SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• A phase 3, randomized, placebo-controlled study evaluated efficacy and safety of TREMFYA in 159 Japanese patients with moderate to severe palmoplantar pustulosis (PPP) who had inadequate response to conventional therapies.^1,2
  • At week 16, both TREMFYA 100 mg and 200 mg groups showed significant improvement in the Palmoplantar Pustulosis Area and Severity Index (PPPASI) score compared with the placebo group. Least-squares (LS) mean change in PPPASI score from baseline was -15.3 (P<0.001) for the TREMFYA 100 mg group and -11.7 (P=0.02) for the TREMFYA 200 mg group vs -7.6 for the placebo group.¹
  • At week 84, mean (standard deviation [SD]) percent improvement from baseline PPPASI and Palmoplantar Pustulosis Severity Index (PPSI) scores were 79.16% (23.827) and 66.1% (27.84), respectively for the combined TREMFYA group (N=133).²
  • Through week 84, 61.8%, 26.8% and 3.8% of treatment-emergent adverse events (TEAEs) in the combined TREMFYA group (N=157) were reported to be mild, moderate, or severe, respectively.²
• A phase 2, multicenter, single-arm study (GAP study) evaluated the efficacy and safety of TREMFYA in European patients with moderate to severe PPP.³
  • At week 24, the primary endpoint of a median reduction in PPPASI was 59.6% (first and third quartile [Q1/Q3]: 35.5% and 85.7%, respectively) compared to baseline (P<0.001).
  • Thirty-seven patients reported 102 treatment-emergent adverse events (TEAEs) with most being mild to moderate in severity.
• Three case reports have described the use of TREMFYA as a treatment of PPP.^4-6

PHASE 3 study

CNTO1959PPP3001 - NCT02641730

Terui et al (2019)¹ and Morita et al (2020)⁷ reported results from a phase 3 (NCT02641730), randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of TREMFYA in 159 Japanese patients with moderate to severe PPP from 40 centers in Japan.

Study Design/Methods

• Patients ≥20 years of age with a PPP diagnosis and an inadequate response to prior conventional treatments for 24 or more weeks before screening, a PPPASI total score of ≥12, and a PPPASI subscore of pustules or vesicles of ≥2 were included.¹
• Select exclusion criteria: patients with plaque-type psoriasis; drug-induced PPP; history of malignancy within 5 years of screening; history or current signs of any severe, progressive or uncontrolled medical conditions; prior treatment with any anti-tumor necrosis factor alpha (TNF-α) within 12 weeks; agents targeting interleukin (IL)-12, IL-17, or IL-23 within 24 months; or systemic immunosuppressants or phototherapy within 4 weeks.¹
• Treatments for PPP (except topical moisturizers) that could affect the course of PPP or study evaluations were prohibited through week 60.²
• Eligible patients were randomized in a 1:1:1 ratio to subcutaneous (SC) TREMFYA 100 mg (n=54), SC TREMFYA 200 mg (n=52), or SC placebo (n=53).¹
• Patients in the TREMFYA 100 mg and 200 mg arms received SC injections at weeks 0, 4, 12 and every 8 weeks (q8w) thereafter. Placebo patients received SC injections at weeks 0, 4, and 12.¹ 
• At week 16, placebo group patients were randomized in a 1:1 ratio to receive TREMFYA 100 mg or 200 mg at week 16, 20 and q8w thereafter through week 60.¹ 
• The primary efficacy endpoint was the change from baseline in the PPPASI total score at week 16.¹ 
• Major secondary endpoints included change from baseline in PPSI total score and proportion of patients who achieved a PPPASI-50 response at week 16.¹ 
  • The PPSI total score is the sum of individual subscores for each sign (erythema, pustules or vesicles, and desquamation or scale) on either of the palms or soles, whichever was observed during screening to have had the most severely affected areas.
• Other secondary end points included change from baseline in PPPASI and PPSI score over time, proportions of patients who achieved PPPASI-50/75/90/100 response (≥50%, ≥75%, ≥90%, or 100% improvement in PPPASI score from baseline), PPSI-50/75/90/100 responses (≥50%, ≥75%, ≥90%, or 100% improvement in PPSI score from baseline) over time, and change from baseline in the physician’s global assessment (PGA) score for patient’s overall (palms and soles) palmoplantar skin lesions status (0, clear; 5, very severe).¹ 
• Patient-reported outcomes (PROs) included¹:
  • Dermatology Life Quality Index (DLQI): possible score range, 0-30
  • 36-Item Short Form Health Survey (SF-36): includes physical component summary score and mental component summary score
  • EuroQOL-5 Dimensions Questionnaire (EQ-5D): possible score range of visual analog scale (VAS), 0 (worst imaginable health state) to 100 (best imaginable state)
• Samples were collected at weeks 0, 4, and 16 for detection of TREMFYA antibodies.¹ 
• Change from baseline in PPPASI score through week 16 was analyzed using a mixed model for repeated measures with treatment (TREMFYA 100 mg, TREMFYA 200 mg or placebo); smoking status (smoking or nonsmoking); week 2, 4, 8, 12, and 16, and treatment-by-week interaction as fixed effects; and baseline PPPASI score as a covariate.¹ 
• The change from baseline in PPSI through week 16 was also analyzed using the mixed model for repeated-measures.¹ 
• Serum cytokines (IL-17A, IL-17F, IL-22, TNF-α, and interferon gamma [IFN-ɣ]) were measured using Singulex technology for all patients at weeks 0, 16, 48, 72, along with 25 normal healthy controls.⁷

Results

Patient Characteristics

• The median age of patients in the study was 53.3 (SD, 10.94) and 79.2% (126/159) of patients were female.¹
• Through week 52, the study agent was discontinued in 15.1% (24/159) of patients mainly due to TEAEs.
• Baseline disease characteristics were generally comparable among groups except for the percentage of patients with a PPPASI score of 40 or greater.
• Mean PPPASI total score was 27.6 (SD, 11.07) for all patients.
• The percentage of smokers at baseline was similar across the groups.

Efficacy

• Primary and major secondary endpoints at week 16 are summarized in Table: Primary and Major Secondary Efficacy Endpoints at Week 16 (Intention-to-Treat Analysis Set).

• The proportions of patients achieving a PPPASI-50 response increased over time and at week 52 were 83.3% (45/54) in the TREMFYA 100 mg group and 84.6% (44/52) in the TREMFYA 200 mg group.¹
• Through week 16, higher proportions of patients in the TREMFYA groups achieved a PPPASI-75 response (TREMFYA 100 mg: 20.4% [11/54], P=0.01; TREMFYA 200 mg: 11.5% [6/52], P=0.12) compared with placebo (3.8% [2/53]).
• At week 52, the proportion of patients achieving a PPPASI-75 response reached 55.6% patients (30/54) in the TREMFYA 100 mg group and 59.6% (31/52) in the TREMFYA 200 mg group.
• At week 52, PPPASI-90 response was achieved by 29.6% of patients (16/54) in the 100 mg group and 36.5% (19/52) in the TREMFYA 200 mg group.
• PPSI subscores of none (0) or slight (1) were comparable between all groups at week 52.
• Through week 16, no significant treatment effect was observed based on the proportions of patients achieving a PGA score of cleared (0) or almost cleared (1).
• In a post hoc analysis assessing PGA 0/1/2 response, a higher response rate was observed for the TREMFYA 100 mg group (46.3% [25/54]) compared with the placebo group (20.8% [11/53]).
• The proportions of patients who achieved a PGA 0/1/2 response at week 52 were comparable between TREMFYA 100 mg (72.2% [39/54]) and TREMFYA 200 mg (76.9% [40/52]).

Health-Related Quality of Life Measures

• At week 16, the TREMFYA groups showed a significant decrease (improvement) in DLQI scores from baseline compared with the placebo group (LS mean differences: TREMFYA 100 mg, -2.6; P<0.001 and TREMFYA 200 mg, -1.6; P=0.03).¹
• At week 52, generally similar improvements in DLQI scores were observed across treatment groups.
• Numerically greater SF-36 physical component summary scores were observed for the TREMFYA vs placebo groups, although the differences were not statistically significant.
• No notable difference in SF-36 mental component summary scores was observed for the TREMFYA vs placebo groups.
• At week 16, both TREMFYA groups demonstrated significant improvements in EQ-5D VAS (LS mean differences: TREMFYA 100 mg, 6.2; P=0.04 and TREMFYA 200 mg, 6.4; P=0.04) and index scores (LS mean differences: TREMFYA 100 mg, 0.07; P=0.01 and TREMFYA 200 mg, 0.06; P=0.02) compared with placebo.

Serum Biomarker Analysis

• IL-17A reduction after treatment with TREMFYA was significant (P<0.01) at weeks 48 and 72 (not significant at week 16) for both doses, with maximal reduction of 1.8-fold.⁷
• Reduction of IL-17F was 1.8-fold (P<0.01) for the TREMFYA 100 mg group at week 16, 1.6-fold for TREMFYA 200 mg (P=0.016) at week 16, and >2-fold at weeks 48 and 72 (all P<0.01), with maximal reduction of 2.5-fold by week 72.
• Reduction of IL-22 by TREMFYA was significant (P<0.01) at weeks 16, 48, and 72 for both doses, with maximal reduction of 3.0-fold by week 72 for TREMFYA 200 mg.
• Lower levels of IL-17A, IL-17F, and IL-22 at week 72 were associated with greater PPPASI percent improvement at week 72.
• Greater reduction in circulating IL-22 at week 16 was associated with greater PPPASI percent improvement at week 72.

Safety

• No deaths, opportunistic infections, cases of active tuberculosis, or major adverse cardiovascular events were reported.¹
• No cases of anaphylactic, serum sickness-like, or hypersensitivity reactions were observed during the study.
• All injection-site reactions were nonserious and mild; none required dose interruption or withdrawal.
• Through week 52, the proportions of patients reporting 1 or more TEAEs were 85.2% (46/54) in the TREMFYA 100 mg group and 94.2% (49/52) in the TREMFYA 200 mg group.
• A summary of TEAEs through week 16 in all patients that received at least 1 dose of study drug is summarized in Table: Summary of TEAEs through Week 16.

Obuko et al (2021)² reported efficacy and safety results from the phase 3 (NCT02641730), randomized, double-blind, placebo-controlled study of TREMFYA in Japanese patients with moderate to severe PPP through week 84.

Study Design/Methods

• Details of the study design/methods are described above.^1,2
• The study consisted of 3 phases: screening (6 weeks), blinded treatment (week 0-60), and observational (week 60-84).² 
• There were no restrictions on the use of concomitant treatments for PPP after week 60.² 
• Other secondary efficacy endpoints were evaluated through week 84.²
  • Changes from baseline in the PPPASI total score and PPSI total score
  • Proportions of patients achieving the following over time: PPPASI-50/75/90/100; PPSI-50/75/90/100; PPSI subscores of 0 or 1 for erythema, pustular/vesicle, and desquamation/scale; PGA of 0 or 1; PGA score of 0/1 with a ≥2-grade baseline improvement
  • PROs: change from baseline via SF-36 score, EQ-5D, and DLQI
• From weeks 72-84, only TEAE considered related to the study treatment were collected.² 

Results

Patient Characteristics

• A total of 159 patients were randomized with 133 patients completing the study at week 84 (25 patients discontinued the study treatment through week 60; 1 patient discontinued between weeks 60 and 84).²

Efficacy

• A synopsis of details on other secondary efficacy endpoints is summarized in Table: Other Secondary Efficacy Endpoints at Weeks 60 and 84.

Patient-Reported Outcomes

• PROs evaluating SF-36, EQ-5D, and DLQI scores at week 84 are summarized in Table: Other Secondary Endpoints Related to Patient Reported Outcomes at Week 84.

Safety

• No deaths, cases of active tuberculosis, or major adverse cardiovascular events were reported.
• No cases of anaphylactic or serum sickness-like reactions were observed during the study.
• One serious TEAE of gastric cancer was reported in the placebo to TREMFYA 100 mg group.
• In the TREMFYA combined group, the majority of TEAE were mild (61.8%) or moderate (26.8%).
• A synopsis of TEAEs through week 84 is summarized in Table: Summary of TEAEs through Week 84.

PHASE 2 study

German GAP Study

Wilsmann-Theis et al (2025)³ reported efficacy and safety results from a phase 2, multicenter, single-arm study of TREMFYA in European patients with moderate to severe PPP through week 24.

Study Design/Methods

• Patients (≥18 years of age) with a diagnosis of moderate to severe PPP (defined as PPPASI score ≥12) for at least 6 months, with or without concomitant plaque psoriasis (body surface area <10%) were included.
• Patients treated with an IL-23 inhibitor or any therapy targeting TNF-a or IL-17 within the last 3 months; ustekinumab within the last 4 months; other PPP-directed therapies, psoralen plus ultraviolet A (PUVA) phototherapy, conventional therapies, or apremilast within the last 28 days; or ultraviolet B or topical therapies within the last 14 days before baseline were excluded.
• Patients received TREMFYA 100 mg SC at weeks 0, 4, 12, and 20.
• Blood samples were collected at baseline and at weeks 4, 12, and 24 of treatment for safety evaluation and exploratory analyses.
• The primary endpoint was reduction (percent change) in PPPASI score at week 24 compared with baseline.
• The secondary endpoints were absolute and percent changes in PPPASI and DLQI scores over time, change in pustule count compared with baseline, and change in pain and pruritus over the past week (determined by a numeric rating scale [NRS]) relative to baseline.
• The full analysis set included all patients who received at least 1 dose of the study drug.

Results

Patient Characteristics

• A total of 50 patients received TREMFYA. For baseline characteristics, see Table: Select Baseline Characteristics.

Efficacy

• At week 24, the primary endpoint of a median reduction in PPPASI was 59.6% (Q1/Q3: 35.3% and 85.7%, respectively) compared to baseline (P<0.001).
• At week 24, the proportion of patients achieving ≥50% improvement in the PPPASI total score from baseline (PPPASI-50) and ≥75% improvement in the PPPASI total score from baseline (PPPASI-75) was 66% (33/50) and 34% (17/50), respectively.  
• At week 24, the pustule count showed a median reduction of 76.9% (Q1/Q3, 38.9%/100.0%; P<0.001) compared to baseline.

Dermatology Life Quality Index

• The median DLQI reduced from 15.0 (Q1/Q3, 8.0/19.0) at baseline to 5.0 (Q1/Q3, 2.0/11.0) at week 24.
• The NRS score for pain reduced from median 7.0 (Q1/Q3, 5.0/8.0) at baseline to 4.0 (Q1/Q3, 1.0/6.0), and the NRS pruritus score reduced from 7.0 (Q1/Q3, 5.0/8.0) at baseline to 4.0 (Q1/Q3, 2.0/7.0) at week 24.

Serum Biomarker Analysis

• At baseline, patients with PPP showed a significantly higher serum IL-19 level compared to healthy patients (mean±SD, 88.8±92.1 vs 23.0±37.2 pg/mL; P<0.001), and a positive correlation between the baseline IL-19 level and PPPASI score (r_s=0.55; P<0.001) was observed.
• Patients receiving TREMFYA had a significant reduction in the serum IL-19 level at weeks 12 and 24, with the reduction at week 4 correlating with improvements in the PPPASI score (r_s=0.41; P<0.01) and the pustule count (r_s=0.39; P<0.05) at week 24.

Safety

• A total of 102 TEAEs were reported in 37 patients, with most being mild to moderate in severity.
  • Among these, 17 (16.7%) were deemed treatment related.
  • The most common TEAEs reported by patients were nasopharyngitis (n=5) and arthralgia (n=4).
• Four serious adverse events (SAEs) were reported in 2 patients and were deemed unrelated to TREMFYA treatment.
• Two patients discontinued TREMFYA treatment due to a TEAE.
• No events of death were reported during the study.

Case reportS

Inoue et al (2023)⁴ reported the use of TREMFYA in a 66-year-old male patient with PPP, multiple venous occlusions, and pustulotic arthro-osteitis (PAO).

• The patient reported a 2-month history of arthralgia involving both shoulders and a 6-year history of sterile pustules on the plantar aspect of the foot. Medical history included alveolar pyorrhea and a 26-year smoking habit (20 cigarettes/day). No personal or familial psoriasis or rheumatic disease was noted.
• The patient was diagnosed with PPP based on a physical examination which revealed erythematous plaques with desquamation, brown macules, and scattered pustules on soles and palms; skin biopsy indicating intraepidermal pustules with neutrophils, acanthosis, and no parakeratosis; and a negative pustular aspirate culture.
• The patient was lost to follow-up post-diagnosis. After a year, he returned with pain and swelling in his left arm and hemithorax, worsened palmoplantar lesions (PPPASI, 12.8), and extra-palmoplantar involvement in the right shoulder.
• Laboratory investigations revealed elevated inflammatory markers: C-reactive protein (CRP) 7.0 mg/dL, erythrocyte sedimentation rate 112 mm/h, and D-dimer 3.2 µg/mL. Three-dimensional computed tomography (CT) scans demonstrated abnormal ossifications in bilateral sternoclavicular joints and pseudarthrosis of the right clavicle. Contrast CT confirmed multiple venous occlusions associated with PAO.
• Arthritis assessment involved: Bath Ankylosing Spondylitis Functional Index (BASFI), 60; pain VAS, 10; CRP levels, 7 mg/dL; and grip strength (kg), right 24/left 24.
• Initial treatment included vitamin D3, corticosteroid ointment, prednisolone 10 mg/day, and sulfasalazine 1000 mg/day.
• TREMFYA was started after 2 months due to lack of improvement in arthritis and skin lesions.
• Significant improvement was observed after 7 months with fewer new pustules on the soles (especially left foot and both toes), improved right shoulder lesions (PPPASI: 3.6), and improved arthritis outcomes (BASFI: 40, pain VAS: 3, CRP: 3 mg/dL, grip strength [kg]: right 29/left 29).

Jung et al (2023)⁵ reported the use of TREMFYA in a 51-year-old male patient with PPP.

• The patient reported a 10-year history of pustules, erythema, and scales on palms and soles, without a history of plaque-type psoriasis.
• Initial treatment with oral retinoid for typical PPP manifestations proved ineffective. Oral cyclosporine and methotrexate were discontinued due to severe myalgia and nausea.
• Sequential administration of biologics included:
  • Ustekinumab 45 mg: Alleviated symptoms after the third dose, but efficacy declined from the seventh to the 11th injection, leading to an 8-month treatment discontinuation.
  • Secukinumab 300 mg: Showed improvement after the third dose followed by deterioration with erythema, scales, and pustules on both palms from the fifth to the 10th injection, resulting in a 2-month cessation.
• TREMFYA 100 mg was initiated at weeks 0 and 4, and then q8w.
  • PPPASI score reduced to 8.8 from 18.4 at baseline, after the third dose.
  • Significant improvement in erythema and pustules was observed, with complete lesion clearance after the fifth injection.
  • PPPASI-100 response was sustained through the 17th dose.

Duderstadt et al (2021)⁶ reported the use of TREMFYA in a 59-year-old female patient with PPP.

• The patient developed PPP in 2006. Her medical history and clinical examination showed no signs of plaque psoriasis, psoriatic arthritis or psoriatic onycho-pachydermo-periostitis. Patient medical history included intake of acetylsalicylic acid and oxcarbazepine, and history of smoking (3 pack years).
• Past therapeutic regimens, such as local and long-term systemic steroids (10 mg/day) and PUVA-photochemotherapy combined with acitretin, yielded insufficient effect.
• Other systemic therapies such as cyclosporine and apremilast showed no effectiveness while fumaric acid esters and methotrexate were interrupted due to intolerability.
• Clinical examination in 2019 showed multiple pustules on palms and soles. There were pustules on the fingertips and dystrophic nails (Investigator Global Assessment [IGA] score 4, PPPASI 3) consistent with clinical presentation of acrodermatitis continua suppurativa.
• Due to reoccurrence of resisting pustules, plaques, pruritus, and reduced quality of life, TREMFYA was initiated. An almost total clearance of the palmoplantar skin and improvement of onychodystrophy were observed within 3 months of TREMFYA initiation (IGA 1, PPPASI 1). Responses were maintained at last presentation 8 months later.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 20 January 2025.