Dose Modification of Induction Risankizumab in a Liver Transplant J-Pouch Patient With de Novo Crohn's Disease

Background:
Risankizumab, a monoclonal antibody that targets the p19 subunit of interleukin-23, is approved for both moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC) patients. The standard induction regimen for CD involves 3 doses of 600 mg at weeks 0, 4, and 8. However, dose modification during the induction period has not been reported in literature, particularly to mitigate potential drug toxicity.
Methods:
A 49-year-old male with a history of inflammatory bowel disease (IBD) presented to the IBD clinic for management. Originally diagnosed at age 15 with UC pancolitis, he required a total abdominal colectomy and ileoanal pouch anastomosis at age 21 for refractory disease. His post-surgical course was complicated by chronic antibiotic-dependent pouchitis. He was diagnosed with primary sclerosing cholangitis (PSC) at age 39 and underwent orthotopic liver transplant (OLT) for PSC and 3.5-cm cholangiocarcinoma found on explant. He received 3 months of adjuvant chemotherapy post-transplant. After his OLT, immunosuppression was weaned, and he became symptomatic. Pouchoscopy revealed scattered deep ileal ulcers. Biopsies showed chronic active inflammation. He was started on vedolizumab for de novo CD of the pouch and proximal small bowel, but required hospitalization due to acute cellular rejection (ACR) after the third vedolizumab induction dose. Vedolizumab was discontinued based on his hepatologist’s recommendation, and he continued a prolonged steroid taper. However, he remained symptomatic at lower steroid doses. Magnetic resonance enterography (MRE) showed a focal small bowel inflammatory stricture, and the patient was referred to the IBD clinic for further management. After consultation between his providers, he was started on risankizumab. Due to concerns for hepatotoxicity, the first induction dose was modified. He received 300 mg initially, followed by another 300 mg 2 weeks later, with weekly liver function tests for close monitoring. He then completed the standard induction dosing of Skyrizi at 600 mg at weeks 4 and 8. Clinically, he remained symptomatic and prednisone-dependent. After the first maintenance dose of 360 mg, the patient was hospitalized and was found to have recurrent PSC in the OLT. Despite this, risankizumab was continued, with reassessment after 6 months of treatment.
Results:
The patient clinically improved, and a pouchoscopy confirmed endoscopic remission, demonstrating bowel healing with no active inflammation.
Conclusions:
There is a lack of evidence supporting the splitting of risankizumab doses in OLT patients. However, given the patient’s history of ACR post-OLT on vedolizumab, there was clinical hesitation in initiating therapy at standard dosing. After close collaboration between his providers risankizumab was chosen with modified induction dosing to minimize risk of hepatotoxicity. Although this was mitigated, the modified induction dosing of risankizumab may have altered the drug’s pharmacokinetics, potentially delaying clinical and endoscopic response. In clinical practice, it would be reasonable to consider changing therapy given the delay in response, which could risk losing a safe and effective treatment option for OLT patients with IBD. This case underscores the importance of carefully monitoring dose modifications and the safety of risankizumab in this population. Further research is needed to better understand the pharmacokinetics and safety of risankizumab dose modifications in PSC post-OLT IBD patients.