Summary

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• A phase 1 study (UNISTAR) evaluated the efficacy and safety of STELARA in pediatric patients with moderately to severely active Crohn’s disease (CD).^1,2
• Additionally, a prospective study, 11 retrospective studies, and 2 registries evaluated the use of STELARA in pediatric patients with CD.^3-18

CLINICAL DATA

Phase 1 Clinical Study

Rosh et al (2021)¹ evaluated the pharmacokinetics (PK), efficacy and safety of STELARA in pediatric patients with moderately to severely active CD or fistulizing CD for ≥3 months in a phase 1, multicenter, 16-week, double-blind induction dose-ranging study (UNISTAR).

Study Design/Methods

• Patients with moderately to severely active CD who were 2 to <18 years of age (body weight ≥10 kg) were included. Additionally, patients also had a Pediatric CD Activity Index (PCDAI) score >30 and at least an abnormal C-reactive protein (CRP; >0.3 mg/dL) or fecal calprotectin (FCP; >250 µg/g), or ulcerations in the ileum and/or colon.
• All patients received previous or current treatment for CD, including oral corticosteroids and/or immunomodulators (eg, azathioprine, 6-mercaptopurine, methotrexate); however, they were required to be stable prior to study start. Patients who failed or were intolerant to anti-tumor necrosis factor (TNF) therapy were also allowed to participate.
• Randomization (1:1) was performed for induction to 1 of 2 weight-based intravenous (IV) doses:
  • Lower IV induction dose: 3 mg/kg if body weight 10 kg to <40 kg or 130 mg if body weight ≥40 kg.
  • Higher IV induction dose: 9 mg/kg if body weight 10 kg to <40 kg or 390 mg if body weight ≥40 kg.
• At week 8, patients received a single subcutaneous (SC) maintenance dose of STELARA 2 mg/kg if body weight 10 kg to <40 kg or 90 mg if body weight ≥40 kg.

Results

Baseline Characteristics

• A total of 44 patients were randomized to either the lower dose STELARA IV induction (n=23) or the higher dose STELARA IV induction (n=21). The median age was 13 years (interquartile range [IQR], 12-16); 59% of patients had a body weight ≥40 kg and 91% had prior exposure to biologics (infliximab, adalimumab, and vedolizumab).
• A total of 73% (32/44) of patients were receiving ≥1 concomitant medications for CD at baseline which included immunomodulators (39%), oral corticosteroids (32%), oral aminosalicylates (21%), and antibiotics (5%).
• Through week 16, 9.1% (4/44) of patients discontinued STELARA due to adverse events (AEs; worsening of CD [n=2] and lack of efficacy per the investigator [n=2]).

Pharmacokinetics

• Mean serum ustekinumab concentrations (SUC) were 51.3 μg/mL, 7.7 μg/mL, 3.0 μg/mL, and 1.6 μg/mL at weeks 0 (after infusion), 3, 6, and 8, respectively, for the lower induction dose group. Mean SUC for the higher induction dose group at the same time points were 149.0 μg/mL, 23.7 μg/mL, 9.1 μg/mL, and 4.8 μg/mL, respectively.

Clinical and Endoscopic Outcomes

• Clinical and endoscopic outcomes (clinical response, clinical remission, endoscopic response, and endoscopic remission) from week 3, week 8, and week 16 are shown in Table: Summary of Clinical Outcomes at Weeks 3, 8, and 16.

Corticosteroid Use

• Steroid use from baseline to week 16 decreased in both lower (30% to 13%) and higher dose groups (33% to 19%).
  • At weeks 8 and 16, 22% (5/23) of patients in the lower dose group were in steroid-free clinical remission; in the higher dose group, 10% (2/21) and 24% (5/21) of patients were in steroid-free clinical remission at weeks 8 and 16, respectively.

Inflammatory Biomarkers

• In the lower dose group, 16.7% (3/18) of patients had normalized CRP levels at weeks 8 and 16, while in the higher dose group, 28.6% (4/14) and 21.4% (3/14) of patients had normalized CRP levels at weeks 8 and 16, respectively.
• Median (IQR) change in CRP concentration from baseline at week 8 vs change from baseline at week 16 was -0.7 (-8.0 to 0.1) mg/L vs 0 (-9.3 to 0) mg/L in the lower dose group and -0.3 (-14.4 to 0.3) mg/L vs -0.8 (-8.7 to 0) mg/L in the higher dose group, respectively.
• Median (IQR) change in FCP concentration from baseline at week 8 vs change from baseline at week 16 was 0 (-2395.0 to 418.0) mg/kg vs 0 (-3438.0 to 190.0) mg/kg in the lower dose group and -37.0 (-1347.0 to 553.0) mg/kg vs 0 (-‍1126.0 to 654.0) mg/kg in the higher dose group, respectively.

Clinical Outcomes and Pharmacokinetics

• Clinical response at week 8 was achieved in 63.2% (12/19) of patients in the higher SUC group (>1.38 μg/mL) and 45% (9/20) of patients in the lower SUC group (≤1.38 μg/mL).
• Median improvement from baseline in PCDAI score at week 8 was 20 for patients in the higher SUC group (>1.4 μg/mL) and 17.5 for patients in the lower SUC group (≤1.4 μg/mL).
• There was no observable correlation between SUC and clinical remission at week 8.

Safety

• A total of 73% of patients reported ≥1 AE through week 16 which included 83% in the lower dose group and 62% in the higher dose group.
• Serious AEs (SAEs) were reported in 16% of patients (lower dose group, 26%; higher dose group, 5%) with CD exacerbation being the most frequent (lower dose group, 9%; higher dose group, 5%).
• Infections (upper respiratory tract infection, anal abscess, clostridium difficile, eczema infected, gastroenteritis, gastroenteritis viral, and nasopharyngitis) were reported in 39% of patients (lower dose: 39%, n=9; higher dose: 38%, n=8).
• A total of 2 patients discontinued treatment due to AEs (n=1, each dosing group) and no malignancies, deaths, injection-site reactions, anaphylaxis, serum sickness-like events, opportunistic infections, or antibodies to STELARA were reported through week 16.

Long Term Extension of UNISTAR

Turner et al (2023)² evaluated the PK, immunogenicity, efficacy, and safety of STELARA in pediatric patients with moderately to severely active CD in the long-term extension (LTE) of the UNISTAR study through week 268.

Study Design/Methods

• Patients who responded to STELARA at week 16 entered the LTE and continued STELARA maintenance therapy every 8 weeks up to week 268.
• The primary visit, representing outcomes after approximately 1 year of STELARA therapy, occurred at week 48.

Results

Baseline Characteristics

• Among patients who received STELARA, 77% (34/44) responded and entered the LTE.
• A total of 77% (26), 47% (16), 35% (12), and 24% (8) of patients, respectively, received STELARA at weeks 48, 104, 152, and 208.
• At baseline, the median age was 13.0 years (range, 6.0-17.0); 47% and 18% of patients weighed <40 kg and <30 kg, respectively; 71% of patients had abnormal CRP levels; and 94% of patients had a history of treatment failure with anti-TNF therapy.

Pharmacokinetics and Immunogenicity

• The median SUC were lower in patients weighing <40 kg vs those weighing ≥40 kg; however, the concentrations were generally consistent from weeks 16 to 268 and remained detectable through week 200.
• Antibodies to STELARA were observed in 3% (1/34) patients.

Clinical Outcomes

• At week 48, clinical response and remission were achieved in 59% (20/34) and 41% (14/34) patients, respectively.

Inflammatory Biomarkers

• At week 48, CRP normalization (<3 mg/L) was achieved in 59% (16/27) of patients.

Safety

• Through week 240 (final safety visit), ≥1 AE was reported in 91% of patients. Treatment discontinuation due to AEs was reported in 15% of patients (most common AE, worsening of CD).
• Infections and SAEs were reported in 74% and 32% of patients, respectively.
  • Most SAEs were gastrointestinal disorders associated with CD.
• No incidences of injection-site reactions, serious infections, malignancies, or deaths were reported.

Prospective Study

Keller et al (2023)³ evaluated the association between ustekinumab trough levels and sonographic transmural healing in pediatric patients with inflammatory bowel disease (IBD) treated with STELARA.

Study Design/Methods

• The study included patients with IBD (aged ≤18 years) receiving maintenance STELARA treatment, who underwent intestinal ultrasound (IUS) examination and serum ustekinumab trough levels (UTL) at a tertiary center.
• Patients with IUS and UTL performed on 2 events >6 months apart were included in a per-event analysis.
• The primary outcome was the comparison of UTL between patients with and without transmural healing (defined as bowel wall thickness <3 mm and no hyperemia [bowels with hyperemia] on color Doppler, using the Mann-Whitney U test).
• Secondary outcome was the comparison of UTL for each IUS parameter.

Results

• Among 44 children with IBD, 34 had CD.
• The baseline characteristics of patients with CD were as follows:
  • Median age: 14.9 years (IQR, 12.9-16.6)
  • Median disease duration: 3.83 years (IQR, 1.76-5.07)
  • Median time between UTL and IUS: 0 days (IQR, 0-26.5)
• Overall, 18 (53%) patients with CD achieved transmural healing.
  • Higher UTL was associated with transmural healing (11.7 [5.3-17.0] µg/mL) vs without transmural healing (5.5 [4.2-11.0] µg/mL; P=0.013).
• Optimal UTL cut-point for transmural healing detection was 11.4 ug/mL for patients with CD (AUROC, 0.661; sensitivity, 59%; specificity, 79%).

Retrospective Studies

Koudsi et al (2023)⁴ conducted a retrospective, multicenter study assessing the effectiveness and safety of STELARA in pediatric patients with CD at pediatric IBD centers in France affiliated with Groupe d’Etude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID).

Study Design/Methods

• The study included patients aged ≤18 years who had received STELARA.
• All patients received the initial STELARA IV dose (6mg/kg), followed by a 90 mg SC dose after 8 weeks.
• Disease activity was assessed using the Pediatric Crohn Disease Activity Index (PCDAI), categorized as remission (<10), mild (<30), moderate (≥30-40), and severe (≥40) disease. A clinically significant response to therapy was defined as a score change of ≥12.5 points.

Results

Baseline Characteristics

• A total of 53 children with IBD were included, of whom 48 (90.6%) patients had CD.
• The median follow-up duration was 10.5 months (range, 1-51).
• Among the 48 patients with CD, 30 (65.2%) had ileocolonic disease, 11 (23.9%) had colonic disease, and 5 (10.9%) had an isolated ileal inflammation.
• Mean PCDAI at baseline was 28.7 in 35 patients, <15 in 9 patients, and >45 in 6 patients.

Effectiveness

• At 3 months post-induction, compared to baseline among CD and UC patients:
  • Mean weight increased significantly from 45 kg (21.5-70.5) to 49 kg (23.3-73), P<0.001.
  • Body mass index (BMI) increased from 19 kg/m² (13-32.6) to 20 kg/m² (15.7-33.6), P<0.001.
  • CRP levels significantly decreased at 3 months (P<0.05) and at the last follow-up (P<0.001).
  • Blood albumin levels significantly increased at 3 months (P<0.005) and at the last follow-up (P<0.001).
  • ESR was significantly lower (P<0.001) and hematocrit rate was significantly higher (P<0.005) at the last follow-up.
• PCDAI score significantly decreased at 3 months (P<0.05) with 17 (48%) patients achieving a PCDAI <15, increasing to 20 (57%) patients at the last follow-up.
• Among CD and UC patients at baseline, 9 (16%) patients were steroid-free, increasing to 31 (58%) at 3 months and 33 (62%) at the last follow-up.
• Among the 20 (42%) patients with perineal CD at baseline, 9 had active perineal lesions at STELARA induction, with 1 patient developing perineal inflammation during treatment. Improvement in lesions was observed in 5 (50%) patients with STELARA treatment.
• Among 20 patients with perianal and non-perianal CD, the mean PCDAI at induction was 25.6 (range, 5-55) and 30.8 (range, 5-85), respectively.
  • After 3 months of treatment, these values were 22.5 (range, 2.5-75) and 14.3 (range, 0-37.5), respectively (P=0.17).
  • At the last follow-up, the values were 19 (range, 0-60) and 8.5 (range, 0-35), respectively (P=0.04).

Safety

• At 13-month follow-up among CD and UC patients, 9 patients experienced AEs, with fatigue (n=3 [3%]) and headache (n=3 [3%]) being more frequent. Treatment was discontinued in one patient due to recurrent respiratory tract infections.

Takeuchi et al (2021)⁵ conducted a retrospective, single-center cohort study assessing the efficacy and safety of STELARA in pediatric patients with CD at a pediatric IBD center in Japan.

Study Design/Methods

• The study included patients aged ≤20 years who had received the first dose of STELARA and were followed up for a minimum of 26 weeks.
• The primary outcome was steroid-free clinical remission rate (defined as clinical remission [wPCDAI<10] without corticosteroids) at weeks 26 and 52.
• Secondary outcomes included steroid-free clinical remission rate beyond week 52 (for patients followed over 1 year), changes in wPCDAI and Simple Endoscopic Score for Crohn’s Disease (SES-CD), dose changes and the interval of STELARA treatment, and safety.

Results

• A total of 17 patients with a median age of 10.3 years (IQR, 6.9-13.2) at diagnosis were included.
• Overall, steroid-free clinical remission rates were 59% and 50% at weeks 26 and 52, respectively.
• Steroid-free clinical remission rate over 1 year was 70%; all patients in steroid-free clinical remission at baseline remained in remission at the last follow-up.
• Of the 11 patients aged >10 years at the first dose, steroid-free clinical remission rates were 73% (8/11), 67% (4/6), and 83% (5/6) at week 26, week 52, and over 1 year, respectively. Of the 6 patients aged ≤10 years at the first dose, steroid-free clinical remission rates were 33% (2/6), 25% (1/4), and 50% (2/4) at week 26, week 52, and over 1 year, respectively.
• At the final visit, 50% (3/6) patients achieved steroid-free clinical remission.
• Of the 7 patients who achieved steroid-free clinical remission, all achieved endoscopic response (reduction in SES-CD ≥50%) and 43% (3) of patients achieved endoscopic remission (SES-CD ≤2).
• Six patients had perianal disease at the time of diagnosis, with 4 requiring seton placement prior to STELARA treatment. Except for 1 patient with severe perianal disease (very early onset-irritable bowel syndrome), perianal diseases did not flare-up in the others with severe perianal disease.
• Two patients with active perianal diseases were reported to have significant improvement during follow-up.
• Mild to moderate AEs were reported in 65% of patients, including upper respiratory tract infection (n=10), acute viral gastroenteritis (n=2), cystitis (n=1), pneumonia (n=1).
• Mild elevation of transaminases (n=1) and mild elevation of serum creatinine level (n=1) were reported.
• No infusion reactions or injection-site reactions were reported, and no patient discontinued STELARA due to AEs.

Du et al (2020)⁶ conducted a retrospective chart review of pediatric patients (11-17 years of age) with CD who received at least one dose of STELARA to determine efficacy; including the association of maintenance STELARA trough concentrations with clinical outcome.

• Patients received the standard STELARA induction and maintenance dosing per the Food and Drug Administration (FDA) labeling for adult patients with CD.
• A total of 30 patients who received STELARA were included (patients were on treatment for 6-46 months).
• All patients were previously TNF blocker exposed.
• At 8 weeks after IV STELARA induction, 81% (21/26) and 15% (4/26) of patients were in clinical response and clinical remission, respectively (determined by physician global assessment).
• At 26-52 weeks after IV induction during maintenance, 87% (26/30) and 40% (12/30) of patients were in clinical response and clinical remission, respectively.
• A total of 7 patients discontinued STELARA including 3 patients who stopped treatment in the first 52 weeks due to non-response or an AE (n=1, diagnosis of Ewing’s sarcoma; n=1, development of caseating pulmonary granulomas.)
• In 18 patients with available ustekinumab concentrations, 63% (5/8) of patients with concentrations >4.5 µg/mL and 40% (4/10) of patients with concentrations <4.5 µg/mL were in clinical remission (P=0.3) during maintenance. There was no correlation between patient's weight and ustekinumab concentration. A total of 5 patients achieved ustekinumab concentrations >4 µg/mL after dose adjustments and 2 patients subsequently achieved clinical remission.
• No antibodies to STELARA were reported.

Pujol-Muncunill et al (2020)⁷ evaluated the efficacy and safety of STELARA in pediatric patients with refractory CD (96% were previously treated with a TNF blocker; 22% were previously treated with vedolizumab) in a multicenter retrospective study (STEP-CD Study).

• Children with CD (2-18 years of age) from 23 centers worldwide who were treated with at least one dose of STELARA were included.
• The primary outcome was corticosteroid (CS) and exclusive enteral nutrition (EEN; defined by wPCDAI <12.5 free remission at week 6.
• Secondary outcomes were CS and EEN free remission at week 12 and 52 and safety.
• A total of 101 patients with a mean age of 15.4 years (IQR: 12.7 to 17.2) were included.
• The median wPCDAI at treatment initiation was 38.7 (IQR: 25 to 57.5).
• The most common IV induction dose was STELARA 6 mg/kg and 79% of patients had a maintenance dose of STELARA 90 mg SC every 8 weeks.
• At week 6, among 74 patients, 38% achieved the primary outcome. CS and EEN-free remission were achieved at week 12 (n=65) and week 52 (n=49) in 40% and 50% of patients, respectively.
• There were 6 AEs reported (3 infections, 1 infusion reaction, 1 abnormal laboratory result, 1 vasculitis of the tongue) and 7 patients had clinical deterioration due to the disease (3 hospitalized).
• No reports of malignancies during follow-up (mean duration of treatment: 14.1 months [IQR: 9.1 to 18.9]).
• One death occurred during follow-up which was considered by the authors as unrelated to STELARA.

Chaisson et al (2019)⁸ conducted a retrospective observational cohort study of pediatric CD patients treated with STELARA at a single tertiary pediatric hospital.

• A retrospective chart review identified 25 children and young adults with CD (median age 16.2 years) who received STELARA.
• Most patients had ileocolonic (n=15, 60%) or colonic (n=7, 30%) involvement.
• Stricturing or penetrating disease was observed in 24% (6) and perianal disease in 36% (9) of patients.
• All patients received a TNF blocker before STELARA (15 received >1 TNF blocker).
• Compared to the 6-month period before STELARA induction, there was a decline of CRP from a median of 4.1 to 0.9 mg/dL, a decline of ESR from a median of 55 to 39.5 mm/hr, a decline of platelets from a median of 422 to 337 K/mcL, and a median weight increase of 3% after STELARA induction. Median values for albumin and hemoglobin were similar before and after induction.
• PCDAI data (available in 16 patients) was calculated at a median of 22 days before and 177 days after STELARA induction. A total of 7 patients (44%) had PCDAI improvement of ≥12.5 (steroid-free) and 6 (38%) had an improvement of ≥5 after STELARA induction.
• STELARA dose escalation was required in 28% (7) of patients to achieve or maintain response.
• During a median follow-up of 14 months since the start of treatment, no infectious complications or anaphylactic reactions were reported.
• Two patients had poor response and underwent surgery within 6 months of induction.
• One patient died from unrelated causes.

Chavannes et al (2019)⁹ conducted a multicenter retrospective study of SC STELARA in children (<18 years of age) with moderate to severe CD who failed, lost response, or were intolerant to at least one biological treatment.

• Disease activity was analyzed using the abbreviated Pediatric Crohn’s Disease Activity Index (aPCDAI) with a score of <10 indicative of clinical remission.
• The primary outcome was the proportion of patients achieving clinical remission over the first 12 months of treatment.
• Secondary outcomes included clinical response (defined as a decrease in aPCDAI ≥15), percentage of patients with CRP normalization, albumin level changes from baseline to 3 and 12 months, steroid-free remission at 12 months. Additionally, changes in height, weight, and BMI between baseline and 12 months were evaluated, as well as safety during the follow-up period.
• A total of 44 patients were included and 6 different induction regimens were used with the most common induction dosing as 90 mg weekly for 3 weeks followed by a maintenance dose of 90 mg every 8 weeks. At latest follow-up, 29.5% (13/44) of patients had an escalation to a maintenance dose of every 4 weeks, due to persistent symptoms.
• A total of 12 patients stopped treatment within the first year and the remainder were followed for at least 12 months.
• Clinical remission was achieved in 36.4% (16/44; P=0.006) of patients at 3 months and 38.6% (17/44; P=0.006) of patients at 12 months.
• A total of 47.8% (21/44) of patients achieved clinical response at both 3 and 12 months.
• Of the 30 patients with an elevated baseline CRP, the level normalized in 33.3% (10; P=0.004) of patients at 3 months and in 26.7% (8; P=0.01) of patients at 12 months.
• The median (IQR) albumin level was 34.5 g/L (32.0-38.9), 36.7 g/L (34.2-41.1), and 40.2 g/L (38.0-43.0) at baseline, 3 and 12 months, respectively.
• A total of 27.3% (12/44) of patients were in steroid-free remission at 12 months.
• When imputing for missing data, using the linear mixed model [LMM] analysis, there was an increase of 0.072 (±0.044) in height Z-scores from baseline to 12 months (P=0.2441). Over the same time, there was also a significant increase in weight Z-scores of 0.48 [±0.13; P=0.0008]) and a significant increase in BMI Z-score of 0.66 [±0.16; P=0.0003].
• Two patients had an SAE (association with the medication was not clear), 6 patients had mild AEs, and the AE rate was 12.4 per 1000 patient-months of follow-up.
• AEs were not the reason for discontinuing treatment during the maintenance phase, as those patients discontinued due to poor clinical response.

Kim et al (2019)¹⁰ evaluated the efficacy and safety of STELARA in pediatric patients with CD at a single tertiary pediatric hospital.

• A retrospective chart review identified 12 patients treated with STELARA.
• The median age at CD diagnosis was 11.4 years, and the median time prior to receiving the first dose of STELARA was 5.4 years (included a median trial of 2 prior biologics).
• Five patients had complicated CD: stricturing (n=5, 42%) and penetrating (n=1, 8%).
• For induction, most patients received STELARA 260 mg IV (n=7, 58%), and for maintenance, most patients received STELARA 90 mg SC every 8 weeks (n=10, 83%) at last clinic visit.
• The median duration of STELARA treatment was 25.7 (range 11.4-85.9) days.
• The median aPCDAI decreased from 17.5 at time of first dose to 5.0 at time of the last clinic visit (P=0.03). There were clinically but not statistically significant changes in CRP, albumin, and hematocrit.
• Four patients (33.3%) were hospitalized since the first dose of STELARA with 1 (8.3%) attributed to a CD flare.
• No instances of anaphylaxis and no significant infections were reported.

Rao et al (2019)¹¹ reported on the use of STELARA in pediatric CD in 2 hospitals.

• The review included 10 pediatric patients <18 years of age who started STELARA.
• Biological response at week 8 was defined as a 50% reduction in CRP where the baseline CRP was >5 mg/L.
• All patients had failed ≥1 TNF blockers and 8 patients had failed 2 TNF blockers.
• Patients received IV STELARA at baseline and SC every 8 weeks dosing thereafter.
• The biologic response rate was 50% at week 8 and both patients on steroids at baseline had discontinued these by week 8.
• Two patients discontinued treatment prior to week 16 due to primary nonresponse, both of whom required intestinal resection.
• Where paired data were available, there was a significant increase in mean weight from baseline (38.9 kg, n=7) to week 8 (42.7 kg, n=7, P=0.003) and week 16 (44.0 kg, n=3, P=0.001).
• Where paired data were available, mean CRP improved from 38 mg/L at baseline (n=7) to 22 mg/L at week 8, and 9 mg/L at week 16 (n=4). This did not reach significance.
• No AEs were reported.

Martinez-Vinson et al (2017)¹² conducted a retrospective observational study of pediatric patients with CD who received STELARA SC at a single tertiary pediatric center.

• Twelve patients with CD (refractory luminal CD, n=11; perineal CD, n=1) received STELARA induction due to failure of several therapies, including anti-TNF agents.
• One patient with an SAE stopped STELARA after the first injection.
• Of the 11 patients still receiving STELARA at 3 months, an initial response was achieved in 9 patients, including 5 patients who achieved remission.
  • Among the remaining 2 patients, one needed a colectomy after the first injection of STELARA. STELARA was continued after surgery.
  • The other patient required the addition of methotrexate due to a lack of response.
• At 1-year follow-up, there were 9 responders who were still on STELARA therapy and experienced a clinical benefit without a need for steroids. Among these 9 patients, 7 were in clinical remission.

Bishop et al (2016)¹³ performed a single-center retrospective review of 4 adolescent patients with CD who received induction and maintenance STELARA therapy.

• A retrospective chart review was utilized to evaluate each patient’s clinical data, disease phenotype (based on Paris classification), treatment history, and laboratory and growth parameters at initiation of STELARA treatment and at the most recent dose or last follow-up. AEs while on STELARA were also reported.
• An aPCDAI was utilized to calculate each patient’s disease activity (<10=remission; 10 to 15=mild disease; 16 to 25=moderate disease; >25=severe disease).
• STELARA induction therapy was 90 mg SC at weeks 0 and 4. The maintenance therapy was 90 mg SC every 8 weeks after induction. No immunomodulators were given concomitantly.
• Two male and 2 female adolescents were treated with STELARA, ages ranging from 12-‍17 years with varying disease phenotypes.
• All 4 patients had non-stricturing, non-penetrating disease and colonic involvement (1 patient also had ileal disease; 2 had perianal disease with fistula and abscess). All patients had CRP elevation and anemia. Hypoalbuminemia was seen in 3/4 patients.
• All patients had received prior doses of corticosteroids, methotrexate, azathioprine/6-mercaptopurine, infliximab, and adalimumab. Patients were primary responders to the first anti-TNF agent but either had a loss of response (n=3) or allergy (n=1). For the second anti-TNF agent the patients received, 2 patients showed loss of response, 1 patient had an allergic reaction, and 1 developed a severe rash.
• Patient 1 is a male who’s had CD for 3.8 years and was initiated on STELARA at age 12. This patient has had 5 prior hospitalizations, and an aPCDAI score of 30 (severe). Comorbidities include Henoch-Schonlein purpura and adalimumab induced skin lesions. The patient received 5 doses of STELARA.
• Patient 2 is a female who’s had CD for 5.4 years and was initiated on STELARA at age 16. This patient has had 4 prior hospitalizations and has received certolizumab pegol previously. This patient’s aPCDAI score was 35 (severe) and she had no comorbidities. The patient received 10 doses of STELARA.
• Patient 3 is a female who’s had CD for 3.1 years and was initiated on STELARA at age 13. She has had 9 prior hospitalizations, and an aPCDAI score of 10 (mild). Comorbidities included skin/oral CD and hypercoagulability due to thalidomide. The patient received 6 doses of STELARA.
• Patient 4 is a male who’s had CD for 4.6 years and was initiated on STELARA at age 17. He has had 1 prior hospitalization and an aPCDAI score of 20 (moderate). Comorbidities included psoriasis. The patient received 9 doses of STELARA.
• Patients 2 and 4 were responsive to STELARA therapy and displayed a decrease in aPCDAI scores within 4-8 weeks after initiation. Both patients were initiated on prednisone before STELARA induction and were tapered off during STELARA therapy. Both patients remained on STELARA therapy after clinical response.
• Patient 2, after 14 months of therapy, had a loss of response with symptoms occurring 2-3 weeks before the next STELARA dose. She received the dose at 7 instead of 8 weeks and as of the last follow-up reported no active symptoms (aPCDAI of zero with normal blood counts and CRP).
• Patient 4 showed clinical improvement in psoriasis, pain, and non-bloody diarrhea with STELARA. He did not show improvement in his body mass index and CRP levels. His aPCDAI score remained at 5 because of mild diarrhea, with no other active symptoms.
• Patients 1 and 3 stopped STELARA therapy due to worsening of symptoms, complications, or no improvement.
• Patient 1 was hospitalized 4 times due to flare-ups, Clostridium difficile infection, and perianal abscess recurrences. He discontinued STELARA therapy and received thalidomide treatment and ileocecal resection surgery.
• Patient 3 was hospitalized 5 times due to continual weight loss, fever due to upper respiratory tract infection, urinary tract infection, central line infection and CD flare-up. Due to the flare-up, she received steroids, discontinued STELARA, and was initiated on vedolizumab.

Chavannes et al (2016)¹⁴ reported a retrospective, open-label study evaluating pediatric patients with refractory CD treated with STELARA.

• A total of 12 pediatric patients with a median age of 16 years (range, 10-18 years) and a median disease duration of 3.5 years (range, 1-9 years) were included in this study.
• All but 1 patient had non-penetrating, non-stricturing disease. Every patient had previously failed therapy or was intolerant to either thiopurines (9 patients) or methotrexate (8 patients).
• After a median duration of 10 months, eleven patients had discontinued therapy with infliximab (3 for primary non-response; 5 for secondary loss of response; 3 for allergies/AEs). Eight patients had failed therapy with adalimumab.
• STELARA SC induction therapy was dosed at 45 mg (weight ≤45 kg) or 90 mg (weight >45 kg). Induction doses were given at weeks 0, 1 and 2.
• Maintenance therapy was administered to 10 patients at 45 mg or 90 mg SC every 8 weeks based on induction doses. Dose escalation was needed in 8 patients.
• Following induction therapy, clinical response was observed in 7 patients and clinical remission was observed in 1 patient. Four patients had no clinical response.
• Median follow-up was 6 months (range, 2-18 months) for those who continued maintenance therapy. A total of 3 patients discontinued STELARA therapy due to loss of response or no response. At their last follow-up, 3 patients were in clinical remission at 18 months, 3 had clinical response at a median of 2 months, and 1 patient relapsed.
• Post-injection migraines were reported in 2 patients.

Registry-Based Studies

REALITI

Adler et al (2024)¹⁵, Saeed et al (2024)¹⁶ and Steiner et al (2024)¹⁷ reported results from a real-world evidence study (REALITI) that evaluated the effectiveness and safety of STELARA in pediatric patients with CD using data from ImproveCareNow (ICN) registry.

Study Design/Methods

• The study included pediatric patients, aged 2 to <18 years, with reference data from young adults (aged 18-25 years) with CD.
• Three readers independently scored reports blinded to clinical information and each other's scores.¹⁵
• Demographic and clinical data, recorded prospectively in ICN, were summarized, and compared between patients with and without endoscopy.¹⁵
• Clinical remission was defined as short Pediatric CD Activity Index (sPCDAI) ≤10 and endoscopic remission as Simplified Endoscopic Mucosal Assessment of CD (SEMA-CD) ≤1.

Results

Baseline Characteristics

• A total of 479 patients with CD treated with STELARA were included (n=348, pediatric patients; n=131, young adults).

Assessment of Mucosal Inflammation

• A total of 114 pediatric patients with moderate to severe CD (sPCDAI ≥30) were analyzed at week 52 (n=77, with endoscopic assessment; n=37, without endoscopic assessment).¹⁵
• At baseline, the median age for all patients was 16.0 years (IQR, 15-16).¹⁵
• Patients with endoscopic assessments vs patients without were predominantly female (56% vs 41%) and had more ileocolonic disease activity (73% vs 54%), perianal disease (39% vs 35%), and stricturing phenotype (B2; 10% vs 5%), respectively.¹⁵
• At baseline, the median sPCDAI was 40 (IQR, 35-50) in all 114 patients and the median SEMA-CD was 8.5 (IQR, 5-13) in 38 patients.¹⁵
• A total of 77 patients had ≥1 report during the study and 20 patients had a report at week 52.¹⁵
• At week 52, endoscopic remission was achieved by 4/20 (20%) patients (95% CI, 8.1-41.6) with lower remission rates were observed in patients with baseline endoscopic assessments (n=17/77 [22.1%]; 95% CI, 14.3-32.5) compared to those without (n=10/37 [27.0%]; 95% CI, 15.4-43.0).¹⁵

Pediatric Patients vs Young Adults

• An analysis of pediatric patients (n=348) compared to young adults (n=131) was conducted.¹⁶
• At baseline, the majority of pediatric patients (98.9%) and young adults (95.4%) had received prior biologic therapy, with approximately half (47.1% and 50.4%, respectively) also receiving corticosteroids.¹⁶
• A total of 49.7% of pediatric patients, compared to 44.8% of young adults had moderate to severe CD (sPCDAI ≥30).¹⁶
• At week 52, clinical remission was achieved in 105/348 (30.2%) pediatric patients (95% CI, 25.6-35.2) vs 37/131 (28.2%) young adults (95% CI, 21.2-36.5).¹⁶
• At week 52, the rates of discontinuation were similar in pediatric patients (21.0%) and young adults (22.9%).¹⁶
• When comparing pediatric patients to young adults, IBD-related hospitalizations were reported in 31.9% vs 19.8% of patients, IBD-related surgery occurred in 16.1% vs 9.2% of patients, serious infections occurred in 7.5% vs 3.8% of patients, and the rates of opportunistic infections were 1.4% vs 0%.¹⁶
• There were no events of tuberculosis, malignancy, or anaphylaxis requiring STELARA discontinuation.¹⁶
• One death was reported among pediatric patients, which was considered as unrelated to IBD or STELARA treatment by investigators; no deaths were reported among young adults.¹⁶

Pediatric Patients vs Young Adults Weighing >40 Kg

• An analysis was conducted on 114 pediatric patients who weighed >40 kg with a sPCDAI ≥30, compared to 51 young adults with moderately to severely active CD.¹⁷
• All pediatric patients were treatment refractory (99.1%, no response to prior biologics; <1%, biologic naïve).¹⁷
• At week 52, clinical remission was achieved in 26/114 (22.8%) pediatric patients (95% CI, 16.1-31.3) vs 11/51 (21.6%) young adults (95% CI, 12.5-34.6).¹⁷
• At week 52, the rates of discontinuation were similar in pediatric patients (25.4%) and young adults (25.5%).¹⁷
• When comparing pediatric patients to young adults, IBD-related hospitalizations were reported in 36.0% vs 21.6% of patients, IBD-related surgery occurred in 14.0% vs 11.8% of patients, serious infections occurred in 9.6% vs 3.9% of patients, and the rates of opportunistic infections were 1.8% vs 0%.¹⁷
• There were no reports of tuberculosis, malignancy, or anaphylaxis requiring STELARA discontinuation. No deaths were reported in either group.¹⁷

DEVELOP

Koletzko et al (2024)¹⁸ assessed STELARA safety in pediatric patients with CD using data from DEVELOP, a multi-center, global, prospective, observational, longitudinal registry of long-term safety of infliximab (and other treatments) in pediatric patients with IBD.

Study Design/Methods

• The study included pediatric patients aged <18 years.
• Patients were categorized into 2 groups based on weight: <40 kg group and ≥40 kg group.

Results

Baseline Characteristics

• A total of 150 patients were included (n=31, <40 kg group; n=119, ≥40 kg group).
• Most of the treated patients were between 12 and 17 years old (92.0%). About 91% of patients initially received STELARA every 8 weeks (q8w). At the last known dose, 64% received STELARA q8w, and 22% received STELARA every 4 weeks.
• Overall, 65.3% of patients had prior IBD surgery, 98% received prior biologic therapy and 72% received ≥2 biologics prior to STELARA.

Safety

• During follow-up, 37 patients (24.7%) discontinued STELARA, with a mean (SD) time to discontinuation of 16.7 (17.00) months, while 84 patients (56.0%) were exposed to STELARA for ≥24 months.
• Rates (events per 100 patient-years) of AEs, SAEs, serious infections, CD-related hospitalizations, and IBD-related surgeries are shown in Table: Rates of AEs, SAEs, Serious Infections, CD-Related Hospitalizations, and IBD-Related Surgeries Among STELARA Treated Patients.
• One malignancy (malignant carcinoid tumor) was reported in an 18-year-old female in the ≥40kg group, with a history of prior therapy with vedolizumab, methotrexate, and 6-mercaptopurine. There were no reports of deaths or opportunistic infections.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 10 February 2024.