Secukinumab Shows High and Sustained Efficacy in Nail Psoriasis

2.5-year Results From the Randomized Placebo-controlled TRANSFIGURE Study

K. Reich; J. Sullivan; P. Arenberger; S. Jazayeri; U. Mrowietz; M. Augustin; B. Elewski; R. You; P. Regnault; J.A. Frueh

Disclosures

The British Journal of Dermatology. 2021;184(3):425-436. 

In This Article

Results

Patients

Of the 249 patients screened, 198 were randomized in Treatment Period 1 (up to week 16) to secukinumab 300 mg (n = 66), secukinumab 150 mg (n = 67) and placebo (n = 65). The majority of the patients (n = 186, 93·9%) completed Treatment Period 1 and entered Treatment Period 2 (up to week 132). Here, patients who received placebo were rerandomized to secukinumab 150-mg (n = 29) and 300-mg (n = 29) groups. More than two-thirds of all patients (n = 131, 68·6%) completed Treatment Period 2 (Figure 2).

Figure 2.

Participant disposition.

The BL demographics of randomized patients were comparable between all treatment arms (Table 1). At BL, mean NAPSI score across all groups was 42·6, the mean PASI score was 20·3, and the mean BSA was 26·7, which is indicative of a target patient population with moderate-to-severe psoriasis with significant nail involvement. At BL, the majority of the patients had nearly all 10 fingernails affected by psoriasis. The mean total number of fingernails impaired at BL was 9·6. The incidence of PsA was similar across the three groups with a mean of 25·8%.

Efficacy

The primary endpoint, NAPSI and all secondary study endpoints were met, demonstrating superiority of secukinumab over placebo after 16 weeks of placebo-controlled treatment (Treatment Period 1).[29] During Treatment Period 2, the percentage change from BL in NAPSI score observed at the end of week 16 continued to decrease (showing an improvement in nail psoriasis disease severity) with a peak reduction observed at week 64 in the secukinumab 150-mg group (−71·3%) and at week 116 in the secukinumab 300-mg group (−76·7%) (as observed). The reduction from BL was sustained up to 2·5 years with a mean NAPSI improvement of −73·3% and −63·6% (as observed) (Figure 3) and −70·5 % and −52·9% (last observation carried forward) from BL with the secukinumab 300-mg and 150-mg groups, respectively. A higher percentage reduction was observed in the secukinumab 300-mg group compared with the secukinumab 150-mg group at all timepoints. The percentage of patients who achieved almost clear nail psoriasis (NAPSI 0–2) increased over time.

Figure 3.

Secukinumab showed sustained improvements in nail psoriasis up to 2·5 years (as observed). BL, baseline; NAPSI, Nail Psoriasis Severity Index.

At BL, 76% and 70% of patients in the secukinumab 300-mg and 150-mg groups had all 10 fingernails affected by psoriasis, respectively. At week 16, the percentage of patients with involvement of 10 fingernails was reduced to 42% and 49% for secukinumab 300 mg and 150 mg, respectively. These improvements were sustained during the entire treatment period up to 2·5 years (10 fingernails; 11% and 15% in the secukinumab 300-mg and 150-mg groups, respectively). A visible and progressive improvement in the symptoms of nail psoriasis over 2·5 years was also observed in patients receiving secukinumab treatment (Figure 4).

Figure 4.

Visible improvement in nail psoriasis following secukinumab treatment up to 2·5 years.

The proportion of patients who achieved PASI 75, 90, 100 and IGA mod 2011 0/1 at week 16 was sustained and thereafter the percentage of PASI responders remained consistent through 2·5 years (Figure 5). A high proportion of patients maintained clear or almost clear skin up to 2·5 years with higher response rates in the secukinumab 300-mg group vs. the 150-mg group (PASI 90 response 63% and 45%, PASI 100 response 29% and 25% for secukinumab 300 mg and 150 mg, respectively) (multiple imputation). In both treatment groups, the mean PASI score decreased over time until week 16 and thereafter remained stable up to 2·5 years. Greater improvements in skin clearance, indicated by a reduction in mean PASI scores, were observed in the secukinumab 300-mg group compared with the secukinumab 150-mg group at all timepoints.

Figure 5.

Secukinumab showed improvements in achievement of clear or almost clear skin up to 2·5 years. (a) Percentage PASI 75 responders. (b) Percentage PASI 90 responders. (c) Percentage PASI 100 responders. (d) Percentage IGA mod 2011 0/1 responders. IGA mod 2011, Novartis Investigator's Global Assessment modified in 2011; PASI, Psoriasis Area and Severity Index.

At BL, the majority of the patients had an IGA mod 2011 score of 3 (moderate) or 4 (severe). At week 16, 34% of patients in the secukinumab 300-mg group had an IGA mod 2011 score of 0 (clear) and 41% of patients had a score of 1 (almost clear). These response rates were sustained up to 2·5 years in both treatment groups.

Patient-reported Outcomes

Overall, for most of the HRQoL efficacy endpoints secukinumab 300 mg showed greater benefits compared with the secukinumab 150-mg group throughout the study period.

Nail Assessment in Psoriasis and Psoriatic Arthritis - Quality of Life

Overall, 50% of patients at BL reported pain and discomfort in fingers and found it difficult to work with their hands owing to nail psoriasis. The mean total NAPPA-QoL score improved considerably during Treatment Period 2 in both secukinumab treatment groups and was sustained up to 2·5 years. Patients showed reductions (improvements) in total mean NAPPA-QoL score from BL to 2·5 years of −52·4% and −18·1% with secukinumab 300 mg and 150 mg, respectively (Figure 6). This indicted a highly reduced impact of nail psoriasis on patients' QoL.

Figure 6.

Secukinumab showed sustained improvements in NAPPA-QoL scores at 2·5 years. NAPPA-QoL is a 14-item nail-specific QoL questionnaire that assesses specific conditions in the past week using Likert scales from 0 to 4. The three domains analysed are 'nail changes', 'emotions' and 'everyday life'. BL, baseline; NAPPA, Nail Assessment in Psoriasis and Psoriatic Arthritis; QoL, quality of life

Nail Assessment in Psoriasis and Psoriatic Arthritis - Patient Benefit Index

During Treatment Period 2, considerable improvements were observed in NAPPA-PBI mean score, which measured patient preferences and attainment of treatment goals. NAPPA-PBI mean score further improved continuously from BL up to 2·5 years in the secukinumab 150-mg and 300-mg groups, respectively. At 2·5 years, 70% and 71% of patients achieved a weighted NAPPA-PBI global score of ≥ 2 with secukinumab 300 mg and 150 mg, respectively (Figure 7).

Figure 7.

Secukinumab showed improvement in patient-reported benefit assessed by NAPPA-PBI global score of ≥ 2 at 2·5 years. NAPPA-PBI is a 24-item questionnaire that assesses patient-defined needs before and patient-rated benefits after treatment using a Likert scale ranging from 0 (no benefit) to 4 (highest possible benefit). NAPPA, Nail Assessment in Psoriasis and Psoriatic Arthritis; PBI, patient benefit index. aA score ≥ 2 indicates responders who have demonstrated some benefit from treatment. A global score is calculated based on weighted single items and focuses on five domains including 'social', 'psychological', 'therapy', 'physical' and 'confidence'.

EuroQol 5-Dimension Health Status Questionnaire

Overall, the improvements relative to placebo in all categories (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) of the EQ-5D observed in Treatment Period 1 continued in Treatment Period 2 and were sustained thereafter up to 2·5 years in both secukinumab groups. Patients reported rapid improvement in their nail psoriasis following secukinumab treatment, which not only allowed them to lead a normal working life and conduct their daily activities without much pain and discomfort, but also to feel better emotionally. At BL, the most affected dimension of the EQ-5D was pain/discomfort. The percentage of patients reporting moderate-to-severe pain decreased by nearly 50% at 2·5 years (Figure 8). The patients' HRQoL improved over time as assessed by the mean EQ-5D overall health assessment score, which increased and was sustained up to 2·5 years [absolute change from BL was 11·2 (BL 67·9) and 12·4 (BL 60·1) for secukinumab 300 mg and 150 mg, respectively].

Figure 8.

Secukinumab strongly reduces the quality-of-life (QoL) burden across all five domains of the EQ-5D. The EQ-5D is a descriptive system comprising five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), and an EQ visual analogue scale (0–100) where the patient self-rates their health ranging from 'best imaginable health state' to 'worst imaginable health state'. Data are shown as last observation carried forward. BL, baseline; EQ-5D, EuroQol 5-Dimension; QoL, quality of life.

Dermatology Life Quality Index

At BL, the mean total DLQI scores were 13·2 and 14·1 for the secukinumab 300-mg and 150-mg groups, respectively. Improvements in mean total DLQI scores, which were observed in Treatment Period 1 in both secukinumab treatment groups, compared with placebo for all individual scores (symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment), were sustained in Treatment Period 2. At 2·5 years, the mean total DLQI score decreased by 68·4% and 60·9% in the secukinumab 300-mg and 150-mg groups, respectively.

At 2·5 years, DLQI 0/1 response (indicating that psoriasis has no effect at all on the patient's life) was achieved in 54% and 46% of patients in the secukinumab 300-mg and 150-mg mg groups, respectively (Figure 9).

Figure 9.

Secukinumab shows sustained improvement in quality of life as shown by Dermatology Life Quality Index (DLQI) response (0 or 1) at 2·5 years.

Subject Global Assessment

The improvements in SGA scores observed in Treatment Period 1 were sustained in Treatment Period 2. The percentage increase from BL in median SGA score (42·0 and 34·5 for secukinumab 300 mg and 150 mg, respectively) was sustained and further improved up to 2·5 years in both secukinumab treatment arms (88·7% and 61·7% for secukinumab 300 mg and 150 mg, respectively) (Figure 10).

Figure 10.

Secukinumab showed sustained improvements in Subject's Global Assessment (SGA) of nail psoriasis (scale 0–100) at 2·5 years.

Safety

The safety profile was favourable and consistent with that observed in previous phase III trials for psoriasis and PsA. During the treatment period, 88·4% of patients receiving any secukinumab dose experienced at least one treatment-emergent AE. At 2·5 years, the proportion of patients, experiencing at least one AE was comparable between the 300-mg group (88%) and the 150-mg group (89%) vs. 63% seen during the 16-week placebo treatment duration. There were no secukinumab dose-dependent increases in incidence of AEs.

AEs in the system organ class 'infections and infestations' were reported most often (72%, 65% and 32% for secukinumab 300 mg, 150 mg and placebo, respectively). The most common AEs according to the Medical Dictionary for Regulatory Activities preferred term, in both the secukinumab groups, were nasopharyngitis, upper respiratory tract infections and headache (Table 2).

During the 2·5-year treatment period, the incidence of serious AEs (SAEs) was low (10% and 10% of patients in the 300-mg and 150-mg groups, respectively). The incidence of SAEs was 2% during the 16-week placebo phase. Among selected AEs, one case of neutropenia was reported in the secukinumab 150-mg group, which was considered a suspected SAE and the patient was discontinued from the study. Among the reported neoplasms, SAEs included basal cell carcinoma (reported in a patient in the secukinumab 150-mg group) and tonsil cancer (reported in a patient in the secukinumab 300-mg group).

In the any secukinumab 300-mg group, three patients reported mild oral candidiasis and one patient reported mild vulvovaginal candidiasis. In the any secukinumab 150-mg group, one patient reported moderate oral candidiasis and two patients reported moderate vulvovaginal candidiasis. None of these AEs were considered as serious. One patient in the secukinumab 300-mg group experienced a nonserious staphylococcal infection of moderate severity.

One patient in the secukinumab 300-mg group was reported a major adverse cardiovascular event (myocardial infarction, haemoptysis), which was considered a suspected SAE, but did not lead to treatment interruption or study discontinuation. There were no deaths reported in this study.

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