SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• The safety of TREMFYA in adults with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD) were evaluated in the QUASAR and GALAXI clinical trial program, respectively. Summarized below is malignancy data from these 2 programs.^1,2
• The safety of TREMFYA, including the occurrence of malignancies, was evaluated for up to 1 year through a pooled safety analysis of phase 2/3 clinical trials of TREMFYA in patients with moderately to severely active CD or UC.³ 

CLINICAL DATA

GALAXI – Crohn’s Disease

Panaccione et al (2024)¹ reported the safety of TREMFYA in adult patients with moderately to severely active CD through GALAXI 2 and 3. GALAXI 2 and 3 were two phase 3, identically designed, randomized, double-blind, active comparator, placebo-controlled treat-through trials.

• Of the 299 patients who received TREMFYA 200 mg intravenous (IV) induction followed by TREMFYA 200 mg subcutaneous (SC) every 4 weeks (q4w) through week 48, malignancy was reported in 1 (0.3%) patient.
• No cases of malignancy were reported through week 48 in the following groups:
  • Placebo IV → SC (N=153)
  • TREMFYA 200 mg IV q4w → 100 mg SC every 8 weeks (q8w) [N=296]
  • Ustekinumab ~6 mg/kg IV → 90 mg SC q8w (N=300)

QUASAR – Ulcerative Colitis

The safety of TREMFYA was evaluated through 2 phase 3, randomized, double-blind, placebo-controlled, studies in adult patients with moderately to severely active UC (QUASAR). This included a 12-week induction study and a 44-week randomized, withdrawal maintenance study.²

• Through week 12 of induction, 2 participants in the TREMFYA 200 mg IV group with significant risk factors had treatment-emergent malignancies⁴:
  • Patient 1: On day 23, squamous cell carcinoma was reported in a 66-year-old white participant with a past medical history of previously resected squamous cell carcinoma and concomitant corticosteroid use.
  • Patient 2: On day 32, basal cell carcinoma was reported in a 60-year-old white participant with concomitant corticosteroid use.
• Through week 44 of maintenance, malignancies were reported in 5 participants⁵:
  • Two participants (60-year-old female and 48-year-old female) in the placebo group each had 1 malignancy of non-melanoma skin cancer (basal cell carcinoma).
    • One of these participants also reported a basal cell carcinoma (60-year-old female) while receiving TREMFYA during the induction period.
  • Two participants (64-year-old female and 51-year-old female) in the placebo group had breast cancer.
  • One 42-year-old female participant in the TREMFYA 200 mg SC q4w group had adenocarcinoma of the rectum without dissemination or metastasis. This participant had a 9-year history of extensive UC, which is associated with an increased risk of colorectal cancer.
  • Among all treated participants, 4 additional malignancies were reported in 3 participants:
    • One 40-year-old female participant in the nonrandomized placebo group had breast cancer.
    • One 43-year-old male participant in the nonrandomized TREMFYA 200 mg SC q4w group with a risk factor of hypertension had clear cell renal cell carcinoma.
    • One 66-year-old female participant randomized to the maintenance placebo group and then dose adjusted to TREMFYA 200 mg had 2 malignancies of squamous cell carcinoma of skin. This participant also had malignancies of squamous cell carcinoma reported in the placebo-controlled induction period.

Pooled Safety Analysis of Phase 2/3 Studies in Crohn's Disease and Ulcerative Colitis

• Patients with moderately to severely active CD or UC through up to 1 year were included:³ 
  • UC: n=1514 from QUASAR induction study 1, 2 and the maintenance study
  • CD: n=1492 from GALAXI 1,2 and 3; GRAVITI (subcutaneous induction therapy with TREMFYA).
  • UC: VEGA study (Guselkumab plus golimumab combination therapy versus TREMFYA or golimumab monotherapy [VEGA]).
• TREMFYA studies were pooled for the induction period (GALAXI, GRAVITI, & QUASAR; Weeks 0-12 [VEGA excluded due to no PBO control]) and through 1 year (GALAXI, GRAVITI, QUASAR, & VEGA).
• In this pooled analysis, safety events were normalized to 100 patient-years (PY) of follow-up with corresponding confidence intervals.
• Through 1 year, rates of malignancy are reported in Table: Total Patient Years of Follow Up and Occurrence of Malignancies per 100 Patient Year. 

 Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 03 February 2025.