Retention, Effectiveness, and Safety of Secukinumab in Plaque Psoriasis: 5-Year Results from SERENA

Abstract

Introduction

Secukinumab has demonstrated sustained efficacy and a favorable safety profile in clinical trials, providing relief from psoriatic symptoms.

Objective

To assess the long-term, real-world retention, effectiveness, and safety of secukinumab in routine clinical practice for the treatment of moderate to severe plaque psoriasis (PsO).

Methods

SERENA (CAIN457A3403) is a longitudinal, observational study conducted at 438 sites and 19 countries for up to 5 years in adult patients with moderate to severe PsO, psoriatic arthritis, and ankylosing spondylitis. Patients received secukinumab treatment for ≥ 16 weeks before enrollment. This manuscript presents the 5-year data from the SERENA study in patients with moderate to severe PsO.

Results

Overall, 1740 patients (67.5% male), with a mean age of 48.3 years and mean body mass index of 28.8 kg/m², were included in the analysis. The estimated secukinumab retention rates were 88.5%, 76.3%, 68.6%, 63.1%, and 58.5% at years 1, 2, 3, 4, and 5, respectively. For the 913 patients who discontinued the study, the most common reasons included lack of efficacy (25.4%), patient decision (7.6%), physician decision (5.5%), and loss to follow-up (4.8%). The mean ± standard deviation (SD) absolute Psoriasis Area and Severity Index (PASI) score was 21.1 ± 13.0 at treatment initiation (n = 1545). At enrollment, the mean ± SD PASI score reduced to 2.6 ± 4.2 and remained low at year 1 (2.3 ± 4.3) through year 5 (1.4 ± 2.8). A higher proportion of patients who were biologic naïve and those with a shorter disease duration achieved PASI90 and PASI100 responses and demonstrated higher retention rates than those in patients previously treated with biologics and those with a longer disease duration. The safety profile was consistent with known data, with no new safety signals identified.

Conclusions

Secukinumab showed high treatment retention, sustained effectiveness, and a consistent safety profile up to 5 years of follow-up in the real-world population of patients with PsO observed in SERENA.

Graphical abstract available for this article.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at 10.1007/s13555-026-01722-0.

Plain Language Summary

Plaque psoriasis is a skin condition that causes red, scaly patches and can greatly affect a person’s quality of life. Secukinumab is a medicine specifically designed to block interleukin-17A, a protein found in high amounts in people with plaque psoriasis. Studies have shown that secukinumab works well and is generally safe, but it is important to understand patients’ experiences with secukinumab in everyday life over time. The SERENA study followed 1740 adults with moderate to severe plaque psoriasis across 19 countries for up to 5 years. All participants had been taking secukinumab for at least 16 weeks before joining the study. This study assessed the number of people who continued using secukinumab over time (retention), its long-term effectiveness in controlling psoriasis symptoms, and its safety. The results showed that almost 60% of people were still using secukinumab after 5 years. Most people experienced improvement in their skin symptoms, with many achieving clear or almost clear skin that lasted throughout the study. People who started secukinumab earlier in their disease, or who had not used similar medicines before, tended to do even better. Only a small number of people developed psoriatic arthritis, a joint condition that can occur in people with psoriasis. Given the descriptive nature of this observational study, these findings should be interpreted carefully. No new safety risks were found. In summary, secukinumab helped people manage plaque psoriasis effectively and safely over time and may also reduce the risk of development of psoriatic arthritis.

Supplementary Information

The online version contains supplementary material available at 10.1007/s13555-026-01722-0.

Key Summary Points

Why carry out this study?

The SERENA study was undertaken to address the need for long-term real-world data on the use of secukinumab in patients with moderate to severe plaque psoriasis. It aimed to evaluate the retention, effectiveness, safety, and treatment patterns of secukinumab over a 5-year period in a real-world setting.

What was learned from the study?

This study provides robust real-world evidence that secukinumab demonstrates high treatment retention, sustained effectiveness, and a consistent safety profile over a 5-year period. It highlights the positive impact of secukinumab on patient-reported outcomes, showing significant improvements in skin clearance and quality of life.

The findings emphasize the importance of early intervention with secukinumab to achieve better long-term outcomes in the management of plaque psoriasis. The high retention rates and sustained effectiveness suggest that secukinumab can be a valuable long-term treatment option in managing moderate to severe plaque psoriasis, thereby improving both disease control and patients’ quality of life.

Digital Features

This article is published with digital features, including an infographic, to facilitate understanding of the article. To view digital features for this article go to 10.6084/m9.figshare.31457647.

Introduction

Psoriasis is a chronic immune-mediated inflammatory disease, with plaque psoriasis (PsO) being the most common form [1, 2]. PsO typically presents as erythematous, scaly plaques on elbows and knees but can also affect the palms, soles, nails, scalp, and genitals [3–7]. Symptoms such as pruritus, pain, and discomfort significantly impact patients’ physical and psychological well-being, impairing daily functioning, self-esteem, and social interactions [8–13]. PsO is also associated with systemic inflammation, increasing the risk of comorbidities (psoriatic arthritis [PsA], metabolic syndrome, and cardiovascular disease) [14–18], which collectively impact health-related quality of life (HRQoL) [7, 19, 20].

Secukinumab, a fully human monoclonal antibody targeting IL-17A, has demonstrated rapid, sustained efficacy, and a favorable safety profile in clinical trials, providing relief from psoriatic symptoms and improving HRQoL [21–30]. While biologics improve PsO outcomes, maintaining a long-term treatment response is essential due to the chronic nature of the condition. Most evidence on treatment durability comes from clinical trials, which may not represent real-world experiences [23, 31], making real-world evidence essential for evaluating treatment retention, long-term safety, and the effects of treatment interruptions on disease control and quality of life (QoL) [32, 33].

The SERENA study was designed to assess long-term real-world data on secukinumab in patients with moderate to severe PsO [34, 35]. This observational study, spanning Europe and Israel, evaluated retention rates, effectiveness, safety, and treatment patterns of secukinumab over 5 years [35]. The interim analysis of the SERENA study was previously published [36]. We herein present the 5-year real-world outcomes of secukinumab in patients with moderate to severe PsO.

Study Objective

The primary objective was to assess the long-term retention of secukinumab in routine clinical practice for the treatment of moderate to severe PsO. Additional objectives were to describe the long-term effectiveness and safety of secukinumab.

Methods

Study Design

The SERENA study (CAIN457A3403) is a longitudinal, non-interventional study with prospective and retrospective collection of primary data on the retention, safety, and effectiveness of secukinumab in patients with moderate to severe chronic PsO, active PsA, or active ankylosing spondylitis [35].

The study was conducted at 438 sites across Europe (Austria, Belgium, Bulgaria, Croatia, Czech Republic, Estonia, France, Germany, Greece, Hungary, Ireland, Italy, the Netherlands, Portugal, Russia, Slovenia, Switzerland, and the UK) and Israel, enrolling approximately 2700 patients. No patients with PsO were enrolled from France or the UK. Patients participated in the study for up to 5 years (60 months), exiting early if they discontinued secukinumab or for other reasons while continuing secukinumab. Visits were documented every 6 months after enrollment. The study ended when all patients completed ≥ 2 years of follow-up, unless they chose to exit the study, or after the 5-year visit was documented for approximately 1000 patients (including a representative number of patients for all three indications), whichever occurred later.

Study Population

The full inclusion and exclusion criteria have been reported previously [35]. Briefly, adult patients with a diagnosis (assessed by the treating physician) of active moderate to severe PsO receiving secukinumab according to the approved product label were included in the study. All patients received ≥ 16 weeks of secukinumab treatment before enrollment into the study.

Outcomes and Assessments

This analysis presents the final data for patients with PsO enrolled between October 2016 and October 2018, observed for up to 5 years. All previous biologic treatments taken for PsO were recorded without a time limit, whereas other prior PsO treatments were documented only if used within 6 months before enrollment.

Secukinumab retention rates were measured from study enrollment, defined as the percentage of patients not discontinuing treatment. Data collection occurred prospectively every 6 months for up to 5 years. Retention rates were also analyzed by disease duration at first visit (< 1, ≥ 1–< 2, ≥ 2–< 5, ≥ 5–< 15, ≥ 15 years) over the 5-year period.

Effectiveness assessments included the Psoriasis Area and Severity Index (PASI), which evaluates the severity of lesions and the area affected (score: 0–72); Physician’s Global Assessment (PGA) score for PsO; and QoL as assessed by the Dermatology Life Quality Index (DLQI; score: 0–30). PASI response was also assessed by disease duration through 5 years. Data were collected retrospectively from the start of secukinumab treatment and were not available for all patients or for all effectiveness parameters. Incidence rates of developing PsA during the 5-year follow-up were also assessed on the basis of PsA reported by the investigators.

Safety data were collected from the start of secukinumab treatment, from 1842 patients observed for up to 5 years. The safety analysis included all patients who received ≥ 1 secukinumab dose after providing informed consent. Safety assessment included treatment-emergent adverse events (AEs), serious AEs (SAEs), and AEs of special interest: major adverse cardiovascular events (MACE) defined using MedDRA v26.1 (identified per Novartis MedDRA query [NMQ] term “myocardial infarction, stroke, and CV death”), Candida infection (any AE within Candida infection MedDRA high-level term [HLT]), inflammatory bowel disease (IBD; identified per NMQ for IBD), malignancy (standardized MedDRA query [SMQ] term “malignancies and unspecified tumor”), and injection-site reactions (MedDRA HLT). Exposure-adjusted incidence rates (EAIR) were calculated as the number of patients with ≥ 1 AE per 100 patient-years at risk. For patients experiencing an event, time at risk was calculated up to the first event; for others, it was measured to the end of participation.

Treatment Interruption

Treatment interruption was analyzed for patients who had a secukinumab treatment interruption of over 2 months (3 months since last injection); shorter gaps were excluded. For patients with > 1 interruptions, only the longest was analyzed. PASI and PGA scores were assessed before, during, and after the interruption when available. Data collection took place ≥ 1 month after restarting treatment, with the closest available assessment to 6 months post-interruption used.

Statistical Analysis

Retention rates were derived from Kaplan–Meier estimates. Efficacy analyses were conducted using descriptive statistics based on observed data, and no imputation methods were applied for missing data. Two-sided 95% confidence intervals (CIs) were provided for all binary response rates. For safety, percentages of patients with AEs and EAIRs in terms of per 100 patient-years were presented over the 5-year follow-up period.

All patients provided written informed consent before enrollment. The study protocol was approved by the institutional review board of each participating center according to local regulations. The trial is conducted in accordance with the Guidelines for Good Pharmacoepidemiology Practices (GPP) of the International Society for Pharmacoepidemiology (ISPE; ISPE 2008), the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, the Declaration of Helsinki, and local regulations for each country.

Results

Patient Disposition and Characteristics at the Time of Enrollment

Due to unfulfilled inclusion/exclusion criteria, 102 of 1842 patients in the safety analysis were excluded from the retention and effectiveness analyses. Therefore, 1740 patients were included in the effectiveness analysis; 67.5% were male, with a mean age of 48.3 years and mean body mass index of 28.8 kg/m² (Table 1). The mean ± standard deviation (SD) time since PsO diagnosis was 17.3 ± 13.2 years, with 48% having the disease for ≥ 15 years. Overall, 21.8% had a previous PsA diagnosis at time of first secukinumab treatment. The mean time to PsA diagnosis from first PsO diagnosis was 14.8 ± 11.8 years. Patients received secukinumab for a mean duration of 1.05 ± 0.6 years before enrollment.

Table 1.

Patient characteristics and demographics at the time of enrollment

Demographic/characteristic	Psoriasis (N = 1740)
Age (years), mean ± SD	48.3 ± 13.5
Gender, male, n (%)	1175 (67.5)
Race, White, n (%)	1639 (94.2)
Weight (kg), mean ± SD (N = 1353)	87.4 ± 20.4
BMI (kg/m2), mean ± SD (N = 1338)	28.83 ± 6.07
Overweight, BMI ≥ 25–< 30 (kg/m2), n (%)	502 (28.9)
Obesity, BMI ≥ 30 (kg/m2), n (%)	475 (27.3)
Smoking status, n (%)
Current	539 (31.0)
Former	238 (13.7)
Never	689 (39.6)
Time since first diagnosis of plaque psoriasis (years), mean ± SD	17.31 ± 13.23
Duration with any secukinumab treatment prior to enrollment (years), mean ± SD	1.05 ± 0.64
Concomitant PsA at the time of first secukinumab treatment, n (%) (N = 1733)	377 (21.8)
Total PASI score, mean ± SD
At the first secukinumab treatment	21.06 ± 13.02
At the time of enrollment (n = 1605)	2.57 ± 4.16
Total PGA score at the time of enrollment (n = 731), mean ± SD	1.08 ± 1.25
Clinical characteristics at the time of diagnosis
Medical history term by severity of psoriasis diagnosis
Severe, n (%)	856 (49.2)
Mild, n (%)	856 (49.2)

N refers to the number of patients in the population, while n refers to the number of patients with non-missing data. BMI body mass index, PASI Psoriasis Area and Severity Index, PGA Physician’s Global Assessment, PsA psoriatic arthritis, SD standard deviation

Prior to secukinumab treatment, 65.2% were biologic naïve. Among those previously treated with biologics, about half received one biologic, while the remainder ≥ 2 (Table 2). During secukinumab treatment, most received no concomitant treatment (51.6%) or only concomitant topical agents (34.9%) (Table S1).

Table 2.

Percentage of patients with psoriasis by treatment type prior to secukinumab initiation

Psoriasis treatments taken prior to secukinumab initiation,a n (%)	Psoriasis (N = 1740)
No documented psoriasis treatment	703 (40.4)
Topical treatments	293 (16.8)
Conventional systemic treatments (and phototherapy)	547 (31.4)
Biologic treatments	606 (34.8)
Biologic treatments taken prior to secukinumab initiation, n (%)
Adalimumab	350 (20.1)
Etanercept	250 (14.4)
Infliximab	132 (7.6)
Ustekinumab	258 (14.8)
Other biologic treatment	45 (2.6)
Biologic treatments taken prior to secukinumab initiation, n (%)
Biologic naïve	1134 (65.2)
Previous treatment with a biologic	606 (34.8)
1 biologic	298 (17.1)
2 biologics	150 (8.6)
≥ 3 biologics	158 (9.1)

N refers to the number of patients in the population, while n refers to the number of patients with non-missing data

^aPatients may be counted in more than one prior treatment category

Secukinumab Retention

The Kaplan–Meier-estimated retention rates at years 1, 2, 3, 4, and 5 were 88.5%, 76.3%, 68.6%, 63.1%, and 58.5%, respectively (Fig. 1a). For patients who were biologic naïve, the rates at years 1 and 5 were 91.4% and 65.6%, respectively, and for patients pretreated with biologics, the rates were 83.0% and 45.2%, respectively (Fig. 1b).

Fig. 1.

Time to secukinumab treatment discontinuation for patients with psoriasis (a) and for those with psoriasis stratified by biologic pretreated versus biologic naïve (b) (survival probability). Since enrollment in the study

Patients with a shorter disease duration (< 5 years) had higher retention rates than those with a longer disease duration (≥ 5 years) throughout the study period (Fig. S1). The year-5 retention rate for patients with a disease duration of < 1 year was higher (81%, N = 42) than that in the ≥ 1–< 2 years subgroup (71.4%, N = 84) and in the ≥ 2–< 5-year subgroup (61.8%, N = 157).

Of the 913 patients who discontinued the study, the most common reasons were lack of efficacy (25.4%), patient decision (7.6%), physician decision (5.5%) and loss to follow-up (4.8%; Table 3). The proportion of patients who discontinued the study due to lack of efficacy was higher in the subgroup with a longer disease duration than in that with a shorter disease duration. The proportions of patients discontinuing the study due to lack of efficacy by disease durations of < 1, ≥ 1–< 2, ≥ 2–< 5, ≥ 5–< 15, and ≥ 15 years were 5.8%, 16.2%, 17.5%, 26.8%, and 28.4%, respectively.

Table 3.

Reasons for study discontinuation

Reasons for study discontinuation	Psoriasis (N = 1740)
Discontinued, n (%)	913 (52.5)
Lack of efficacy	442 (25.4)
Patient decision	132 (7.6)
Physician decision	95 (5.5)
Lost to follow-up	83 (4.8)
Adverse event	81 (4.7)
Administrative reason	41 (2.4)
Withdrawal of informed consent	20 (1.1)
Death	18 (1.0)
Due to COVID-19 outbreak-related (not an AE)	1 (0.1)

N refers to the total number of patients, while n refers to the number of patients with non-missing data. AE adverse event, COVID-19 coronavirus disease 2019,

Secukinumab Effectiveness

The mean ± SD absolute PASI score was 21.1 ± 13.0 at the start of treatment (n = 1545). At enrollment, the mean ± SD PASI score reduced to 2.6 ± 4.2 (n = 1605) and remained low through year 5 (1.4 ± 2.8; n = 623; Fig. 2). Mean PASI score decreased from first secukinumab dose to year 1 and remained low through year 5 across all subgroups by disease duration (eTable S2). The proportion of patients achieving a PASI scores of ≤ 3, ≤ 2, and ≤ 1 at year 5 was 88.6%, 79.6%, and 65.5%, respectively (Fig. 3).

Fig. 2.

Absolute PASI score at secukinumab treatment start and during the study. PASI scores based on observed data. Enrollment refers to the time point at which patients received secukinumab treatment for at least 16 weeks. Patients were treated with secukinumab for a mean ± SD duration of 1.05 ± 0.64 years prior to enrollment. n refers to the number of patients with evaluation (i.e., with non-missing data). PASI Psoriasis Area and Severity Index

Fig. 3.

Proportion of patients by PASI score categories after secukinumab treatment start and during the study. Percentages are based on the number of patients with observed data. Enrollment refers to the time point at which patients were treated with secukinumab for at least 16 weeks. N refers to the total number of patients. PASI Psoriasis Area and Severity Index

PASI90 responses following secukinumab treatment at years 1, 2, 3, 4, and 5 were 63.3%, 61.8%, 64.0%, 67.9%, and 67.3%, respectively. A higher proportion of patients also sustained a PASI100 response from year 1 to year 5 (Fig. 4). The proportion of patients achieving PASI90 and PASI100 was higher in patients who were biologic naïve versus those pretreated with biologics and in those with a shorter disease duration (eFig. S2). A higher proportion of patients with shorter disease duration (< 2 years) achieved PASI90 and PASI100 responses than those with longer disease duration (> 5 years) (eFig. S3). Furthermore, a higher proportion of patients in the subgroup with disease duration < 1 year achieved PASI90 and PASI100 response than those in the ≥ 1–< 2 years year subgroup at year 5.

Fig. 4.

Proportion of patients achieving PASI 90 and PASI 100 after start of secukinumab. Percentages are based on the number of patients with observed data. Patients were treated with secukinumab for a mean ± SD duration of 1.05 ± 0.64 years prior to enrollment. n refers to the number of patients with observed data. PASI Psoriasis Area and Severity Index

The proportion of patients achieving a PGA score of 0 or 1 (clear or almost clear skin) was 72.0% (526/731), 77.6% (577/744), 81.3% (491/604), 79.3% (382/482), 78.5% (354/451), and 84.1% (301/358) at enrollment (secukinumab treatment for ≥ 16 weeks), year 1, year 2, year 3, year 4, and year 5, respectively (Fig. 5a). The proportion of patients achieving a DLQI score of 0 or 1 (little to no impact on QoL) was 61.3% (924/1508), 63.9% (833/1303), 66.5% (675/1015), 70.7% (591/836), 71.7% (537/749), and 72.8% (446/613) at enrollment, year 1, year 2, year 3, year 4, and year 5, respectively (Fig. 5b).

Fig. 5.

Proportion of patients with responses of a PGA score of 0/1 (a) and a DLQI score of 0/1 (b) from enrollment through year 5. Percentages are based on the number of patients with observed data. Patients were treated with secukinumab for a mean ± SD duration of 1.05 ± 0.64 years prior to enrollment. Enrollment refers to the time point at which patients were treated with secukinumab for at least 16 weeks. n refers to the number of patients with observed data. DLQI Dermatology Life Quality Index, PGA Physician’s Global Assessment

PsA Development

The proportion of patients developing PsA after the first secukinumab treatment or during the study was 4.5%, with an EAIR of 1.0. After the first secukinumab treatment, the EAIR for developing PsA increased with increasing disease duration, with EAIR of 0.61, 0.63, 1.04, and 1.19 for disease durations of < 2, ≥ 2–< 5, ≥ 5–< 15, and ≥ 15 years, respectively. The proportion of patients developing PsA was lower in those with a shorter disease duration than in those with a longer disease duration (eTable S3).

Treatment Interruption

Overall, 189 patients with PsO experienced secukinumab treatment interruption lasting > 2 months (Table 4). The most common reasons were AEs (22.8%), patient decision (13.8%), coronavirus disease 2019 (COVID-19) outbreak-related reasons that were not an AE (9.5%), “other” (7.4%), and lack of patient adherence (6.9%). The median (quartile [Q] 1, Q3) duration of treatment interruption was 120.0 (83.0, 193.0) days.

Table 4.

Characterization of secukinumab treatment interruption including PASI score in relation to a treatment interruption

	Psoriasis (N = 1740)
Number of patients reporting a treatment interruption,a n (%)	189 (10.9)
Duration of treatment interruption (days), median (Q1, Q3)	120.0 (83.0, 193.0)
Treatment phase directly after treatment interruption, n (%)
Initiation phase/loading	58 (30.7)
Maintenance dosing/non-loading	131 (69.3)
Duration of treatment with secukinumab (days), median (Q1, Q3)
Before interruption	616.0 (226.0, 1163.0)
After interruption	654.0 (328.5, 1272.0)
Most common reasons for treatment interruption,b n (%)
Adverse events	43 (22.8)
Patient decision	26 (13.8)
COVID-19-outbreak-related (not an adverse event)	18 (9.5)
Other	14 (7.4)
Lack of patient’s adherence	13 (6.9)
Missing	66 (34.9)
PASI relative to treatment interruption, mean ± SD, n
Last assessment prior	8.74 ± 10.73, 143
First assessment during	2.03 ± 3.26, 18
Assessment closest to 6 months after	2.25 ± 2.63, 141
PGA score relative to treatment interruption, mean ± SD, n
Last assessment prior	1.39 ± 1.28, 54
First assessment during	2.17 ± 1.60, 6
Assessment closest to 6 months after	1.48 ± 1.33, 54

N refers to the number of patients in the study population, while n refers to the number of patients with non-missing data. AE adverse event, COVID-19 coronavirus disease 2019, PASI Psoriasis Area and Severity Index, PGA Physician’s Global Assessment, Q1–Q3 interquartile range, SD standard deviation

^aTreatment interruption was defined as lasting longer than 2 months (i.e., 3 months since the last injection of secukinumab); shorter treatment interruptions were not included. If a patient had more than one treatment interruption, then the interruption with the longest duration was included in the analysis

^bOccurring in more than 5% of the total reported treatment interruptions

The mean ± SD PASI score closest to 6 months after interruption was low in both patients who restarted with a loading phase (2.2 ± 1.9, n = 45) or with maintenance dosing (2.3 ± 2.9, n = 96). The median duration of secukinumab treatment before treatment interruption was 616.0 (226.0, 1163.0) days. After treatment interruption, the median duration of secukinumab treatment was 654.0 (328.5, 1272.0) days. Absolute mean ± SD PASI scores before, during, and 6 months after interruption were 8.7 ± 10.7 (n = 143), 2.03 ± 3.26 (n = 18), and 2.25 ± 2.63 (n = 141), respectively. Mean ± SD PGA scores before, during, and 6 months after interruption were 1.39 ± 1.28 (n = 54), 2.17 ± 1.60 (n = 6), and 1.48 ± 1.33 (n = 54), respectively.

Safety

The safety profile of secukinumab in the SERENA study, based on 5980.0 years of total secukinumab exposure, was consistent with the known safety profile of secukinumab, with no new safety signals reported (Table 5). Overall, 4208 AEs were reported in 1297 patients (70.4%), and 385 SAEs were reported in 239 patients (13.0%). SAEs with a fatal outcome were reported in 21 patients (1.1%), and none were considered related to secukinumab treatment. AEs led to secukinumab discontinuation in 541 patients (29.4%).

Table 5.

Adverse events observed during the total study (safety analysis set)

Treatment-emergent AEs	Psoriasis (N = 1842)
Total exposure time (years)	5980.0
Mean exposure time (years)	3.2
Number of AEs	4208
Number of patients with at least one AE, n (%)	1297 (70.4)
Number of patients with AEs leading to death,a n (%)	21 (1.1)
Number of SAEs	385
Number of patients with at least one SAE, n (%)	239 (13.0)
Discontinued study treatment due to AE, n (%)	541 (29.4)

	n (%)	EAIR
Most common AEs by system organ classb
Infections and infestations	601 (32.6)	12.88
Skin and subcutaneous tissue disorders	500 (27.1)	9.56
Musculoskeletal and connective tissue disorders	316 (17.2)	5.75
AEs of special interest
Malignancy (SMQ)	49 (2.7)	0.81
Basal-cell carcinoma (PT)	5 (0.3)	0.28
Malignant melanoma (PT)	4 (0.2)	0.07
Prostate cancer (PT)	3 (0.2)	0.05
Candida infections (HLT)	57 (3.1)	0.95
Oral candidiasis (PT)	28 (1.5)	0.46
Candida infection (PT)	21 (1.1)	0.34
Skin Candida (PT)	5 (0.3)	0.08
Vulvovaginal candidiasis (PT)	3 (0.2)	0.05
Major adverse cardiovascular events (NMQ)	24 (1.3)	0.39
Myocardial infarction (PT)	10 (0.5)	0.16
Cerebrovascular accident (PT)	5 (0.3)	0.08
Inflammatory bowel disease (NMQ)	5 (0.3)	0.08
Injection-site reaction (HLT)	11 (0.6)	0.18

N refers to the total number of patients, while n refers to the number of patients in the group with non-missing data. AE adverse event, EAIR exposure-adjusted incidence rates, HLT high-level term, NMQ Novartis MedDRA query, PT preferred term, SAE serious adverse event, SMQ standardized MedDRA query

^aCause of death was not considered to be related to secukinumab treatment; of the 21 patients, 2 discontinued the study due to adverse events (metastatic melanoma and pancreatic head carcinoma) that eventually led to death, and 1 patient did not fulfill the eligibility criteria or had protocol deviations and was therefore not included in the target population

^bIncidence rate > 2

Infections and infestations were the most commonly reported AEs by MedDRA system organ class (32.6% of patients; EAIR: 12.88), followed by skin and subcutaneous tissue disorders (27.1%; EAIR: 9.56). Candida infections were experienced by 3.1% of patients (EAIR: 0.95), of which the most commonly reported preferred terms were oral candidiasis (1.5%; EAIR: 0.46), Candida infection (1.1%; EAIR: 0.34), and skin Candida (0.3%; EAIR: 0.08). Overall, 2.7% of patients reported any malignancy (EAIR: 0.81), the most common of which was basal-cell carcinoma, experienced by 0.3% of patients (EAIR: 0.28). MACE was experienced by 1.3% of patients (EAIR: 0.39). The identified risks of IBD and injection-site reaction were reported in 0.3% (EAIR: 0.08) and 0.6% (EAIR: 0.18) of patients, respectively.

Discussion

SERENA is the first European observational study to collect long-term real-world data for secukinumab on retention, effectiveness, safety, and effects on QoL in patients with active moderate to severe PsO. In an interim analysis of the SERENA study, secukinumab treatment showed sustained effectiveness and a high treatment persistence up to 3 years of follow-up in real-world patients with moderate to severe PsO [36].

This final analysis of SERENA study demonstrated a high retention rate of secukinumab over 5 years, which is particularly important in the context of chronic diseases such as PsO, where long-term management is crucial for maintaining disease control. Furthermore, high retention rates can be linked to positive patient experiences, indicating both clinical effectiveness and satisfaction among patients and physicians.

Secukinumab demonstrated sustained effectiveness with a high proportion of patients maintaining PASI90 and PASI100 responses, and a significant proportion of patients achieving PASI scores of ≤ 3, ≤ 2, and ≤ 1 up to year 5. These results align with previous long-term extension trials, ERASURE/FIXTURE and SCULPTURE, which demonstrated that secukinumab provides sustained efficacy over 5 years of treatment in a randomized controlled trial (RCT) setting [23, 31].

Retention rates were higher in patients who were biologic naïve compared with those who had been pretreated with biologics, and in patients with a shorter disease duration. Furthermore, a higher proportion of patients who were biologic naïve and those with a shorter disease duration achieved PASI90 and PASI100 responses, indicating better outcomes with early treatment. Overall, these results suggest that initiating secukinumab treatment earlier in the course of the disease may have a more durable effect in terms of long-term adherence and improved outcomes. These data are in line with the STEPIn study, which showed that early intervention with secukinumab led to high and sustained skin clearance at 52 weeks in new-onset (disease duration of ≤ 1 year) moderate to severe PsO [37]. Molecular findings revealed that secukinumab normalized DNA methylation in lesional skin to non-lesional levels in new-onset PsO, but not in long-standing disease (≥ 5 years), where a “molecular scar” persisted, indicating that early intervention with secukinumab may prevent the development of an epigenetic scar [38].

Patients in the SERENA study reported significant improvements in patient-reported outcomes, with 84% achieving clear or almost clear skin and 73% reporting little to no impact of PsO on their QoL after 5 years. This is particularly important given the chronic and often debilitating nature of PsO, which can severely impact daily functioning and social interactions.

Only a small proportion of patients (4.5%) developed PsA after the first secukinumab treatment, with an EAIR of 1.00 per 100 patient-years, in the SERENA study. In a pooled analysis of three phase 3 trials (ERASURE, FIXTURE, SCULPTURE), only 2.1% of patients without PsA at baseline developed PsA over 5 years of continuous secukinumab treatment, translating to an incidence rate of 0.76 per 100 patient-years, which was approximately 72% lower than that reported in historical, biologic naïve controls [39]. Additionally, a retrospective cohort study found that patients with PsO treated with IL-17 inhibitors had a significantly lower risk of developing PsA over 5 years than those treated with IL-12/23 or TNF inhibitors, and a numerically lower risk than those on IL-23 inhibitors. Taken together, these findings suggest that secukinumab use may be associated with a reduced risk of PsA development in patients with PsO [40].

Patients had a mean exposure duration of 4.5 years from first secukinumab treatment. The safety profile of secukinumab during the SERENA study was consistent with the known safety profile [24, 30].

In the treatment interruption analysis, PASI score (8.74 ± 10.73) was unusually high at the last assessment prior to treatment interruption, considering the entry criteria of ≥ 16 weeks of secukinumab treatment before enrollment. This may be due to more severe disease prior to interruption in the subgroup of patients with available PASI assessments, or to a small number of patients with high PASI scores skewing the results. Furthermore, the most frequent reasons for treatment interruption include AEs, patient decision, and lack of patient adherence, which could also be associated with an increased PASI score. The mean PASI score at 6 months post-treatment interruption was low; however, it should be noted that interruption data during treatment was available only for a small number of patients.

Limitations

Given its observational design, the study did not include a control group, and all efficacy analyses were conducted using observed data. In a one-arm observational set-up, interpretation regarding the impact of secukinumab in comparison to possible background risks need to be done with caution. As the inclusion criterion required patients with ≥ 16 weeks of secukinumab treatment prior to study entry, patients who discontinued during the first 16 weeks of treatment did not enter the study. This may have introduced selection and survivor bias, potentially leading to an overestimation of the overall retention rate. However, this is inherent to the design of open-label, real-world studies. It is also noteworthy that the retention rates were calculated from the start of the study, without accounting for the prior exposure to secukinumab, which could have contributed to an underestimation of the overall retention rates. The high quality of data captured over a 5-year follow-up in a real-world setting provides essential insights into the retention, effectiveness, and safety of secukinumab in patients with PsO.

Conclusions

The SERENA study provides robust real-world evidence on the long-term use of secukinumab in patients with moderate to severe PsO. The findings highlight not only the sustained effectiveness, good safety profile, and positive impact of secukinumab on HRQoL but also suggests its association with reduced risk of PsA development. These results reinforce secukinumab’s role as a potential long‑term treatment option in PsO management and highlight the importance of early intervention to improve treatment outcomes in patients with PsO.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

All authors participated in the conceptualization, drafting and revising of the manuscript, and approval of the final version of the article.

Funding

This study and the Rapid Service fee for Dermatology and Therapy was sponsored and funded by Novartis Pharma AG, Basel, Switzerland.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Novartis is committed to sharing with qualified external researchers access to data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided are anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

Declarations

Conflict of Interest

Matthias Augustin has received consulting fees and/or speaker fees and/or institutional research support from the following pharmaceutical companies manufacturing drugs for psoriasis: AbbVie, Almirall, Amgen, Biogen, Boehringer, Bristol-Myers Squibb, Celgene, Celltrion, Centocor, Eli Lilly, Fresenius, GSK, Hexal, Janssen, Klinge, LEO Pharma, MC2, Medac, Merck, MSD, Mylan, Novartis, Pfizer, Sandoz, Sun Pharma, UCB, and Viatris. Paul-Gunther Sator has been an advisor and/or received speaker honoraria or travel expense reimbursements and/or received grants and/or participated in clinical trials for AbbVie, Actelion, Amgen, Almirall, Janssen, Novartis, LEO Pharma, Pfizer, MSD, Celgene, Maruho, ALK, Galderma Abbott, UCB, Gilead, and Eli-Lilly. Ralph von Kiedrowski declares that, through his own company CMS GmbH, he has received honoraria for lectures, consultancy work, and studies from AbbVie, Almirall, Biofrontera, Biogen, Celgene, Dr. Pfleger, Foamix, Janssen Cilag, LEO Pharma, Lilly, Medac, MSD, Novartis, Pfizer, Tigercat, and UCB. Dimitris Rigopoulos has received consultancy fees, payment for lectures and support for travel to scientific meetings from Celgene, Novartis, Janssen, and AbbVie. Marco Romanelli has participated in the advisory board of AbbVie, Eli Lilly, Novartis, and Urgo. Pierre-Dominique Ghislain has received speaker fees, participated in clinical trials and/or advisory boards for Pfizer, MSD, AbbVie, Janssen-Cilag, Merck-Serono, LEO Pharma, Novartis, UCB, Amgen, Eli Lilly, Galderma, BMS, Meda, Maruho, Flen, Menarini, Almirall, PellePharm, and Mylan. Tiago Torres has received speaker fees, participated in clinical trials and/or advisory boards for AbbVie, Almirall, Amgen, Arena Pharmaceuticals, BIOCAD, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Janssen, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Pfizer, Samsung-Bioepis, Sanofi-Genzyme, and Sandoz. Tiago Torres is an Editorial Board member of Dermatology and Therapy for Atopic Dermatitis. Tiago was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Dimitrios Ioannides has received speaker fees, participated in clinical trials and/or advisory boards for AbbVie, Eli Lilly, Genesis, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, and UCB. Cynthia Vizcaya, Andreas Clemens, and Weibin Bao are employees and shareholders of Novartis. Christelle C. Pieterse is an employee of Syneos Health, Amsterdam, the Netherlands, contracting for Novartis. Barbara Schulz is an associate at GKM Gesellschaft fuer Therapieforschung mbH, Lessingstrasse, München, Germany, which provides services to Novartis. Piotr Jagiello was employed by Novartis at the time of the study. Curdin Conrad served as scientific advisor and/or clinical study investigator and/or paid speaker for AbbVie, Actelion, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Galderma, Incyte, Janssen, LEO Pharma, Eli Lilly, MSD, Novartis, Pfizer, Samsung, and UCB.

Ethical Approval

All patients provided written informed consent before enrollment. The study protocol was approved by the institutional review board of each participating center according to local regulations. The trial is conducted in accordance with the Guidelines for Good Pharmacoepidemiology Practices (GPP) of the International Society for Pharmacoepidemiology (ISPE 2008), the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, the Declaration of Helsinki, and local regulations for each country.