Ustekinumab IV 6 mg/kg Loading Dose Re-induction Improves Clinical and Endoscopic Response in Crohnʼs Disease: A Case Series (2018)

CASE: Ustekinumab, a monoclonal antibody to the p40 subunit shared by interleukins-12,23, is approved for treatment of patients with moderate to severe Crohn's disease(CD) with a weight-based intravenous ustekinumab induction followed by subcutaneous maintenance therapy (Feagan et al, 2016). TNF inhibitors are associated with clinical and endoscopic response. Among anti-TNF experienced patients receiving induction at Week 6, higher serum drug concentrations are associated with clinical response, suggesting that there may be a therapeutic benefit to optimizing ustekinumab drug concentrations to augment clinical response (Sandborn et al, 2012). We present our preliminary experience at a tertiary care center to support this hypothesis. We report 3 patients with moderate to severe anti-TNF experienced CD initiated on ustekinumab therapy, who had minimal response after non-weight based subcutaneous induction; loading with intravenous weight-based Ustekinumab led to clinical and/or endoscopic improvement (Table 1). Patient 1 was a 35-year-old woman with ileocolonic CD with prior intestinal resections and colectomy with ileoanal pouch who had failed multiple anti-TNF therapies and vedolizumab. The patient had improvement in clinical and endoscopic measures after intravenous reloading with ustekinumab. Initiation of ustekinumab combination therapy as well as steroids did not improve disease activity; however, pouchoscopy three months after reloading dose showed improvement in endoscopic disease activity, and the patient was able to wean off corticosteroids. Patient 2 was a 44-year-old man with history of Crohn's ileocolitis with perianal fistulas with prior small bowel resections. The patient was a primary non-responder to Infliximab and did not respond to Vedolizumab combination therapy. He was initiated on ustekinumab combination therapy with improvement in ulceration at the ileocolonic anastomosis; however, he had ongoing abdominal pain, diarrhea, and perianal drainage. After intravenous induction with ustekinumab, his clinical symptoms improved and was able to taper off steroids. Patient 3 was a 26-year-old man with history of ileocolonic Crohn's disease who had secondary loss of response to Infliximab therapy, primary non-response to adalimumab, and was started on ustekinumab combination therapy. He was subsequently hospitalized with an intra-abdominal abscess requiring drainage and antibiotics. After intravenous reinduction of ustekinumab, he had clinical and endoscopic response and successfully tapered off steroids. All 3 patients showed improvement in clinical response after intravenous dosing of ustekinumab with successful tapering of corticosteroids. Endoscopic evaluations showed endoscopic as well as histologic improvement. With further development of therapeutic drug monitoring for ustekinumab, drug concentrations may aid in the use of intravenous loading of ustekinumab, identifying appropriate patients where a rescue dose may augment a sub-optimal response. Based on these preliminary findings, re-induction dosing of ustekinumab in patients on maintenance therapy with sub-optimal clinical response or ongoing steroid dependence may improve outcomes. Prospective studies in patients with Crohn's disease receiving ustekinumab therapy are warranted to elucidate the best approach for optimizing drug therapy.