SUMMARY

• The company cannot recommend any practices, procedures, usage, or dosing that deviate from the approved labeling.
• A post hoc analysis was conducted to evaluate the efficacy of STELARA among patients with Crohn's disease (CD) who received treat-to-target (T2T) maintenance strategy vs standard-of-care (SoC) approach using data from a phase 3b, randomized study.¹
• Retrospective studies and data from a registry of patients with CD who required dose escalation with STELARA during maintenance therapy with 90 mg subcutaneous (SC) every 8 weeks (q8w) are summarized below.^2-17

CLINICAL DATA

Phase 3b Study: STARDUST Trial

Danese et al (2022)¹ reported the efficacy and safety results from an open-label, phase 3b, multicenter, randomized study in adult patients with moderately to severely active CD comparing a T2T maintenance strategy based on early endoscopy, dose intensification, and regular biomarker and clinical symptom monitoring vs a clinically driven SoC maintenance strategy.

• Overall, 205 patients from the T2T group and 218 patients from the SoC group were treated at maintenance baseline (week 16/20).
• Of the 205 patients treated at maintenance baseline in the T2T group, 84 and 121 patients received STELARA 90 mg SC q8w and every 12 weeks (q12w), respectively.
  • Twenty-one (25%) of 84 patients who initially received STELARA 90 mg q8w were dose-escalated to every 4 weeks (q4w) by week 48; 28 other patients were dose-escalated to q4w but discontinued treatment before week 48.
• Of the 218 patients treated at maintenance baseline in the SoC group, 102 patients received STELARA 90 mg SC q8w.
• A comparative post-hoc analysis of endoscopic, clinical, and biomarker endpoints at week 48 (last observation carried forward [LOCF]) between patients in the T2T group who were assigned to q8w and continued or dose-escalated to q4w (n=84) and the patients in the SoC group who were assigned to and continued on q8w (n=102) is presented in Table: LOCF Analysis of Endoscopic Response, Clinical Outcomes, and Biomarker Response at Week 48.

Retrospective Studies

Olmedo-Martín et al (2023)² conducted a multicenter, retrospective, observational study to evaluate the effectiveness of STELARA dose escalation in patients with CD from June 15, 2022, to January 15, 2023.

• Patients included in this study were those who had active CD (Harvey-Bradshaw Index [HBI] ≥5), received at least 1 intravenous (IV) induction dose (6 mg/kg) and at least 1 SC dose and underwent dose escalation. Dose escalation was defined as receiving maintenance dose of 90 mg SC q4w or every 6 weeks (q6w) or IV reinduction (6 mg/kg) combined with shortening of dosing interval to q4w.
• The primary outcome was steroid-free clinical response (decrease of HBI ≥3 points from baseline) at week 16 after STELARA dose escalation.
• The secondary outcomes were steroid-free clinical remission (HBI ≤4), combined biologic response (reduction in fecal calprotectin [FCP] and C-reactive protein [CRP] levels by 50% from baseline) and combined biologic remission (FCP <250 µg/g and CRP <5 mg/dL) at week 16 after STELARA dose escalation.
• A total of 273 patients received STELARA treatment. The median (interquartile range [IQR]) duration of disease was 13 (8-18) years.
  • Thirty-three percent (n=91) underwent dose escalation due to insufficient primary response in 28.6% (n=26) and loss of response in 71.4% (n=65).
• Steroid-free and biologic response and remission at week 16 and last follow-up visit, are presented in Table: Treatment Outcomes After Dose Escalation at Week 16 and Last Follow-up Visit.

• STELARA was discontinued due to lack of response in 10/91 patients before week 16.
• The median duration of follow-up in patients who continued STELARA was 64 weeks (IQR: 39-92 weeks).
• After week 16, 5 additional patients discontinued STELARA due to lack of response. Twenty of the 45 patients receiving systemic corticosteroids at the time of dose escalation were able to be discontinued.
• Two of 20 patients who did not respond at week 16 after dose escalation subsequently responded to treatment. STELARA was switched to another biologic in 8 patients.
• Overall, 4 patients reported adverse events (AEs) after dose escalation. All were mild and did not lead to hospitalizations or discontinuations (2 patients with mild herpes infection, 2 with arthralgia) and 5 patients underwent surgical resection during dose escalation, with no immediate postsurgical complications.

Dalal et al (2023)³ conducted a retrospective cohort study of adult patients with CD undergoing dose intensification of STELARA 90 mg q8w to q4w or q6w.

• The primary outcome was corticosteroid-free clinical remission at 24±2 months (CFCR-24), defined as HBI <5 with no use of oral or IV corticosteroids within 30 days preceding assessment. The secondary outcome was corticosteroid-free clinical remission at 12±2 months (CFCR-12).
• Patients who discontinued STELARA due to lack of efficacy before reaching the endpoints were classified as treatment failures. Other additional outcomes included endoscopic response (>50% reduction in the Simple Endoscopic Score for Crohn’s Disease [SES-CD]) and remission (SES-CD ≤4), and bowel resection surgery.
• In total, 123 patients underwent dose intensification; the median follow-up was 1024 days (IQR: 708-1295 days; 321 patient-years), and median disease duration at the time of dose intensification was 13.7 years (IQR: 8.6-20.6 years).
• STELARA dose escalations included the q6w or q4w intervals, with most of the patients receiving q4w dosing (52.8%).
• CFCR-24 and CFCR-12 were observed in 60.6% (63/104) and 57.3% (67/117) of patients, respectively. Among 58 patients in CFCR-12 with documented assessment at 24 months, 84.5% (49/58) of patients remained in CFCR.
• Endoscopic response was observed in 59% (49/83) of patients after a median of 400 days (IQR: 212-632 days) after dose intensification. Endoscopic remission was observed in 43.4% (36/83) of patients.
• Bowel resection surgery occurred in 8.9% (11/123) of patients.
• STELARA was discontinued in 19.5% (24/123) of patients.
  • The primary reasons for discontinuation were loss of response (70.8%) and AEs (12.5%).
  • AEs leading to treatment discontinuation were observed in 3 patients which included arthralgia, abdominal wall abscess, and excessive drowsiness with weight gain.

Johnson et al (2023)⁴ conducted a real-world retrospective review of SUCCESS, a multicenter consortium of STELARA-treated CD patients (N=1113), to evaluate the effectiveness and safety of STELARA in routine clinical practice, including dose escalation for nonresponse, incomplete response, or loss of remission after 12-month follow-up.

• Outcomes of 681 patients with either primary nonresponse or incomplete response (<50% reduction in symptom activity) and 102 patients who lost remission during the follow-up period who underwent STELARA dose optimization are reported in Table: Response to Dose Optimization.

Abdelmoula et al (2023)⁵ conducted a multicenter, retrospective, observational, cohort study (MUST [Meta-optimization of Ustekinumab]) to compare the efficacy of STELARA 90 mg SC q4w vs q8w dosing after IV induction in patients with severely active CD through 1 year.

• Severely active CD was defined as HBI >16 and stool frequency ≥4 and abdominal pain ≥2 over 1 week plus ≥1 objective evidence of inflammation (CRP ≥5 mg/L, FCP ≥250 µg/g, radiologic, and/or endoscopic signs of disease activity).
• The primary endpoint was clinical remission at week 52 based on a 2-item patient-reported outcome ([PRO-2], defined by stool frequency ≤2-8 and abdominal pain ≤1) and FCP <250 µg/g and/or CRP <5 mg/L.
• The major secondary endpoints included PRO-2 remission, endoscopic improvement, and steroid-free clinical remission at week 52.
• Among 203 patients included in the study, 59 and 144 received STELARA q4w (MUST group) and q8w (STD group), respectively.
• At week 52, a significantly higher clinical remission rate was achieved in the MUST vs STD group, with an adjusted difference of 15.8% (95% confidence interval [CI], 0.21-0.94; P=0.029).
• The adjusted difference between the 2 groups for PRO-2 remission was 3.7% (95% CI, 0.45-1.66; P=not significant [NS]).
• Endoscopic improvement was comparable between the 2 groups (61.9% vs 61.5%; P=NS).
• All patients, except 1 (STD group), were weaned off steroids at week 52.
• No significant difference was observed in the rate of AEs between the 2 groups (42.4% vs 34.7%).

Dalal et al (2021)⁶ conducted a retrospective cohort study to identify predictors of treatment failure with STELARA 90 mg SC after dose intensification (from q8w to a shorter dosing interval) for patients with CD from January 2016 to January 2019.

• CD activity was measured using the HBI score 3 months prior and at visits within 12 months after dose intensification.
• The primary outcome was failure to achieve corticosteroid-free remission (HBI <5) within 12 months after dose intensification.
• The secondary outcome was discontinuation of STELARA with initiation of a new biologic therapy assessed at 12 months of follow-up after intensification.
• Additional outcomes assessed within 12 months after intensification included clinical response (re-induction of pre-intensification HBI ≥3 points), endoscopic improvement, normalization of elevated CRP, and normalization of elevated FCP.
• Of the 238 patients initiated on STELARA, 123 (51.7%) underwent dose intensification. The median time from STELARA baseline to intensification was 307 (IQR: 168-557) days.
• Dose intensifications to shorter intervals included q4w (n=64), every 5 weeks (n=1), q6w (n=55), and every 7 weeks (n=3).
• Corticosteroid-free remission was reported in 23/42 (54.8%) patients and 18/33 (54.6%) patients in q4w and q6w groups, respectively (P=NS).
• Discontinuation of STELARA with initiation of a new biologic occurred in 8/44 (18.2%) patients receiving STELARA q4w and in 3/40 (7.5%) patients receiving STELARA q6w (P=NS).
• Clinical response occurred in 23/38 (60.5%) and 17/29 (58.6%) of patients receiving STELARA q4w and q6w, respectively, (P=NS).
• Endoscopic improvement and the normalization of elevated CRP and FCP were similar among patients receiving STELARA q4w and q6w, (P=NS for each of the outcomes).
• Despite meeting criteria for clinical remission (n=31, 25.2%), reasons for dose intensification included loss of clinical response (n=92, 74.8%) along with the following: symptom recurrence before 8 weeks (n=10/31), endoscopic inflammation (8/31), low serum ustekinumab concentration (n=4/31), elevated FCP (3/31), bowel inflammation on computed tomography (CT)/magnetic resonance imaging (MRI) (3/31), perianal disease symptoms (2/31), and patient preference (1/31).
• A sensitivity analysis was conducted comparing outcomes by the number of previous biologic therapies. This analysis showed patients were more likely to discontinue STELARA and initiate a new biologic after dose intensification if they previously used 2 biologics (25.7%) compared to patients that used 1 biologic (8.3%) or ≥3 biologics (2.5%), (P<0.01).

Ollech et al (2021)⁷ performed a retrospective study to determine the effectiveness of shortening the dose interval to STELARA 90 mg SC q4w in patients with CD who did not respond to q8w dosing.

• A total of 506 patients received STELARA during the study period and 110 of these patients were dose escalated to receive STELARA q4w. The median time to interval shortening was 7.5 (IQR: 4.2-13.2) months after treatment initiation.
• All patients included in the study had either clinical symptoms (HBI >4), active inflammation by endoscopy, an elevated CRP (CRP >5 mg/L), or FCP >250 µg/g while receiving STELARA 90 mg SC q8w.
• Patients were followed for a median of 9 months (IQR: 5.8-14.4) after interval shortening and outcomes included clinical (HBI), biologic (CRP and FCP), and endoscopic.
• Seventy-eight (71%) patients had HBI measurements collected before and after dose escalation; the median HBI before and after dose escalation were 4.5 and 3, respectively (P=0.002; median time between assessments of 6 months).
  • Of the 51 patients who had an HBI >4 before interval shortening (median HBI: 7), 14 (28%) patients achieved clinical remission (HBI ≤4) after dose escalation.
  • During follow-up: clinical remission after interval shortening was reported in 56 (50.9%) patients with a median time to documented clinical remission of 5 months (IQR: 2-8 months).
• Sixty (55%) patients had CRP measurements before and after dose escalation; the median CRP before and after dose escalation were 8 mg/L and 3 mg/L, respectively (P=0.031; median time between tests of 7 months).
  • Normalization of CRP (<5 mg/dL) occurred in 13 of 59 (22%) patients who had a CRP ≥5 mg/dL before dose escalation (median CRP: 13 mg/dL).
  • During follow-up: biologic remission (CRP <5 mg/L) was reported in 32 (29.1%) patients with a median time from interval shortening to biologic remission of 5.5 months (IQR: 2.5-8.5 months).
• Eight (7%) patients had FCP measurements before and after dose escalation; the median FCP before and after dose escalation were 378 µg/g and 157 µg/g, respectively (P=NS; median time between tests of 13 months).
  • Four (50%), 1 (13%), and 3 (38%) patients had improved, stable, and worsening FCP measurements, respectively.
  • Of the 7 out of 8 patients with elevated (>250 µg/g) FCP before dose escalation, the median FCP decreased from 405 µg/g to 348 µg/g.
• Eleven (10%) patients had endoscopic assessment documented before and after dose escalation; the median SES-CD before and after dose escalation were 8.5 (IQR: 6-14) and 4.5 (IQR: 1.5-10), respectively (P=NS; median time between assessments of 13 months).
  • Four (36%) patients who had baseline moderate to severe disease had quiescent disease after escalation, and 1 patient who had quiescent endoscopic disease before escalation had active endoscopic disease after dose escalation.
• Discontinuation of STELARA after interval shortening occurred in 23 (20.9%) patients.
  • The most common reason for discontinuation was failure or loss of response to STELARA (n=18).

Sipponen et al (2021)⁸ conducted a nationwide, real-world, retrospective chart review study assessing STELARA dosing dynamic and optimization as well as identifying clinical predictors of dose intensification in patients with CD from the FINUSTE2 study, an extension of the FINUST study, which included 48 adults with CD treated with STELARA 90 mg.

• Data regarding changes to STELARA dosing during treatment and the reason for such changes were collected at any time throughout the study.
• Dose optimization (shortening/prolongation of the dosing interval) was reported in 55/140 (39.3%) patients.
  • Among these patients, dose intensification (shortening of the dosing interval) occurred in 47 (85.5%) patients and 41/47 (87.2%) patients persisted on dose intensification to the end of the follow-up period.
• For patients with dose intensification, the mean duration of STELARA treatment was 14.9±6.4 months and the mean follow-up time was 15.7±6.0 months.
• The STELARA dosing interval was shortened in 24.8% (25/101) of patients on q8w dosing and in 56.4% (22/39) of patients on q12w dosing.
• At the end of follow-up, 16.4% of patients were on dosing intervals of STELARA that were shorter than q8w (the shortest interval was q4w).
• Reasons for shortening of the dosing interval included insufficient response (71.2%), loss of response (13.5%), and others (eg, STELARA concentrations and disease symptoms, 15.4%).
• Mean duration from STELARA induction to the first dose intensification was 9.4 months (standard deviation [SD], 5.4; median, 8.3).
• Median baseline CRP was significantly higher in dose-intensified patients compared to patients without changes in dosing interval (10 mg/L, IQR: 5-18 vs 6 mg/L, IQR: <3-13; P=0.027, respectively).
• No statistically significant differences were seen in the proportion of patients with STELARA dose intensification when grouping according to the number of prior biologic therapies.
• Of the 47 patients who required a shortened dosing interval of STELARA, 22 (46.8%) patients were treated with corticosteroids at baseline. In comparison, among the 93 patients who did not require dose intensification, 36 (38.7%) patients were treated with corticosteroids at baseline.

Fumery et al (2020)⁹ conducted a multicenter, retrospective cohort study, evaluating the efficacy and safety of STELARA 90 mg SC q4w in patients with CD who had incomplete response or loss of response to STELARA 90 mg q8w.

• Patients with active CD (defined by HBI ≥4 and at least 1 objective sign of inflammation [CRP ≥5 mg/L and/or FCP ≥250 µg/g and/or radiologic and/or endoscopic evidence of disease activity]) who required STELARA dose escalation to 90 mg q4w for loss of response or incomplete response (lack of improvement of clinical symptoms) to STELARA 90 mg q8w were included.
• Short-term clinical response was defined as a decrease of HBI ≥3 after dose escalation compared to baseline, with a decision to continue the same dose, and was evaluated at the first clinic visit after dose escalation.
• Clinical remission was defined as an HBI <4.
• Endoscopic remission was defined as an absence of ulceration.
• A total of 100 patients with a median age of 34.9 years (IQR: 28.1-46.3 years) were included.
• The median duration of STELARA therapy before dose escalation was 5 months (IQR: 2.8-9 months).
• At the time of dose escalation, 29% (29/100) and 27% (27/100) received co-treatment with corticosteroids and immunosuppressants, respectively.
• Incomplete response (74%, 74/100) and luminal disease (77%, 77/100) were the main indications for STELARA escalation.
• After a median of 2.4 months (IQR: 1.3-3 months) following STELARA dose escalation, short-term clinical response, clinical remission, and CFCR were reported in 61% (61/100), 31% (31/100), and 27% (27/100) of patients, respectively.
• The median value of HBI dropped from 8 at baseline (IQR: 5-11.2) to 5.0 (IQR: 3-7) (P=0.001).
• The median CRP level decreased from 12.3 mg/L (IQR: 5-30.5 mg/L) to 9.6 mg/L (IQR: 3.2-18.0 mg/L) (P=NS).
• At 6 months, follow-up information was available for 69 of 100 patients.
  • Of these patients, 49% (34) were in CFCR.
  • The median HBI was 4 (IQR: 2.5-6) and the median CRP level was 8.5 mg/L (IQR: 2.25-17.3 mg/L).
  • Among the 35 non-responders to STELARA dose escalation in the short term, 6 (17.1%) achieved clinical remission.
• After a median follow-up of 8.2 months (IQR: 5.6-12.4 months), 61% (61/100) of patients were receiving STELARA.
  • At the end of follow-up, 26% of patients were in CFCR.
  • Patients withdrew STELARA due to absence of response to dose escalation (38%, n=23), loss of response (21%, n=13), or pregnancy (5%, n=3).
  • After a median of 7.4 months (IQR: 5.5-13.2 months) since optimization, 9 patients de-escalated STELARA dosing schedule: seven to 90 mg q8w and two to 90 mg q6w.
• Sixteen patients had dose escalation for perianal disease and 7 patients for both perianal and luminal CD. Among these patients, 61% (14/23) had an immediate response per physician judgment. Five patients had perianal fistula closure and 4 patients experienced CD worsening which required perianal surgery.
• Of the 39 patients with colonoscopy after a median interval of 5.9 months (IQR: 2.4-7.8 months) after STELARA dose escalation, 14 (35.9%) had endoscopic remission.
• After a median follow-up of 8.2 months (IQR: 5.6-12.5 months), 27% (27/100) of patients were hospitalized for CD. A total of 19% (19/100) of patients underwent major abdominal surgery.
• A total of 13 AEs were reported in 12 patients (12%), which included 8 infections (no deaths or malignancies reported). STELARA q4w was continued in all patients who experienced an AE.
• Severe AEs were reported in 5 patients who were hospitalized but none led to definitive STELARA withdrawal (n=2, pyelonephritis; n=1, pharyngitis/epiglottitis; n=1, pneumonitis; n=1, infectious colitis).

Glass et al (2020)¹⁰ assessed the safety and efficacy of STELARA dose escalation in patients with luminal and perianal CD through a single center cohort study.

• Dose escalation was defined as increasing frequency to q4w or q6w.
• The primary outcomes were improvement in perianal disease determined by the treating clinician and a composite outcome reflecting disease response (at least 1 of the following: steroid-free clinical response, objective improvement in disease activity on follow up CT/MRI/endoscopy, or normalization of CRP).
• Secondary outcomes included inflammatory bowel disease (IBD)-related surgery and AEs.
• 38 patients underwent dose escalation: 28 (74%) patients were escalated to q4w dosing, and 10 (26%) patients were escalated to q6w dosing. Patients were followed up to 6 months after dose escalation.
• Escalation was performed in 18/38 (48%) patients due to primary non-response.
• The median time to dose escalation from STELARA initiation was 10 months (IQR: 2-24 months). The median follow-up time was 4.5 months.
• Prior exposure to anti-tumor necrosis factor (TNF) and anti-integrin therapy was reported in 92% and 74% of patients, respectively.
• Overall, 19/38 patients who underwent dose escalation met the primary composite outcome of disease response and 12/24 (50%) patients with active perianal disease showed evidence of improvement after escalation.
  • Of the patients on steroids at the time of escalation, 6/10 (60%) achieved steroid-free response.
  • Endoscopic improvement was seen in 8/11 (72%) patients who underwent a follow-up endoscopy.
• Pre-escalation, the median CRP was 9.55 mg/L; after escalation, 9/33 (27%) patients had normalization of CRP.
• IBD-related surgery was required after dose escalation in 3/38 (8%) patients.
• AEs were reported in 2 patients (injection site erythema and C. difficile infection).

Kopylov et al (2020)¹¹ evaluated the efficacy and safety of STELARA dose escalation to q4w or q6w, or a combination of IV re-induction and dose escalation in patients with active CD after non-response or loss of response to STELARA 90 mg SC q8w maintenance therapy in a multicenter retrospective cohort study.

• Patients in the study received ≥2 doses of STELARA (IV induction of 6 mg/kg followed by 90 mg SC injection q8w) and were either dose-escalated to q4w or q6w or received an IV re-induction (6 mg/kg) instead of a scheduled SC dose or received a combination of SC escalation to q4w or q6w dosing and IV re-induction.
• The primary endpoint was clinical response at week 16 after dose escalation, which was defined as a change in HBI ≥3 or a change in Crohn’s Disease Activity Index (CDAI) ≥70.
• A total of 142 patients were included in the study, and of those, 91 patients (64.1%) were escalated to q4w dosing, 20 patients (14.1%) were escalated to q6w dosing, and 17 patients (12%) had a combination of IV reinduction and dosing interval shortening.
• At week 16, clinical response was achieved by 48 patients who received q4w dose escalation, 10 patients who received q6w dose escalation, and 10 patients who received q4w dose escalation with IV reinduction.
• A total of 17 of 91 patients (18.7%) who escalated to q4w dosing, 1 of 20 patients (5%) who escalated to q6w dosing, and 1 of 17 patients (5.9%) who received both SC dose escalation and IV reinduction discontinued STELARA due to clinical non-response, respectively.

Haider et al (2020)¹² assessed the efficacy of STELARA dose escalation to q4w for patients (n=143) with refractory CD.

• The primary outcomes were clinical response (Physician Global Assessment [PGA >1]) and clinical remission (PGA=0).
• Additionally, changes in clinical parameters were evaluated for patients with dose escalation (beginning with the time of dose switch [~42 weeks]) and compared with patients who were classified as “failing” standard dosing (q8w) at 42 weeks but were not dose escalated.
• Of 143 patients in this study, there were 15 patients who received STELARA q8w and 15 patients who received STELARA q4w.
• The mean PGA for patients in the q8w group was 1.4±0.1 and 2.0±0.2 for patients in the q4w group, (P=0.02).
• In the q4w group, PGA decreased by -0.47 from the dose escalation to the end of follow-up.
  • Remission was achieved in 2 (13.3%) patients and 5 (33.3%) patients had further clinical response (measured by reduction in PGA).
  • No further change in PGA was observed in 8 (53.3%) patients at the end of follow-up.
  • No patients in the q4w group experienced worsening of clinical disease.
• In the q8w group, PGA increased to 0.23 from 42 weeks to the end of follow-up, (P<0.02).
  • At the end of follow-up, worsening of clinical disease (increase in PGA) was seen in 6 (40%) patients receiving STELARA q8w.
• Steroid therapy remained in 7 (47%) and 3 (14%) patients receiving STELARA q4w and q8w at the end of follow-up, respectively, (P=NS).
• From 42 weeks to the end of follow-up, CRP increased a mean of 0.41 mg/L and decreased a mean of 0.33 mg/L in patients treated q8w and q4w, respectively, (P<0.01).

Yadav et al (2020)¹³ conducted a retrospective observation study of STELARA dose escalation to q4w in adult patients with CD who had a partial response or
non-response to standard q8w dosing.

• Outcomes were compared in q8w partial responders and non-responders from the date of starting STELARA q8w dosing to the date of escalation to q4w dosing, vs the date of escalation to q4w dosing to the end of patient follow-up.
  • These patients were subcategorized as partial responders or non-responders based on changes in FCP, albumin, CRP, and PGA Disease Severity (1=mild, 2=moderate, 3=severe).
• A total of 8 patients were q8w non-responders, and 19 patients were q8w partial responders. In the q8w partial responder group, biomarkers decreased by up to 21% and 100% of these patients experienced clinical improvement or remained at mild disease while on q4w dosing. See Table: CD Outcomes in Partial Responders to STELARA After Dose Escalation.

• In the q8w non-responder group, biomarkers decreased by up to 91% and 100% of patients saw clinical improvement or remained at mild disease while on q4w dosing.
• In both groups, 50% of patients taking steroids on q8w dosing were no longer taking steroids or were at a reduced dose at the end of follow-up with q4w dosing.

Bundschuh et al (2019)¹⁴ examined the real-world efficacy and safety of STELARA in patients with CD and evaluated if STELARA dose escalation helps to recapture clinical response.

• Through electronic medical records, patients who received an initial weight-based STELARA infusion between April 2017 and April 2018 were identified.
• Patients were followed from STELARA initiation through May 2019 or the date of STELARA discontinuation, whichever came first.
• Patients who lost response to STELARA 90 mg injection q8w and were dose escalated to either q4w or q6w dosing were identified.
• By reviewing clinical documentation and assessing for a reduction of ≥3 in the modified Harvey-Bradshaw Index (mHBI) after ≥8 weeks following dose escalation, the rate of recaptured clinical response to dose escalation was determined.
• A total of 27 patients with CD were included in the study which included 11 patients with dose escalation and 16 patients who did not receive dose escalation.
  • Of the 11 patients who received dose escalation, 9 were switched to an q4w regimen and 2 were switched to an q6w dosing regimen.
  • After dose escalation in the 11 patients, the median mHBI improved from 9 to 7 and the rate of recaptured clinical response was 55% (6/11) based on clinical documentation and 27% (3/11) based on mHBI.
  • A total of 8 of the 11 patients (73%) who received dose escalation remained on the escalation regimen and the other 3 patients were discontinued from the dose escalation regimen (primary non-response, n=2; secondary non-response, n=1).
  • A total of 1 AE occurred in the dose escalation group (a case of pneumonia) and 5 AEs (infusion reaction, n=1; infection, n=2; minor AE, n=2) occurred in the group who didn’t receive dose escalation.

Cohen et al (2019)¹⁵ evaluated the response to STELARA dose escalation in a real-world cohort of patients with active CD.

• Retrospectively, patients with CD who had partial or no clinical response to standard STELARA induction and/or maintenance and required dose escalation to 90 mg q4w or q6w were identified.
• Patients who did not receive STELARA IV induction or had clinically inactive disease at the time of dose escalation were not included.
• Response and remission were based on PGA.
• Clinical response to dose escalation was the primary outcome, and secondary outcomes included clinical remission and endoscopic response to dose escalation.
• Multivariable regression with backward elimination was performed to identify predictors of clinical response to dose escalation.
• A total of 68 patients received STELARA dose escalation. Overall, 67.8% of patients had clinical response at week 8 after the STELARA induction dose.
  • Following dose escalation, 79.4% (54/68) of patients had a clinical response and 30.9% achieved clinical remission within 3-6 months.
  • Of the patients with available endoscopic follow-up data (n=39), 59% and 20.5% achieved endoscopic response and endoscopic remission, respectively.
  • Between responders and non-responders to STELARA dose escalation, baseline characteristics were similar except for a higher proportion of responders having had clinical response to the STELARA induction dose (P=0.004).
  • On multivariable regression analysis, response to STELARA induction therapy was the only independent predictor of response to dose escalation (odds ratio: 7.01; 95% CI, 1.83-27.07; P=0.005).

Young et al (2018)¹⁶ conducted a retrospective cohort study of patients with CD and analyzed the response of STELARA dose escalation during q8w maintenance dosing.

• Among 122 consecutive patients on STELARA (median follow-up of 146 days) 21 patients (17%) required dose intensification: 10 due to poor initial response, 7 patients due to primary non-response, and 4 due to secondary loss of response.
• The dose escalation utilized was: increase in frequency to q4w (n=11), q6w (n=5), or a combination of IV booster and frequency increase to q6w or q6w (n=5).
• Median follow-up after dose intensification was 177 days and a total of 11 patients (52%) had clinical response after dose escalation (5 of 11 [45%] patients on
  q4w dosing regimen, 4 of 5 [80%] patients on the q6w dosing regimen, and 2 of 5 [40%] patients on the combination IV booster and frequency increase dosing regimen).
• Of the 11 patients who had clinical response after dose escalation, 2 (18%) were primary non-responders to induction while 9 (82%) had poor initial clinical response.
• Of the 4 patients with secondary loss of response who required dose intensification, none were able to regain response from dose escalation.
• Side effects reported were dizziness, fatigue, nausea, abdominal pain, dehydration, diarrhea, arthritis, and a perianal abscess.

REGISTRY DATA

ENEIDA Registry

García et al (2024)¹⁷ conducted a multicenter, retrospective, observational study to evaluate the durability, effectiveness, and safety of STELARA in patients with CD who failed or were intolerant to anti-TNF. The study included patients from the ENEIDA registry, enrolled between January 1, 2012, to December 30, 2020.

• Patients were started on a STELARA IV induction dose (~6 mg/kg), followed by STELARA 90 mg SC q8w or q12w. Loss of response was defined as an HBI>4 leading to dose escalation, addition of another medication or change to another drug or surgery.
• Effectiveness was evaluated using HBI at weeks 8 and 16 during the induction phase and every 6 months during the maintenance phase.
• In total, 628 patients were treated with STELARA. The median time of follow-up and median therapy exposure were 2.8 years (IQR: 2-3.6 years) and 1.5 years (IQR: 0.7-2.6 years), respectively.
• Overall, 360 patients lost response over time and 232 (39%) patients required STELARA dose intensification during the maintenance phase.
• STELARA dose intensification to q4w was done in 207 patients, respectively.
  • Clinical response to STELARA dose intensification, per the investigator, was achieved in 143 (65%) patients.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 20 June 2024.