patients with Inflammatory Bowel Disease (IBD) often experience a large loss of primary or secondary response to treatment, so the search for biomarkers to guide the therapeutic strategy is an unmet need in this disease.
Within the framework of the European Congress of Gastroenterology (UEG 2022), the results on advances in personalized treatment for Crohn’s disease and ulcerative colitis were presented. This is a substudy carried out in patients with both pathologies who participated in the phase III maintenance trial of ustekinumab (anti-IL12-23 drug), as explained Mª Dolores Martín Arranzhead of the IBD Unit of the University Hospital of La Paz, in an interview with GM.
Ustekinumab is an IgG1 monoclonal antibody thatblocks the inflammatory cascade binding to the p40 subunit of the interleukins IL-12 and IL-23″, says Martín Arranz. This drug, in addition to its use in adults with ulcerative colitis and Crohn’s disease, is also approved for the treatment of adult patients and children older than six years with psoriasis and adults with psoriatic arthritis.
Specifically, the study analyzed the presence of the HLA-DQA1*05 allele in 675 patients. The relationship between the presence of this mutation -which “appears in approximately 40 percent of the population in our environment”- and the appearance of antibodies against ustekinumab (Stelara) which decrease its efficacy, “without also observing a difference according to the use of concomitant immunosuppressant”, explains Martín Arranz.
“This implies that the presence of this allele does not condition the appearance of immunogenicity and, therefore, loss of response with treatment with ustekinumab, unlike the findings recently described with anti-TNF drugs”, concludes the expert.
“Many patients taking anti-TNF drugs experience unwanted side effects, as well as immunogenic failure and, therefore, a more frequent loss of response, which is associated with the presence of the HLA-DQ1*A5 allele,” says the expert. . Thus, new data demonstrating that patients with this HLA allele do not experience the same loss of response with ustekinumab continue in the path of personalized medicine in IBD.
Choose the most appropriate treatment
In Spain, some 360,000 people (almost 1 percent of the population) have IBD, fundamentally divided into Crohn’s disease and ulcerative colitis. “It is generally diagnosed in young patients, before the age of 30, and has a notable impact on quality of life,” explains Martín Arranz, who adds that, although the cause is not fully known, it falls within the spectrum of immune-mediated diseases. .
“In IBD we must move towards an increasingly personalized medicine, and we need to know the prognostic factors of response to treatments to choose the most appropriate for our patients.“, he points out. For this reason, he considers that the existence of “a genetic marker that may entail a greater risk of loss of efficacy of anti-TNF drugs, but which is not related to loss of response to ustekinumab, is a additional data to consider in our therapeutic algorithmespecially in those patients in whom the use of immunosuppressant wants to be avoided”.