P313 Long-term durability and safety of anti-TNF agents compared with change to a different mechanism of action as a second-line biological treatment after first anti-TNF failure in Crohn´s disease: results from the Andalusian CambiaCrohn study
Vázquez Morón, J.M.(1);Martín Rodríguez, M.D.M.(2);Olmedo Martin, R.(3);Hernández Martínez, Á.(4);Núñez Ortiz, A.(5);Rueda Sánchez, J.(6);Argüelles Arias, F.(7);Caballero Mateos, A.(8);Iglesias Flores, E.(9);Viejo Almanzor, A.(10);Pallarés Manrique, H.(11);
(1)Hospital Juan Ramon Jimenez, Department of Digestive Diseases UGC, Huelva, Spain;(2)Hospital Universitario Virgen de la Nieves, Gastroenterology Unit, Granada, Spain;(3)Hospital Regional Universitario de Málaga, Gastroenterology Unit, Málaga, Spain;(4)Hospital Universitario Torrecárdenas, Gastroenterology Unit, Almería, Spain;(5)Hospital Universitario Virgen del Rocío, Gastroenterology Unit, Sevilla, Spain;(6)Hospital Universitario Virgen de Valme, Gastroenterology Unit, Sevilla, Spain;(7)Hospital Universitario Virgen Macarena, Gastroenterology Unit, Sevilla, Spain;(8)Hospital Santa Ana de Motril, Gastroenterology Unit, Granada, Spain;(9)Hospital Universitario Reina Sofía, Gastroenterology Unit, Córdoba, Spain;(10)Hospital Puerta del Mar, Gastroenterology Unit, Cádiz, Spain;(11)Hospital Juan Ramón Jiménez, Gastroenterology Unit, Huelva, Spain
Background
After failure to a first aTNF agent in Crohn's disease (CD), a second aTNF shows higher rates of failure and discontinuation. Initiating a therapy with a different mechanism of action (MoA) such as ustekinumab (UST) or vedolizumab (VDZ) could lead to a greater durability of second-line biological treatment with a higher safety profile.
Methods
A retrospective and multicenter study (10 hospitals in Andalusia). We included patients with active CD (Harvey-Bradsaw index >4) who had failed a first aTNF agent and started a second-line biological with other aTNF or other MoA (UST or VDZ) between July 2017 and February 2020. The aim was to evaluate the long-term durability and safety of aTNF agents compared with other MoA as a second-line biological treatment.
Results
249 CD patients were included; There were no significant differences between both groups in age, sex, disease duration, location, CD behavior, perianal disease, smoking habit or concomitant corticosteroid use. Whereas there were significant differences in the proportion of patients with abdominal surgery (29.5% aTNF group vs 42.5% othermMoA, p=0.032), and concomitant immunomodulators (41.9% aTNF vs 25.8% other MoA, p=0.008). Second-line biological treatment was aTNF in 129 patients (57 IFX and 72 ADA) and other MoA in 120 (97 UST and 23 VDZ). Second aTNF was discontinued in 81/129 patients (62.8%) after a median follow-up of 21 months (mo). Whereas 24/120 patients (20%) discontinued other MoA after a median follow-up of 41mo (p< 0.001). The rate of discontinuation per patient-year of follow-up was 20.9% for aTNF and 6.7% for other MoA. The probability of maintaining aTNF or other MoA was 64.4% vs 88.3% at 12mo, 46.5% vs 81.7% at 24mo and 31% vs 80% at 36mo (p<0.001). Discontinuation rates during follow-up were 68.4% for IFX, 58.3% for ADA, 39.1% for VDZ and 15.5% for UST (p<0.001). Reasons for discontinuation were 32.4% primary non-response (63.6% aTNF and 36.4% other MoA), 51% loss of response (82.7% aTNF and 17.3% other MoA) and 16.7% intolerance or adverse events (82.3% aTNF and 17.7% other MoA). Adverse events were reported in 31/249 patients (12%), 25/31 with aTNF and 6/31 with other MoA (5 vs 0 infusion reactions, 4 vs 1 mild infections, 1 vs 0 severe infections, 10 vs 2 cutaneous injury, 2 vs 1 arthralgias and 3 vs 2 other event).
Conclusion
In our clinical practice, a second-line aTNF associated with significantly lower long-term drug survival compared to changing to a different MoA. Lower rates of discontinuation were observed with change to a different MoA, especially to ustekinumab. Ustekinumab and vedolizumab showed a better safety profile than infliximab or adalimumab as second-line biologic in CD.