Kerri Glassner, DO, Caroline Perry, BS, Amanda Wilhite, PA-C, Bincy Abraham, MD, FACG
Houston Methodist Hospital, Houston, TX
Introduction: Ustekinumab is an IL-12/23 inhibitor used for the treatment of Crohn’s disease (CD). Previous studies have suggested that dose escalation to every 4-week intervals can be beneficial in patients who do not achieve a clinical response on every 8-week maintenance dosing. However, safety and efficacy is unknown in CD patients escalated to more frequently than every 4-week intervals in patients who continue to have low trough drug levels.
Methods: We performed a retrospective chart review of patients on ustekinumab for CD who had dosing escalation to every two weeks(Q2) due to persistent low drug levels (< 5µg/mL) despite being on q4 weeks (Q4) maintenance dosing and clinically losing response.
Results: Out of 200 CD patients on ustekinumab 90mg subcutaneous (SQ) maintenance in our IBD program, 112 underwent reactive therapeutic drug monitoring for loss of response or incomplete response to therapy. Of the 112 with drug levels, none had anti-drug antibodies, but 80 patients had levels < 5mcg/mL. All 80 patients were frequency escalated to q4 week dosing. Of these, 12 patients continued to have low ustekinumab trough levels at week 4 (< 5 mcg/mL) and thus were escalated to Q2 week dosing. Eight of the 12 patients had IV reinduction dosing prior to dose escalation to Q2 frequency. Of the 12 patients, 6 (50%) required surgery for their active Crohn’s disease. These patients were on Q2 week dosing for median of 16 weeks (range 1- 68) prior to surgery. All 6 (100%) were able to be de-escalate to less frequent dosing after surgery. Two patients that were unable to de-escalate their dosing frequency are planning for surgery in the near future. The remaining four patients were able to de-escalate to Q4 dosing after clinical response. See full details in Table 1. No adverse events unrelated to their Crohn’s disease, including infections or other safety markers were noted.
Discussion: Low levels of ustekinumab despite escalation of dosing to every 2 weeks may suggest a need for Crohn’s disease related surgery. In our study, all patients who underwent surgery were able to de-escalate to lower dosing frequency suggesting that high inflammatory disease burden contributed to the low levels of ustekinumab. Further studies are needed to assess the safety and efficacy of high frequency dosing of ustekinumab.
Citation: Kerri Glassner, DO, Caroline Perry, BS, Amanda Wilhite, PA-C, Bincy Abraham, MD, FACG. P0500 - LOW LEVELS OF USTEKINUMAB DESPITE DOSE ESCALATION IS A RISK FACTOR FOR SURGERY. Program No. P0500. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.