Abstract Background Crohn’s disease (CD) management in patients who have exhausted multiple biologic options remains challenging. Limited data exist on JAK1 inhibitor efficacy in this population outside clinical trial settings. This registry-based study examines upadacitinib outcomes in a heavily pretreated Spanish CD cohort, with emphasis on treatment efficacy across varying degrees of prior biologic exposure. Methods Ambispective multicenter registry enrolling 190 CD patients starting upadacitinib across 12 Andalusian hospitals (UPITA-Crohn). Clinical remission was operationalized as Harvey-Bradshaw Index 5, while clinical-biochemical remission integrated HBI 5 with inflammatory biomarkers (CRP 5 mg/L, fecal calprotectin 250 μg/g). Steroid-sparing response was assessed from week 12 onwards. Between-group analyses stratified participants by number of preceding failed biologics. Results The cohort (n = 190) had a mean age of 41.3 years, predominantly male (45.5%), with ileocolonic predominance (45.3%) and substantial disease burden (mean duration 12.9 years). Treatment characteristics and efectiveness results of this heavily pretreated population are shown in table 1 and 2. The magnitude of clinical response was unaffected by prior biologic burden. At 6 months, remission rates were virtually identical in patients with single versus multiple prior failures (52.8% vs. 55.2%; p = 0.478). Steroid-free remission rates similarly showed no meaningful difference (16.7% vs. 9.4%; p = 0.190), with only borderline trends at 12 months (p = 0.142). Treatment discontinuation affected 47 patients (24.7%): 14 by week 12, 41 by month 6, 47 by month 12, predominantly from insufficient response. Adverse events were documented in 36 instances affecting 18.9% of patients (n = 36/190). The most frequent adverse events included infections (n = 9), acne (n = 8), and anemia (n = 4), followed by herpes zoster (n = 3), cutaneous lesions (n = 3), and elevated transaminases (n = 3). Eight patients (4.2%) discontinued treatment due to serious adverse events: two for infections, and one each for popliteal thrombosis, myocardial infarction, stroke, herpes zoster, and anemia. Conclusion Upadacitinib demonstrates durable clinical efficacy in this large real-world cohort of multiply-refractory CD, with response rates exceeding 60% at 12 weeks and sustained remission through one year. Critically, prior biologic exposure—even multiple sequential failures—does not substantially diminish treatment efficacy. While careful safety surveillance remains warranted, upadacitinib offers a promising alternative for CD patients exhausted of conventional biologic options, independent of prior treatment complexity. Conflict of interest: Dr. Caballero Mateos, Antonio M: has received fees for lectures, consultancy work, or research support from: Lilly, Abbvie, Johnson & Johnson, Takeda, Pfizer, Alfasigma, Ferring, Farmasierra, Kern. Rodriguez Gonzalez, Francisco Jose: None Camargo Camero, Raquel: None Ruíz Sánchez, Alicia: None Agulleiro, Idoia: None Hernandez Martinez, Alvaro: None Lazaro Saez, Marta: None Martin Rodríguez, María Del Mar: As a speaker or recipient of educational funding from MSD, Takeda, Janssen, Johnson & Johnson, Dr. Falk Pharma, Abbvie, Tillotts Pharma, Chiesi, Otsuka Pharmaceutical, Pfizer, Galápagos, Ferring and Lilly. Valdes, Teresa: none Argüelles Arias, Federico: I have recivied research support or speaker bureau from AbbVie, Amgen, AstraZeneca, Celltrion, Ferring, Falk Pharma, Alfa Sigma, Janssen/J&J, Neopharm, Pfizer, MSD, Takeda, STADA Arzneimittel, Sandoz, Lilly Gomez Delgado, Elena: None Trapero Martinez, Ana María: None Saldaña, Leticia: None Bailón Gaona, Cristina: None Benítez Cantero, José Manuel: None Sáez Díaz, Antonia: None Olmedo-martín, Raúl: Dr. Raúl Olmedo-Martín has served as a speaker and consultant for Janssen, Abvvie, Kern, Takeda, Lilly, Otsuka, Ferring and Alfasigma
Mateos et al. (Thu,) studied this question.