Background: The use of corticosteroids (CS) in the management of Crohn's disease (CD) is limited by important toxicity. Ustekinumab (UST) has been shown to induce (UNITI 1&2) and maintain (IM-UNITI) clinical response and remission in CD. We evaluated the efficacy of UST on the achievement of CS-free remission and response in participants in IM-UNITI.
Methods: IM-UNITI was a Ph3, double-blind placebo (PBO)-controlled maintenance trial in moderate-severe CD pts who achieved clinical response to UST at wk 8 in one of two UST IV induction UNITI studies. Pts could enter the induction studies while receiving CS; the dose remained stable throughout the 8 wk induction trials. Pts on CS and in clinical response upon entry into IM-UNITI began mandatory CS tapering at wk 0 of maintenance. At wk 44, CS-free remission, CS-free response, and CS-free remission without the use of CS for at least 30 and 90 days were assessed in the primary randomized population regardless of baseline CS use. Similarly, CS-free remission and CS-free response were also assessed at wk 44 in pts who were receiving CS at enrollment baseline.
Results: A significantly greater proportion of pts in the UST 90mg q8w group (46.9%, p=0.004) and a nominally significant greater proportion of pts in the 90mg q12w group (42.6%, p=0.035) were in CS-free remission at wk 44 compared with the PBO group (29.8%) (Table). Likewise, a greater proportion of pts in the UST 90mg q12w group (51.2%, p=0.024) and 90mg q8w group (50.8%, p=0.026) were in CS-free response at wk 44 compared with pts the PBO group (36.6%). The proportions of pts in the PBO group that were in remission and off CS for 30 and 90 days (29.8% and 29%, respectively) were lower than in the 90mg q12w (42.6% and 41.1%, respectively) and 90mg q8w group (46.9% and 45.3%, respectively; p<0.05 for all comparisons vs PBO).
Among the subgroup of pts receiving CS at baseline (44.8%), a greater proportion of these pts in the combined UST group discontinued CS and achieved clinical remission or clinical response at wk 44 (30.2% and 33.6%, respectively) compared with the PBO group (15.5% and 19.0%, respectively; p<0.05 for both). A numerically higher proportion of pts in each of the two dosing groups (q12w and q8w) achieved CS-free remission and response at wk 44 compared with PBO.
Conclusions: UST achieved a higher rate of CS-free remission and response vs. PBO and this CS-sparing effect was observed over 44 wks of treatment. For pts on CS at study entry, UST showed evidence of benefit reducing the need for CS while still achieving clinical response/remission.