SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• Patients with pustular psoriasis were excluded from VOYAGE 1, VOYAGE 2, NAVIGATE, and ORION phase 3 clinical trials which assessed the safety and efficacy of TREMFYA in patients with moderate to severe plaque psoriasis who were eligible for systemic therapy or phototherapy.^1-4
• A phase 3, single-arm, open-label study evaluated the efficacy and safety of TREMFYA in Japanese patients with generalized pustular psoriasis (GPP) from 23 sites across Japan.⁵
  • A total of 7 (77.8%) GPP patients achieved treatment success (Clinical Global Impression [CGI] “very much improved” [22.2%, n=2] or “much improved” [22.2%, n=2] or “minimally improved” [33.3%, n=3]) at week 16.
• A prospective study and case reports in patients with GPP receiving TREMFYA are summarized below.^6-8

Clinical data

Phase 3 Study

Sano et al (2018)⁵ reported results from a phase 3, single-arm, open-label study evaluating the efficacy and safety of TREMFYA in Japanese patients with GPP and erythrodermic psoriasis (EP) from 23 sites in Japan.

Study Design/Methods

• Select inclusion criteria: patients ≥20 years of age diagnosed with GPP (Japan Dermatology Association [JDA] severity index <14) or with EP having lesions covering more than 80% of the body surface area (BSA); patients who were candidates for phototherapy or systemic treatment for psoriasis.
• Select exclusion criteria: patients with guttate psoriasis; drug-induced psoriasis; history of malignancy within 5 years of screening; history or current signs of any severe, progressive, or uncontrolled medical conditions; prior treatment with adalimumab within 8 weeks; infliximab within 12 weeks; agents targeting interleukin (IL)-12, IL-17, or IL-23 within 6 months; granulocyte and monocyte apheresis therapy within 3 months; or systemic immunosuppressants or phototherapy within 4 weeks.
• TREMFYA 50 mg was administered subcutaneously (SC) at weeks 0, 4, and every 8 weeks (q8w) thereafter until week 52.
• Dose escalation to TREMFYA 100 mg q8w was permitted for patients with CGI rating of “no change” or “worsened” at any scheduled study visit beginning at week 20, as well as for patients with CGI “minimally improved” depending on investigator discretion.
• Concomitant topical therapies were permitted throughout the study and methotrexate or retinoids were allowed if initiated 1 week before first administration of TREMFYA.
• The primary efficacy endpoint was the proportion of patients achieving treatment success, defined as “very much improved,” “much improved,” or “minimally improved” CGI scores (based on 7-point scale) at week 16.
• Secondary efficacy endpoints were assessed through week 52 and included:
  • Proportion of patients achieving treatment success over time
  • Change from baseline in JDA severity index total score for patients with GPP
  • Change from baseline in BSA involvement for patients with EP
  • Proportion of patients achieving an Investigator’s Global Assessment (IGA) score of cleared or minimal (0/1)
  • Percentage improvement in Psoriasis Area and Severity Index (PASI)
  • Change from baseline in the Dermatology Life Quality Index (DLQI)
  • Percentage of patients achieving DLQI 0/1 among those with a baseline DLQI score of more than 1
  • Percentage of patients with a reduction of 5 points or more in the DLQI
  • Change from baseline in the Physical Component Scores (PCS), Mental Component Scores (MCS) of the 36-item Short-Form Health Assessment Questionnaire (SF-36)
• Safety was monitored until the week-52 database lock.
• All patients who received at least 1 dose of TREMFYA were included in both the efficacy and safety analysis.
• Missing data were treated as such and imputation was not employed.

Results

Patient Characteristics

• Twenty-one patients (GPP, n=10) were enrolled in the study and of these patients, 18 completed the week-52 visit (GPP, n=8).
• Two patients with GPP discontinued, one due to a serious adverse event (AE) of squamous cell carcinoma of the skin and the other due to lack of efficacy.
• The mean age of patients in the study was 48.9 years and 76.2% of patients were male.
• Median disease duration was 9 years (range, 0-35 years).
• Patients with GPP had JDA severity index scores of either “mild” (0-6, n=8) or “moderate” (7-10, n=2) at baseline.

Efficacy

• A total of 7 (77.8%) GPP patients achieved treatment success (CGI “very much improved” [22.2%, n=2] or “much improved” [22.2%, n=2] or “minimally improved” [33.3%, n=3]) at week 16.
• At week 20, 5 patients with GPP underwent dose escalation.
  • Among these patients, treatment success rate increased from 2 (40%) patients at week 20 to 4 (100%) patients at week 52.
• Secondary efficacy outcomes of GPP patients are shown in Table: Secondary Efficacy Outcomes of TREMFYA Treatment in Patients with Generalized Pustular Psoriasis through Week 52.

Safety

• Treatment-emergent adverse events (TEAEs) through week 52 are shown in Table: Safety Outcomes through Week 52.

• All TEAEs were mild to moderate in severity except for the case of squamous cell carcinoma which was severe.
• No deaths or injection-site reactions were reported.

Prospective study

Lu et al (2024)⁶ presented efficacy and safety results of a prospective, single-center observational cohort study of patients with GPP, treated with adalimumab, secukinumab, and guselkumab, conducted from December 2021-August 2023.

Study Design/Methods

• The study included adult patients (>18 years of age) diagnosed with GPP and the following inclusion criteria: no intake of GPP medications 2 weeks prior to the study and an absence of contraindications for biologic therapy and acitretin. Patients with a history of other severe skin conditions and previous treatment with other biologic agents were excluded.
• Disease severity was documented at weeks 0, 4, 8, and 12.
• TREMFYA 100 mg was administered SC at weeks 0, 4, and 12.
• All patients concomitantly took acitretin 20 mg by mouth daily with meals as requested by investigators during TREMFYA treatment and through the 6-month period following discontinuation of TREMFYA treatment.
• The primary endpoint was 75% improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score (GPPASI 75) at week 12.
• Select secondary endpoints were GPPASI 75, 90% improvement of GPPASI score (GPPASI 90), and Generalized Pustular Psoriasis Physician Global Assessment (GGPGA) 0/1.
• Recurrence rates were determined by reappearance of pustular lesions following discontinuation of TREMFYA treatment.
• Safety was assessed by occurrence of AEs related to treatment throughout the study.

Results

• Of the 50 patients included in the study, 16 patients were treated with TREMFYA.
• Select baseline patient characteristics included:
  • Average age of 52.0 years (standard deviation, 18.2)
  • Median body mass index of 23.3 kg/m² (interquartile range [IQR]; 21.8, 24.6)
  • History of plaque psoriasis of 14/16 of patients (87.5%)
  • Median psoriasis duration of 14 years (IQR; 11, 21.5)
• Relevant baseline disease characteristics included:
  • Median GPPASI of 21.9 (IQR, 14.6, 26.6)
  • GGPGA 4 in 3/16 patients (18.8%), GGPGA 3 in 5/16 patients (31.2%), and GGPGA 2 in 8/16 patients (50%)

Efficacy

• The primary endpoint, GPPASI 75 was achieved in 16/16 patients receiving TREMFYA (100%).
• Select secondary endpoints are presented in Table: Select Secondary Endpoints in Patients Receiving TREMFYA.

Safety

• AEs that occurred in patients receiving TREMFYA during follow-up included: red and swollen (1/16, 6.2%), injection site pain (3/16, 18.8%), upper respiratory tract infection (1/16, 6.2%), dry mucosa (13/16, 81.2%), peeling hands and feet (11/16, 68.8%), dyslipidemia (4/16, 25%), and COVID-19 infection (11/16, 68.8%).
• Investigators determined the majority of AEs observed in the study were associated with acitretin.

Case Report

Part (2024)⁷ described a case of a patient with GPP who was treated with TREMFYA.

• A 60-year-old female patient presented with a 15-year history of GPP: widespread and confluent erythematous-desquamative plaques with numerous small pustules (BSA 70%, Physician Global Assessment [PGA] 3, and DLQI 26).
• Previous treatment included topical therapies including, moderate to high corticosteroids, tacrolimus, as well as systemic therapies, including acitretin 50 mg daily for 3 years, cyclosporine 4 mg/kg for 12 months, methotrexate 20 mg per week for 5 years, and long-term systemic corticosteroids 0.25-1 mg/kg, which were administered as monotherapy or as a concomitant medication with antipsoriatic drugs and provided minimal symptom relief.
• The patient was initiated on TREMFYA 100 mg SC at weeks 0, 4 and then q8w thereafter.
• Three months after receiving the first dose of TREMFYA, the patient achieved resolution in pathological skin changes (PGA, 0), improvements in quality of life (DLQI, 4), and psoriatic arthritis (PsA; Disease Activity Score 28-joint count C-reactive protein [DAS28-CRP], 2.17), indicating a low disease activity.
• After 4 weeks of treatment with TREMFYA, systemic corticosteroids were tapered and discontinued, without any rebound or new GPP flares.

Yamamoto et al (2023)⁸ described the use of TREMFYA in a 52-year-old female patient with a 20-year history of acrodermatitis continua of Hallopeau that evolved into GPP.

• Patient had erythematous plaques with nail deformities, which were refractory to topical corticosteroids, ultraviolet therapy, and cyclosporine. The erythematous plaques and pustules spread to the trunk, lower extremities, and the sole of the foot.
• The patient was diagnosed with GPP based on histological findings and initiated on etretinate and cyclosporine. Nail deformities on the fingers and pustules on the sole of the foot were refractory to etretinate and cyclosporine.
• Apremilast replaced cyclosporine treatment, which showed partial response.
• Etretinate and apremilast were discontinued and TREMFYA was initiated. Patient had improvement in nail deformities after 12 months of treatment.
• Patient continued with treatment on TREMFYA for more than 2 years without relapse or any AEs.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 27 December 2024.

Summarized in this response are data specific to patients receiving TREMFYA with GPP only.