DOP085Baseline predictors and clinical outcomes of risankizumab dose optimization: a real-world multicenter retrospective study

Abstract Background A subset of risankizumab (RZB)-treated patients experience suboptimal or secondary loss of response to standard dosing. We explored factors associated with future RZB dose-optimization, and outcomes of optimization in a multicenter consortium of adults with Crohn’s Disease (CD). Methods Baseline characteristics at time of RZB initiation and subsequent clinical, endoscopic, and biochemical outcomes were collected in a multi-center cohort. Outcomes for dose-optimized RZB were reported as clinical response and remission (based on HBI or PGA when HBI unavailable), endoscopic remission (based on SEMA-CD or absence of ulcers when SEMA-CD not available), and biochemical response. Characteristics were compared between standard and dose-optimized groups using chi-square and two-sample t-tests. Additional models adjusting for age and sex assessed predictors of dose optimization. Results We identified 309 patients treated with standard dose and 58 for whom dose-optimized RZB was recommended. Of the 58, 29 were excluded from outcomes analysis due to lack of follow-up (n = 19) or insurance denial of dose optimization (n = 10). Demographic information is outlined in Table 1. Baseline characteristics associated with future dose optimization included number of prior advanced therapies (ATs) (OR, 1.29, p 0.001), prior anti-TNF (OR,4.06; p = 0.022), and prior ustekinumab (UST) use (OR,1.82; p = 0.053) (Table 2). The 29 patients included in the outcome analysis received dose-optimized RZB for primary non-response (n = 2), partial response (n = 23), or secondary loss of response (n = 4) after a median of 321 days (IQR, 234-440) from index RZB start. Median follow-up after dose optimization was 217 days (IQR, 147-331). All patients were AT-exposed (Table 1). Baseline clinical symptoms were present in 27 patients (93.1%), with median HBI of 6.5 (IQR, 6.0-8.0). Active endoscopic disease was observed in 11/12 patients (91.7%) who had baseline endoscopy. Dosing was every 4 weeks in 19 (65.5%), every 6 weeks in 9 (31.0%), and combined IV re-induction plus every 4-weeks in 1 (3.4%) patient. Clinical response and remission was seen in 16 (55.2%) and 12 (41.4%) patients, respectively. A ≥ 50% CRP reduction was seen in 5/12 (41.7%) patients with baseline elevated CRP. Among 7 patients with baseline active endoscopic disease with available follow-up, 3 (42.9%) achieved endoscopic remission. No adverse events were reported. Conclusion In this multi-center retrospective cohort, prior AT-exposure (especially anti-TNF) was associated with need for RZB dose-optimization. Dose optimization successfully captured clinical response in a significant proportion of patients who experienced partial response or loss of response to RZB. Conflict of interest: Johnson, Amanda: Research grant: Abbvie, Spyre Therapeutics Ramesh, Prajith Raj: None Said, Hyder: No conflict of interest Huang, Katherine: No conflict of interest Devi, Jalpa: none Pekow, Joel R.: CVS Health - Consulting Abbvie, Eli Lilly, Pfizer, Johnson and Johnson - Stocks Alhobayb, Tamara: No conflict of interest Bassmeyer, Blake: No conflict of interest Mohamed, Mouhand: No conflict of interest Shivashankar, Raina: Abbvie and BMS - speaker bureau Janssen and Celltrion - grant for IBD fellowship funding Pfizer - consultant Rathi, Jaya: No conflict of interest Luu, Bryan: No conflict of interest Khan, Abdul: No conflict of interest Loftus, Jr, Edward: Grant: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Gilead, Janssen, Pfizer, Receptos, Robarts Clinical Trials, Takeda, Theravance, UCB. Personal Fees: AbbVie, Allergan, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, Iterative Scopes, Janssen, Ono Pharma, Pfizer, Sun Pharma, Takeda, UCB. Bishu, Shrinivas: None Patel, Anish: speaker: abbvie, J & J, Lilly, BMS, Pfizer, Phathom, Takeda consultant: abbvie Shukla, Richa: Speakers bureau - Abbvie and Lilly Yarur, Andres: Personal Fees: Consultant for Takeda, Pfizer, Roche, Merck, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Johnson and Johnson. Ungaro, Ryan: Personal Fees: AbbVie, Bristol Myers Squibb, Genentech, Lilly, Pfizer, Janssen, Takeda Deepak, Parakkal: Parakkal Deepak has received research support under a sponsored research agreement unrelated to the data in the abstract from AbbVie, Johnson and Johnson, Sanofi, Merck, Teva, Direct Biologics, Tr1x, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals, Roche Genentech, Eli Lilly, AstraZeneca, Spyre and Agomab, has received consulting fees from Johnson and Johnson, Abbvie, Merck, Sobi, Celltrion, Fresenius Kabi, Asahi Kasei Pharma, Sandoz and CorEvitas, LLC and has served on the board of the Srategic Alliance for Intercultural Advocacy in GI.