P5382 - Advanced Combination Therapy of Upadacitinib and Biologic Therapy in Refractory Inflammatory Bowel Disease Patients

Wafa Alkarni, MBBS¹, Hend Almuhaya, MBBS¹, Naif Alrossais, MBBS¹, Sameer Desai, ¹, Abdulelah Almutairdi, MD¹, Badr Al Bawardy, MD², Mashary Attamimi, MD¹
1King Faisal Specialist Hospital and Research Centre, Riyadh, Ar Riyad, Saudi Arabia; 2Yale New Haven Hospital, New Haven, USA; King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, New Haven, CT

Introduction: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), has increased globally in recent decades. Despite therapeutic advances, remission rates remain modest (30–40% at 12 months). This study aims to assess the safety and efficacy of advanced combination therapy (ACT) using upadacitinib and another biologic in patients with IBD.

Methods: This is a retrospective, single centre study that included patients ≥14 years with confirmed IBD [CD, UC, IBD-unclassified (IBD-U)] who received upadacitinib plus another biologic for ≥4 months. Eligible patients had refractory IBD, defined as failure of ≥2 therapies with different mechanisms of action and active disease clinically or endoscopically. Primary outcome: clinical remission at 4 months. Secondary outcomes: clinical/endoscopic response, endoscopic remission during follow-up, and adverse events during treatment.

Results: A total of 14 patients with refractory IBD were started on ACT (n=10 females [71%]; n=10 with CD [71%]), with a median disease duration of 7 years and a median follow-up of 8 months. All CD patients had Ilecolonic involvement, penetrating disease was present in (n=6; 60%), and (n=8; 80%) had perianal disease. Among UC patients (n=4), 2 (50%) had pancolitis and 2 (50%) had left-sided colitis. The median number of prior advanced therapies was two. At baseline, 62% had elevated C-reactive protein (CRP) and 93% had elevated fecal calprotectin (FCP). Endoscopic assessment revealed active disease in all patients (Table 1). Ustekinumab was the most commonly used concurrent biologic with upadacitinib (n=8; 57%), followed by vedolizumab (n=4; 29%) and risankizumab (n=2; 14%). Upadacitinib was initiated at a dose of 45 mg in most patients (n=13; 93%); (n=5; 36%) received a maintenance dose of 30 mg, while the remaining continued on 45 mg. At 4 months, (n=5; 36%) achieved clinical remission, and (n=6; 43%) showed a clinical response. Endoscopic data were available for 8 patients: (n=2; 25%) achieved remission, (n=2; 25%) showed a response, and (n=4; 50%) had no endoscopic improvement (Figure 1). Two patients (n=2; 14%) developed non-serious infections during ACT. One UC patient (7%) underwent colectomy for uncontrolled disease.



Discussion: ACT with upadacitinib and another biologic demonstrated promising clinical and endoscopic outcomes in refractory IBD and appeared to be well tolerated. Larger studies with longer follow-up duration are needed to further elucidate its long-term efficacy and safety.


Figure: Table 1: Demographics and other clinical characteristics



Figure: Figure 1: Clinical and endoscopic outcomes

Disclosures:
Wafa Alkarni indicated no relevant financial relationships.
Hend Almuhaya indicated no relevant financial relationships.
Naif Alrossais indicated no relevant financial relationships.
Sameer Desai indicated no relevant financial relationships.
Abdulelah Almutairdi: AbbVie – Advisory Committee/Board Member, Speakers Bureau. Amgen – Advisory Committee/Board Member. Bristol myers squibb – Advisory Committee/Board Member, Speakers Bureau. Janssen – Advisory Committee/Board Member, Speakers Bureau. Lilly – Advisory Committee/Board Member. Pfizer – Advisory Committee/Board Member. Takeda – Advisory Committee/Board Member, Speakers Bureau.
Badr Al Bawardy: AbbVie – Advisor or Review Panel Member, Consultant, Speakers Bureau. Bristol Myers Squibb – Advisory Committee/Board Member, Speakers Bureau. Eli Lilly – Advisory Committee/Board Member, Speakers Bureau. Hikma – Speakers Bureau. Janssen – Advisory Committee/Board Member, Speakers Bureau. Pfizer – Advisory Committee/Board Member. TAKEDA – Advisor or Review Panel Member, Speakers Bureau.
Mashary Attamimi: AbbVie – Speakers Bureau. Hikma – Speakers Bureau. Janssen – Speakers Bureau. Lilly – Speakers Bureau. Pfizer – Speakers Bureau. Sandoz – Speakers Bureau. Takeda – Speakers Bureau.

Wafa Alkarni, MBBS¹, Hend Almuhaya, MBBS¹, Naif Alrossais, MBBS¹, Sameer Desai, ¹, Abdulelah Almutairdi, MD¹, Badr Al Bawardy, MD², Mashary Attamimi, MD¹. P5382 - Advanced Combination Therapy of Upadacitinib and Biologic Therapy in Refractory Inflammatory Bowel Disease Patients, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.