FormalPara Key Summary Points

Why carry out this study?

Given the impact of psoriasis on the daily activities and psychology of patients, it is important to collect patients’ insights on their disease in clinical trials to better understand whether the changes in the physical presentation of psoriasis symptoms during the treatment course had any impact on health-related quality of life (HRQoL).

PURE is a real-world registry evaluating secukinumab and other approved therapies (biologic therapy, oral systemic therapy, and phototherapy) for the management of moderate-to-severe plaque psoriasis in Canada and Latin America.

In this interim analysis, the effectiveness of secukinumab has been evaluated using Psoriasis Area and Severity Index (PASI) total scores, PASI component sub-scores (erythema, thickening, and scaling), and PASI scores for each body region, for the resolution of symptoms of moderate-to-severe plaque psoriasis up to 36 months, in patients from Canada and Latin America.

Considering the limited evidence to complement the clinical observations with the impact of psoriasis on patients' HRQoL, we also evaluated the trends in the components of Psoriasis Symptom Diary, a patient-reported outcome tool, up to 36 months in the PURE registry in this analysis.

What was learned from the study?

An early and sustained improvement in disease severity was observed with secukinumab treatment as demonstrated by the 36-month results. This improvement was also reflected in different body regions (head/neck, trunk, upper limbs, and lower limbs), where the lower limbs required a relatively longer time for the reduction of disease severity than the other body regions.

The PASI score components (erythema, thickening, and scaling) demonstrated improvements as early as 3 months and were sustained throughout the follow-up period of 36 months.

Overall, secukinumab treatment showed a positive impact on disease activity and HRQoL as evaluated using PASI and Psoriasis Symptom Diary, respectively.

Introduction

Psoriasis is a systemic immune-mediated, inflammatory disease involving the skin. In some patients, joint manifestations are also present and further contribute to the disease impact. A typical area affected by psoriasis is characterized by erythema, thickening, and scaling of plaques [1, 2]. Moderate-to-severe plaque psoriasis tends to be accompanied by a profound impact on patients’ health-related quality of life (HRQoL) [1]. Disease severity of psoriasis is assessed using the Psoriasis Area and Severity Index (PASI), a widely employed physician-rendered tool. PASI is a weighted, cumulative, numeric, and validated measure of psoriasis severity and the surface area affected in four constituent body regions (head/neck, trunk, upper limbs, and lower limbs) [3]. The analysis of PASI scores by body regions would allow a comprehensive evaluation of disease severity as well as treatment response, even for difficult to treat localized areas. However, very limited data is available on treatment response corresponding to changes in PASI score across body regions [4, 5]. Given the impact of psoriasis on the daily activities and well-being of patients, it is important to understand the impact of disease severity on patient’s HRQoL. The Psoriasis Symptom Diary was thus designed in accordance with the recommendations from the United States (US) Food and Drug Administration guidelines [6, 7], with the specific aim of generating patient-reported endpoints for moderate-to-severe chronic plaque psoriasis. Such patient-reported outcome (PRO) tools would also be helpful for healthcare professionals to gain an understanding of the disease severity and impact on patients. Moreover, the Psoriasis Symptom Diary is an important validated patient-rendered tool, which can be useful in situations such as the COVID-19 pandemic, when physician–patient interaction can be conducted only virtually through telephone or video conferencing.

Secukinumab is a human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), a cornerstone cytokine involved in psoriasis pathogenesis [8,9,10,11,12]. It has shown rapid onset of action and sustained effectiveness with a favorable safety profile in the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis, in real-world registries such as CorEvitas [13] in North America, BADBIR [14] in the United Kingdom, PROSE [15] in 17 countries across Europe, and PROSPECT [16] in Germany. PURE is a real-world registry evaluating secukinumab and other approved therapies (biologic therapy, oral systemic therapy, and phototherapy) for the management of moderate-to-severe plaque psoriasis in Canada and Latin America [17].

This analysis reports the effectiveness of overall secukinumab treatment in the resolution of moderate-to-severe plaque psoriasis, as well as on the individual components of PASI scores in different body regions over 36 months. This analysis also reports trends in the individual components of the Psoriasis Symptom Diary over a period of 36 months.

Methods

Study Design

PURE is an observational, prospective, international, two-cohort registry of adult Patients with moderate-to-severe chronic plaqUe psoRiasis in Latin AmErica (Argentina, Brazil, Costa Rica, Guatemala, Mexico, Panama, and the Dominican Republic) and Canada. The registry has been ongoing since 2015, enrolling 2362 adult patients (secukinumab or other treatments in a 1:1 ratio) from 81 community- and hospital-based specialty sites. In this registry, nearly 89.0% of the patients were from Canada. The study includes a 5-year follow-up at completion, with recommended assessments at baseline, 3 and 6 months, and every 6 months thereafter. Changes in treatment can occur independently from the study at the physician’s discretion [15] (Fig. 1).

Fig. 1
figure 1

Study design. *Maximum 5-year follow-up; recommended follow-up schedule: every 3 months for the first 2 visits, and every 6 months thereafter. IL interleukin, N total number of patients

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Inclusion and Exclusion Criteria

Patients (aged ≥ 18 years) who were diagnosed with moderate-to-severe chronic plaque psoriasis by a specialist were included in the study. The clinical decision to start psoriasis treatment (secukinumab, other biologic therapy, oral systemic therapy, or phototherapy) was reached previously and was independent of study enrollment. Treatments were prescribed in accordance with the product monograph per the local standard of care and regional regulatory and/or reimbursement policies. Patients who were unwilling or unable to comply with the study requirements or those involved in a clinical trial of an investigational drug, concurrently or within the last 30 days were excluded from the study.

Baseline Demographics and Disease Characteristics

Demographic characteristics of the patients, including age, sex, ethnicity, body weight, time since diagnosis, previous biologic exposure, and medical history were recorded at enrollment. The medical history was coded by MedDRA version 20.0. Disease severity was assessed using the PASI, Investigator’s Global Assessment (IGA), and body surface area (BSA) measurements, while disease impact was evaluated using the Psoriasis Symptom Diary.

Outcomes Evaluated

Psoriasis Area and Severity Index (PASI)

PASI is routinely used to evaluate psoriasis severity. It is a composite score of average erythema, thickening, and scaling of each affected area, graded as 0–4 for increasing severity, and weighted by the proportion of BSA affected [3, 18, 19]. PASI total score (0–72) is the cumulative score of the PASI regional score weighted by body region (head/neck [10%], upper limbs [20%], trunk [30%], and lower limbs [40%]) [18].

Psoriasis Symptom Diary

The Psoriasis Symptom Diary is a 16-item psoriasis-specific PRO tool that subjectively assess the severity of key signs and symptoms of plaque psoriasis (including alterations in skin color, severity of scaling, pain, cracking, burning, stinging, and itching) and how each component affects the daily activities/psychology of patients [7]. Factors evaluated for disease burden from a patient’s perspective included (i) hiding the affected skin; being bothered by (ii) scaling, (iii) pain, (iv) cracking, (v) burning, (vi) stinging, and (vii) itching; (viii) avoiding activities with other people; and (ix) embarrassment.

Data Evaluation

In this study, the mean (standard deviation [SD]) scores for the PASI (total PASI and regional PASI) and Psoriasis Symptom Diary components were evaluated at months 3, 6, 12, 18, 24, 30, and 36. Safety was assessed by the incidence of adverse events (AEs) and serious AEs (SAEs). AEs were assessed using a hierarchical list of medication exposures, (in descending order of priority: secukinumab, other biologics followed by non-biologics) and were attributed to the medication exposure closest to the top of the hierarchy. The number of patients (N) receiving secukinumab treatment who reached a specific time point at which the PASI and Psoriasis Symptom Diary scores were calculated in this analysis.

Statistical Analysis

All data analyses were performed using statistical software (SAS version 9.4, SAS Institute, Cary, NC, USA). Quantitative parameters were summarized as the number of available data, mean ± SD, median, minimum, and maximum values, and 95% confidence interval (95% CI) for the mean. Categorical variables were summarized as the number and proportion of participants belonging to each category. Testing for statistical significance was not performed. The analysis population included participants derived from study treatment cohort 1 (initiated with secukinumab) and study treatment cohort 2 (initiated with other therapies). Analysis timepoints for the outcome measures such as PASI, IGA, and Psoriasis Symptom Diary, were adjusted by the start date of secukinumab for cohort 2 participants. Total PASI score was calculated using the validated PASI scoring system. PASI regional score was calculated on a 100% scale, ranging from 0 to 72. The percentage of BSA was considered.

Ethical Consideration

All patients provided informed consent to participate in the PURE study. The PURE study design was reviewed by the ethics committees or institutional review boards and was conducted in accordance with the principles of the Declaration of Helsinki.

Results

Baseline Demographics and Disease Characteristics

As of January 24, 2020, 848 patients were initiated on secukinumab as per the physician’s decision. At baseline, the overall mean (± SD) age of patients enrolled in the registry was 49.7 (13.83) years (Table 1). At baseline, the mean (± SD) total PASI score was 13.3 (9.02; N = 840) and the mean affected BSA was 17.0% (15.75; N = 839) (Table 1). The detailed medical history of the patients enrolled in the study is presented in Table 2.

Table 1 Patient demographics and disease characteristics at baseline
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Table 2 Overall medical history by system organ class and preferred term
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Effectiveness of Secukinumab

Total PASI Scores

The baseline total PASI score (mean [± SD; N]: 13.3 [9.02; 840]) showed an early decrease at 3 months (2.3 [3.99; 732]) and remained consistently low up to 36 months (1.6 [2.26; 73]; Fig. 2). The mean (± SD) percentage of BSA affected by psoriasis was 17.0% (15.75) at baseline, which reduced to 2.7% (6.02) at 3 months and 1.6% (3.29) at 18 months, with the reductions being sustained up to 36 months (1.2% [2.26]; Fig. 3). The baseline mean (± SD; N) PASI scores for erythema, thickening, and scaling were 4.8 (3.21; 836), 4.3 (3.00; 836), and 4.2 (3.04; 835), respectively. Early reductions from baseline in the mean (± SD; N) PASI scores for erythema, thickening, and scaling was observed at 3 months (0.9 [1.44; 730], 0.7 [1.33; 730], and 0.7 [1.30; 730], respectively), with sustained responses up to 36 months (0.5 [0.77; 72], 0.5 [0.77; 72], and 0.5 [0.76; 72], respectively; Fig. 4).

Fig. 2
figure 2

Total PASI score in secukinumab-treated patients over time. N number of patients, PASI Psoriasis Area and Severity Index

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Fig. 3
figure 3

Total BSA (%) over time in secukinumab-treated patients. N number of patients, BSA body surface area

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Fig. 4
figure 4

PASI score for erythema, thickening, and scaling over time in secukinumab-treated patients. M month, PASI Psoriasis Area and Severity Index

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Regional PASI Scores

Disease extent was more pronounced in the upper and lower limbs than in the head/neck and trunk as evidenced by higher PASI regional scores and a larger affected BSA at baseline. A faster reduction in disease activity was observed in the head/neck and trunk, while a relatively slower reduction in disease activity was seen in the limbs, as evidenced by the affected BSA, especially in the lower limbs, at 18, 24, and 36 months (Fig. 5). All body regions demonstrated an improvement in the PASI regional score as early as 3 months, which was sustained up to 18 and 36 months (Fig. 5). The improvement in the PASI regional score was consistent across the erythema, thickening, and scaling subscales. The proportion of patients with very severe erythema, thickening, and scaling reached 0% at 36 months, except for scaling in the lower limbs, which was 1.4% (Table 3). The proportion of patients with severity rated as “none” was consistently higher at 36 months than at baseline for all body regions (Table 3).

Fig. 5
figure 5

PASI regional score and anatomical area (%) affected by psoriasis over the study period. PASI Psoriasis Area and Severity Index

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Table 3 Subcomponents of erythema, thickening, and scaling by body region during the study period
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Total IGA Scores

A higher proportion of patients achieved clear/almost clear skin at 3 months (66.6%; N = 734), which was sustained at 18 months (65.4%; N = 329), 24 months (66.0%; N = 235), and 36 months (61.4%; N = 75) than at baseline (1.8%; N = 841). Hence, the proportion of patients reporting clear/almost clear skin increased at 3 months and was sustained up to 36 months (Fig. 6).

Fig. 6
figure 6

Proportion of patients who achieved clear/almost clear skin from baseline to up to month 36 after secukinumab treatment initiation as assessed using IGA. IGA Investigator’s Global Assessment, M month, N number of patients

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Psoriasis Symptom Diary Scores

Patient-reported mean scores for the Psoriasis Symptom Diary components for disease severity showed an early reduction from baseline scores, as early as at 3 months, in noticeable skin color, severity of scaling, pain, cracking, burning, stinging, and itching with secukinumab treatment (Fig. 7a), which were sustained up to 36 months (Fig. 7a). A similar trend in the Psoriasis Symptom Diary components for disease burden were also observed; an early reduction, as early as 3 months, from baseline scores, which was sustained up to 36 months (Fig. 7b).

Fig. 7
figure 7

a Disease severity in secukinumab-treated patients based on Psoriasis Symptom Diary. b Impact of disease burden on secukinumab-treated patients based on Psoriasis Symptom Diary. M month

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Long-Term Safety of Secukinumab

Of the 848 patients exposed to secukinumab, 605 (71.3%) reported an AE. Infections and infestations (34.8%) were the most commonly affected system organ class AEs, followed by musculoskeletal and connective tissue disorders (15.1%), general disorders and administration-site conditions (12.9%), and gastrointestinal disorders (12.1%; Table 4). Twelve (1.4%) patients had injection site reaction-related AEs. AEs leading to treatment discontinuation occurred in 120 (14.2%) patients. SAEs were reported in 67 (7.9%) patients, of which 48 (5.7%) patients had SAEs that led to hospitalization or prolonged hospitalization and 9 (1.1%) patients discontinued treatment due to SAEs. Deaths were reported in four patients (bone marrow cancer [n = 1], cardiac arrest [n = 1], subarachnoid hemorrhage [n = 1], and mesenteric ischemia [n = 1]), which were judged not being related to study treatment by the investigator. No new safety signals were reported during the 36-month observation period.

Table 4 Overall safety profile (up to month 36)
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Discussion

Secukinumab has shown consistent efficacy and safety in clinical trials and real-world studies [9, 14, 15]. Here, we have reported its effectiveness as assessed objectively by a treating physician with the aid of routinely used psoriasis assessment tools as well as subjectively through PROs in patients with moderate-to-severe plaque psoriasis.

In this PURE registry analysis, patients treated with secukinumab experienced early benefits, as early as 3 months, which were sustained up to 36 months. These trends were observed for both total and regional PASI scores. The mean PASI regional scores showed an early improvement at 3 months from baseline across the body regions following secukinumab treatment that was sustained up to 36 months. A similar trend in early and sustained benefits was observed even when the total PASI scores were qualitatively categorized into scores for erythema, thickening, and scaling, confirming the effectiveness of secukinumab in reducing the overall disease severity as well as disease severity across body regions and component symptoms.

The severity and incidence of psoriasis across body regions have a profound negative impact on patients. Facial and scalp psoriasis is known to have a greater impact on patient’s HRQoL because of their high visibility [20, 21]. The response to psoriasis treatment varies according to its incidence in different body regions [20, 22]. In this PURE registry analysis, a rapid reduction in disease activity was seen in the head/neck and trunk, unlike in the limbs, which were more affected at baseline and needed a relatively longer time for reduction in disease activity. These findings are consistent with the post hoc results from the pooled analysis of two phase 3 clinical trials (CLEAR and CLARITY), where the time to achieve complete skin clearance was shorter for the head/neck (mean PASI score at week 52: 1.0; week 16: 1.0; baseline: 17.1) and trunk (mean PASI score at week 52: 0.8; week 16: 0.9; baseline: 19.5) than for the upper limbs (mean PASI score at week 52: 1.6; week 16: 1.4; baseline: 19.9) and lower limbs (mean PASI score at week 52: 2.0; week 16: 2.0; baseline: 24.0), indicating that the limbs were the most difficult-to-treat regions [23]. This trend of faster reduction in disease activity for the head/neck and trunk versus limbs is also observed with other IL-17A inhibitors and tumor necrosis factor-alpha inhibitors [5, 24].

In this PURE registry analysis, the benefits across body regions were also reflected by the reduced disease severity across all PASI components. The early decrease in PASI total and component scores was supported by a higher proportion of patients achieving clear or almost clear skin, as assessed using the IGA, from baseline to 3 months. Hence, across different measures of physician-reported scores, secukinumab treatment showed a reduction in disease severity.

There is limited evidence that complements the clinical observations with PROs in patients with moderate-to-severe plaque psoriasis. In this analysis, patient perspectives based on their responses to key questions related to the noticeable color of skin, cracking, and scaling (components of the Psoriasis Symptom Diary) were descriptively correlated with erythema, thickening, and scaling (components of PASI, physicians’ perspectives) respectively. A reduced negative impact of moderate-to-severe psoriasis symptoms was observed on patient’s HRQoL, as reflected by the scores obtained from the Psoriasis Symptom Diary questionnaire. This study provides a qualitative demonstration of the trends in disease severity with secukinumab treatment, which are reflected in patient responses and independently provides complementary insights using physician- and patient-reported outcomes. In the previously published reports, secukinumab-treated patients from two pivotal phase 3 clinical trials (ERASURE and FIXTURE), who had completed the Psoriasis Symptom Diary at baseline and week 12, reported rapid improvement in three key patient-reported symptoms [25, 26]. The long-term safety profile of secukinumab as observed in this analysis was consistent with its established safety profile; no new or unexpected signals were reported.

This PURE registry analysis provides insights into the real-world effectiveness of secukinumab, from both physician and patient perspectives; however, as with other observational studies, there are certain limitations. Data must be interpreted with caution, as the analysis was descriptive in nature and the number of patients who reached the 36-month follow-up visit was small. It is noteworthy that the number of patients at any specific time point represents those who reached a milestone during their follow-up and does not represent a linear loss to follow-up.

Conclusions

The 36-month results from the PURE registry showed an early and sustained improvement in disease severity following secukinumab treatment. The effectiveness trend was observed in all body regions, albeit with important differences in the pattern of effectiveness in the lower limbs. Patient perspectives as observed in the outcomes from Psoriasis Symptom Diary demonstrated a reduced impact of disease severity and improved HRQoL, which was consistent with physician perspectives in patients with moderate-to-severe plaque psoriasis in Canada and Latin America.