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Perianal fistulizing Crohn’s disease (pCD) is associated with higher direct medical costs compared to luminal CD. Data on indirect costs, including productivity losses, are scarce, limiting our understanding of the full societal burden of pCD. Therefore, we evaluated the societal impact of active pCD by quantifying both direct and indirect costs and to explore how these costs vary according to disease duration. A prospective study was performed in which patients with active pCD (draining fistula, visible external fistula orifice and/or an active fistula on imaging) were included within 41 hospitals in the Netherlands between September 2022 and March 2023. Follow-up duration was one year. The medical (direct) in-hospital costs, including IBD medication, hospital visits, radiological and endoscopic procedures, and surgical interventions, were extracted from electronic medical records. Out-of-hospital (direct) costs were assessed with an adapted version of the iMTA Medical Consumption Questionnaire (iMCQ). Indirect costs, comprising absenteeism and presenteeism, were measured with the iMTA Productivity Cost Questionnaire (iPCQ). Both were collected at baseline, 3, 6, and 12 months. The Dutch costing manual was used to determine cost prices. Missing data were imputed using multilevel multiple imputation by a lineair mixed model based on predictive mean matching. Costs were presented as mean annual costs per patient in the year 2023. A total of 440 patients were included (mean age 40 (SD 13.4); 53% female; median pCD duration 3.2 years [IQR 1.2-7.5], 66% were treated with anti-TNF agents). The mean annual costs per patient were €40.976 (95% confidence interval 37420-44532). Medication costs accounted for €14.954 (13839-16068) of which €14.683 (13567-15800) were attributable to biologicals. Hospital visits were €3.206 (2680-3733). Radiological assessments and endoscopic procedures contributed €400 (357-444) while surgical interventions, including treatment with Darvadstrocel, amounted to €5.421 (3877-6965) per patient per year. Out-of-hospital medical costs (general practitioners, psychosocial workers) averaged €550 (331-769). Annual indirect costs were €16.885 (13186-20585) per patient, comprising absenteeism (€12.975, 9402-16547; and presenteeism (€3.911, 3210-4611). Indirect costs remained stable across pCD duration (Figure 1, 2). The total annual costs per patient with active pCD are substantial and remain high independent of disease duration. Costs are primarily driven by biological therapies and productivity loss due to absenteeism. Absenteeism consistently accounts for more than 25% of total costs, underscoring the impact of active pCD on the ability to work and the overall societal burden. Conflict of interest: Ms. Verweij, Merel: No conflict of interest Bak, Michiel: Grant: Unrestricted research grant from Falk Pharma Benelux Other: Speaker fees from AbbVie Heemskerk, Stella: No conflict of interest Post, Richard: No conflict of interest Stassen, Laurents: Grant: Karl Storz GmbH Other: Diagnostic Green USA Buskens, Christianne J.: Grant: C. Buskens has received an unrestricted grant from Boehringer Ingelheim and Roche Personal Fees: C. Buskens has received consultancy fees and/or speaker’s honoraria from Tillotts, Takeda, MSD and Janssen Pronk, Annelies: No conflict of interest Van Der Bilt, Jarmila: No conflict of interest Gecse, Krisztina B.: Grant: Abbvie, Pfizer Inc, Celltrion and Galapagos/Alfasigma Personal Fees: Consultancy fees from AbbVie, Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Pfizer Inc., and Takeda and speaker’s honoraria from Celltrion, Eli Lilly, Janssen Pharmaceuticals, Pfizer Inc. and Takeda. De Boer, Nanne: No conflict of interest Witjes, Caroline: No conflict of interest Fitzpatrick, Claire: No conflict of interest Pierik, Marieke: Grant: TKI, MLDS, Galapagos, Janssen-Cilag, Takeda, Pfizer Other: Financial support to institution for consultancy or lectures: Takeda, Janssen-Cilag, BMS, MSD, Abbvie, Galapagos, Ferring Breukink, Stephanie: No conflict of interest Nissen, Loes: No conflict of interest Verdaasdonk, Emiel: No conflict of interest Gilissen, Lennard: none Bloemen, Johanne: No conflict of interest West, Rachel: No conflict of interest Kortekaas, Robert: No conflict of interest Mares, Wout: No conflict of interest De Jong, Gabie: No conflict of interest Janssen, Sita: No conflict of interest Bloemendaal, Bob: No conflict of interest Sikkema, Marjolein: No conflict of interest Zimmerman, David: No conflict of interest Peeters, Koen: No conflict of interest Van der Meulen - de Jong, Andrea Elisabeth: No conflict of interest van Schaik, Fiona: FDM van Schaik has received consultancy fees from Takeda, Galapagos and AbbVie, speaker’s honoraria from Galapagos, Lilly, AbbVie and Janssen-Cilag B.V., hospitality fees from Ferring and dr. Falk Farma and an unrestricted research grant from Takeda. Richir, Milan: No conflict of interest Dongen, Koen: No conflict of interest Duijvestein, Marjolijn: Grant: Speaking fees from Bristol Meyers Squibb, Takeda, Galapagos, Janssen, Dr. Falk, Advisory board fees from Abbvie, Bristol Meyers Squibb, Celltrion, Galapagos/Alfasigma, Janssen, Takeda Grant/Research support: Pfizer, Bristol Meyers Squibb, Galapagos, Alfasigma, Janssen, Lilly Hoogenboom, Froukje J.: No conflict of interest Visschedijk, Marijn: No conflict of interest Molendijk, Ilse: Advisory board and / or financial compensation from the following companies: Abbvie, Dr. Falk and Johnson & Johnson Van Ruler, Oddeke: No conflict of interest De Vries, Annemarie C.: Grant: Grants, advisory boards: Pfizer, Galapagos, Takeda, Janssen
12080 Background: Chemotherapy-induced peripheral neuropathy (CIPN) and Neutropenia are significant side effects associated with many cancer drugs and are highly prevalent in mCRC patients receiving oxaliplatin-based regimens. CIPN can severely impact quality of life (QoL) and may require dose vacation, reduction or interruption. CIPN pathology is complex and not completely understood; preclinical and clinical data have shown inflammatory (IL-6, Il-8, IL-10) and immune involvement as well as elevated levels of sphingolipids, a class of bioactive signaling molecules. Neutropenia can also be a potentially severe side effect and may occur in up to 40% of mCRC patients receiving FOLFOX. BXQ-350 is a nanovesicle formulation of Saposin C, an allosteric activator of sphingolipid metabolism that normalizes dysregulated sphingolipid metabolism by lowering S1P, GM3 and GluCer levels while it increases ceramide level, promoting a return to homeostasis. Methods: BXQ-350 is being investigated in a Phase 1b/2 study in combination with mFOLFOX7 and Bevacizumab (SoC) in newly diagnosed mCRC patients (NCT05322590). Primary objectives are to assess safety and preliminary efficacy of this combination, and to determine cumulative oxaliplatin dose. Secondary objectives include intensity, frequency and time to onset of CIPN. Results: The Phase Ib trial enrolled 33 oxaliplatin dosing evaluable patients; all patients completed the primary treatment period (6 months of SoC treatment plus BXQ-350). Amongst the 33 patients, 19 completed the full 12 Cycles of oxaliplatin dosing, 28 completed at least 8 Cycles with only 2 patients having dosing halted before Cycle 8 due to CIPN. There were no reported Grade 4 and only 3 reported Grade 3 CIPN AEs, all occurred after Cycle 12. Analysis of Neurofibrillary Light Chain (NfL) biomarkers suggests concordance with physician and patient reported outcomes. Grade 3 or higher Neutropenia was meaningfully reduced to 5% in mCRC patients receiving FOLFOX plus Bevacizumab. Conclusions: Results show that BXQ-350 was safe and well tolerated in the combination. Data suggest that BXQ-350 may provide additional clinical benefits and may reduce intensity or delay onset of CIPN while meaningfully reducing Grade 3 or higher Neutropenia, allowing for increased cumulative dosing of oxaliplatin and relative dose intensity in 1L mCRC. Clinical trial information: NCT05322590 .
