

“With medications, patients can be controlled quite well, but if they don’t work or become ineffective, they will develop problems associated with IBD, which is also a very socially limiting disease,” he says.

Thus, in patients with moderate to severe active disease who have not responded to traditional treatment, biological therapyThat is, drugs that act at the molecular level to control inflammation and regulate the immune system are making a big difference in the fight against IBD, with greater effectiveness than other drugs in reducing flare-ups and hospitalizations… However, not all pediatric patients perform equally well.

For the purpose of providing more effective and personalized medical care For these minors, the Marañon Pharmacogenetics Laboratory launched an observational study in 2016, which is still ongoing and whose results will represent a “before” and “after” for these patients.

“We have identified genetic markers that predict treatment response in children with IBD.“,” explains Lopez Fernandez.

These variants allow us to know in advance which patients will respond positively for many years, and which may struggle with treatment. “The outcome,” he continues, “is not so black and white, but rather these markers allow us to predict the group of patients who will do well and very poorly with a certain group of biologics, as well as the average outcome.” In any case, this is a significant advance for these patients, given their young age and the fact that they will have to be treated for life, since “they are still a little blind,” he admits.

“Ultimately, this advance will allow children to be placed in one group and receive one treatment, and others in another. But we are still developing it,” says Cesar Sanchez, senior physician in the pediatric gastroenterology, hepatology and nutrition department at the Gregorio Marañon Clinic.

So far in this observational study, they have been treating patients as usual and analysing their response.

This is a large pediatric patient database at the national level. So the initial project included 340 pediatric patients with IBD, and at this point they already have “450 participants were treated with the biologic drugs infliximab and adalimumab,” says Sanchez.

Near two of three biologic drugs currently approved in Spain for the treatment of inflammatory bowel disease in children. But on the market there are more than 10 of them and some give themselves for the sake of compassion,” he adds.

In some cases, the genetic variables that predict which children will respond best to certain treatments are the same as those in adults, but in others, they are not. In particular, the researchers identified genetic variants in Genes CXCL12, ATG16L1 and PHACTR3 which are significantly associated with response to biological therapy in children with IBD.

In addition, they identified specific biomarkers that predict response to various biologic drugs used in the treatment of ulcerative colitis and Crohn’s disease.

The results of this study led to the creation of an algorithm for classifying patients by risk of treatment failure, which will facilitate personalized and more precise therapy. The next step will be to conduct clinical trials.

Restore life

Mario’s biological treatment is going well. See Gregorio Marañon every eight weeks, or every four or six weeks if there’s a flare-up. “The treatment is helping me, I’m happy,” he says. You’ve had it since 2019, and it’s been working ever since.

“My son came back to life after he was put into treatment. He learned to live with the disease, The problem is the outbreaks, and there haven’t been any for two years. “The last time the outbreak lasted a month,” says his mother, Raquel, not her real name, who, seeing that it seems like a long time to us, explains that it was, in fact, “not a long time, it lasted six-seven months.”

“The pain when a fistula appears is terrible. They made five drainages at the same time”

“It’s very painful. It hurts so much that he can’t sleep, and the painkillers only give him relief for two or three hours. It’s terrible. When it happens to him, he doesn’t leave the house because he can’t move. He has to lie on his side, he can’t even take a step because of the pain,” his mother explains.

“The flare-up is progressive, fortunately when it happens I call Cesar and he tells me to go with him. She is seen, operated on, drained. “He had five drains at once,” says this mother, who advises other parents to be patient. “With biological clearance they will improve, but it is not instantaneous. It is something progressive, but eventually, although it may take a long time, eventually it is under control,” he says.

It occurs more often in boys than in girls, but equally often in adults.

►20% of pediatric patients for inflammatory bowel diseases debut before the age of 10 and 5% before the age of five. The genetic factor is the main cause in these early-onset patients. “Children’s IBD is more common in men, while the incidence in adults is the same for both sexes,” says Cesar Sanchez, who explains that the incidence of the disease is increasing significantly, as is its early diagnosis: “In 20 years, the incidence of the disease in minors is doubled. “Twenty years ago, 10% of patients were children, and today it is 25%.