SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• The efficacy and safety of combination therapy with TREMFYA and golimumab versus TREMFYA or golimumab monotherapy was evaluated in a phase 2, randomized, double-blind, controlled, multicenter, proof-of-concept study in adult patients with moderately to severely active ulcerative colitis (UC). Efficacy and safety results through weeks 38 and 50, respectively, are reported below.¹

CLINICAL DATA

Phase 2 Study

Feagan et al (2023)¹ conducted a phase 2, randomized, double-blind, controlled, multicenter, proof-of-concept study that evaluated the efficacy and safety of TREMFYA in combination with golimumab compared with monotherapy with TREMFYA or golimumab in adult patients with moderately to severely active UC.

Study Design/Methods

• Patients who were naïve to tumor necrosis factor (TNF), interleukin (IL)-12/23, or IL-23p19 antagonists, with inadequate response or intolerance to oral or intravenous (IV) immunosuppressants or corticosteroids, were randomized to receive 1 of the following:
  • Combination therapy: TREMFYA 200 mg IV and golimumab 200 mg subcutaneously (SC) at week 0, golimumab 100 mg SC at weeks 2, 6, and 10, and TREMFYA 200 mg IV at weeks 4 and 8, followed by TREMFYA 100 mg SC every 8 weeks (q8w) until week 32
  • TREMFYA monotherapy: 200 mg IV at weeks 0, 4, and 8, followed by 100 mg SC q8w until week 32
  • Golimumab monotherapy: 200 mg SC at week 0, followed by 100 mg SC at week 2, and then every 4 weeks (q4w) until week 34
• The primary endpoint was clinical response (defined as a decrease from baseline in the Mayo score by ≥30% and ≥3 points, with either a decrease in rectal bleeding subscore by ≥1 point or a rectal bleeding subscore of 0 or 1) at week 12.
• The major secondary endpoint was clinical remission (defined as Mayo score of ≤2, with no individual subscore of >1) at week 12.
• Other prespecified endpoints included:
  • Clinical remission based on the modified Mayo score (mMayo; defined as a stool frequency subscore of 0 or 1 with no increase from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present)
  • 7-day and 60-day corticosteroid-free clinical remission
  • Symptomatic remission (defined as Mayo stool frequency subscore of 0 or 1 with no increase from baseline and a rectal bleeding subscore of 0)
  • Endoscopic improvement (defined as Mayo endoscopy subscore of 0 or 1, with no friability)
  • Endoscopic normalization (defined as Mayo endoscopy subscore of 0)
  • Histologic remission (defined as absence of neutrophils from the mucosa [both lamina propria and epithelium], no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system²
  • Composite histologic-endoscopic remission and normalization
  • Fecal calprotectin (FCP) concentrations
  • Inflammatory Bowel Disease Questionnaire (IBDQ) scores, change in IBDQ scores from baseline, IBDQ response (defined as ≥16-point increase from baseline in the IBDQ score), and IBDQ remission (defined as IBDQ score of ≥170)
• Safety was assessed through week 50 (16 weeks after the final dose of study intervention at week 34).
• For statistical analysis, no adjustment was made for multiple comparisons; therefore, the P values were nominal, and statistical significance had not been established.

Results

Patient Characteristics

• Overall, 214 patients were included in the study (combination therapy, n=71; TREMFYA monotherapy, n=71; golimumab monotherapy, n=72).
  • A history of inadequate response, intolerance, or dependence on immunosuppressants or corticosteroids was reported in 45% and 85% of patients in the combination therapy, 34% and 90% in the TREMFYA monotherapy, and 26% and 90% in the golimumab monotherapy groups, respectively.

Efficacy at Week 12

• For efficacy results at week 12, see Table: Efficacy at Week 12 in the Modified Intention-to-Treat Population.

Efficacy at Week 38

• Overall, 28 (13%) patients prematurely discontinued treatment before the last dose of study intervention (week 34), and 35 (16%) patients prematurely discontinued the study before the safety follow-up visit (between weeks 30 and 50).
• For efficacy results at week 38, see Table: Efficacy at Week 38 in the Modified Intention-to-Treat Population.

Effects on Molecular Changes at Weeks 4 and 38

• At baseline, colonic biopsies were obtained from 195 patients, of whom 42 were analyzed at week 4 and 172 at week 38.³
• RNA sequencing (RNAseq) was used to generate transcriptional profiles.³
• Gene correlation network analysis, in conjunction with publicly available single-cell RNAseq data was used to define transcriptional modules associated with disease molecular features. Gene set variation analysis (GSVA) was used to quantitatively assess changes in biologic modules with treatment.³
• At week 4, significant reductions (P<0.05) in molecular features were observed with combination therapy (n=10) compared to TREMFYA monotherapy (n=19) and golimumab monotherapy (n=13).³
  • These reductions included transcriptomic modules representing the IL-23 pathway, interferon response, and inflammatory epithelial and myeloid transcriptional states associated with endoscopic improvement (Mayo endoscopy subscore of 0 or 1) at week 4 (combination therapy, n=5/11; golimumab monotherapy, n=1/13; TREMFYA monotherapy, n=2/19).
• Reduction in inflammatory modules (P<0.05) continued through week 38 with combination vs monotherapy induction.³
• At week 4, module changes showed a stronger correlation between TREMFYA monotherapy and combination therapy (correlation coefficient [R]=0.8) than golimumab therapy and combination therapy (R=0.52), with processes associated with epithelial and stromal biology, and mucosal inflammation. In contrast, the combination effect on specific neutrophil/myeloid biology at week 4 resembled golimumab more than TREMFYA, supporting the early role of golimumab in targeting innate inflammation.³

Safety through Week 12

• For safety results through week 12, see Table: Adverse Events through Week 12.
• Serious adverse events (SAEs) were reported in 1 (1%) patient in the combination therapy group (concurrent sepsis and influenza B), 2 (3%) patients in the TREMFYA monotherapy group (intestinal obstruction and atrial fibrillation), and 1 (1%) patient in the golimumab monotherapy group (UC exacerbation).
• No deaths, malignancies, tuberculosis (TB), or opportunistic infections were reported through week 12.

Safety through Week 50

• Before the final dose of study intervention at week 34, 28 (13%) patients discontinued treatment prematurely, and before the safety follow-up visit between weeks 30 and 50, 35 (16%) patients discontinued the study prematurely.
  • Coronavirus disease 2019 (COVID-19)-related events led to discontinuation of the study in 1 patient in the golimumab monotherapy group and 2 patients in the TREMFYA monotherapy group.
• For safety results through week 50, see Table: Adverse Events through Week 50.
• The most common SAEs were serious infections.
• Two deaths were reported between weeks 34 and 50: 1 patient died of poisoning from an unknown substance in the combination therapy group and another died of COVID-19 in the TREMFYA monotherapy group.
• In the combination therapy group, 1 patient developed TB at week 18 and 1 patient was diagnosed with cytomegalovirus (CMV) colitis at week 14.
• In the TREMFYA monotherapy group, 1 patient was diagnosed with malignant colon adenocarcinoma at week 38.

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.