P746 Real-world Effectiveness and Safety of Advanced Combination Therapy in Patients with Inflammatory Bowel Disease: A Multi-center Brazilian Study
Authors: Feitosa F C , Queiroz N S F , Parra R S , Azevedo M F C D , Schiavetti B L P , Flores C , Fróes R D S B , Boarini L R , Boratto S D F , Junior A J T A , Junior N L T G , Nóbrega F J F , Teixeira E F L , Rzetelna H , Damião A O M C , Motta M P , Sassaki L Y , Souza H S P D , Luporini R L , Ferreira S D C F , Chebli L A , Chebli J M F 
Published: January 2024

Background

Advanced Combination Therapy (ACT) involves the concurrent use of biologic agents and/or small molecules and is a viable consideration for patients with concurrent immune-mediated diseases (IMIDs), uncontrolled extraintestinal manifestations (EIMs), or refractory disease. This study aims to evaluate the real-world effectiveness of ACT in a cohort of patients with inflammatory bowel disease (IBD).

Methods

We conducted a retrospective multi-center study, including patients with active IBD initiating ACT within the last 3 years. Collected variables encompassed demographics, prior and current IBD medications, disease activity assessed by the Mayo score for ulcerative colitis (UC) and the Harvey-Bradshaw index (HBI) for Crohn’s disease (CD) at weeks 16 and 24, C-reactive protein levels (CRP), and fecal calprotectin (FC) levels. Primary outcomes were clinical response at week 16, and clinical remission at week 24. Secondary outcomes included variations in CRP and FC levels from baseline, along with the occurrence of adverse events (AE).

Results

A total of 57 patients were included in the study (35 with CD, 22 with UC), with a mean age of 39 years (SD±15.04), and 59.6% were female. The primary indication for initiating ACT was refractory disease in 49 patients, concomitant IMIDs in 8 patients, and both conditions in 3 patients. The mean follow-up was 46 weeks (SD: ±36.14 weeks). Overall, 54 patients (91.43%) had previous exposure to anti-TNF, 35 (61.40%) to ustekinumab (UST), and 24 (42.1%) to vedolizumab (VDZ). The most prevalent ACT regimens were UST + adalimumab (ADA) in 19 patients (33.34%), VDZ+ADA in 9 patients (15.79%), VDZ+UST in 9 patients (15.79%), and VDZ+tofacitinib in 7 patients (12.28%). The rate of clinical response at week 16 was 85.71% for CD and 86.26% for UC, and the proportion of patients in clinical remission at week 24 was 48.57% for CD and 40.91% for UC (Figure 1). Statistically significant differences were observed in baseline CRP levels vs. week 24 levels in CD patients (16.83 mg/dL vs. 6.26 mg/dL; p &lt; 0.0001) and in UC patients (14.5 mg/dL vs. 4.42 mg/dL; p &lt; 0.0147). Similarly, differences in baseline fecal calprotectin levels vs. levels at weeks 16-24 were statistically significant in CD patients (2307.84 mg/g vs. 865.64 mg/g; p &lt; 0.0175) and in UC patients (3309.7 mg/g vs. 971.06 mg/g; p &lt; 0.013). Nine patients (15.79%) experienced mild adverse events (AEs), none leading to treatment discontinuation.

Conclusion

In a population with refractory IBD, ACT demonstrated good tolerability and induced a significant number of patients to achieve clinical response and remission. Larger studies with extended follow-up periods are warranted to further assess the long-term outcomes of ACT in this population.