SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• Please refer to the local labeling for information on the recommended dosing and administration of TREMFYA in adult patients with moderate to severe plaque psoriasis.  
• A phase 3b, randomized, double-blind, parallel group, multicenter study evaluated the safety and efficacy of TREMFYA in 880 super responder (SR) and non-super responder (nSR) adult patients with moderate to severe psoriasis.^1,2
• A phase 2, randomized, placebo/active comparator-controlled, multicenter, dose-ranging study of TREMFYA vs placebo or adalimumab was conducted in 293 adult patients with moderate to severe plaque psoriasis.³
• A retrospective, multicenter, case series was conducted evaluating the efficacy and safety of TREMFYA following dosing interval shortening in 27 patients with plaque psoriasis.⁴

CLINICAL DATA

Phase 3

Eyerich et al (2022)¹ and Schäkel et al (2022)² reported results from the GUIDE study, a phase 3b, randomized, double-blind, parallel group, multicenter study that evaluated the safety and efficacy of TREMFYA in 880 adult patients with moderate to severe psoriasis.

Study Design/Methods

• Select inclusion criteria: adults (aged ≥18 years) who have a plaque psoriasis disease duration of ≤2 years or >2 years from symptom onset to time of screening visit; moderate to severe plaque psoriasis defined by Psoriasis Area and Severity Index (PASI) score >10 or body surface area (BSA) >10%, and Dermatology Life Quality Index (DLQI) score >10; no signs or symptoms suggestive of active tuberculosis (TB); no administration of live virus or live bacterial vaccination during study or 3 months after last administration study drug; and no administration of Bacille Calmette-Guerin (BCG) vaccine during or within 12 months after last administration of study drug.⁵
• Select exclusion criteria: previous receipt of interleukin (IL)-23 inhibitor; previous receipt of any systemic immunosuppressant (eg, methotrexate, azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, tacrolimus), or anakinra within 4 weeks of the first administration of study drug; positive test for hepatitis B virus infection or seropositive for antibodies to hepatitis C virus (HCV; unless 2 negative HCV RNA test results 6 months apart after completing antiviral treatment and prior to baseline and have a third negative HCV RNA test result at baseline).⁵
• SR patients were defined as patients who experienced complete skin clearance (absolute PASI=0) at week 20 and week 28 with TREMFYA 100 mg every 8 weeks (q8w).²
• nSR patients were defined as patients who had PASI >0 at weeks 20 or 28.
• The study consisted of screening part 1 (weeks 0-28), part 2 (weeks 28-68), and part 3 (long-term extension, weeks 68-116).¹
  • Part 1
    • Patients (N=880) received TREMFYA 100 mg at week 0, week 4, and q8w thereafter until week 28.
  • Part 2
    • SR patients from part 1 (n=297) were randomized (1:1) to receive TREMFYA 100 mg q8w (group 2a; n=148) or 100 mg every 16 weeks (q16w) (group 2b; n=149) until week 60. Patients with disease duration ≤2 years were equally distributed into both treatment arms. SR patients with loss of response (PASI >5) at any visit were retreated with TREMFYA 100 mg q8w for 3 treatments from the date of loss of response (group 2d).
    • nSR patients (group 2c; n=525) continue receiving TREMFYA 100 mg q8w until week 60.
  • Part 3
    • SR patients from groups 2a and 2b with PASI <3 at week 68 will enter part 3 of the study and will be withdrawn from TREMFYA. Patients in part 3 had follow-up visits every 12 weeks until week 116. Patients in part 3 with loss of response (PASI >5) at any visit will be retreated with TREMFYA 100 mg q8w for 3 treatments (group 3c).
    • Patients from groups 2a and 2b with PASI ≥3 at week 68 will be retreated with TREMFYA 100 mg q8w for 3 treatments (group 3c).
• The primary endpoint was the proportion of SR patients (TREMFYA 100 mg q8w vs TREMFYA 100 mg q16w) with PASI <3 at week 68.
• Secondary endpoints included the proportion of SR patients (TREMFYA 100 mg q8w vs TREMFYA 100 mg q16w) with PASI <3, PASI ≤1, PASI=0, mean PASI, and DLQI 0/1 at week 68; and the proportion of nSR patients with PASI <3, PASI ≤1, PASI=0, DLQI <5, and DLQI 0/1 at week 68.

Results

Baseline Characteristics

• A total of 822 patients received TREMFYA in part 2 of the study, which comprised 297 (36.1%) SR patients and 525 (63.9%) nSR patients. Baseline characteristics are described in Table: Baseline Characteristics.

Efficacy

• The proportion of SR patients that achieved a PASI <3 at week 68 was 91.9% (137/149) in the TREMFYA 100 mg q16w treatment arm (2b) and 92.6% (137/148) in the TREMFYA 100 mg q8w treatment arm (2a) (non-inferiority; P=0.001).²
• Additional efficacy endpoints are described in Table: Efficacy Endpoints at Week 68 for SR and nSR Patients.
• Of the 880 patients enrolled in the study, 303 (34.4%) patients were SR.
  • The proportion of patients with SR status was greater in patients with a short disease duration (≤2 years from psoriasis symptom onset; 43.7%, 156/357) than long disease duration (>2 years from psoriasis symptom onset; 28.1%; 147/523, P<0.001).
  • The proportion of patients with SR status was greater in biologic-naïve patients (37.2%; 276/741) than biologic-experienced patients (≥1 biologic therapy; 17.1%; 21/123, P<0.001).

Safety

• TREMFYA was well tolerated with a similar incidence of adverse events (AEs), regardless of dosing interval, and no new safety events were identified. Safety events from part 1 (weeks 0-28) and part 2 (weeks 28-68) are described in Table: Safety Events in Part 1 (Weeks 0-28) and Part 2 (Weeks 28-68).

Phase 2

Gordon et al (2015)³ reported results from X-PLORE, a 52-week, phase 2, randomized, placebo/active-comparator controlled, multicenter, dose-ranging study of TREMFYA vs placebo or adalimumab in 293 adult patients with moderate to severe plaque psoriasis.

Study Design/Methods

• Adults (≥18 years of age) with a diagnosis of plaque psoriasis for ≥6 months who were candidates for phototherapy or systemic therapy, had a baseline PASI score ≥12, and had ≥10% of their BSA involved were eligible.
• The study consisted of a screening phase (weeks -4 to 0), a treatment phase (weeks 0 to 40), and a follow-up phase through 1 year (weeks 40 to 52).
• At baseline, 293 patients were randomly assigned to receive subcutaneously administered placebo (42 patients), 1 of 5 TREMFYA regimens (5 mg at weeks 0 and 4 and every 12 weeks thereafter [41 patients], 15 mg q8w [41 patients], 50 mg at weeks 0 and 4 and every 12 weeks thereafter [42 patients], 100 mg q8w [42 patients], or 200 mg at weeks 0 and 4 and every 12 weeks thereafter [42 patients]), or adalimumab (80 mg at week 0 and 40 mg at week 1 and every other week thereafter through week 39 [43 patients]).
• At week 16, placebo patients crossed over to receive TREMFYA 100 mg q8w with treatment continuing for all groups through week 40.

Results

Efficacy

• Efficacy outcomes are described in Table: Efficacy Outcomes at Week 16.

• Responses were generally maintained from week 24 to week 40.
• At week 40, the proportion of patients with a Physician’s Global Assessment (PGA) score of 0 or 1 was higher in the 50-mg, 100-mg, and 200-mg TREMFYA groups than in the adalimumab group: 71%, 77%, and 81%, respectively, vs 49%.

Safety

• Key safety events are described in Table: Key Safety Events from Weeks 0-16 (Placebo-controlled Period) and Weeks 16-52.

• Through week 16:
  • The proportions of patients reporting 1 or more AEs were similar across the treatment groups (placebo, 52% [22/42]; TREMFYA, 50% [103/207]; adalimumab, 56% [24/43]).
  • Infection was the most commonly reported AE (placebo, 14% [6/42]; TREMFYA, 20% [41/207]; adalimumab, 12% [5/43]).
  • Serious infections were reported in 2 patients in the 50-mg TREMFYA group (appendicitis and lung abscess).
  • Injection-site reactions occurred in 1%, 1%, and 6% of patients in the placebo, TREMFYA, and adalimumab groups, respectively.
• Weeks 16-52
  • AEs were reported in 49% (115/235) of patients treated with TREMFYA and in 61% (23/38) of patients in the adalimumab group.
  • Infections were the most commonly reported AE (30% [70/235] of TREMFYA-treated patients and 37% [14/38] of adalimumab-treated patients). One serious infection (pneumonia) was reported in a patient treated with adalimumab.
  • One malignancy was reported through week 52 in a patient treated with TREMFYA.
  • There were 3 reports of major adverse cardiovascular events (1 in the TREMFYA 5 mg group and 2 in the TREMFYA 100 mg group). One death was reported from myocardial infarction.
  • Antibodies to TREMFYA were detected in 6% (15/240) of patients with evaluable serum samples.
  • No events of anaphylaxis or serum sickness-like reactions were reported.

Retrospective Chart Review

Mufti et al (2020)⁴ reported results from a retrospective multicenter case series investigating the efficacy and safety of TREMFYA following dosing interval shortening in 27 patients with plaque psoriasis.  

Methods

• A retrospective chart review was conducted at 2 academic hospitals and 1 community dermatology clinic in Ontario, Canada.
• Responders were defined as having a PASI 75 response 3 to 6 months after dosing interval shortening when compared to the PASI score immediately prior to dosing interval shortening of TREMFYA or a PGA score of 0 or 1.
• Safety was assessed by recording the reported AEs after the dosing interval shortening.

Results

Baseline

• Of the 27 patients in this study, 6 (22.2%) patients shortened their dosing interval to 100 mg every 6 weeks, and 21 (77.8%) patients had their dosing interval shortened to 100 mg every 4 weeks.
• The mean PASI score was 7.1±6.4 for 18/27 patients who had PASI scores recorded at the time of dosing interval adjustment.
• The remaining patients had PGA scores of 0 (n=0), 1 (n=1), 2 (n=4), 3 (n=3), and 4 (n=1) at the time of dosing interval adjustment.

Efficacy

• After shortening the dosing interval, a PGA 0 response was recorded in 6/27 (22.2%) patients, and a PGA 1 response was recorded in 14/27 (51.9%) patients.
• Overall, 20/27 (74.4%) of patients responded with a clinically significant clearance of plaque psoriasis after switching to a shortened TREMFYA dosing interval based on study endpoints.
• Seven patients (26.0%) were non-responders to a shortened dosing interval regimen with TREMFYA.
  • One of the 7 non-responders was switched to ustekinumab, 3/7 were switched to risankizumab and 3/7 continued TREMFYA with their shortened dosing interval adjustment.

Safety

• Three AEs were reported including 1 patient who reported a common cold, and 1 patient who reported gastrointestinal-related symptoms (nausea, vomiting), headache, and dizziness.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 06 August 2024.