SUMMARY

• The company cannot recommend any practices, procedures or usage that deviate from the approved labeling.
• Clinical studies have described the use of TREMFYA in patients with nail psoriasis (PsO).^1-6
• In the VOYAGE 1 study of patients with moderate to severe plaque PsO, the mean±standard deviation (SD) percentage improvement in the Nail Psoriasis Severity Index (NAPSI) score in the TREMFYA group at weeks 16, 24, and 48 was 34.4±42.46, 49.8±44.16, and 68.1±43.00, respectively.¹
• In the VOYAGE 2 study of patients with moderate to severe plaque PsO, the mean±SD percentage improvement in the NAPSI score in the TREMFYA group at weeks 16 and 24 was 39.6±45.6 and 55.0±46.8, respectively.²
• A post hoc analysis of the VOYAGE 2 study evaluated nail PsO response in patients initially randomized to TREMFYA who were Psoriasis Area and Severity Index [PASI] 90 responders (achieved ≥90% improvement in the PASI score) at week 28 and were rerandomized at week 28 to receive placebo (TREMFYA withdrawal group) or TREMFYA (TREMFYA continuation group) every 8 weeks.³
• A post hoc analysis of the VOYAGE 1 and VOYAGE 2 studies evaluated nail PsO outcomes for TREMFYA vs adalimumab and/or placebo in an Asian subpopulation.⁴
• A post hoc analysis of the IXORA-R study compared nail PsO outcomes for ixekizumab vs TREMFYA in patients with moderate to severe plaque PsO (fingernail Physician Global Assessment [f-PGA] >0).⁵

CLINICAL DATA

VOYAGE 1

Blauvelt et al (2017)¹ assessed improvement in nail PsO in the VOYAGE 1 study, a phase 3, multicenter, randomized, double-blind, placebo and active comparator-controlled study evaluating the efficacy and safety of TREMFYA compared to placebo and adalimumab in 837 patients with moderate to severe plaque PsO.

Study Design/Methods

• Adult patients (≥18 years of age) with a diagnosis of plaque PsO for ≥6 months who were candidates for phototherapy or systemic therapy, and had a baseline Investigator’s Global Assessment (IGA) score ≥3, a PASI score ≥12, and ≥10% of their body surface area (BSA) involved were eligible for enrollment.¹
• The study design is shown in Figure: VOYAGE 1 Study Design.

• Improvement in nail PsO was evaluated by the f-PGA (range from 0-4 [0, clear; 1, almost clear; 2, mild; 3, moderate; 4, severe]), and NAPSI (range from 0-8 [higher scores indicate more severe disease]).

Results

Patient Characteristics

• Baseline nail PsO characteristics are noted in Table: Baseline Nail PsO Characteristics - Randomized Patients in VOYAGE 1.

Efficacy

• Nail PsO outcomes at weeks 16, 24, and 48 are noted in Table: Nail PsO Outcomes at Weeks 16, 24, and 48 - Randomized Patients in VOYAGE 1.
• The proportion of patients achieving f-PGA 0/1 (cleared/minimal) and percent improvement in NAPSI score were significantly higher for TREMFYA vs placebo at week 16.
• Although the f-PGA responses were comparable at week 24, TREMFYA was superior to adalimumab by week 48.
• Mean percent improvements in NAPSI score were comparable between TREMFYA and adalimumab at weeks 24 and 48.

VOYAGE 2

Reich et al (2017)² assessed improvement in nail PsO in the VOYAGE 2 study, a phase 3, multicenter, randomized, double-blind, placebo and active comparator-controlled study evaluating the efficacy and safety of TREMFYA compared to placebo and adalimumab in 992 patients with moderate to severe plaque PsO.

Study Design/Methods

• Adult patients (≥18 years of age) with a diagnosis of plaque PsO for ≥6 months who were candidates for phototherapy or systemic therapy, and had a baseline IGA score ≥3, a PASI score ≥12, and ≥10% of their BSA involved were eligible for enrollment.
• The study design is shown in Figure: VOYAGE 2 Study Design.

• Improvement in nail PsO was evaluated by f-PGA and NAPSI.

Results

Patient Characteristics

• Baseline nail PsO characteristics are noted in Table: Baseline Nail PsO Characteristics - Randomized Patients in VOYAGE 2.

Efficacy

• Nail PsO outcomes at weeks 16 and 24 are noted in Table: Nail PsO Outcomes at Weeks 16 and 24 - Randomized Patients in VOYAGE 2.
• Patients treated with TREMFYA achieved greater improvement in f-PGA score 0/1 and percent improvement in NAPSI score compared with placebo at week 16.
• At week 24, f-PGA score 0/1 and percent improvement in NAPSI score were comparable in patients receiving TREMFYA vs adalimumab.

Tillett et al (2023)³ assessed nail PsO response in a post hoc analysis of the VOYAGE 2 study in patients with a high risk of developing psoriatic arthritis (PsA) due to the presence of nail PsO at baseline.

Study Design/Methods

• Patients who had moderate to severe plaque PsO and nail PsO at baseline and were PASI 90 responders at week 28 with TREMFYA were rerandomized at week 28 to receive placebo (TREMFYA response withdrawal group) or TREMFYA every 8 weeks (TREMFYA response continuation group). Patients who did not achieve PASI 90 at week 28 (nonresponders) continued to receive TREMFYA therapy (TREMFYA nonresponse continuation group). Patients who achieved PASI 90 at week 28 with adalimumab were switched to receive placebo at week 28 (adalimumab withdrawal group), and those who did not achieve PASI 90 were switched to TREMFYA at week 28 (adalimumab to TREMFYA crossover group).
• NAPSI (grading the most affected nail) and f-PGA scores at weeks 0, 16, 24, and 48 were reported.
• Comparative results were descriptive and based on numerical differences.

Results

Patient Characteristics

• Overall, 272/496 patients who received TREMFYA and 132/248 patients who received adalimumab at baseline, had nail PsO involvement, and did not discontinue treatment before week 28 were included in the post hoc analysis.
• Baseline nail PsO characteristics are noted in Table: Baseline Nail PsO Characteristics - Rerandomized Patients per Treatment Response in VOYAGE 2.

Efficacy

• The NAPSI, f-PGA, PASI, and Dermatology Life Quality Index (DLQI) scores for patients in the TREMFYA response withdrawal and nonresponse continuation groups and adalimumab withdrawal and crossover to TREMFYA groups through week 48 are summarized in Table: NAPSI, f-PGA, PASI, and DLQI Scores through Week 48 by Treatment Subgroups in VOYAGE 2.

• Overall, 36/101 patients in the TREMFYA response withdrawal group maintained a PASI 90 response (≥PASI 90 from baseline) at weeks 28 through 48, whereas 64 patients were unable to maintain a PASI 90 response. Patients who maintained a PASI 90 response also maintained a high level of nail response, see Table: NAPSI, f-PGA, PASI, and DLQI Scores through Week 48 in the TREMFYA Responder Withdrawal Group Stratified by Maintenance of PASI 90 at Week 48.

Prior Biologic Use and Efficacy

• NAPSI was evaluated in patients in the TREMFYA response continuation group and TREMFYA response withdrawal group through week 48 stratified by prior biologic use. NAPSI increased in both bio-naïve and bio-experienced patients of the TREMFYA withdrawal group, see Table: NAPSI and PASI Response through Week 48 Stratified by Prior Biologic Use.

Pooled Efficacy Analysis of VOYAGE 1 and VOYAGE 2

Jo et al (2023)⁴ conducted a post hoc analysis evaluating the efficacy of TREMFYA for the treatment of PsO in difficult-to-treat regions, specifically in the Asian subpopulations (Taiwan and South Korea) from VOYAGE 1 and VOYAGE 2.

Study Design/Methods

• For the VOYAGE 1 and VOYAGE 2 study designs, please refer to Figures: VOYAGE 1 Study Design and VOYAGE 2 Study Design.
• The TREMFYA and adalimumab groups were compared with the placebo group at week 16, and the active treatment groups (TREMFYA vs adalimumab) were compared at week 24. Patients who were crossed over from placebo to TREMFYA were excluded from the week 24 analysis.
• Endpoints included the proportion of patients achieving f-PGA (clear or minimal fingernail PsO) and mean percentage of improvement in the target NAPSI scores at weeks 16 and 24.
• Efficacy was also evaluated in a pooled subset of patients with or without prior biologic experience from baseline through week 24.
• Complete clearance was defined as a score of 0 for f-PGA and a 100% improvement in the target NAPSI score.

Results

Patient Characteristics

• Among the 1829 patients randomized in VOYAGE 1 and VOYAGE 2, 257 were Asian patients of which, 199 were eligible for inclusion in this study.
• Baseline nail PsO characteristics are noted in Table: Baseline Nail PsO Characteristics - Asian Patients in VOYAGE 1 and VOYAGE 2.

Efficacy

• Nail PsO outcomes at weeks 16 and 24 are noted in Table: Nail PsO Outcomes at Weeks 16 and 24 - Asian Patients in VOYAGE 1 and VOYAGE 2.

IXORA-R

Blauvelt et al (2020)^5,6 evaluated the efficacy and safety of ixekizumab and TREMFYA in a multicenter, randomized, double-blind, parallel-group, head-to-head, phase IV study in 1027 patients with moderate to severe plaque PsO.

Study Design/Methods

• Eligible patients (≥18 years of age) had moderate to severe plaque PsO for ≥6 months, PASI ≥12, static Physician’s Global Assessment (sPGA) score ≥3, body surface area (BSA) involvement ≥10%, and were candidates for phototherapy and/or systemic therapy.^5,6
• Patients were excluded if they had a predominant pattern of pustular, erythrodermic and/or guttate forms of PsO; a history of drug-induced PsO or a clinically significant flare of PsO during the 12 weeks before baseline; used tanning booths 4 weeks before baseline; used any biologic agent within specified periods prior to baseline; used any interleukin (IL)-23p19 antagonists; or had any condition or contraindication as addressed in the local labeling for TREMFYA.⁵
• Patients were randomized in a 1:1 ratio to receive either subcutaneous (SC) TREMFYA 100 mg at weeks 0, 4, and every 8 weeks thereafter or SC ixekizumab 160 mg loading dose (two 80-mg injections) at week 0 followed by 80 mg every 2 weeks from week 2 to week 12 and then 80 mg every 4 weeks through week 24. To maintain blinding, patients in the TREMFYA group received 1 placebo injection at weeks 0, 2, 6, 8, 10 and 16.^5,6
• Patients were assessed at baseline, weeks 1, 2, 4, 6, 8, 10, 12, 16, 20 and 24.^5,6
• The primary endpoint was the proportion of patients who achieved a PASI 100 response at week 12 (complete clearance). The sample size was estimated to have 98% power for testing the superiority of ixekizumab to TREMFYA at a two-sided 5% type I error rate. ^5,6
• Missing data for binary measures were imputed as nonresponse.^5,6
• Exploratory and post hoc analysis were not adjusted for multiple comparisons.^5,6
• PsO of the fingernails was evaluated using f-PGA at baseline and week 24.

Results

Patient Characteristics

• A total of 1027 patients were randomized to receive TREMFYA (n=507) or ixekizumab (n=520).⁵
• The mean BSA involved at baseline was 23.8% and 24.1%, and the mean PASI score at baseline was 19.3 and 19.5 in the TREMFYA and ixekizumab groups, respectively.⁵
• At baseline, 16% (83/520) of patients in the ixekizumab group and 12% (59/507) of patients in the TREMFYA group had moderate to severe nail PsO (f-PGA score ≥3).
• A post hoc analysis of all patients with nail PsO at baseline (f-PGA >0) included 51% (264/517) and 47% (239/507) of patients in the ixekizumab and TREMFYA groups, respectively.
• Of the 1027 patients randomized, 91% (459/507) of patients in the TREMFYA arm and 89% (465/520) of patients in the ixekizumab arm completed the study through week 24.⁶

Efficacy

• The number of patients that achieved a f-PGA score of 0 or 1 with ≥2-point improvement from baseline at week 24 was 75% (62/83) and 54% (32/59) in the ixekizumab and TREMFYA groups, respectively (P=0.020).⁶
• At week 24, a f-PGA score of 0 with ≥2-point improvement from baseline was achieved by 52% (43/83) and 31% (18/59) of patients in the ixekizumab and TREMFYA groups, respectively (P=0.007).⁶
• In a post hoc analysis of all patients with nail PsO (f-PGA >0), 63% (165/264) and 44% (106/239) of patients in the ixekizumab and TREMFYA groups, respectively, achieved complete clearance of nail PsO (f-PGA 0) at week 24 (P<0.001).⁶

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 25 October 2024.

Summarized in this response are relevant data from phase 3 clinical trials (VOYAGE 1, VOYAGE 2) and a phase 4 clinical trial (IXORA-R) in adult patients with moderate to severe plaque PsO.