Can Remission Be Restored in IBD Patients Receiving Ustekinumab Who Have Lost Response?

Introduction: Ustekinumab is an anti-interleukin 12 and 23 antibody FDA approved for the management of psoriasis (2009), PSA (2013), CD (2016), and recently UC (2019). As in the case with all biologicals and small molecules we administer to IBD patients, loss of response occurs with variable frequency. In this report of five patients, we restored remission by decreasing the maintenance dosing interval from 8 weeks to 4 weeks. Case description/methods: In our tertiary referral clinic we identified two patients with CD (one male and one female), whom each had enjoyed clinical remission (HBI < 5) receiving ustekinumab (mean duration three years). Mild malaise, increased stool frequency, and arthralgias recurred in both. Each had a rise in their HBI scores (7 and 8). Three patients with UC, all males whom had received ustekinumab (mean duration 14 months) were felt to be in remission (partial Mayo scores 0) presented for follow up with loose/frequent stools, bleeding, and malaise. One experienced arthralgias and one with abdominal discomfort. The new pMayo scores of 6, 9, and 9 suggested relapse. All five were evaluated for Clostridium difficile, other enteric pathogens, had drug levels, fecal calprotectin, CRP, routine chemistries and CBC obtained. Every patient had received ustekinumab at standard maintenance dosing of 90mg every 8 weeks. None of the patients acquired enteric infections. The UC patients had increases from their baseline fecal calprotectin, which were previously normal. One of the CD patients whom had a normal fecal calprotectin during clinical remission had a modest increase while the other did not. None of the patients had a change in CRP. All patients had drug levels < 1.2 mcg/ml (range 0.93-1.1 mcg/ml). Maintenance therapy was decreased from 8 to 4 weeks with mean followup time of 4 months (range 3-6 months) found all patients in clinical remission (HBI < 5; pMayo < 2). Trough levels had risen to > 4 (range 4.3-6.5) in all patients. Discussion: Loss of response is an unfortunate yet common occurrence observed in the management of IBD patients. Therapeutic drug monitoring allows us the opportunity to adjust drug administration to achieve ideal levels. Research has shown trough ustekinumab levels ≥2.0 mcg/ml are associated with response during induction. In this open label study, we found subjects with loss of remission had suboptimal drug levels. Upon a decrease in maintenance dosing intervals, each patient experienced restored remission correlating with adequate ustekinumab trough levels.