P519 Analysis of the effectiveness and safety of switching from originator to biosimilar adalimumab in patients with Inflammatory Bowel Disease

Casanova, M.J.(1);Chaparro, M.(1);Nantes, Ó.(2);Varela, P.(3);Vela-González, M.(4);Montserrat, R.(5);Sierra, O.G.(6);Riestra, S.(7);Barreiro-de Acosta, M.(8);Martín-Rodríguez, M.M.(9);Gargallo-Puyuelo, C.J.(10);Reygosa, C.(11);Muñoz, R.(12);García de la Filia-Molina, I.(13);Núñez-Ortiz, A.(14);Kolle, L.(15);Calafat, M.(16);Huguet, J.M.(17);Iglesias-Flores, E.(18);Martínez-Pérez, T.J.(19);Bosch, O.(20);Duque-Alcorta, J.M.(21);Frago-Larramona, S.(22);Sánchez-Azofra, M.(23);Van Domselaar, M.(24);González-Cosano, V.M.(25);Bujanda, L.(26);Rubio, S.(2);Mancebo, A.(3);Castro, B.(5);García-López, S.(6);de Francisco, R.(7);Nieto, L.(8);Laredo, V.(10);Gutiérrez, A.(12);Mesonero, F.(13);Leo-Carnerero, E.(14);Cañete, F.(16);Ruiz, L.(17);Gisbert, J.P.(1);

(1)Hospital Universitario de La Princesa- Instituto de Investigación Sanitaria Princesa IIS-IP and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBEREHD, Gastroenterology, Madrid, Spain;(2)Hospital Universitario de Navarra- Instituto de Investigación Sanitaria de Navarra IdiSNA, Gastroenterology, Pamplona, Spain;(3)Hospital Universitario de Cabueñes, Gastroenterology, Gijón, Spain;(4)Hospital Universitario Nuestra Señora de la Candelaria, Gastroenterology, Santa Cruz de Tenerife, Spain;(5)Hospital Universitario Marqués de Valdecilla- Instituto de Investigación Sanitaria Valdecilla IDIVAL, Gastroenterology, Santander, Spain;(6)Hospital Universitario Miguel Servet, Gastroenterology, Zaragoza, Spain;(7)Hospital Universitario Central de Asturias- Instituto de Investigación Sanitaria del Principado de Asturias ISPA, Gastroenterology, Oviedo, Spain;(8)Hospital Clínico Universitario de Santiago de Compostela, Gastroenterology, Santiago de Compostela, Spain;(9)Hospital Universitario Virgen de las Nieves, Gastroenterology, Granada, Spain;(10)Hospital Clínico Lozano Blesa- Instituto de Investigación Sanitaria Aragón IIS Aragón- and CIBEREHD, Gastroenterology, Zaragoza, Spain;(11)Hospital Universitario de Canarias, Gastroenterology, La Laguna, Spain;(12)Hospital General Universitario de Alicante- Instituto de Investigación Sanitaria y Biomédica de Alicante ISABIAL and CIBEREHD, Gastroenterology, Alicante, Spain;(13)Hospital Universitario Ramón y Cajal, Gastroenterology, Madrid, Spain;(14)Hospital Universitario Virgen del Rocío, Gastroenterology, Sevilla, Spain;(15)Hospital General de La Palma, Gastroenterology, Santa Cruz de Tenerife, Spain;(16)Hospital Universitario Germans Trias i Pujol- and CIBEREHD, Gastroenterology, Badalona, Spain;(17)Consorcio Hospital General Universitario de Valencia, Gastroenterology, Valencia, Spain;(18)Hospital Universitario Reina Sofía- Instituto Maimónides de Investigación Biomédica de Córdoba IMIBIC, Gastroenterology, Córdoba, Spain;(19)Hospital Virgen de La Luz, Gastroenterology, Cuenca, Spain;(20)Fundación Jiménez Díaz, Gastroenterology, Madrid, Spain;(21)Hospital Universitario San Agustín, Gastroenterology, Avilés, Spain;(22)Hospital Santa Bárbara, Gastroenterology, Soria, Spain;(23)Hospital Universitario de La Paz, Gastroenterology, Madrid, Spain;(24)Hospital Universitario de Torrejón, Gastroenterology, Madrid, Spain;(25)Hospital de Montilla, Gastroenterology, Córdoba, Spain;(26)Hospital Universitario de Donostia- Instituto Biodonostia- Universidad del País Vasco UPV/EHU- CIBEREHD, Gastroenterology, Donostia, Spain; ADA-SWITCH


Aims: 1) to compare persistence on adalimumab treatment over time in inflammatory bowel disease (IBD) patients who maintained adalimumab reference [non-switch cohort (NC)] vs. those who switched from adalimumab reference to adalimumab biosimilar [switch cohort (SC)]; 2) to compare loss of effectiveness of adalimumab treatment in the NC vs. SC; 3) to identify factors associated with discontinuation of adalimumab therapy; 4) to identify the factors associated with relapse in both cohorts; and 5) to evaluate the safety of both strategies.


Retrospective, observational, multicentre study. Patients under adalimumab reference who were in clinical remission at standard dose of adalimumab reference, and in whom adalimumab was the first anti-TNF administered, were included. Clinical remission was defined as a Harvey-Bradshaw index ≤4 points in Crohn’s disease, a partial Mayo score ≤2 in ulcerative colitis, and the absence of fistula drainage despite gentle finger compression in perianal disease. The follow-up time was at least 6 months since start of study observation period. The Kaplan-Meier method with log-rank test was used to evaluate the cumulative incidence of treatment discontinuation. Cox regression model was used to investigate factors potentially associated with therapy discontinuation.


A total of 505 patients were included (45% women, 87% Crohn’s disease): 229 in the SC and 276 in the NC. The median follow-up was 12 months in the SC and 23 months in the NC (p<0.01). The incidence rate of adalimumab discontinuation was 10% [95% confidence interval (95%CI)=6-14%], and 7% (95%CI=5-10%) per patient-year in the SC and in the NC, respectively (p=0.035). The probability of maintaining adalimumab was 92% at 12 months and 77% at 24 months in the SC, and 97% at 12 months and 86% at 24 months in the NC. In the multivariable analysis, the switch to adalimumab biosimilar, adjusted for the level of C-reactive protein at baseline, was not associated with therapy discontinuation. 18% of the patients relapsed in the SC vs. 21% in the NC. The incidence of relapse was 17% (95%CI=13-23%) in the SC, and 12% (95%CI=10-16%) per patient-year in the NC (p=0.04). The cumulative incidence of relapse was 11% at 12 months and 38% at 24 months in the SC, and 11% at 12 months and 22% at 24 months in the NC. In the multivariable analysis, the switch to adalimumab biosimilar (adjusted by type of IBD) was associated with a higher risk of relapse (HR=1.5, 95%CI=1.008-2.36). 4% of the patients had adverse events in the SC vs. 8% in the NC (p>0.05).


The incidence rate of relapse was slightly higher in the SC; however, this fact had no impact on persistence on the drug. Switching from adalimumab reference to adalimumab biosimilar was safe.