PD-011 Efficacy, Safety and Timing of Dose Adjustment of Subcutaneous Ustekinumab Maintenance in Moderate –Severe Crohn's Disease Patients in IM-UNITI

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Abstract

Background:

Ustekinumab (UST) has been shown to induce and maintain clinical response and remission in moderate to severe Crohn's disease (CD) in 2 induction (UNITI-1 and 2) and 1 maintenance (IM-UNITI) randomized, placebo controlled Phase 3 trials. The efficacy of UST after dose adjustment following loss of response (LOR) was also examined in the randomized patients in IM-UNITI, starting at week 8.

Methods:

Patients achieving clinical response after single dose IV induction were randomized to SC maintenance placebo (PBO), UST 90 mg every 12 weeks (q12w) or UST every 8 weeks (q8w). Patients who met LOR criteria, defined as a CDAI score of ≥220 and a ≥100 point increase from the maintenance baseline CDAI score, between weeks 8 and 32 of the maintenance trial could undergo a single dose adjustment as follows: PBO→q8w, q12w→q8w, and q8w→q8w (no dose adjustment) and were assessed for clinical response (≥100 point decrease in CDAI) and clinical remission (CDAI <150) 16 weeks later.

Results:

Among the UST induction responders, 51 (39%), 29 (22%), and 28 (22%) patients in the PBO, q12w and q8w groups, respectively, underwent dose adjustment after meeting LOR criteria. Among these patients, clinical remission and clinical response were observed in 39% and 71% of patients adjusting PBO→q8w, 41% and 55% in the q12w→q8w group, and 32% and 46% in the q8w→q8w group when assessed 16 weeks later. Of the 29 patients adjusting from q12w→q8w, 16 (55%) adjusted by week 12 of the maintenance trial, with 11 patients (38%) who adjusted by week 8. Among these 16 early q12w→q8w dose adjusters, median induction baseline CDAI scores were higher than the overall randomized population (326.5 versus 315) and median CDAI at the time of LOR was 307. Nonetheless, of these 16 patients who dose adjusted prior to receiving their second SC dose, 7 (43.8%) were in clinical remission and 10 (62.5%) were in clinical response 16 weeks later. Among all patients who underwent dose adjustment, median change in CDAI after adjustment was −121, −141 and −78.5 in the PBO→q8w, q12w→q8w and q8w→q8w groups, respectively. No increases or changes in patterns of adverse events were seen among patients who dose adjusted.

Conclusions:

In patients who met LOR criteria, dose adjustment from UST 90 mg q12w to 90 mg q8w provided some additional clinical benefit compared to patients who remained on UST 90 mg q8w. Patients with higher disease burden at induction baseline may benefit from maintenance dosing of UST 90 mg q8w.

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