SUMMARY

• Please refer to the local labeling for relevant information regarding tuberculosis (TB) infection.
• In an integrated analysis of 11 phase 2 and 3 clinical trials (X-PLORE, VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, Japan Registration, Phase 2 psoriatic arthritis [PsA], DISCOVER-1, DISCOVER-2, and COSMOS), no cases of new-onset TB or latent tuberculosis infection (LTBI) activation were reported up to 5 years of treatment with TREMFYA.¹
• In a pooled safety analysis of 11 phase 2 and 3 clinical trials (X-PLORE, VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, Japan Registration, Phase 2 PsA, DISCOVER-1, DISCOVER-2, and COSMOS), no cases of active TB infections were reported.²
• In a pooled safety analysis of 7 phase 2 and 3 clinical trials (X-PLORE, VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, and Japan Registration) through 5 years, no cases of active TB infections were reported.³
• In a pooled safety analysis of VOYAGE 1 and VOYAGE 2 clinical studies through 5 years (week 264), no events of TB infections were reported.^4,5
• In the NAVIGATE, ORION, and ECLIPSE clinical studies, there were no reported cases of active TB through week 40, 60, and 56, respectively.^6-8 
• In the DISCOVER-1 and DISCOVER-2 clinical studies, no cases of active TB were reported through weeks 60 and 112, respectively.^9-13

CLINICAL DATA in Plaque psoriasis and ACTIVE psoriatic arthritis

Puig et al (2024)¹ reported the safety of TREMFYA in an integrated analysis of data from 11 randomized, double-blind, phase 2 and 3 studies in patients with LTBI and moderate to severe plaque psoriasis (PsO) or active PsA treated for up to 5 years.

Study Design/Methods

• All plaque PsO studies (X-PLORE, VOYAGE 1, VOYAGE 2, ORION, and Japan Registration) included a placebo-controlled period (weeks 0-16), except for NAVIGATE (active comparator: ustekinumab) and ECLIPSE (active comparator: secukinumab).
• All active PsA studies (Phase 2, DISCOVER-1, DISCOVER-2, and COSMOS) included a placebo-controlled period (weeks 0-24).
• Safety data were analyzed for the placebo-controlled period for patients treated with placebo and TREMFYA and through the end of the reporting period for patients treated with TREMFYA.
• Safety was reported year-by-year for the placebo-controlled period and through the end of follow-up (PsO, up to 5 years; PsA, up to 2 years). For the safety reporting periods of the clinical studies included in the integrated analysis, see Table: Summary of the Included Phase 2/3 Studies.

Results

• Of 5255 patients randomized at baseline, 374 (7.1%) tested positive for LTBI and received treatment with TB medication. For more details, see Table: Baseline Demographics and LTBI Treatment for LTBI-Positive Patients.
• Overall, 89.8% of patients received monotherapy for LTBI.

• No cases of new-onset TB or LTBI activation were reported among patients treated with TREMFYA.

Strober et al (2024)² evaluated the safety of TREMFYA in an integrated pooled analysis of data from 11 randomized, phase 2 and 3 plaque PsO and PsA studies.

Study Design/Methods

• All plaque PsO studies (X-PLORE, VOYAGE 1, VOYAGE 2, ORION, Japan Registration) included a placebo-controlled period (weeks 0-16), except NAVIGATE (active comparator: ustekinumab) and ECLIPSE (active comparator: secukinumab).
• All active PsA studies (Phase 2, DISCOVER-1, DISCOVER-2, COSMOS) included a placebo-controlled period (weeks 0-24).
• This long-term safety analysis included a total of 4399 patients (PsO, n=2891; PsA, n=1508) who received ≥1 administration of TREMFYA for a total follow-up of 10,787 patient-years; see Table: Safety Reporting Period for Clinical Studies Included in the Integrated Analysis.
• The median duration of TREMFYA exposure was 1.7 years, 3.5 years, and 1.2 years in the pooled population, PsO group, and PsA group, respectively.

Results

• No cases of active TB were reported in TREMFYA-treated patients across all studies.

clinical data in MODERATE TO SEVERE plaque psoriasis

Placebo- and Active Comparator-Controlled Trials

The safety and efficacy of TREMFYA in patients diagnosed with moderate to severe plaque PsO were evaluated in a phase 2 (X-PLORE) and 5 phase 3 (VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, and Japan Registration) multicenter, randomized, double-blind studies.^{3,4,6-8,14-17}

Pooled Safety Analysis: X-PLORE, VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, and Japan Registration

Lebwohl et al (2023)³ summarizes pooled safety data of TREMFYA treatment for up to 5 years in patients with moderate to severe plaque PsO across 7 phase 2/3 clinical trials (X-PLORE, VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, and Japan Registration).

• All studies, including X-PLORE, a phase 2 clinical trial (n=293), and Japan phase 3 registration (n=192) had a placebo-controlled period, except for NAVIGATE (active comparator: ustekinumab) and ECLIPSE (active comparator: secukinumab).
• Long-term safety included data from all patients treated with ≥1 dose of TREMFYA.
• The safety reporting periods for TREMFYA exposure were defined as: X-PLORE, week 0-52; VOYAGE 1 and VOYAGE 2, week 0-264; NAVIGATE, week 16-60; ORION, week 0-40; ECLIPSE, week 0-56; Japan Registration, week 0-156.
• These studies included patients originally randomized to adalimumab (VOYAGE 1 and VOYAGE 2) or placebo (X-PLORE, VOYAGE 1, VOYAGE 2, ORION, Japan Registration) at baseline who crossed over and were treated with TREMFYA.

Results

• There were no cases of active TB.
• At baseline, 173 TREMFYA-treated patients had LTBI across studies. There were no cases of LTBI reactivation in any TREMFYA-treated patients through the end of long-term follow-up.

VOYAGE 1 and VOYAGE 2

Blauvelt et al (2022)⁴ evaluated the safety of TREMFYA using pooled data from the VOYAGE 1 and VOYAGE 2 studies through 5 years.

Study Design/Methods

• In the VOYAGE 1 and VOYAGE 2 studies, patients were screened for LTBI prior to being randomized to TREMFYA, adalimumab, or placebo.⁵
• Eligible patients had no history of LTBI or active TB.⁵ 
  • Patients with LTBI based on positive TB test during screening (QuantiFERON-TB Gold or Purified Protein Derivative testing) were eligible if active TB was ruled out and appropriate LTBI treatment was initiated prior to or simultaneously with the first study agent administration, or if appropriate LTBI treatment was completed within 5 years prior to first administration.
• Placebo-treated patients crossed over to TREMFYA at week 16, and all patients received open-label TREMFYA treatment every 8 weeks (q8w) through week 252, beginning at week 52 (VOYAGE 1) or week 76 (VOYAGE 2).

Results

• No events of TB infection were reported through 5 years (week 264).⁴

Puig et al (2020)⁵ evaluated safety of TREMFYA, adalimumab, or placebo in patients with moderate to severe PsO with LTBI receiving LTBI treatment (LTBI+) and patients without LTBI (LTBI-) using pooled data from the VOYAGE 1 and VOYAGE 2 studies through week 100.

Results

• A total of 1721 patients were randomized in the VOYAGE 1 and VOYAGE 2 studies, and, of these, 130 patients (TREMFYA, n=69; adalimumab, n=36; placebo, n=25) tested positive for LTBI and received concomitant LTBI treatments (LTBI+). See Table: Baseline Demographics, Previous Medication Treatments, and LTBI Treatments Among LTBI+ Patients in VOYAGE 1 and VOYAGE 2 through Week 100.
  • A total of 13 patients who started LTBI treatment after initiating study drug (mean of 70 days), of which 9 patients were QuantiFERON-TB Gold positive at baseline but did not start LTBI treatment, were classified as major protocol deviations.
  • Three of the 13 patients were QuantiFERON-TB Gold negative at baseline but received LTBI treatment during the study (1 TREMFYA-treated patient received rifabutin for Helicobacter pylori, 1 adalimumab-treated patient initiated LTBI treatment during the trial, and 1 adalimumab-treated patient developed new onset active TB and was treated accordingly).
  • One additional placebo-treated patient with missing QuantiFERON-TB Gold results at baseline was treated with LTBI treatment prior to discontinuing the study after week 3.

• No cases of TB were reported among TREMFYA-treated patients through week 100.

NAVIGATE

Langley et al (2018)⁶ evaluated efficacy (through week 52) and safety (during weeks 16-60) of TREMFYA in NAVIGATE, a phase 3, randomized, double-blind, active-comparator controlled study in patients with moderate to severe plaque PsO with an inadequate response to ustekinumab.

Results

• There were no reported cases of active TB in TREMFYA-treated patients during week 16 through week 60.

ORION

Ferris et al (2020)⁷ reported results from a phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, and pharmacokinetics of TREMFYA through week 40 compared to placebo, both administered via the One-Press patient-controlled injection device.

Results

• There were no reported cases of active TB reported through week 40.

ECLIPSE

Reich et al (2019)⁸ reported results from ECLIPSE, a head-to-head study of TREMFYA and secukinumab in adult patients with moderate to severe PsO up to week 56.

Results

• There were no reported cases of TB in TREMFYA-treated patients through week 56.

CLINICAL DATA in ACTIVE psoriatic arthritis

Placebo-Controlled Clinical Trials

The safety and efficacy of TREMFYA in patients diagnosed with active PsA were evaluated in 2 phase 3 (DISCOVER-1 and DISCOVER-2) multicenter, randomized, double-blind studies.^6,9

DISCOVER-1 and DISCOVER-2

Deodhar et al (2020)⁹ and Mease et al (2020)¹¹ conducted the phase 3, randomized, double-blind, multicenter, placebo-controlled DISCOVER-1 and DISCOVER-2 studies, respectively.

• DISCOVER-1 was conducted in adult patients with active PsA who were biologic-naïve or had a prior biologic experience of ≤2 anti-tumor necrosis factor alpha (anti-TNFα) treatments and had inadequate response to or intolerance of standard therapies, including nonbiologic disease modifying antirheumatic drugs (DMARDs), apremilast, and nonsteroidal anti-inflammatory drugs (NSAIDs).⁹
• DISCOVER-2 was conducted in adult patients with active PsA who were biologic-naïve and had inadequate response to or intolerance of standard therapies, including nonbiologic DMARDs, apremilast, and NSAIDs.¹¹

Study Design/Methods

• In DISCOVER-1 and DISCOVER-2, patients were screened for TB prior to being randomized to TREMFYA 100 mg q8w, TREMFYA 100 mg every 4 weeks (q4w), or placebo.^9,11
• Patients were considered eligible according to the following TB screening criteria^18,19:
  • No history of LTBI or active TB prior to screening. Patients with LTBI based on a positive TB test during screening (QuantiFERON^®-TB Gold or tuberculin skin test conducted within 8 weeks prior to the first administration of study agent) were eligible if active TB was ruled out and appropriate LTBI treatment was initiated prior to the first administration of study agent or if appropriate LTBI treatment was completed within 5 years prior to the first administration.
    • Patients with persistently indeterminate QuantiFERON^®-TB Gold test results were enrolled without treatment for LTBI if active TB was ruled out, chest radiograph showed no abnormality suggestive of TB (active or old, inactive TB), and no additional risk factors for TB, as determined by the investigator.
  • No signs or symptoms suggestive of active TB upon medical history and/or physical examination.
  • No recent close contact with a person with active TB or, if there had been such contact, were referred to a physician specializing in TB to undergo additional evaluation and, if warranted, received appropriate treatment for LTBI prior to the first administration of study agent.
  • Chest radiograph (posterior-anterior view) obtained within 3 months prior to the first administration of study agent, with no evidence of current, active TB or old, inactive TB.

Results

• In DISCOVER-1, 624 patients were screened, of whom 18 did not meet the criteria for TB and 381 were randomized to receive TREMFYA 100 mg q8w (n=127), TREMFYA 100 mg q4w (n=128), or placebo (n=126). Of the 381 patients, 90% completed treatment through 1 year.^9,10
  • No cases of active TB were reported through week 60.^9,10
• In DISCOVER-2, 1153 patients were screened, of whom 32 did not meet the criteria for TB and 739 were randomized to receive TREMFYA 100 mg q8w (n=248), TREMFYA 100 mg q4w (n=245), or placebo (n=246). A total of 93% and 88% of these patients completed 1 year and 100 weeks of treatment, respectively.^11-13
  • No cases of active TB were reported through week 112.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 28 January 2025.

Data included in this response are from the phase 2 and 3 clinical trials of TREMFYA in patients with plaque PsO or PsA (X-PLORE, VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, Japan Registration, Phase 2 PsA, DISCOVER-1, DISCOVER-2, and COSMOS). Additional information from pooled safety analyses across the PsO and/or PsA studies is also included.