PTH-077 De-escalating therapy in patients with crohn’s disease receiving adalimumab: subgroup analysis of the calm study

Introduction This analysis evaluated the impact of de-escalating therapy on mucosal healing 48 weeks (wks) after randomization in patients (pts) with Crohn’s disease (CD) in the CALM study. Methods Pts with moderate-to-severe CD naïve to immunomodulators and biologics were randomized 1:1 to a tight control group (TCG) or clinical management group (CMG) after 8 wks of prednisone therapy. Treatment was escalated from no treatment to 40 mg adalimumab (ADA) every other wk (EOW) to 40 mg ADA every wk (EW) to 40 mg ADA EW+2.5 mg/kg azathioprine (AZA)/day at 12, 24, and 36 wks after randomization based on failure criteria (CD Activity Index [CDAI]=200 or decrease <70 points [1 wk pre-randomisation] or <100 points versus baseline [at wk 11, 23, 35] and prednisone use for the CMG; CDAI=150, C-reactive protein=5 mg/L, faecal calprotectin=250µg/g, and prednisone use for the TCG). At 24 and 36 wks, if failure criteria were not met, patients de-escalated ADA EW dose to 40 mg ADA EOW. Pts re-escalated if failure criteria were met at the next visit. The primary endpoint (mucosal healing [CD Endoscopic Index of Severity <4] and no deep ulcers at 48 wks post-randomisation) was evaluated in pts who de-escalated treatment. Analyses were performed in pts who completed the study and did not move to rescue therapy. Non-responder imputation was used for missing data. Results 15 pts in the CMG and 31 pts in the TCG de-escalated treatment during the study. Of those, 2 pts in the CMG and 8 pts in the TCG re-escalated to 40 mg ADA EW. Overall, 54% of pts in the CMG and 61% of pts in the TCG who de-escalated to 40 mg ADA EOW ± AZA achieved the primary endpoint (table 1). Of the pts who re-escalated to ADA EW, 0% in the CMG, and 75% in the TCG achieved the primary endpoint (table 1). The overall adverse event rates have been previously reported (Colombel, 2018) Conclusions Our data suggest that repeated dose optimization based on tight control is a more refined approach resulting in mucosal healing compared with clinical management. Larger data sets are needed to confirm our observation on repeated dose optimization. Reference Colombel, et al. Lancet 2018;390:2779–89.

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