P0578Second-line adalimumab is a viable therapeutic option after infliximab failure in perianal Crohn’s disease: a real-world study

Abstract Background Perianal fistulising Crohn’s disease (pfCD) is a challenging phenotype that markedly affects quality of life. Anti-TNF therapy, particularly infliximab, is commonly used first-line, yet primary non-response and secondary loss of response remain frequent. Adalimumab is often used second-line despite limited evidence. This study evaluated real-world outcomes of first- versus second-line adalimumab in pfCD to inform therapeutic sequencing. Methods A multicentre retrospective cohort study included adult pfCD patients treated between 2005 and 2024. The primary outcome compared adalimumab second-line (after infliximab) versus first-line using changes in the Perianal Disease Activity Index (PDAI). Secondary outcomes were hospitalisation and antibiotic use. Response was assessed at early (£24 weeks) and late (24 weeks) time points. Analyses used Mann–Whitney U for continuous and Fisher’s exact for categorical variables. Results Of 167 patients, 107 received adalimumab first-line and 60 second-line. Among those previously exposed to infliximab, 45% stopped due to loss of response after initial response, 16% had non-response despite adequate levels, 25% ceased due to intolerance or adverse effects, and 11% due to patient preference. Second-line patients were older, had higher BMI, fewer smokers, and more stricturing disease, with similar immunomodulator use. PDAI pain improvement was greater with first-line therapy early (46% vs 4%, p 0.01) but not late (50% vs 9%, p = 0.07). Hospitalisations, including for surgical management, were higher second-line (13% vs 11%, p = 0.04) at 24 weeks. No differences were observed in PDAI discharge sub scores, clinical healing or response, or antibiotic use. More first-line patients remained on adalimumab (77% vs 28%, p 0.01) over follow-up (median 82 months, IQR 73), although treatment duration before cessation was similar (40 vs 40 months, p = 0.47). Dose escalation was comparable (54% vs 37%, p = 0.71). The distinction between true non-response and secondary loss of response was limited by the absence of pharmacokinetic data and incomplete documentation. Conclusion In pfCD, first-line adalimumab delivers greater improvements in PDAI pain sub scores and fewer hospitalisations on late outcomes assessment compared with second-line use. Adalimumab is effective after infliximab failure despite its similar mechanism of action, positioning it as a viable second-line option. Future studies incorporating standardised clinical and patient-reported outcome measures with radiological endpoints are needed to refine therapeutic sequencing in this high-risk population. Conflict of interest: Dr. Hartley, Imogen: Scholarship to attend conference- Celltrion Tassone, Daniel: No conflict of interest Winata, Leon Shin-ha: No conflict of interest Sy, Meredith: No conflict of interest Chow, Jocelyn Hui Ching: No conflict of interest McCurdy, Jeffrey: No conflict of interest Ravikulan, Abhimati: No conflict of interest Gabrielson, Stefan: No conflict of interest Su, Heidi: Advisory Board - Takeda, Johnson & Johnson Speaker fees - Takeda, Johnson & Johnson, GSK Xia, Bowen: No conflict of interest Keung, Charlotte: No conflict of interest Lai, Karen Hei-Tung: No conflict of interest Mak, Joyce Wing Yan: No conflict of interest Welman, Christopher J: No conflict of interest Thin, Lena: Pfizer- advisory board fees, research grants Takeda- research grant, advisory board fees JNJ- advisory board fees Abbvie- advisory board fees Neuroscientific - advisory committee Celltriom- advisory board fees Chen, Lynna: No conflict of interest Nguyen, Andrew: No conflict of interest Srinivasan, Ashish: AS has served as a speaker for Arrotex Pharmaceuticals and has received advisory fees or conference support from AstraZeneca, AbbVie, Takeda Pharmaceuticals, and Dr Falk Pharma. Wu, Hsin-Yun: No conflict of interest Wei, Shu Chen: Consultancy fees: AbbVie, Bristol Myers Squibb, Cornerstones, Ferring Pharmaceuticals Inc., Janssen/J & J, Pfizer, Sanofi, SPYRE, Takeda, ThermoFisher. Lectures and/or speakers’ bureau payments: AbbVie, Bristol Myers Squibb, Celltrion, CornerStones, Excelisior, Ferring Pharmaceuticals Inc., Janssen/J & J, Pfizer, Takeda, ThermoFisher. Van Wees, Jacoba: No conflict of interest Sparrow, Miles P.: Educational grants or research support – Gilead, Celltrion Speaker’s fees – Janssen, Abbvie, Ferring, Takeda, Pfizer, Celltrion, Eli Lilly, Dr. Falk Pharma Advisory boards or consultancy fees – Janssen, Takeda, Pfizer, Celgene, Abbvie, MSD, Emerge Health, Gilead, BMS, Celltrion, Eli Lilly, Alimentiv Lai, Mark: No conflict of interest Kalasabail, Sanjna: No conflict of interest Borok, Nira: No conflict of interest Connor, Susan Jane: Grant: Research Support: Abbvie, Agency for Clinical Innovation, Amgen, BMS, Chiesi, Celltrion, DrFalk, Ferring, Janssen, Medical Research Future Fund, Pfizer, South Western Sydney Local Health District, Sydney Partnership for Health, Research and Enterprise, Takeda and The Leona M and Harry B Helmsley Charitable Trust Personal Fees: Ad Boards: Abbvie, Amgen, BMS, Celltrion, Eli Lilly, Ferring, GSK, Janssen, Organon, Pfizer, Takeda Speaker Fees: Abbvie, Cornerstones Health, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Sydney IBD School, Takeda Educational Support: DrFalk, Sandoz, Takeda Chen, Cheng-Yu: No conflict of interest Shibu, Roney: No conflict of interest Mohsen, Waled: No conflict of interest An, Yoon-Kyo: Yoon-Kyo An has received speaking and consulting fees from Abbvie, Bristol Myers Squibb, Celltrion, Chiesi, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Shire and Takeda served on advisory boards member for Abbvie, Bristol Myers Squibb, Chiesi, Janssen, NPS Medicine wise, Microba received research and educational funding from Abbvie, Celltrion, Dr Falk, Janssen, Pfizer, Sandoz and Takeda. Tan, Ethan: No conflict of interest Xu, Ziheng: No conflict of interest Garg, Mayur: No conflict of interest Lo, Sheng Wei: No conflict of interest De Cruz, Peter: No conflict of interest Pelly, Theo: No conflict of interest Hart, Ailsa: Grant: Takeda Personal Fees: Abbvie, Amgen, Arena, AZ, Falk, Celltrion, Eli Lilly, Ferring, Genentech/ Roche, GSK, Pfizer, Takeda, Napp, Pharmacosmos, Janssen (J & J), Bristol-Myers Squibb, Gilead, Galapagos, Alfasigma Ding, Nik John Sheng: Grant: Forcrohn’s, ECCO, GESA Personal Fees: Abbvie, Pfizer, Ferring ANZIBD Consortium, ANZIBD Consortium: No conflict of interest