SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling. Please refer to the local labeling for relevant information.
• Pooled VOYAGE 1 and VOYAGE 2 data from a subpopulation of patients defined by body weight and/or body mass index (BMI) at weeks 16, 24, 28, and 156 were measured.^1-3
• Reich et al (2022) conducted a post hoc analysis of pooled VOYAGE 1 and VOYAGE 2 data to describe baseline characteristics of weight and BMI in TREMFYA-treated patients achieving a super response status.⁴
• Constanza et al (2021) performed a post hoc analysis of the 5-year (252 week) VOYAGE 1 data to evaluate the baseline characteristics, including BMI, of patients achieving complete skin clearance Psoriasis Area and Severity Index (PASI) score of 0 for ≥156 consecutive weeks of TREMFYA treatment.⁵
• Blauvelt et al (2022) showed the efficacy of TREMFYA vs secukinumab in patients with moderate-to severe plaque psoriasis (PsO), defined by subpopulations, including baseline body weight and BMI in the ECLIPSE study.⁶
• Ritchlin et al (2022) conducted a post hoc analysis to evaluate the efficacy of TREMFYA through 52 weeks in subgroups of pooled PsA patients from the DISCOVER 1 and DISCOVER 2 studies.⁷
• Ritchlin et al (2022) conducted a post hoc analysis of the DISCOVER 2 study to assess the efficacy of TREMFYA in the Group for Research and Assessment of PsO and PsA (GRAPPA)-recommended domains across diverse baseline characteristics, including BMI, through week 100.⁸
• McInnes et al (2022) conducted a post hoc analysis of the COSMOS study to assess the maintenance of TREMFYA response across disease domains through 1 year in patients with psoriatic arthritis (PsA) and an inadequate response to tumor necrosis factor (TNF) inhibitors, defined by subgroups, including BMI.⁹
• Safety outcomes by weight were not summarized because the studies either did not report safety outcomes or conclude that safety outcomes were similar to previous studies (ie, VOYAGE 1, VOYAGE 2, ECLIPSE, DISCOVER 1, DISCOVER 2, and COSMOS).^1-9

CLINICAL DATA – plaque psoriasis

VOYAGE 1 and VOYAGE 2

Papp et al (2018)¹ and Gordon et al (2018)² reported results from a pooled subgroup analysis of VOYAGE 1 and VOYAGE 2 patients defined by body weight and BMI.

Methods

• In VOYAGE 1 and VOYAGE 2, patients with plaque PsO were randomized 2:1:2 into TREMFYA 100 mg at weeks 0, 4, 12, and 20; placebo (PBO) at weeks 0, 4, and 12 followed by TREMFYA 100 mg at weeks 16 and 20; and adalimumab (ADA) 80 mg at week 0, 40 mg at week 1, and then every 2 weeks (Q2W) through week 23.
• Co-primary endpoints were the proportions of patients treated with TREMFYA:
  • Compared to PBO achieving ≥90% improvement in PASI score (PASI 90) at week 16
  • Compared to PBO and ADA achieving Investigator’s Global Assessment (IGA 0/1 [cleared or minimal]) responses at week 16
• Secondary endpoints were the proportions of patients treated with TREMFYA:
  • Compared to PBO and ADA achieving IGA 0/1 (cleared or minimal) responses at week 24
  • Compared to PBO and ADA achieving IGA 0 responses at week 24
  • Compared to ADA achieving PASI 90 at week 24
• Response rates across endpoints were evaluated for predetermined subgroups such as:
  • Baseline weight (kg): ≤90, >90
  • Baseline BMI (kg/m²): normal (<25), overweight (≥25 to <30), obese (≥30)
  • Baseline weight quartiles (kg): <74.6, ≥74.6 to <86.4, ≥86.4 to <100, ≥100

Results

• Pooled baseline weight and BMI for patients from VOYAGE 1 (n=837) and VOYAGE 2 and VOYAGE 2 (n=992) are summarized in Table: Pooled Baseline Demographics by Weight and Body Mass Index from VOYAGE 1 and VOYAGE 2.

• The TREMFYA group achieved higher clinical responses of IGA 0/1 (cleared or minimal) compared to placebo and ADA at weeks 16 and 24 (all 95% confidence interval [CI] excluding 0), respectively, for all baseline weight strata, defined either by a weight cut-off of 90 kg or by weight quartiles (<74.6 kg; ≥74.6 to <86.4 kg; ≥86.4 to <100 kg; and ≥100 kg). See Table: Pooled VOYAGE 1 and VOYAGE 2 Subgroup Analysis Providing the Proportion of Patients at Weeks 16 and 24 that Achieved an IGA Score of 0/1 or IGA 0 by Weight.

• Pooled data from VOYAGE 1 and VOYAGE 2 at weeks 16 and 24 demonstrated that patients in the TREMFYA groups achieved higher clinical responses for PASI 90 compared to PBO and ADA, respectively, across all weight quartiles. See Table: Proportion of Patients in Pooled VOYAGE 1 and VOYAGE 2 Studies Achieving PASI90 across Weight Quartiles through Weeks 16 and 24.

Blauvelt et al (2019)³ assessed the efficacy of TREMFYA through up to week 156 (3 years) across patient demographic subgroups, including those based on weight, from the pooled VOYAGE 1 and VOYAGE 2 studies.

Methods

• In VOYAGE 1 and VOYAGE 2, patients with plaque PsO were randomized 2:1:2 into TREMFYA 100 mg at weeks 0, 4, 12, and then every 8 weeks (Q8W) thereafter; PBO at weeks 0, 4, and 12 followed by TREMFYA 100 mg at weeks 16 and 20 and then Q8W thereafter; and ADA 80 mg at week 0, 40 mg at week 1, and then Q2W through week 47 (VOYAGE 1) or week 23 (VOYAGE 2).
• In VOYAGE 1, all patients received open-label TREMFYA 100 mg Q8W during weeks 52 to 156. VOYAGE 2 incorporated a randomized withdrawal study design, followed by open-label treatment with TREMFYA during weeks 76 to 156.
• Data for patients receiving TREMFYA during the open-label period of VOYAGE 1 and VOYAGE 2 were combined in pooled analysis.
• Treatment failure rules were applied for patients who discontinued due to any reason related to efficacy (loss of response, worsening of PsO, use of a prohibited PsO medication) as non-response.

Results

• A pooled VOYAGE 1 and VOYAGE 2 subgroup analysis was conducted to show the results of TREMFYA-treated patients achieving an IGA 0/1 score based on weight through week 156. See Table: Proportion of Patients in Pooled VOYAGE 1 and VOYAGE 2 Subgroup Analysis Achieving IGA Score of 0/1 (Cleared or Minimal) Based on Weight Through Week 156.

Reich et al (2022)⁴ conducted a post hoc analysis of pooled VOYAGE 1 and VOYAGE 2 data to describe baseline characteristics of weight and BMI in TREMFYA-treated patients achieving a super response status (PASI 100 response at weeks 20 and 28).

Methods

• VOYAGE 1 and VOYAGE 2 had identical study designs up to week 28.
  • In VOYAGE 1, the ADA group received ADA 40 mg Q2W through week 28.
  • In VOYAGE 2, the ADA group received ADA 40 mg Q2W through week 23 and then received no study drug until week 28.
• Super response (SR) status was defined as patients who received TREMFYA and achieved PASI 100 (absolute PASI = 0) response at weeks 20 and 28.
• In addition to patients not achieving PASI 100 at weeks 20 and 28, non-super response (nSR) status also included patients who met treatment failure rules and those missing efficacy data.
• Pooled VOYAGE 1 and VOYAGE 2 data compared baseline demographic profiles such as weight and BMI of TREMFYA-treated patients who achieved a SR vs. nSR status.
• Stepwise logistic regression analysis was performed to determine which factors were predictive of SR status.

Results

• Among the pooled patient population, there were 664 patients randomized to TREMFYA at week 0. See Table: Proportion of Patients in Pooled VOYAGE 1 and VOYAGE 2 Studies Achieving Super-Response Based on Baseline Body Weight and Body Mass Index.

• Baseline body weight (≤90 kg vs. >90 kg) was one of the few factors that suggested it was a significant predictor of SR status with an odds ratio (95% CI) of 1.42 (1.026–1.977, P=0.034).

VOYAGE 1

Constanza et al (2021)⁵ performed a post hoc analysis of the 5-year (252 week) VOYAGE 1 data to evaluate the baseline characteristics, including BMI, of patients achieving complete skin clearance PASI score of 0 for ≥156 consecutive weeks of treatment with TREMFYA.

Methods

• VOYAGE 1 data from weeks 0 to 252 were included in this analysis.
• Baseline demographics of TREMFYA-treated patients maintaining PASI=0 (complete skin clearance) for ≥156 consecutive weeks were compared to patients who never achieved PASI=0 (comparator group), utilizing descriptive statistics.

Results

• There were 112 and 79 patients in the PASI=0 and the comparator groups, respectively.
• Mean baseline BMI (95% CI):
  • PASI=0 group: 28.5 (27.3, 29.7) kg/m²
  • Comparator group: 30.2 (28.7, 31.7) kg/m²
• Proportion of obese patients (BMI ≥30 kg/m²):
  • PASI=0 group: 32.1%
  • Comparator group: 48.1%

ECLIPSE

Blauvelt et al (2022)⁶ showed the efficacy of TREMFYA vs secukinumab in subpopulations, including baseline body weight and BMI, of patients with moderate-to severe plaque PsO from the ECLIPSE study.

Methods

• In the ECLIPSE study, patients with plaque PsO were randomized 1:1 to receive TREMFYA 100 mg subcutaneously (SC) at weeks 0, 4, 12 and Q8W thereafter or secukinumab (SEC) 300 mg SC in two 150 mg injections at weeks 0, 1, 2, 3, 4, and every 4 weeks (Q4W) thereafter through week 44.
• Efficacy endpoints for the subgroup analysis included the proportion of TREMFYA-treated patients achieving PASI 90, PASI 100, IGA 0/1, and IGA 0 at week 48 compared to the SEC group.
• Efficacy was analyzed in baseline subpopulations, including body weight and BMI, using descriptive statistics.
• Analyses of PASI 90 and PASI 100 at week 48 by baseline body weight were post hoc analyses.

Results

• Baseline demographics and disease characteristics are seen in Table: Baseline Demographics by Body Weight and Body Mass Index and Disease Characteristics in ECLIPSE Study.

• PASI 90, PASI 100, IGA 0/1, and IGA 0 responses based on baseline body weight is shown in Table: Proportion of Patients in ECLIPSE Study Achieving PASI 90, PASI 100, IGA 0/1, and IGA 0 Based on Baseline Body Weight at Week 48.

• PASI 90, PASI 100, IGA 0/1, and IGA 0 responses based on baseline BMI are shown in Table: Proportion of Patients in ECLIPSE Study Achieving PASI 90, PASI 100, IGA 0/1, and IGA 0 Based on Body Mass Index at Week 48.

CLINICAL DATA – PSORIATIC ARTHRITIS

DISCOVER 1 and DISCOVER 2

Ritchlin et al (2022)⁷ conducted a post hoc analyses to evaluate the efficacy of TREMFYA through 52 weeks in subgroups of PsA patients from the DISCOVER 1 and DISCOVER 2 studies.

Methods

• Adults with a diagnosis of active PsA ≥6 months per CASPAR criteria and who had inadequate responses to standard therapies were enrolled into DISCOVER 1 (≥3 swollen joints, ≥3 tender joints and C-reactive protein (CRP) ≥0.3 mg/ dL) and DISCOVER 2 (≥5 swollen joints, ≥5 tender joints, CRP ≥0.6 mg/dL, and biologic-naïve). Stable doses of select nonbiologic disease-modifying antirheumatic drugs (DMARDs), low dose oral corticosteroids, or non-steroidal anti-inflammatory drugs (NSAIDs) were permitted.
• Patients were randomized 1:1:1 to receive subcutaneous injections of TREMFYA 100 mg at weeks 0, 4 and then Q4W; TREMFYA 100 mg at weeks 0, 4, and then Q8W; or placebo Q4W with crossover to TREMFYA Q4W at week 24. Treatment continued through weeks 48 and 100 for DISCOVER 1 and DISCOVER 2, respectively.
• Efficacy endpoints were measured at week 24 and 52:
  • An improvement of ≥20/50/70% in the ACR criteria (ACR20/50/70)
  • An IGA score of 0 (clear) or 1 (minimal) and ≥2-grade reduction from baseline, or an IGA score of 0, each among patients with baseline BSA ≥3% with PsO and IGA ≥2
  • An improvement of ≥4-point from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score
  • An improvement of ≥0.35-point from baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) 29 score among patients with a baseline HAQ-DI score ≥0.35
  • PsA Disease Activity Score (PASDAS) 30 ≤3.2, indicative of low disease activity (LDA)
  • Minimal disease activity (MDA).
• Efficacy endpoint results were stratified by patient sex, BMI, swollen and tender joint counts, PsA duration, CRP level, and csDMARD use at baseline.

Results by BMI

• A total of 1120 patients were randomized and treated in DISCOVER 1 and DISCOVER 2 studies. Patients pooled from both studies through 52 weeks included 94% (350/373), 93% (350/375) and 90% (335/372) of TREMFYA Q4W, TREMFYA Q8W, and crossover patients, respectively.
• TREMFYA Q4W and Q8W achieved improved joint responses (ACR20/50/70), skin clearance responses (IGA 0/1 or 0), patient-reported outcomes (FACIT-F and HAQ-DI) and composite measures of disease activity (PASDAS LDA and MDA) regardless of baseline BMI at week 24 when compared to placebo.
• Within each patient subgroup, including BMI, response rates at week 24 were maintained or increased at week 52 at the population level. See Table: Proportion of Patients Achieving Joint and Skin Clearance, Patient Reported Outcomes, and Composite Measures of Disease Activity Responses at Weeks 24 and 52 between TREMFYA Treatments and PBO Defined by Baseline BMI.

DISCOVER 2

Ritchlin et al (2022)⁸ conducted a post hoc analysis to evaluate the efficacy of TREMFYA through week 100 in the GRAPPA-recommended domains across diverse baseline characteristics from the DISCOVER 2 study.

Methods

• Adults who were biologic-naïve with active PsA were enrolled in DISCOVER 2 (≥5 swollen joints; ≥5 tender joints; CRP ≥0.6 mg/dL).
• Patients were randomized 1:1:1 to receive subcutaneous injections of TREMFYA 100 mg at weeks 0 and 4 and then Q4W; TREMFYA 100 mg at weeks 0 and 4 and then Q8W; or placebo crossover to TREMFYA Q4W at week 24. Treatment was continued through week 100.
• Efficacy endpoints were measured at week 100:
  • An improvement of ≥50/70% in the ACR criteria (ACR50/70)
  • An IGA score of 0 (clear)
  • A resolution of dactylitis
  • A resolution of enthesitis
  • MDA
• Efficacy endpoint results were stratified by patient sex, BMI, swollen and tender joint counts, PsA duration, CRP level, BSA, PASI, concomitant csDMARD use, and concomitant methotrexate use at baseline.
• Response rates at week 100 were determined using nonresponder imputation for data missing due to patient discontinuation.

Results by BMI

• Among the total 739 randomized patients, 442 completed the study. At baseline, patients in the TREMFYA Q4W and Q8W groups, respectively, had mean swollen joint counts of 12.9 and 11.7, mean tender joint counts of 22.4 and 19.8, PASI of 10.8 and 9.7, and BSA of 18.2% and 17.0%
• TREMFYA Q4W and Q8W response rates of joint improvement (ACR50/70), skin clearance (IGA 0), dactylitis and enthesitis resolutions, and MDA were observed through week 100. See Table: Proportion of Patients in the DISCOVER 2 Study Achieving ACR50, ACR70, IGA 0, Dactylitis and Enthesitis Resolution, and MDA Response Based on BMI at Week 100.

COSMOS

McInnes et al (2022)⁹ conducted a post hoc analysis to evaluate the maintenance of response to TREMFYA across disease domains through 1 year in subgroups of patients with PsA who had an inadequate response to TNF inhibitors in the COSMOS study.

Methods

• Select inclusion criteria: patients ≥18 years old with active PsA, ≥3 swollen joints and ≥3 tender joints, active or documented history of plaque PsO or current nail PsO, and an inadequate response or intolerance to 1-2 TNF inhibitors.^10,11
• The study comprised placebo-controlled (weeks 0-24) and active treatment (weeks 24-48) periods, with the final intervention at week 44.¹⁰
• Patients were randomized 2:1 to receive either TREMFYA 100 mg or placebo SC at weeks 0 and 4 and Q8W thereafter through week 44.¹⁰
• At week 16, patients from either group who experienced <5% improvement from baseline in both swollen and tender joint counts were eligible for early escape (EE) to initiate/increase one of the permitted concomitant medications at the investigator’s discretion. Patients in the TREMFYA group continued the randomized treatment and received placebo at week 16 to maintain blinding, and patients in the placebo group who qualified for EE crossed over to TREMFYA.^9,10
  • Patients who discontinued and/or met the EE criteria prior to week 24 were imputed as non-responders.
  • At week 48, response rates were assessed for the sustainability of responses over time in each patient subgroup by imputing missing data as no response.
• At week 24, all remaining randomized placebo-treated patients were crossed over to receive TREMFYA 100 mg at weeks 24, 28, 36, and 44.¹¹
• The primary endpoint was the American College of Rheumatology (ACR)20 response at week 24.¹⁰
• The efficacy of TREMFYA in subgroups of patients with an inadequate response to TNF inhibitors was evaluated at weeks 24 and 48 using joint (ACR20/50 response), skin (PASI 90/100 response), and multidomain (minimal disease activity [MDA] response) outcome measures.
  • Subgroups were defined by BMI, sex, tender and swollen joint counts, PsA duration, proportion of body surface area (BSA) with PsO, and conventional synthetic disease-modifying antirheumatic drug (csDMARD) use at baseline.
• Safety was assessed through week 56.

Results by BMI

• A total of 285 patients were randomized and treated in the COSMOS study.
• Response rates with TREMFYA Q8W, stratified by BMI, at weeks 24 and 48 in patients with an inadequate response to TNF inhibitors. See Table: Proportion of Patients Achieving Joint, Skin, and MDA Responses at Weeks 24 and 48 between TREMFYA Treatments and PBO Defined by Baseline BMI (NRI).

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 26 November 2024.

Data included in this response are from the following phase 3 clinical trials of TREMFYA in adult patients with plaque PsO or PsA: VOYAGE 1, VOYAGE 2, ECLIPSE, DISCOVER 1, DISCOVER 2, and COSMOS.