SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• Please refer to the local labeling for clinical data on the use of STELARA in adult patients with moderate to severe plaque psoriasis (PsO) and Crohn’s disease (CD).
• The PHOENIX-2 study evaluated the efficacy and safety of STELARA in patients with moderate to severe plaque PsO through 1 year. Symptoms of depression were evaluated through the Hospital Anxiety and Depression Scale-Depression (HADS-D).
  • From baseline to week 12, the proportion of patients with depression decreased in the STELARA group compared with placebo (STELARA 45 mg: 24.7% vs 12.8%; STELARA 90 mg: 31.1% vs 12.5%; placebo: 24.2% vs 12.6%).¹
• An open-label study evaluated the efficacy of STELARA on depression symptoms using self-rated (Beck Depression Inventory [BDI]) and observer-rated (Hamilton Depression Rating Scale [HDRS]) measures in patients with moderate to severe plaque PsO.
  • Depression symptoms improved after STELARA therapy from baseline (BDI, P=0.0002; HDRS, P<0.0001).²
• RUN-CD, is an ongoing, investigator-initiated, noninterventional study, evaluating the induction and maintenance therapies of biologics, including STELARA, in patients with CD. In addition, the effect on anxiety and depression is assessed after a 16-week STELARA therapy induction phase vs other biologic therapies.
  • A significant reduction was observed in the proportion of patients with anxiety and depression from baseline to week 16 in the STELARA group vs other biologic therapies (P<0.05; between group difference, P>0.05).³

Clinical data in Plaque psoriasis

Phase 3 Study - PHOENIX-2

Langley et al (2010)¹ presented results from a phase 3, double-blind, placebo-controlled study (PHOENIX-2) that evaluated the efficacy and safety of STELARA in patients with moderate to severe plaque PsO through 1 year. Symptoms of anxiety, depression, and skin-related quality of life (QoL) were evaluated in patients with moderate to severe plaque PsO receiving STELARA. Data specific to depression are summarized below.

Study Design/Methods

• At baseline, patients were randomized 1:1:1 to receive:
  • STELARA 45 mg or 90 mg at week 0, week 4, and every 12 weeks (q12w) through week 52
  • Placebo at weeks 0 and 4, followed by crossing over to receive either STELARA 45 mg or 90 mg at week 12, week 16, and then q12w
• HADS-D assessed depression symptoms at weeks 0, 12, and 24. The scale consists of 7 questions and the score is measured on a scale of 0 to 21. A lower score indicates less severity.
• Psoriasis Area and Severity Index (PASI) assessed the grade and severity of psoriatic lesions and their response to therapy. The score is measured on a scale of 0 to 72. Higher scores indicate more severe disease.

Results

Patient Characteristics

• Overall, 1230 patients were included, and all groups were comparable in terms of baseline demographics and clinical disease characteristics, see Table: Baseline Demographics and Disease Characteristics.

Change in the HADS-D Scores from Baseline to Weeks 12 and 24

• At week 12, the proportion of patients with depression symptoms at baseline in the STELARA vs placebo group decreased significantly (P<0.001); see Table: Proportion of Patients with Symptoms of Depression at Baseline and Week 12.

• At week 12, 87.4% vs 73.3% of patients in the STELARA vs placebo groups (P<0.001) reported a normal HADS-D score; see Table: Proportion of Patients with Depression Based on the HADS-D Scores at Week 12.

• At week 12, patients showed significantly greater improvement from baseline in the HADS-D scores in the STELARA 45 mg or 90 mg vs placebo group (P<0.001).
• For change in the HADS-D scores from baseline, see Table: Change from Baseline in the HADS-D Scores at Weeks 12 and 24.

Correlation of PASI with HADS-D at Week 12

• At week 12, improvement in the PASI scores demonstrated a statistically significant and modest correlation (correlation coefficient, r=0.32; P<0.0001) with improvement in the HADS-D scores.
  • Among patients who had depression (HADS-D score ≥8) at baseline, improvement in the PASI scores demonstrated a slightly higher correlation with improvement in the HADS-D scores (r=0.41; P<0.0001).

Psychological Adverse Events

• Among the 820 patients randomized to receive STELARA, 5 (0.6%) reported an adverse event (AE) of depression and 2 reported an AE (mild, nonserious) of anxiety during the 12-week placebo-controlled period. No AEs of depression or anxiety were reported in the placebo group.
  • Three patients had a medical history of depression at baseline, and none received antidepressants.
  • All events were mild and did not lead to treatment discontinuation.
  • Adverse events of depression occurred early (before week 8) in the study and were associated with improvements in the PASI score in all patients except for one.

Open-Label Study

Kim et al (2018)² evaluated the efficacy of STELARA on depression symptoms using self-rated BDI and observer-rated HDRS measures in patients with moderate to severe plaque PsO in an open-label study. Any regional changes in glucose metabolism before STELARA therapy and after achieving a 75% reduction in the PASI score (PASI 75) following STELARA therapy were also determined using ¹⁸fluorodeoxyglucose (FDG) positron emission tomography (PET).

Study Design/Methods

• Fifteen patients with moderate to severe plaque PsO and 15 healthy male volunteers for comparison were included in the study. All patients underwent neuropsychiatric assessment with FDG PET.
• STELARA 45 mg (90 mg if baseline body weight ≥100 kg) was administered initially and then 4 weeks later, followed by q12w.
• The neuropsychiatric assessment with FDG PET was performed at baseline and after achieving PASI 75 following STELARA therapy initiation.
  • Prior to brain PET scan, the presence of depression symptoms was determined through patient interviews.
  • Depressive mood was assessed using BDI and psychiatric interviews that employed HDRS. BDI score ranges from 0 (normal) to 63 (severe depression), and HDRS score ranges from 0 (normal) to 53 (very severe depression).

Results

Association Between PsO and Depression Symptoms

• Among the 15 patients with moderate to severe plaque PsO, 3 (20%) had moderate plaque PsO and 12 (80%) had severe plaque PsO.
• At baseline, depression symptoms in patients with moderate to severe plaque PsO vs healthy controls were milder (BDI, 12.7±9.3 vs 7.83±7.88 [P=0.098]; HDRS, 10.3±7.2 vs 4.92±4.12 [P=0.022]).
• No significant correlation was reported between depression symptoms and risk factors of sex, body mass index (BMI), disease duration, pruritus visual analog scale (VAS), or disease severity (initial body surface area, PASI).

Effect of STELARA on Depression Symptoms

• For the changes in depression symptoms after STELARA therapy, see Table: Effect of STELARA on Depression Symptoms.

• The PASI scores showed approximately 90% improvement (P<0.0001) after an average of 2.9 STELARA injections. No significant correlation was observed between improvement in the PASI score and depression symptoms (initial BDI, r²=0.0194; initial HDRS, r²<0.0001).
• No serious AEs were reported with STELARA therapy throughout the study.

Detection of Changes in Depression Symptoms via FDG PET

• No statistically significant difference was observed in the cerebral glucose uptake metabolism in patients with moderate to severe plaque PsO before vs after achieving PASI75 following STELARA therapy.

CLINICAL DATA in crohn’s disease

Ongoing Noninterventional Study - RUN-CD

Bokemeyer et al (2019)³ is conducting an ongoing, investigator-initiated, noninterventional study (RUN-CD) analyzing the effectiveness of induction and maintenance therapies of biologics, including STELARA, in patients with CD in Germany. The study is evaluating steroid-free remission rates and anxiety and depression as markers of QoL in patients with CD after a 16-week induction phase of STELARA compared with other biologic therapies.

• Anxiety and depression were assessed by the EuroQoL 5-dimension (EQ-5D) questionnaire at baseline and at week 16.
• Overall, 174 and 160 patients received STELARA and other biologic therapies, respectively.
• There was a significant reduction in the proportion of patients with anxiety and depression at baseline vs week 16 with STELARA (48.0% vs 36.4%) and other biologics (48.8% vs 34.5%; reduction in both groups, P<0.05; difference between the 2 groups, P>0.05).

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 16 April 2024.