DOP033Multiple advanced therapies in combination for the treatment of inflammatory bowel disease - a bi-national registry

Background There is increasing interest in using ≥2 advanced therapies in inflammatory bowel disease (IBD) for refractory disease, multi-organ involvement and concurrent autoimmune conditions. However, data on prescribing practices are extremely limited, and comparative efficacy and safety remain largely unknown. Prior meta-analyses have included <280 patients, primarily from small case series with heterogeneous reporting and mostly without objective outcomes [1]. Methods We collected a comprehensive binational registry (Australia & Taiwan) of patients with IBD on combined advanced therapies (ATs)/combined immunosuppressive therapies outside of regular prescribing practice used in overlap ≥1 month. Results There were 307 combinations in 257 patients, median age 37 years, 146/257 (56.8%) Crohn’s disease (CD) & 110/257 (42.8%) ulcerative colitis, 111/257 (43.2%) female primarily from Australia (220/257, 85.6%; Taiwan 37/257, 14.4%). Commonest combinations were: Vedolizumab (VED) + Janus kinase inhibitor (JAK) (n = 57, 18.6%), JAK + ustekinumab (UST) (n = 52, 16.9%) & VED + tumour necrosis factor inhibitor (TNFi) (n = 44, 14.3%). Overall, via 5-point Likert scale, the combinations were deemed effective by the clinician in 66.8%. p19 inhibitors (p19i) + JAK, UST + JAK, UST + TNF had the greatest clinician-deemed efficacy rates (effective ≥70%) whereas UST + tacrolimus (TAC), JAK + TAC, & TNFi + JAK were deemed the poorest (<60%) (P=0.032). Clinical remission was achieved in 174/307 (56.7%). In 198/307 (65%), there was confirmed objective improvement (biochemically, endoscopically, and/or radiologically). The commonest adverse events (AEs) were from uncontrolled disease (n = 17, 5.5%), though there were 5/307 (1.6%) serious infections & 11/307 (3.6%) opportunistic infections. Two combinations were associated with life-threatening AEs (Common Terminology Criteria for Adverse Events (CTCAE): 4), both associated with uncontrolled IBD activity. The commonest serious AE (CTCAE 3) was from uncontrolled IBD activity (4/307, 1.3%). There were three deaths, two from uncontrolled IBD activity, one from myeloma progression in a patient with liver cirrhosis. AEs were more frequent in combinations containing JAK & tacrolimus (21/87 (24.1%) & 17/63 (27.0%) respectively, & least frequent with Th17 inhibition (p19i & UST, 16/118 (13.6%), P = 0.03). Conclusion This comprehensive binational registry of combined advanced therapies in IBD, the largest to date, shows that combination use in treatment-resistant IBD is effective in the majority with acceptable safety. However, despite combination of agents, medication inefficacy remains a key area of concern. We demonstrate signals for greater efficacy & safety using several combinations that require further investigation. References: [1]Alayo QA, et al. Systematic Review With Meta-analysis: Safety and Effectiveness of Combining Biologics and Small Molecules in Inflammatory Bowel Disease. Crohns Colitis 360. 2022 Feb 10;4(1):otac002. Conflict of interest: Dr. Chetwood, John: JDC has received speaker fees from Novartis, Takeda, Johnson & Johnson, and Eli Lilly. Le, Puo-Hsien: No conflict of interest Wei, Shu Chen: Consultancy fees: AbbVie, Bristol Myers Squibb, Cornerstones, Ferring Pharmaceuticals Inc., Janssen/J & ampJ, Pfizer, Sanofi, SPYRE, Takeda, ThermoFisher. Lectures and/or speakers’ bureau payments: AbbVie, Bristol Myers Squibb, Celltrion, CornerStones, Excelisior, Ferring Pharmaceuticals Inc., Janssen/J & ampJ, Pfizer, Takeda, ThermoFisher. Wu, Hsin-Yun: No conflict of interest Corte, Crispin: Grants: Ferring, GESA Consulting: Abbvie, Ferring, Celltrion, Chiesi, Janssen, Takeda. Support for travel for meetings to support study: Pfizer, Takeda, Celltrion, Chiesi, Ferring, Falk. Lightowler, Daniel: Speaker Fees: Pfizer, DrFalk, Eli Lily Advisory Board: AbbVie, Eli Lily, Menarini, Janssen, AGPAL Travel: Pfizer, Celgene, Allergen, Janssen, AbbVie Research Support: Janssen, Ferring Education: DrFalk, AbbVie, Janssen, Pfizer Gilmore, Robert: Grant support from the Gastroenterological Society of Australia (GESA) and speaker honoraria from Johnson and Johnson, Pfizer, and education or conference support from Pfizer Chin, Simone: No conflict of interest Garg, Mayur: No conflict of interest Bahmani Kashkooli, Soleiman: Research grants from AbbVie and Janssen. Xu, Ziheng: No conflict of interest Wright, Emily Kate: Speaker Fees, Consultancy and Advisory Boards: AbbVie, Celltrion, Falk, Ferring, Janssen, Pfizer. Research funding/support: AbbVie, Ferring, Janssen. 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 O’Donnell, Jonathan: Grants: AVANT Foundation, Medical Insurance Group of Australia (MIGA) Lewindon, Peter: No conflict of interest Subramanian, Kavitha: No conflict of interest Huang Fu, Janny: No conflict of interest Moore, Gregory Thomas: Advisory boards: AbbVie, Celltrion, Eli Lilly, Gilead, J&J, Pfizer, Takeda Speakers fees: AbbVie, Falk, Ferring, J&J, Pfizer, Roche, Sandoz, Takeda Research support: MRFF, NHMRC, CCA, GESA, Gutsy Group, AbbVie, Janssen, Pfizer, Shire, Takeda Subhaharan, Deloshaan: No conflict of interest Mohsen, Waled: No conflict of interest Tan, Zhi: 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 Ghali, Mark: No conflict of interest Ghaly, Simon: Speaker fees, research grants and travel grants from Dr. Falk pharma, Janssen, Pfizer, AbbVie, Sandoz and Ferring and served on advisory boards for Pfizer and AbbVie. De Cruz, Peter: No conflict of interest Lo, Sheng Wei: No conflict of interest Paramsothy, Sudarshan: SP has served as a consultant for Vedanta Biosciences and has received speaker / advisory board fees from AbbVie, Dr Falk Pharma, Ferring, Janssen and Takeda. Leong, Rupert: advisory board: AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda, Spyre, Roche research grants: Joanna Tiddy USYD, McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer