Abstract Background Inflammatory bowel disease (IBD) is a chronic immune-mediated condition that, in cases of refractory activity or loss of response to conventional treatment, may require advanced therapies such as biologic agents or small molecules. Progression through multiple therapeutic lines in some patients results in a clinically complex subgroup referred to as difficult-to-treat IBD. In Mexico, evidence on therapeutic sequencing and the identification of these cases remains limited. Methods This observational and retrospective analytical study reviewed 298 IBD patient records. Of these, 130 received at least one line of advanced therapy, and 17 (13.07%) required two or more lines. Clinical, demographic, and therapeutic data were collected, and patients were categorized by Montreal classification and number of therapeutic lines. Those with three or more lines were considered difficult-to-treat IBD, defined as failure of biologics or small molecules with at least two different mechanisms of action per recent consensus. Statistical analysis was performed in SPSS v29 using descriptive statistics, Friedman’s test for comparisons across therapeutic-line groups, and Kaplan–Meier curves for treatment persistence. A p-value 0.05 was deemed significant. Results Seventeen IBD patients receiving ≥2 advanced therapy lines were analyzed. The mean age was 40.05 ± 15.29 years, and 70.6% were male. Pancolitis predominated in UC (66.6%), while Crohn’s disease most commonly presented with L3 location (37.5%), B2 behavior (62.5%), and perianal involvement (37.5%). First-line therapy consisted mainly of adalimumab and infliximab (33.5% each), followed by vedolizumab (23.5%) and ustekinumab (5.9%). Ustekinumab was the most frequent second-line option (35.3%), while third- and fourth-line therapies were used in low proportions (5.9% each). Five patients (29.4%) met criteria for difficult-to-treat IBD. The interval between therapy switches progressively shortened (17, 11.5, and 6 months; p 0.001). Kaplan–Meier analysis showed the greatest persistence with second-line therapies, with decreasing duration in third and fourth lines (p 0.001). Among biologics, ustekinumab demonstrated the longest persistence, especially as second-line treatment. Conclusion Therapeutic sequencing in IBD patients revealed complex clinical trajectories, with a subgroup fulfilling criteria for difficult-to-treat disease. Progressive reduction in treatment persistence with each subsequent line was observed, suggesting increased clinical refractoriness and highlighting the need for timely optimization of therapeutic decision making. Conflict of interest: Gonzalez Lopez, Roberto Emmanuel: No conflict of interest Rosales Tellez, Paola: No conflict of interest Chida Romero, Jesus Antonio: No conflict of interest Rodriguez Cruz, Hector: No conflict of interest Hernandez Antolin, Victor: No conflict of interest Sebastian Ocampo, Valeria Natalie: No conflict of interest Contreras Aviles, Estefania: No conflict of interest Cabrera Palma, Guillermo: No conflict of interest Jimenez Bobadilla, Billy: No conflict of interest Lopez Perez, Raquel Yazmin: No conflict of interest Dr. De Leon Rendon, Jorge Luis: Dr. Jorge Luis De León Rendón is a member of Advisory Boards, key opinion leader, and speaker for Abbvie Mexico, Takeda Mexico, and Janssen Mexico. He has served as a key opinion leader and lecturer for Schwabe Pharma Mexico, Servier, Pfizer, Alfasigma, and Siegfried Rhein Mexico. He has received support for research manuscript publication and editing from Takeda and Schwabe Pharma Mexico. Additionally, he has coordinated research studies and medical education programs with Shire, Bristol Myers Squibb, Takeda, Schwabe Pharma, Abbvie, Janssen, MSD, and Roche.
Lopez et al. (Thu,) studied this question.