SUMMARY

• Please refer to the local labeling for relevant information on STELARA and its pharmacokinetics.
• Prospective studies that evaluated the association between serum ustekinumab (UST) drug levels and treatment response in adult patients with Crohn’s disease (CD) who received treatment with STELARA are summarized below.^1-15

clinical data

Prospective Studies

Straatmijer et al (2023)¹ evaluated the association between UST trough levels and biochemical response in adult patients with CD.

Study Design/Methods

• Adult patients with CD from 4 academic centers were prospectively enrolled in this study.
• Primary analysis: To determine the association between UST levels at week 8 and biochemical remission (C-reactive protein [CRP] level ≤5 mg/L or fecal calprotectin [FCP] level ≤250 mg/kg) at week 24.
• Secondary analysis: Quartile analysis and logistic regression to evaluate the association between UST levels at weeks 8 and 16 and rates of biochemical remission at weeks 12 and 24, respectively.
• Corticosteroid-free clinical remission (Harvey-Bradshaw Index [HBI] score ≤4) without concomitant steroid use was evaluated at weeks 12 and 24.

Results

• A total of 90 patients were included in the primary cohort, and 34 patients were included in the independent validation cohort.
• Overall, 62.1% of the study population was female, with a median disease duration of 16 years.
• At week 8, median (interquartile range [IQR]) UST trough levels in the primary and validation cohorts were 4.2 µg/mL (2.8-5.8) and 4.5 µg/mL (3.0-6.7), respectively.
• At week 16, median (IQR) UST trough levels in the primary and validation cohorts were 1.8 µg/mL (1.0-2.9) and 1.8 µg/mL (1.2-4.5), respectively.
• At week 8, significantly higher UST levels were observed among patients who achieved biochemical remission compared to those who did not at both week 12 (6.6 vs 3.9 µg/mL; P<0.01) and week 24 (6.3 vs 3.9 µg/mL; P<0.01):
  • In the logistic regression analysis, higher UST levels at week 8 were associated with higher biochemical remission at weeks 12 (Odds ratio [OR], 1.35; 95% confidence interval [CI], 1.16-1.56; P<0.01) and 24 (OR 1.31; 95% CI, 1.13-1.52; P<0.01).
  • In the quartile analysis, patients with UST levels in the highest quartile (≥6.3 µg/mL) at week 8 had higher biochemical remission rates at weeks 12 and 24.
• Patients who achieved corticosteroid-free clinical remission at weeks 12 and 24 had no significant differences in UST levels at week 8 compared to those without corticosteroid-free clinical remission (P=0.99 and P=0.59, respectively).
  • Logistic regression and quartile analysis demonstrated no significant association between UST levels at week 8 and corticosteroid-free clinical remission at weeks 12 and 24 (logistic regression: week 12, P=0.35; week 24, P=0.86; quartile analysis: week 12, P=0.32; week 24, P=0.74).
• At week 16, significantly higher UST levels were observed among patients who achieved biochemical remission at week 24 vs those who did not (2.84 vs 1.61 µg/mL; P<0.01).
  • In the logistic regression analysis, higher UST levels at week 16 were associated with higher biochemical remission at week 24 (OR 1.19; 95% CI, 1.02-1.40; P<0.01).
  • In the quartile analysis, patients with UST levels in the highest quartile (≥3.00 µg/mL) at week 16 had higher biochemical remission rates at week 24.
• Patients who achieved corticosteroid-free clinical remission at week 24 had no significant differences in UST levels at week 16 compared to those without corticosteroid-free clinical remission (P=0.91).
  • Logistic regression and quartile analysis demonstrated no significant association between UST levels at week 16 and corticosteroid-free clinical remission at week 24 (logistic regression, P=0.45; quartile analysis, P=0.65).
• For the association between UST trough levels and biochemical remission rates, see Table: Quartile Analysis of UST Trough Levels at Week 8 and Biochemical Remission Rates at Weeks 12 and 24 and Quartile Analysis of UST Trough Levels at Week 16 and Biochemical Remission Rates at Week 24.

Di Fonzo et al (2023)² evaluated the association between UST therapeutic drug monitoring (TDM) and endoscopic healing in patients with CD.

Study Design/Methods

• Adult patients with CD treated with a stable dose of STELARA and undergoing ileo-colonoscopy to assess disease activity from a single center were prospectively enrolled.
• TDM groups were categorized based on 3 cutoff values: TDM ≥1 mg/mL, TDM ≥2 mg/mL, and TDM ≥4.5 mg/mL.
• Endoscopic healing was categorized based on the presence or absence of ulceration on endoscopy.

Results

• A total of 62 patients were included in the study.
• The mean±standard deviation (SD) serum UST level was 5.45±4.48 mg/mL.
• Endoscopic healing was reported in 48% of patients.
• No association was observed between TDM levels and presence of ulceration:
  • TDM ≥1 mg/mL: OR 1.49; 95 % CI, 0.30-7.28; P=0.62
  • TDM ≥2 mg/mL: OR 1.30; 95 % CI, 0.41-4.16; P=0.66
  • TDM ≥4.5 mg/mL: OR 1.5; 95 % CI, 0.55-4.11; P=0.43
• No significant difference was observed in the frequency of ulceration based on UST serum quartile levels (P=0.66). Additionally, TDM levels were not sensitive nor specific for the presence of ulceration (area under the curve [AUC], 0.45)

Proietti et al (2022)³ evaluated the association between serum UST levels and treatment response among adult patients with CD who were treated with STELARA.

Study Design/Methods

• Adult patients with CD who started STELARA treatment from a single center were prospectively enrolled in this study.
• The UST levels were compared between patients with and without clinical, biochemical, and endoscopic response or histological remission at week 16.
  • Clinical response was defined as a ≥3-point reduction in HBI score from baseline.
  • Biochemical response was defined as a ≥50% reduction in FCP levels from baseline.
  • Endoscopic response was defined as a ≥50% reduction in the Simple Endoscopic Score for Crohn’s Disease (SES-CD) score or a ≥1point reduction in the Rutgeerts score.
  • Histological remission was defined as Global Histologic Disease Activity Score (GHAS) ≤4.
• Serum samples for testing UST levels were collected at week 16 (on the day of endoscopy).

Results

• A total of 56 patients were included in the study.
• UST was detected in all serum samples. The median (IQR) UST level was 2.12 μg/mL (1.05-3.54).
• Patients who achieved biochemical response had significantly higher UST serum levels as compared with those without biochemical response. However, there were no significant differences in UST serum levels between patients who achieved clinical response, endoscopic response, or histologic remission as compared with those who did not achieve those outcomes. See Table: UST Levels by Clinical, Biochemical, and Endoscopic Response and Histological Remission.

Yanofsky et al (2022)⁴ evaluated the association between serum UST levels and endoscopic disease activity in adults with CD.

Study Design/Methods

• Adult patients with CD who maintained on STELARA treatment from a single center were prospectively enrolled in this study.
• The primary objective was to evaluate the association between serum UST levels and endoscopic remission (SES-CD<3).
• Secondary outcomes included the association between serum UST levels and clinical remission (HBI score <5), biochemical remission, and histological remission (inactive colitis).

Results

• A total of 53 patients were included in the study.
• There was no significant difference between UST levels in patients with or without endoscopic, clinical, or histological remission; see Table: Association Between UST Trough Levels and Endoscopic, Clinical, and Histologic Remission.

• No association was observed between quartiles of UST levels and endoscopic remission.
• Additionally, there was no association between median UST levels and CRP or FCP levels.

Hanžel et al (2021)⁵ studied the relationship between UST exposure parameters (during the first 2 weeks) and subsequent endoscopic and biochemical remission in adult patients with CD on STELARA therapy.

Study Design/Methods

• Adult patients with CD who started STELARA treatment from a single tertiary referral center were prospectively enrolled in this study.
• UST exposure parameters were measured during the first 2 weeks (peak levels measured immediately after IV infusion, week 2 levels and AUC through week 2).
• The primary endpoint was endoscopic remission (defined as an SES-CD score <3 without mucosal ulceration), and the secondary endpoint was biochemical remission (defined as FCP level <100 mg/kg).

Results

UST Levels and Cumulative Exposure (AUC)

• A total of 41 patients were included in the final cohort.
• The median (IQR) UST levels at peak and weeks 2, 4, and 8 were 98.3 µg/mL
  (83.7-114.2), 27.4 µg/mL (22.6-32.2), 15.6 µg/mL (10.3-20.4), and 4.44 µg/mL
  (2.78-7.70), respectively.
• The median (IQR) AUC from initiation to week 2 (AUC_0-2), was 781 µg*day/mL
  (646-896), initiation to week 4 (AUC_0-4) was 1063 µg*day/mL (884-1285), and initiation to week 8 (AUC_0-8) was 1203 µg*day/mL (953-1455).

Endoscopic Remission at Week 24

• The proportion of patients who achieved endoscopic remission at peak UST levels of <88.0 µg/mL, 88.0-105 µg/mL, and >105 µg/mL was 7%, 23%, and 46%, respectively (P=0.010).
• The proportion of patients who achieved endoscopic remission at week 2 UST levels of <24.5 µg/mL, 24.5-30.5 µg/mL, and >30.5 µg/mL was 18%, 25%, and 38%, respectively (P=not significant [NS]).
• The proportion of patients who achieved endoscopic remission at AUC_0-2 of <680 µg*day/mL, 680-860 µg*day/mL, and >860 µg*day/mL was 15%, 25%, and 45%, respectively (P=NS).

Biochemical Remission at Week 24

• The proportion of patients who achieved biochemical remission at peak UST levels of <88.0 µg/mL, 88.0-105 µg/mL, and >105 µg/mL was 29%, 50%, and 92%, respectively (P=0.001).
• The proportion of patients who achieved biochemical remission at week 2 UST levels of <24.5 µg/mL, 24.5-30.5 µg/mL, and >30.5 µg/mL was 27%, 70%, and 83%, respectively (P=0.003).
• The proportion of patients who achieved biochemical remission at AUC_0-2 of <680 µg*day/mL, 680-860 µg*day/mL, and >860 µg*day/mL was 25%, 64%, and 100%, respectively (P<0.001).

Walshe et al (2021)⁶ examined the association between UST levels measured during induction and subsequent clinical and biochemical outcomes in patients with CD.

Study Design/Methods

• Adult patients with CD receiving STELARA treatment were prospectively recruited from a single tertiary referral center.
• UST levels were assessed at weeks 2 and 6 following STELARA IV induction therapy.
• Crohn’s Disease Activity Index (CDAI) scores, CRP levels, and FCP levels were measured at baseline (≤30 days prior to IV induction) and at week 12.
• Remission was defined as CDAI score <150, CRP level <5 mg/L, or FCP level <250 µg/g.
• Response was defined as a reduction of ≥70 points in the CDAI score, normalization of CRP level to ≤5 mg/L, or a 50% reduction in FCP levels.
• Patients were only defined as responders and nonresponders if their baseline values were reflective of active disease (ie, CDAI score >150, CRP level >5 mg/L, or FCP level >250 µg/g).

Results

• A total of 48 UST levels were obtained from 28 patients during induction.

Relationship Between Baseline Factors and Week 6 UST Levels

• Among the 25 patients with available data, median UST levels at week 6 in patients who received STELARA 260 mg (n=6), 390 mg (n=17), and 520 mg (n=2) were 8.6 µg/mL, 16.3 µg/mL, and 25.0 µg/mL, respectively.
• UST levels were significantly higher in patients who received STELARA 390 mg vs 260 mg (P=0.02) and in patients who received STELARA 520 mg vs 390 mg (P=0.03).

Correlation Between Week 6 UST Levels and Week 12 Outcomes

• Week 12 CDAI scores, CRP levels, and FCP levels were available for 18, 22, and 13 patients, respectively.
• There was a significant negative correlation between week 6 UST levels and week 12 CDAI scores and CRP levels. However, there was no significant correlation between week 6 UST and week 12 FCP levels.

Week 12 Remission

• Of the 18 patients with available week 12 CDAI scores, 14 were in remission (CDAI <150) at week 12. Week 6 UST levels were numerically higher in patients who achieved remission (16.6 µg/mL) vs those who did not (12.3 µg/mL; P=NS).
• Of the 22 patients with available week 12 CRP levels, 15 were in remission (CRP <5 mg/L) at week 12. Week 6 UST levels were numerically higher in patients who achieved remission (17.85 µg/mL) vs those who did not (11.15 µg/mL; P=NS).
• Of the 13 patients with available week 12 FCP levels, 12 were in remission (FCP <250 µg/g) at week 12. Week 6 UST levels were numerically higher in patients who achieved remission (20.1 µg/mL) vs those who did not (9.8 µg/mL; P=NS).

Week 12 Response

• Among the 9 patients with elevated CDAI scores at baseline, 6 achieved a response. Week 6 UST levels were numerically higher in responders (16.45 µg/mL) vs nonresponders (12.3 µg/mL; P=NS).
• Among the 10 patients with elevated FCP levels at baseline, 6 achieved normalization of FCP level. Week 6 UST levels were similar in responders (11.25 µg/g) and nonresponders (15.15 µg/g; P=NS).
• Among the 5 patients with elevated CRP levels at baseline, 2 achieved normalization of CRP level. Week 6 UST levels were similar in responders (10.9 mg/L) and nonresponders (5.7 mg/L; P=NS).

STELARA Treatment Intensification

• Week 6 UST levels were lower among patients who underwent STELARA dose intensification within the first year of treatment vs those who did not (12.5 µg/mL vs 19.6 µg/mL; P=0.04).

Arsenescu et al (2020)⁷ analyzed the association between UST trough levels and remission and response in CD at weeks 8 and 16.

Study Design/Methods

• Patients with CD (n=100) who were initiated on IV STELARA treatment at standard weight-based dose and received the first 90 mg subcutaneous (SC) dose were analyzed.
• Remission and response were determined based on clinical, biochemical, endoscopic, and histologic data.
• STELARA maintenance dosing interval was adjusted to achieve a minimum UST trough level of 2 ng/mL.

Results

• UST trough level of >9 ng/mL at week 8 predicted endoscopic and histologic remission at weeks 20 and 52 in 100% and 79% of patients, respectively.
• UST trough level of <2 ng/mL at week 16 or following dose optimization every 4 weeks (q4w) or every 6 weeks (q6w) was associated with 60% and 80% failure at weeks 20 and 52, respectively.

Gómez Espín et al (2021)⁸ investigated the relationship between UST trough levels and clinical outcomes in adult patients with CD who received STELARA maintenance therapy.

Study Design/Methods

• This cross-sectional cohort study included adult patients with CD who received STELARA maintenance therapy for ≥24 weeks from a regional referral hospital.
• Clinical response was defined as a decrease in HBI score of ≥3 points and clinical remission as an HBI score of <5 points.
• Biochemical response was defined as a >50% reduction in the FCP level and biochemical remission as an FCP level <150 µg/g.
• Composite clinical/biochemical remission was defined as a normal HBI score and FCP level.

Results

• A total of 58 patients with CD were included in the study.
• The median UST trough level was 1.78 µg/mL and was <1 µg/mL in 18 (30%) patients. Additionally, the levels were different in patients who received STELARA every 8 weeks (q8w) vs q6w vs q4w (2.03 µg/mL vs 1.35 µg/mL vs 1.05 µg/mL; P=NS).

UST Trough Levels in Clinical Response and Remission and Biochemical Response and Remission

• Clinical response was achieved in 50 (86.2%) patients. The median UST trough level was significantly higher in patients who achieved clinical response vs those who did not (2.20 µg/mL vs 0.68 µg/mL; P=0.009).
• Clinical remission was achieved in 47 (81.0%) patients. The median UST trough level was significantly different in patients who achieved clinical remission vs those who did not (2.25 µg/mL vs 0.65 µg/mL; P=0.006).
• Biochemical response was achieved in 40 (69%) patients. The median UST trough level was significantly higher in patients who achieved biochemical response vs those who did not (2.25 µg/mL vs 0.68 µg/mL; P=0.017).
• Biochemical remission was achieved in 28 (48.3%) patients. The median UST trough level was significantly different in patients who achieved biochemical remission vs those who did not (2.33 µg/mL vs 1.03 µg/mL; P=0.047).

Clinical and Biochemical Remission Above UST Trough Level Cutoffs

• Clinical remission was achieved in 34/36 (94.4%) patients with UST trough levels above the cutoff of 1.4 µg/mL (risk ratio [RR], 11.77; 95% CI, 2.2361.91).
• Biochemical remission was achieved in 17/27 (63.0%) patients with UST trough levels above the cutoff of 2.0 µg/mL (RR, 3.09; 95% CI, 1.06-9.04).

UST Trough Levels in Composite Clinical/Biochemical Remission

• The UST trough level was higher in patients who achieved composite clinical/biochemical remission vs those who did not (2.38 μg/mL vs 1.08 μg/mL; P=0.042).
• The UST trough level best associated with composite clinical/biochemical remission was 2.20 μg/mL (AUC, 0.69; 95% CI, 0.52-0.80; P=0.042).
• There was no statistically significant difference in the median CRP levels in patients with UST trough levels >1.4 μg/mL vs <1.4 μg/mL (0.5 μg/mL vs 0.4 μg/mL; P=NS).

Painchart et al (2020)⁹ evaluated the association between UST trough levels and the response to STELARA induction and maintenance treatment in adult patients with moderate to severe CD.

Study Design/Methods

• Two cohorts of patients from a tertiary IBD center were analyzed: a maintenance cohort (patients who received STELARA for >3 months) and an induction cohort (patients who were initiated on STELARA treatment).
• Outcomes evaluated included: clinical response (a 3-point reduction in HBI score [or by Physician’s Global Assessment (PGA), if HBI score was not applicable]), biological remission (CRP level <5 mg/L during follow-up), and imaging/endoscopic response (an improvement in endoscopic lesions, entero-magnetic resonance imaging [MRI], or perineal MRI between the 2 assessments at STELARA induction and during STELARA maintenance therapy).
• UST trough levels and anti-STELARA antibodies were assessed at weeks 12 and 28 in the induction cohort, and at a single time point in the maintenance cohort.

Results

Induction Cohort

• A total of 23 patients were included in the cohort.
• At week 12, the mean±SD UST trough level was 1.45±1.15 μg/mL.
  • Overall, 13 (57%) patients achieved clinical response. There was no significant difference in median (IQR) UST trough levels among patients who achieved a clinical response vs those who did not (1.16 μg/mL [0.60-1.64] vs 1.56 μg/mL [0.49-2.76]; P=NS).
  • Overall, 11 (48%) patients achieved biological response. There was a significant difference in median (IQR) UST trough levels among patients who achieved a biological response vs those who did not (1.72 μg/mL [1.20-2.73] vs 0.56 μg/mL [0.44-1.18]; P=0.02).
  • The UST threshold of 1.10 μg/mL (AUC, 0.80; sensitivity, 76.9%; specificity, 80%) was the optimal predictor of a biological response to STELARA treatment within 6 months after induction.
  • Antibodies against STELARA were not detectable in any patient.
• At week 28, the mean±SD UST trough level was 1.89±1.48 μg/mL.
  • Overall, 15/20 (75%) patients achieved clinical response. There was no significant difference in median (IQR) UST trough levels among patients who achieved a clinical response vs those who did not (0.92 μg/mL [0.50-2.88]vs 2.74 μg/mL [1.95-3.13]; P=NS).
  • Overall, 8/20 (40%) patients achieved biochemical response. There was no significant difference in median (IQR) UST trough levels among patients who achieved a biological response vs those who did not (0.62 μg/mL [0.41-2.39] vs 1.99 μg/mL [0.83-3.28]; P=NS).
  • Antibodies against STELARA were not detectable in any patient.

Maintenance Cohort

• A total of 49 patients were included in the cohort.
• Mean±SD UST trough level was 1.88±1.40 μg/mL.
• Overall, 36 (73%) patients achieved clinical response. There was no significant difference in median (IQR) UST trough levels among patients who achieved a clinical response vs those who did not (1.36 μg/mL [0.57-2.12] vs 2.74 μg/mL [1.50-4.00]; P=NS).
• Biological remission was achieved in 17/49 (35%) patients. There was no significant difference in median (IQR) UST trough levels among patients who achieved biological remission vs those who did not (1.85 μg/mL [0.93-4.00] vs 1.58 μg/mL [0.60-1.15]; P=NS).
• Imaging/endoscopic response was achieved in 72% of patients. There was no significant difference in median (IQR) UST trough levels among patients who achieved imaging/endoscopic response vs those who did not (1.94 μg/mL [1.40-4.00] vs 2.74 μg/mL [0.37-3.49]; P=NS).
• Antibodies against STELARA were not detectable in any patient.

Glassner et al (2019)¹⁰ evaluated the impact of UST trough levels on treatment based on the clinical, laboratory, and endoscopic outcomes in patients with CD.

Study Design/Methods

• Patients with CD from a single IBD center were included in this study.
• Drug levels were drawn either reactively (due to ongoing clinical symptoms, endoscopic or biologic markers [FCP, erythrocyte sedimentation rate (ESR), CRP], or radiologic tests suggestive of active disease) or proactively (to guide de-escalation of therapy).
• Low drug levels were defined as UST trough level <5 µg/mL.

Results

• Overall, 55 UST trough levels were collected from 46 patients.
• Of the 45 drug levels drawn reactively, 71% were low, and of the 10 drug levels drawn proactively, 90% were low.
• For treatment outcomes based on UST trough levels, see Table: Endoscopic, Histologic, and Clinical Remission and Inflammatory Markers Based on UST Trough Levels.

• In patients who had UST trough levels drawn reactively (n=41), follow-up trough levels were measured in 8 patients after dose adjustment, of which, 7 showed improvement in UST level. However, UST levels were subtherapeutic in 88% of patients.
• Endoscopic follow-up was done in 19/41 patients of which 70% had low UST levels, and 53% showed endoscopic improvement or maintained remission/had mild disease.

Heron et al (2019)¹¹ assessed the role of UST TDM in patients with CD who experienced either a partial response or a secondary loss of response to STELARA therapy.

Study Design/Methods

• Trough UST TDM was performed in patients who had a loss of response based on clinical (HBI score ≥5) and/or objective inflammation (CRP level ≥5, FCP level ≥250, or SES-CD >2).
• Complete remission (HBI score <5, CRP level <5, and FCP level <250) or response (reduction in HBI score by >3 points and a 50% reduction in CRP and FCP levels) was reassessed.

Results

• Overall, 38 instances of clinical loss of response were identified in 35 patients.
• Among the patients with baseline TDM data (n=35), mean UST level was significantly lower in patients with active biochemical or endoscopic inflammation (n=31) vs those with no objective inflammation (n=4; 5.21 µg/mL vs 18.74 µg/mL; P<0.0001).
• Among the patients with active inflammation (n=27) who continued to receive STELARA therapy (29 instances), mean baseline UST level was higher in patients who achieved complete remission (n=10) vs those who did not (n=19; 7.61 µg/mL vs 4.01 µg/mL; P=0.01).
• The mean baseline FCP level was significantly lower in patients who achieved complete remission vs those who did not (414 µg/g vs 993 µg/g; P=0.03).
• Mean posttreatment UST level was significantly higher in patients who achieved complete remission (n=8) vs those who did not (n=14; 13.04 µg/mL vs 8.57 µg/mL; P=0.03).

Soufflet et al (2019)¹² assessed the usefulness of UST TDM in predicting the response to UST induction therapy in patients with active luminal CD.

Study Design/Methods

• Patients with CD who failed prior treatments with anti-tumor necrosis factor (anti-TNF) agents or vedolizumab and had an HBI score of >5, a CRP level of >5 mg/L and/or an FCP level of >250 µg/g were included in this study.
• Disease activity was assessed at weeks 0, 4, 8, and 16.
• Patients who did not achieve a steroid-free clinical and biochemical remission (HBI score ≤4, CRP level <5 mg/L, FCP level <250 µg/g) at week 16 were considered primary nonresponders.

Results

• A total of 51 patients who failed anti-TNF (100%) and vedolizumab (71%) therapies were included.
• At weeks 4, 8, and 16, the median (IQR) UST trough levels were 10.0 µg/mL (7.9-22.0), 5.0 µg/mL (1.3-7.7), and 1.6 µg/mL (0.9-5.1), respectively.
• At week 8, the median (IQR) UST trough levels were significantly higher in responders vs primary nonresponders (6 µg/mL [3.1-8.0] vs 1.3 µg/mL [0.9-5.6]; P=0.03).
• The optimal cutoffs for UST trough levels at weeks 4, 8, and 16 were 13 µg/mL, 2 µg/mL, and 1.4 µg/mL, respectively. UST trough levels of ≥2 µg/mL at week 8 were associated with a response to induction therapy.

Verstockt et al (2019)¹³ evaluated the exposure-response relationships in patients with CD who were initiated on STELARA therapy from a single center.

Study Design/Methods

• Endoscopic response (defined as a ≥50% decrease in SES-CD score from baseline), endoscopic remission (defined as an SES-CD score ≤2), and clinical remission (defined as average daily stool frequency ≤2.8/day and average abdominal pain score ≤1) were assessed at weeks 4, 8, 16, and 24.
• Serum UST levels were measured at baseline, weeks 4, 8, 16, and 24.

Results

• A total of 86 patients with CD were included in the study.

Serum UST Levels

• The median (IQR) serum UST levels at weeks 4 and 8 were 21.3 µg/mL (13.4-25.2) and 7.2 µg/mL (3.4-10.5), respectively.
• During STELARA maintenance therapy, median (IQR) serum UST levels at weeks 16 and 24 were 2.6 µg/mL (1.1-4.2) and 2.1 µg/mL (0.8-3.2), respectively.
• At all time points, serum UST and FCP levels were inversely correlated.

Exposure-Response Relationship

• Quartile analysis showed that significantly fewer patients with serum UST levels in the lowest quartile (Q1) at weeks 4 (0.5-13.4 µg/mL) and 8 (0.3-3.4 µg/mL), experienced a 50% reduction in FCP levels by week 8 (P=0.008 and P<0.001, respectively). A similar association was observed between serum UST levels at weeks 4, 8, 16, and 24 and endoscopic response or remission after 6 months.
• At week 8, a minimal UST exposure of 4.2 µg/mL predicted a 50% reduction in FCP levels (negative predictive value [NPV], 87.0%; P=0.004).
• During maintenance, serum UST levels of 2.3 µg/mL at week 16 and 1.9 µg/mL at week 24 were identified as the minimal exposure threshold required to predict endoscopic response after 6 months (NPV, 87.9% and 85.2%, respectively).
• At all time points, serum UST levels were numerically higher in patients who achieved endoscopic response at week 24 vs those who did not; see Table: Association Between UST Levels and Endoscopic Response.

Battat et al (2017)¹⁴ assessed the association between UST trough levels and clinical, biomarker, and endoscopic outcomes in adult patients with moderate to severe CD.

Study Design/Methods

• Two patient cohorts (longitudinal and crosssectional) were analyzed in the study.
• The longitudinal cohort comprised of patients who prospectively received STELARA 90 mg SC at weeks 0, 1, and 2, during induction and 90 mg SC q8w or q4w (based on clinical response) during maintenance.
• The cross-sectional cohort comprised of patients already on STELARA for ≥26 weeks.
• The combined cohort comprised of data from both cohorts at week ≥26.
• Clinical, biomarker, and endoscopic outcomes, UST trough levels, and antidrug antibodies were assessed at both week 10 postinduction therapy and at week ≥26 during maintenance therapy in the longitudinal cohort and at week ≥26 during maintenance therapy in the crosssectional cohort.
• The primary analysis was the association between UST trough levels and clinical response (reduction in HBI score by ≥3), clinical remission (HBI score <5), steroidfree clinical remission, biomarker normalization (CRP level <5 mg/L or FCP level <200 µg/g), endoscopic response (SES-CD score reduction by ≥50%), or endoscopic remission (SES-CD score ≤2).

Results

• Overall, 62 patients (either refractory or intolerant to anti-TNF agents) were included in the analysis (longitudinal cohort, n=27; cross-sectional cohort, n=35).

Week 10 UST Trough Levels

• At week 10, in the longitudinal cohort, mean±SD UST trough level was 3.4±2.1 µg/mL.
• The mean±SD UST trough levels did not differ significantly between patients with an endoscopic response vs those without (3.0±2.2 µg/mL vs 3.5±1.6 µg/mL; P=NS).¹⁴
• UST trough levels at week 10 did not yield a threshold associated with clinical, biomarker, or endoscopic outcomes at weeks 10 or 26.

Week 26 UST Trough Levels

• At week ≥26, in the combined cohort, mean±SD UST trough level was 4.4±2.0 µg/mL.
• The mean±SD UST trough levels were significantly higher in patients with an endoscopic response vs those without (4.7±2.1 µg/mL vs 3.8±1.6 µg/mL; P=0.03).
• An optimal UST threshold trough level at week ≥26 was found to be 4.5 µg/mL (AUC, 0.67).
• A greater proportion of patients with UST trough levels above 4.5 µg/mL at week ≥26 had an endoscopic response (75.9%) compared with patients who had trough levels below this level (40.7%; P=0.008).
• Clinical outcomes did not differ with UST levels.
• Patients with UST trough levels above 4.5 µg/mL at week ≥26 had a lower mean±SD CRP level (12.6±21.1 mg/L) compared with patients who had trough levels below this level (mean±SD CRP level, 23.9±34.1 mg/L; P=0.04).
• In the combined cohort at ≥26 weeks, 1 patient had undetectable UST trough levels.

Claire et al (2017)¹⁵ evaluated the relationship between UST trough levels and clinical response and remission in patients with CD treated with STELARA.

Study Design/Methods

• Patients with CD refractory to anti-TNF agents from a tertiary referral center were included in this study.
• Clinical response was defined as a decrease in HBI score by 3 points.
• Clinical remission was defined as an HBI score <5, and loss of response as a new increase in HBI score.
• UST trough levels were measured at 12 weeks and at a single time point in patients who received STELARA for >3 months.

Results

• A total of 42 patients who received ≥3 doses of STELARA were included.
• At the end of induction (week 12), 57% of patients achieved clinical response.
  • There was no significant difference in the median (IQR) UST trough levels in patients who achieved clinical response vs those who did not (1160 ng/mL [603-1644] vs 1556 ng/mL [494-2758]; P=NS).
• Overall, 32 (76%) patients received ≥4 doses of STELARA, with dose optimization (q4w) in 11 patients. Clinical response was achieved in 23/32 (72%) patients.
  • There was no significant difference in the median (IQR) UST trough levels in patients who achieved clinical response vs those who did not (1398 ng/mL [477-1979] vs 1548 ng/mL [453-2392]; P=NS).

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 13 January 2025.

Summarized in this response are relevant data from prospective studies.