Secukinumab Therapy In Psoriasis
Overview
Psoriasis is a chronic skin condition characterized by immune-mediated inflammation, significantly affecting patients’ quality of life. Secukinumab, an interleukin 17A inhibitor, has been employed as a systemic treatment for psoriasis. However, its long-term retention rates in a real-world setting in Japan have not been comprehensively studied. In this multicenter, noninterventional retrospective chart review, the study aimed to assess the retention rate of secukinumab and its effectiveness in Japanese psoriasis patients over a period of up to 5 years.
Data from patients who initiated secukinumab treatment after December 26, 2014, were extracted from medical records across seven certified biologics-use sites endorsed by the Japanese Dermatological Association. Patient characteristics, secukinumab retention, factors influencing its retention, reasons for discontinuation, and effectiveness data were gathered. The primary endpoint was the secukinumab retention rate at the 52-week mark.
The analysis encompassed a total of 123 patients. By week 52, 27 patients had discontinued secukinumab, resulting in a retention rate of 78.0% (95% confidence interval: 69.6–84.4). For patients with available Psoriasis Area and Severity Index (PASI) scores, the mean PASI scores at baseline and week 52 were 9.21 ± 7.37 and 1.4 ± 2.6, respectively.
Throughout the study’s duration, the most common reason for discontinuation was an “insufficient response.” Notably, a “history of biologics use” was identified as a significant factor associated with secukinumab discontinuation (hazard ratio: 1.72; p = 0.018).
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This study provides valuable insights into the real-world retention rates and effectiveness of secukinumab in the treatment of psoriasis in Japan, offering clinical guidance for the management of this condition over a 5-year period.
Introduction
Psoriasis is a chronic inflammatory skin disease with the potential to affect both the skin and joints, characterized by abnormal epidermal growth and dysregulated keratinocyte proliferation. Increasingly, psoriasis is recognized as a systemic ailment with skin manifestations. Its global distribution reveals varying prevalence, being highest in Australasia (1.58%) and western Europe (1.52%). In Japan, the overall prevalence is lower at 0.34%, but the condition can be socially stigmatizing and profoundly impact patients’ quality of life.
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Various biologics that target factors such as tumor necrosis factor α, interleukin (IL) 12/23p40, IL-17, or IL-23p19 have been used as systemic treatments for psoriasis. Secukinumab, a human monoclonal IgG1/kappa antibody, is the first approved IL-17A inhibitor with proven efficacy in moderate to severe plaque psoriasis, active psoriatic arthritis (PsA), and generalized pustular psoriasis across adult and pediatric populations. It has also shown promise in treating rheumatic conditions like ankylosing spondylitis, nonradiographic axial spondyloarthritis, and enthesitis-related arthritis.
Japan led the way by approving secukinumab for psoriasis vulgaris and PsA treatment in December 2014. Secukinumab has been prominently featured in real-world usage, contributing to 32.6% of IL-17 inhibitor utilization in patients with psoriasis vulgaris undergoing systemic therapy in the Western Japan Psoriasis Registry.
Although secukinumab’s efficacy in treating psoriasis has been demonstrated over several years in various populations, real-world studies on its drug retention have shown variable outcomes, with some reporting lower retention rates than those observed in clinical trials. Many prior Japanese studies on secukinumab drug retention were single-center, warranting larger-scale, multicenter investigations to better understand the factors influencing secukinumab drug retention and its benefits for different patient groups. In this context, the RAILWAY study was conducted to assess secukinumab’s retention rate and effectiveness in treating psoriasis among Japanese patients in a real-world setting.
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Methods
RAILWAY, a multicenter, noninterventional retrospective chart review study, was conducted in Japan to assess patients with psoriasis who had undergone secukinumab treatment at participating medical institutions. Data were extracted from medical records spanning from November 2, 2020, to September 21, 2021. All seven of the chosen institutions were certified by the Japanese Dermatological Association to administer biologic treatments for skin diseases, including psoriasis. These institutions were selected based on their ability to facilitate the necessary data collection and their willingness to align with the study’s objectives, primarily focusing on evaluating secukinumab retention rates and the factors influencing it.
Participants in the study included patients aged 20 years and older who had been diagnosed with psoriasis vulgaris, with or without Psoriatic Arthritis (PsA), and had received or were receiving secukinumab treatment as prescribed in Japan’s package insert. To prevent selection bias, recruitment from a single institution was limited to no more than 30% of the total patients recruited, and patients who had initiated secukinumab treatment in each institution were included regardless of their actual treatment duration. Informed consent, obtained either in written or oral form, was recorded in the patients’ medical records prior to data collection.
Data collection focused on patients who had commenced secukinumab treatment at the participating institutions after December 26, 2014 (the date of secukinumab’s regulatory approval by the Ministry of Health, Labour and Welfare). Additionally, the index date (the first day of secukinumab treatment) was required to be more than 52 weeks before the date of informed consent collection. Patients with fewer than two follow-up visits at the participating centers after initiating secukinumab were excluded from the study.
The study received approval from institutional review boards and/or independent ethics committees before data collection.
Study assessments and variables encompassed the primary endpoint, which was the secukinumab retention rate at week 52 for patients with psoriasis, with or without PsA. Secondary endpoints included secukinumab retention rates at various time points up to year 5, factors influencing secukinumab retention rates, and the patients’ response to secukinumab treatment.
Baseline characteristics collected for analysis comprised patient demographics, medical history related to psoriasis, prior psoriasis treatments, existing comorbidities, C-reactive protein levels on the index date, Psoriasis Area and Severity Index (PASI), and Dermatology Life Quality Index. Furthermore, the study documented the initial and final dates of secukinumab treatment and the reasons for discontinuation, with discontinuation date defined as the day when the decision to discontinue secukinumab treatment was made, as per individual patient medical records.
Statistical Analysis
In the study, all efficacy endpoints were presented using descriptive statistics. To determine the retention rate, the Kaplan-Meier method was employed, and 95% confidence intervals (CIs) were calculated. No imputation was performed for missing data; they were treated as missing values as per standard protocol. Additionally, a post hoc analysis was conducted to provide descriptive statistics summarizing the characteristics of patients who continued secukinumab treatment at various time points during the study, offering further insights into the patient population under consideration.
Results
In this study, a total of 125 patients were initially enrolled, but two of them had previously participated in a postmarketing clinical study and were subsequently excluded. Among the remaining 123 patients, the study captured a diversity of patients who initiated secukinumab treatment in various years, with 54, 47, 14, and 3 patients commencing in 2015, 2016, 2017, 2018, and 2019, respectively.
Key baseline characteristics of these 123 patients were summarized, including their age at secukinumab initiation, gender distribution, body mass index (BMI), duration of psoriasis, and the presence of concomitant Psoriatic Arthritis (PsA). The majority of patients were men (67.5%), and their mean age at secukinumab initiation was 54.9 ± 13.9 years. The average BMI, as available for 54 patients, was 24.55 ± 4.56 kg/m2. The mean duration of psoriasis was 12.26 ± 11.33 years, and 25.2% of the patients had concomitant PsA. The mean Psoriasis Area and Severity Index (PASI) score at the index date was 9.21 ± 7.37. Over half of the patients (52.8%) had previously received at least one biological treatment, with infliximab being the most commonly used biologic.
The primary outcome of the study was the secukinumab retention rate. The median duration of treatment with secukinumab was 1021.0 days (145 weeks) in the overall patient population. By week 52, 27 out of 123 patients had discontinued secukinumab, resulting in a retention rate of 78.0% at week 52. By year 5, a total of 78 out of 123 patients had discontinued secukinumab, with a median duration of treatment of 1774.0 days (253 weeks) in patients who continued and 603.0 days (86 weeks) in those who discontinued.
The study tracked secukinumab retention rates at various time points, including week 16, week 24, and years 2, 3, 4, and 5. These retention rates were 95.1%, 89.4%, 63.2%, 47.2%, 40.2%, and 33.9%, respectively, demonstrating a decrease in retention over time.
The primary reasons for secukinumab discontinuation were explored. “Insufficient response” was the most common cause, followed by “others” and “adverse events.” The median time to discontinuation due to insufficient response was 585.5 days. A subset of patients discontinued secukinumab at their own discretion or due to an improvement in symptoms or financial considerations. Adverse events accounted for a portion of discontinuations, with some of these events potentially related to secukinumab.
The study also examined factors influencing secukinumab retention. “History of biologics use” and the concomitant use of topical vitamin D3 analogs were identified as factors associated with secukinumab retention. Subgroup analyses revealed that patients with prior biologic treatment experience had lower retention rates compared to biologic-naive/unknown patients.
Additionally, patient characteristics were assessed to identify factors related to long-term secukinumab retention. Characteristics such as concomitant PsA, body mass index (BMI), body weight, smoking status, and concomitant systemic treatment were analyzed.
Effectiveness was assessed by examining the change in PASI scores over time. PASI scores showed an early decline and maintenance of low scores, with over 80% of patients achieving PASI scores ≤3 from week 24 to year 5. A subset of patients even achieved PASI 0 at different time points. The study also compared PASI scores at baseline, week 16, and at the time of secukinumab discontinuation, revealing shifts in PASI score distribution during the treatment course.
This study comprehensively evaluated secukinumab retention rates, factors influencing retention, reasons for discontinuation, and effectiveness in a cohort of patients with psoriasis, shedding light on various aspects of secukinumab treatment in a real-world setting.
Conclusion
The RAILWAY study is a notable multicenter investigation into the real-world drug retention rate of secukinumab in Japan, offering insights over a period of up to 5 years. Patient characteristics in this study were consistent with other published cohorts in Japan, as well as nationwide and regional surveys. The 52-week retention rate in RAILWAY, at 78.0%, aligned with high-end results from Japan and was consistent with a meta-analysis of 16 studies conducted by Augustin et al.
Notably, limited data exists on real-world 2-year or longer retention of secukinumab. Previous studies in Japan reported a 2-year retention rate of 56.6% and a 3-year rate of 25.2%. European studies showed a 2-year survival rate of 74.3% in Spain and a 5-year rate of 69.8% in Greece. RAILWAY contributes valuable information by providing insights into secukinumab retention for up to 5 years, expanding our understanding of long-term drug retention.
However, it’s essential to recognize that drug retention is influenced by various factors and is not a standalone indicator of drug efficacy or safety. These factors include the availability of multiple biologic treatment options that allow tailored treatment choices based on individual patient characteristics. Intriguingly, some patients in the study discontinued secukinumab despite positive efficacy outcomes, while others did so due to insufficient response despite low PASI scores.
Several factors affecting secukinumab retention were identified in the study, including a history of biologics use and the concomitant use of vitamin D3 analog alone and/or a combination product of vitamin D3 and steroids at the start of secukinumab treatment. However, the association between concomitant topical vitamin D3 therapy and long-term drug retention requires further investigation.
Additionally, factors such as BMI, body weight, early treatment response (PASI90), the presence of Psoriatic Arthritis (PsA), smoking history, and concomitant systemic treatment may influence secukinumab retention at various time points. These findings underscore the complexity of drug retention and the importance of examining multiple factors in understanding the real-world use of secukinumab in Japan.
In conclusion, the RAILWAY study contributes valuable insights into the long-term use of secukinumab in a real-world setting in Japan, highlighting the interplay of multiple factors that impact drug retention. Further research is needed to validate and expand upon these findings, providing a more comprehensive understanding of the factors influencing the treatment course.
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