SUMMARY  

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• A phase 2, randomized, double-blind, placebo-controlled trial assessed the safety and efficacy of subcutaneous (SC) TREMFYA or ustekinumab in adult patients with active rheumatoid arthritis (RA) despite treatment with methotrexate (MTX).¹
• The primary endpoint was the proportion of patients who achieved 20% improvement in the American College of Rheumatology criteria (ACR20) response at week 28.¹ 
• At week 28, ACR20 was achieved by 41.3% (45/109) of patients in the combined TREMFYA plus MTX group and 40.0% (22/55) of patients in the placebo (PBO) plus MTX group (P=0.877).¹
  • 38.2% (21/55) in the TREMFYA 50 mg every 8 weeks (q8w) plus MTX group
  • 44.4% (24/54) in the TREMFYA 200 mg q8w plus MTX group
• Through week 48, adverse events (AEs) and serious adverse events (SAEs) were reported as follows:¹
  • AEs occurred in 36.4% (20/55) and 50.0% (27/54) of patients in the TREMFYA
    50 mg q8w plus MTX group and 200 mg q8w plus MTX group, respectively vs 45.5% (25/55) in the PBO plus MTX group.¹
  • SAEs occurred in 0% (0/55) and 5.6% (3/54) of patients in the TREMFYA 50 mg q8w plus MTX group and 200 mg q8w plus MTX group, respectively vs 5.5% (3/55) in the PBO plus MTX group.¹

CLINICAL DATA

Phase 2 Study

Smolen et al (2017)¹ conducted a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of TREMFYA or ustekinumab in adult patients with active RA despite treatment with MTX.

Study Design/Methods

• Selected Inclusion Criteria:
  • 18-80 years of age
  • Active RA (≥6 months) with persistent disease activity
    • Persistent disease activity was defined as:
      • ≥6/66 swollen joint count (SJC)
      • ≥6/68 tender joint count (TJC)
      • Serum C-reactive protein (CRP) level of ≥0.8 mg/dL
  • A positive test for anticyclic citrullinated peptide antibodies or rheumatoid factor
  • All participants had prior MTX therapy at a weekly dose of 10-25 mg for at least 6 months before screening, with a stable dose for at least 12 weeks prior to randomization.
• Exclusion Criteria:
  • History of receiving any approved or investigational biologic agents
• Through week 28, patients were randomized (1:1:1:1:1) to receive:
  • TREMFYA 50 mg SC at weeks 0, 4, and q8w plus MTX
  • TREMFYA 200 mg SC at weeks 0, 4, and q8w plus MTX
  • ustekinumab 90 mg SC at weeks 0, 4, and q8w plus MTX
  • ustekinumab 90 mg SC at weeks 0, 4, and every 12 weeks (q12w) plus MTX
  • PBO at weeks 0, 4, and q8w plus MTX
• Patients in the PBO plus MTX group who demonstrated less than a 10% improvement from baseline in SJC and TJC at week 16 entered double-blind early escape. These patients received ustekinumab 90 mg at weeks 16, 20, and 28. No treatment modifications were made for patients assigned to the TREMFYA or ustekinumab groups.
• Patients were permitted to use stable doses of concomitant glucocorticoids (<10 mg prednisone/day), non-steroidal anti-inflammatory drugs (NSAIDs), and/or other analgesics for RA.
• The primary endpoint was the proportion of patients who achieved an ACR20 response at week 28.
• At week 28, selected secondary endpoints evaluated the following outcomes:
  • 50% improvement in the American College of Rheumatology criteria (ACR50)
  • 70% improvement in the American College of Rheumatology criteria (ACR70)
  • American College of Rheumatology (ACR) core components
  • 28-joint count Disease Activity Score using CRP (DAS28-CRP)
  • Clinical Disease Activity Index (CDAI)
  • Simplified Disease Activity Index (SDAI)
  • Health Assessment Questionnaire-Disability Index (HAQ-DI)
• Immunogenicity and safety analyses were evaluated through week 48.

Results

Efficacy

• Among the 274 randomized patients, the primary endpoint of ACR20 response at week 28 was achieved by 41.3% (45/109) in the combined TREMFYA plus MTX group, 53.6% (59/109) in the combined ustekinumab plus MTX group, and 40.0% (22/55) in the PBO plus MTX group (P=0.877 and P=0.101, respectively). Of note, one patient in the ustekinumab 90 mg q8w plus MTX group discontinued due to an AE.
  • The primary endpoint of ACR20 response at week 28 for each dosing arm was reported as:
    • 38.2% (21/55) in the TREMYA 50 mg q8w plus MTX group
    • 44.4% (24/54) in the TREMFYA 200 mg q8w plus MTX group
    • 53.7% (29/54) in the ustekinumab 90 mg q8w plus MTX group
    • 54.5% (30/55) in the ustekinumab 90 mg q12w plus MTX group
• The results for the selected secondary endpoints evaluated at week 28 are summarized in Table: Selected Secondary Endpoints Evaluated at Week 28¹

• Of note, a total of 22 patients discontinued through week 28 with lack of efficacy (n=10) and AEs (n=8) being most common.

Immunogenicity

• A total of 12 out of 106 (11.3%) patients in the combined TREMFYA plus MTX group tested positive for antibodies to guselkumab (none had neutralizing antibodies).
• The Authors noted, serum guselkumab concentrations were generally similar between patients who tested positive and those who tested negative for antibodies.

Safety

• The results for the safety profile through week 48 are summarized in Table: Selected Adverse Events Through Week 48.

• There were no cases of tuberculosis or opportunistic infections reported.
• Two malignancies were reported during the follow-up period after week 28:
  • Squamous cell carcinoma of the lung in the ustekinumab 90 mg q12w plus MTX group
  • Breast cancer in the TREMFYA 200 mg q8w plus MTX group  
• One death occurred in the ustekinumab 90 mg q8w plus MTX group; the exact cause of death was unknown.

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 18 December 2025.