SUMMARY  

• Please refer to STELARA local labeling for any relevant information on this topic.
• The efficacy and safety of STELARA was evaluated in 3 randomized, double-blind, placebo-controlled phase 3 clinical studies in adult patients with moderately to severely active Crohn’s disease (CD): two 8-week intravenous (IV) induction studies (UNITI-1 and UNITI-2), followed by a 44-week subcutaneous (SC) randomized withdrawal maintenance study (IM-UNITI), representing 52 weeks of therapy.¹
• A post hoc analysis was conducted to evaluate the impact of body mass index (BMI) on the efficacy of STELARA in the IM-UNITI trial. The rates of clinical remission (CR) in patients with underweight BMI did not differ significantly compared with those whose BMI was normal, overweight, or obese at week 44 of the IM-UNITI trial. At week 44, ustekinumab drug level was significantly lower in patients who were obese compared with patients who were overweight (P=0.021) or had an underweight or normal BMI (P=0.014). Although BMI impacts ustekinumab drug levels, there was no impact of BMI on clinical efficacy.²
• A retrospective, observational, cohort study evaluated the association between low muscle mass (LMM) and the efficacy of biologics, including STELARA, in adult patients with moderate-to-severe CD.³

CLINICAL DATA

UNITI Phase 3 Trial Program

The efficacy and safety of STELARA was evaluated in 3 randomized, double-blind, placebo-controlled phase 3 clinical studies in adult patients with moderately to severely active CD. UNITI-1 and UNITI-2 were two 8-week IV induction studies, followed by IM-UNITI, a 44-week SC randomized withdrawal maintenance study, representing 52 weeks of therapy.¹

• Patients were randomized in a 1:1:1 ratio, to receive a single IV infusion of STELARA 130 mg, placebo and a weight-range based dose that approximated 6 mg/kg. The weight-range based STELARA doses approximating 6 mg/kg were as follows:
  • 260 mg (weight ≤55 kg)
  • 390 mg (weight >55 kg and ≤85 kg)
  • 520 mg (weight >85 kg)
• In the IM-UNITI maintenance study, patients who achieved clinical response at week 8 with STELARA during UNITI-1 or UNITI-2 were randomized to receive a SC maintenance regimen of STELARA 90 mg every 8 weeks (Q8W), 90 mg every 12 weeks (Q12W) or placebo for 44 weeks.
• For the baseline weight of patients receiving STELARA in UNITI-1, UNITI-2, and IM-UNITI, see Table: Baseline Characteristics of Weight in UNITI-1, UNITI-2, and IM-UNITI.

IM-UNITI Post Hoc Analysis

Wong et al (2020)² performed a post hoc analysis to evaluate the impact of BMI on the efficacy of STELARA in the 44-week maintenance study (IM-UNITI). The data set used in this analysis was obtained from the Yale Open Data Access project.

Methods

• For the primary efficacy endpoints, patients were stratified into the following subgroups according to their BMI at study baseline:
  • Underweight: <18.5 kg/m²
  • Normal: 18.5 to 25 kg/m²
  • Overweight: 25 to <30 kg/m²
  • Obese: ≥30 kg/m²
• The primary endpoints of interest were CR, defined as Crohn’s Disease Activity Index (CDAI)<150 and corticosteroid-free CR defined as CDAI<150 in patients using corticosteroids at baseline.
• For secondary analysis, BMI was categorized as follows:
  • Underweight/normal: <25 kg/m²
  • Overweight: 25 to <30 kg/m²
  • Obese: ≥30 kg/m²

Results

• A total of 254 patients treated with STELARA were included in this analysis.
  • 28 patients (11%) were underweight.
  • 117 patients (46.1%) had normal BMI.
  • 71 patients (28.0%) were overweight.
  • 38 patients (15.0%) were obese.
• At week 44, rates of CR were numerically higher in patients with underweight BMI (67.9%; 19 of 28 patients), compared with those whose BMI was normal (51.3%; 60 of 117), overweight (45.1%; 32 of 71), or obese (55.3%; 21 of 38); P-values=not significant (NS).
• A comparison of Q8W STELARA to Q12W STELARA arms also showed no significant differences in CR rates among the four BMI cohorts.
• Additionally, there were no significant differences seen in CR rates when comparing patients with prior biologic exposure to those who were biologic naïve. See Table: Rates of Week 44 Clinical Remission Among BMI Cohorts.

BMI as a Predictor of Week 44 CR

• When adjusted for baseline C-reactive protein (CRP) <3 mg/L and baseline immunomodulator use, which were significantly associated with week 44 CR, patients who were obese or overweight were no more likely than those with underweight or normal BMI to achieve week 44 CR (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.64-1.86; P=NS).

BMI as a Predictor of Week 44 Corticosteroid-Free CR

• When adjusted for baseline CRP <3 mg/L and baseline immunomodulator use, which were significantly associated with week 44 corticosteroid-free CR, patients who were obese or overweight were no more likely than those with underweight or normal BMI to achieve week 44 corticosteroid-free CR (OR, 1.21; 95% CI, 0.71-2.06; P=NS).

BMI as a Predictor of Week 44 Endoscopic Remission/Mucosal Healing

• At week 44, among the 28 patients with endoscopic assessment, there was no significant relationship between BMI and week 44 endoscopic remission (ER)/mucosal healing.

Impact of BMI on Ustekinumab Drug Level at Week 44

• The median drug level for the entire cohort of patients was 3.7 mcg/mL. For serum drug levels among BMI groups, see Table: Relationship of BMI with Median Ustekinumab Drug Level (mcg/mL) at Week 44.

• Among patients who had a drug level above the median value of 3.7 mcg/mL, CR rates were not significantly different in patients who were obese (41.2%; 7 of 17 patients) or overweight (59.6%; 28 of 47) as compared with those with underweight or normal BMI (52.8%; 47 of 89).

Impact of BMI on Fecal Calprotectin at Week 44

• The median fecal calprotectin (FC) was as follows:
  • 311 mcg/kg (interquartile range [IQR], 112-555) in patients who were obese.
  • 135 mcg/kg (IQR, 34-514) in patients who were overweight.
  • 298 mcg/kg (IQR, 42-569) in patients with underweight or normal BMI.
• No significant difference was seen in the median FC between patients with underweight or normal BMI vs patients who were obese or overweight. The proportions of patients with FC<250 mcg/kg were similar among the 3 groups.

Retrospective Study

Fang et al (2024)³ conducted a retrospective, observational, cohort study to evaluate the association between LMM and the efficacy of biologics, including STELARA, in adult patients with moderate-to-severe CD.

Methods

• Adult patients who received STELARA for moderate-to-severe CD (defined as a Harvey-Bradshaw Index [HBI] of ≥8 and/or a Simple Endoscopic Score for Crohn’ s Disease [SES-CD] of ≥7) between January 2015 and December 2023 were included in the study.
• Before treatment with biologics, patients underwent computed tomography (CT) at the level of L3 for skeletal muscle area assessment.
  • LMM was defined as a skeletal muscle index (SMI) of <28.4 cm²/m² in females and <39.8 cm²/m² in males. Non-LMM was defined as an SMI of ≥28.4 cm²/m² in females and ≥39.8 cm²/m² in males.
• Study outcomes included the following:
  • Clinical response (defined as a ≥3-points decrease in the HBI) during weeks 8 to 14 and weeks 24 to 30.
  • CR (defined as a decrease in the HBI to ≤4) and biochemical remission (defined as a CRP concentration of ≤5 mg/L) during weeks 8 to 14 and 24 to 30 and at week 52 and 104.
  • Endoscopic response (defined as a ≥50% decrease in the SES-CD) and ER (defined as decrease in the SES-CD to <3) during weeks 24 to 30.
  • Rate of loss of response (defined as clinical worsening following initial clinical improvement, requiring dose escalation or alternating of biologics) during weeks 24 to 30 and at week 52 and 104.

Results

• Of 269 patients with CD, 107 patients were in the STELARA cohort (43 patients with LMM and 64 patients without LMM).
• STELARA efficacy outcomes for the LMM and Non-LMM groups are presented in Table: Efficacy of STELARA Between LMM and Non-LMM Groups.

• According to the multivariate logistic regression analysis, LMM was an independent factor for:
  • A decrease in endoscopic remission at week 24 (OR=0.10, 95% CI, 0.02-0.63, P=0.014) and biochemical remission at week 52 (OR=0.21, 95% CI, 0.05-0.96, P=0.044)
  • A possible predictor of higher loss of response rate at week 24 (OR=8.85, 95% CI, 1.52-51.58, P=0.015) and week 52 (OR=5.53, 95% CI, 1.03-29.69, P=0.046).

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 21 October 2024.