Long-term persistence comparison between guselkumab and secukinumab for the treatment of psoriasis

Abstract

BACKGROUND

Psoriasis is a chronic immune-mediated inflammatory skin disease. Biologic therapies have revolutionized psoriasis management because of their high efficacy and favorable safety profiles. Several biologic agents are available for the treatment of moderate to severe psoriasis. Treatment persistence, defined as the duration from therapy initiation to discontinuation, is crucial for assessing therapeutic success in real-world clinical practice. This study aimed to compare the long-term treatment persistence of secukinumab and guselkumab in patients with moderate to severe psoriasis over a four-year follow-up period.

AIM

To compare the long-term treatment persistence of secukinumab and guselkumab in patients with moderate to severe psoriasis over a four-year follow-up period.

METHODS

We conducted a retrospective observational study involving adult patients with moderate to severe psoriasis who initiated treatment with secukinumab or guselkumab between January 1, 2015 and June 30, 2024. Demographic, clinical, and treatment-related data were collected from two hospitals. The Kaplan-Meier method was applied to estimate treatment persistence over a four-year follow-up period.

RESULTS

A total of 149 patients were analyzed: 87 initiated secukinumab and 62 initiated guselkumab. The persistence rate for guselkumab was higher at 12 months (98.2% vs 82.8%), 24 months (93.0% vs 75.3%), 36 months (87.7% vs 67.9%), and 48 months (87.7% vs 57.3%) compared with secukinumab, with a significant difference in overall persistence between groups (log-rank P = 0.003). No significant differences in persistence were observed based on whether patients were biologic-naïve or biologic-experienced for either treatment. Discontinuation rates were 20.7% for secukinumab and 4.8% for guselkumab, with lack of effectiveness being the primary reason for discontinuation.

CONCLUSION

Guselkumab was associated with higher long-term persistence than secukinumab in this real-world cohort.

Key Words: Psoriasis; Secukinumab; Guselkumab; Persistence; Biologic therapy

Core Tip: This study contributes to the current body of knowledge by providing real-world data on the long-term persistence of secukinumab and guselkumab in patients with moderate to severe psoriasis. The findings indicate that guselkumab is associated with significantly higher long-term persistence compared with secukinumab, highlighting the relevance of treatment selection in clinical decision-making. The insights gained from this study can guide healthcare providers in optimizing therapy with guselkumab and secukinumab, ultimately leading to improved patient outcomes and more effective treatment strategies.

INTRODUCTION

Psoriasis is a chronic immune-mediated inflammatory skin disease that affects 1%-3% of the world population[1]. It is characterized by the presence of well-demarcated erythematous and scaly plaques that are preferentially located on the elbows, knees, and scalp, but can also affect the palms, soles, nails, and joints. Currently, a wide variety of biologic therapies are available that target specific components of the immune system involved in disease pathogenesis[2]. Interleukin-17 (IL-17) inhibitors and interleukin-23 (IL-23) inhibitors are the most innovative therapies in the treatment of moderate to severe plaque psoriasis. Both therapeutic groups offer improved efficacy and safety compared to previous biologic therapies[3]. Most patients with psoriasis eventually fail their biologic treatment over time due to a loss or lack of efficacy, adverse events, and other factors[4]. As a result, it is likely that a patient will receive multiple biologic treatments over the course of their lifetime. Despite the wide therapeutic arsenal, substantial variability exists in the mechanisms of action of biologics, even among agents targeting similar pathways, leading to differences in efficacy and cost. Therefore, the accurate positioning of these drug classes, along with the implementation of cost-effective treatment algorithms, is essential.

Treatment persistence, defined as the time period from therapy initiation to its discontinuation, is considered an important indicator of therapeutic success in real-world clinical practice. This concept is influenced by factors such as efficacy, safety, adherence, and patient satisfaction[5,6]. In the context of psoriasis treatment, it is important to differentiate between biologic-naïve and biologic-experienced (non-naïve) patients[7]. Biologic-naïve patients tend to exhibit longer treatment persistence, better therapeutic response, and a higher threshold for treatment switching.

Guselkumab and secukinumab have been directly compared in the phase 3 randomized ECLIPSE trial, which demonstrated superior PASI 90 response at week 48 with guselkumab compared with secukinumab[8]. Secukinumab and guselkumab are two of the most commonly prescribed modern biologic therapies, especially in current clinical practice. Assessment of treatment persistence may provide valuable insights into the real-world effectiveness of IL-17 and IL-23 inhibitors in patients with psoriasis. Understanding the factors that influence persistence is crucial for healthcare providers to optimize treatment strategies and improve patient outcomes. However, direct, long-term comparisons of persistence between secukinumab and guselkumab in patients with psoriasis are lacking in clinical trials[9]. Furthermore, few studies have conducted indirect comparisons of these agents in real-world settings[4,10-12].

The objective of this study was to evaluate the long-term persistence of secukinumab compared to guselkumab in patients with moderate to severe psoriasis over a 4-year follow-up period. This analysis aims to assess the sustained therapeutic benefit of secukinumab vs guselkumab in long-term management.

MATERIALS AND METHODS

A retrospective observational study was conducted using data from registries and medical records of two regional hospitals. The study population included patients over 18 years of age with chronic plaque psoriasis who initiated biologic therapy with either secukinumab or guselkumab between January 1, 2015 and June 30, 2024, and who completed a minimum of 6 months of treatment. Patients with concomitant psoriatic arthritis were excluded.

Patients were categorized as biologic-naïve (no prior use of biologic therapy) or biologic-experienced (at least one previous biologic therapy). The variables collected included sex, age, baseline Psoriasis Area and Severity Index (PASI), baseline Dermatology Life Quality Index (DLQI), current and prior biologic treatments, treatment initiation date, dosing regimen, and reasons for discontinuation (loss of efficacy, adverse events, or other causes). Major adverse events leading to drug discontinuation were documented. Adherence of secukinumab and guselkumab was measured using the medication possession ratio (MPR) from the dispensing records of the Hospital Pharmacy Department. Persistence of secukinumab and guselkumab was calculated as the time from treatment initiation to discontinuation, if applicable. No formal grace period was applied; persistence was calculated from the first dispensing date to the last dispensing date, temporary treatment interruptions were not considered discontinuations unless treatment was definitively stopped by the treating physician, and switching to another biologic was considered a discontinuation event. Persistence time was measured in months. For patients who were still receiving treatment, persistence was calculated based on the end date of follow-up (June 30, 2024). Patients lost to follow-up, defined as those who did not visit their dermatologist or pharmacist for one year, were considered censored in the persistence analysis. Demographic and clinical data were extracted from the electronic medical records (Integrador^® and Abucasis^®) of Hospital de Sagunto and Hospital Universitario de Alzira, respectively. Data used to assess treatment persistence were retrieved through the Outpatient Clinic Hospital Pharmacy software Farmis_Oncopharm^® (IMF, Valencia, Spain), which is used in both hospitals.

Statistical analysis was performed using SPSS^® software (version 25.0). Continuous variables were described using medians and interquartile ranges (IQR), whereas categorical variables were summarized with frequencies and percentages. Biologic treatment persistence was assessed using the Kaplan-Meier survival analysis, and comparisons between groups were conducted using the log-rank test. No adjusted Cox proportional hazards model was performed because the limited sample size and low number of discontinuation events, particularly in the guselkumab group, could have resulted in overfitting and unstable effect estimates; therefore, unadjusted Kaplan-Meier and log-rank analyses were considered the most appropriate approach for this dataset.

Adherence was measured using MPR. It estimates the percentage of time a patient has access to their medication. Treatment adherence was obtained from the dispensing records of the Hospital Pharmacy Department. Individualized secukinumab and guselkumab dispensing data and corresponding dates during the study period were collected using Outpatient Clinic Hospital Pharmacy software DISPENSA, [Oncopharm^® Health Information Technology, Valencia, Spain] which facilitates dispensing and monitoring of outpatient treatment. The MPR rate was calculated using data from the pharmacy dispensing records corresponding to the overall secukinumab and guselkumab treatment[13].

The study was approved by the hospital Clinical Research Ethics Committee with the code IIS-F-PG-27-04 and was conducted in accordance with the principles of the Declaration of Helsinki.

RESULTS

A total of 149 patients were included in the analysis. Eighty-seven patients (58.4%) received secukinumab and 62 (41.6%) received guselkumab. Baseline demographic and disease characteristics are summarized in Table 1. The median age of patients in the secukinumab group was 53.7 years (IQR 11.8-18.5), similar to 50.1 years (IQR 11.2-17.9) in the guselkumab group. The proportion of male patients was 46.0% in the secukinumab group and 66.1% in the guselkumab group (P = 0.023). Baseline disease severity, as measured by PASI, was similar between the groups. The median PASI score was 15.0 (IQR 12.1-17.9) in the secukinumab group and 15.4 (IQR 13.7-17.1) in the guselkumab group. DLQI scores at baseline were also comparable, with a median score of 12.9 (IQR 8.6-17.2) for secukinumab and 12.4 (IQR 4.6-20.2) for guselkumab. All patients included in the study had an MPR ≥ 85%, thus were considered adherent.

Table 1 Demographic and clinical characteristics of the patients included in the study, n (%)/median (inter-quartile range)/median ± inter-quartile range.

	Secukinumab	Guselkumab	P value
Number of patients	87 (58.4)	62 (41.6)	-
Age (years)	53.7 (11.8-18.5)	50.1 (11.2-17.9)	NR
Male sex	40 (46.0)	41 (66.1)	0.023
PAS	15.0 (12.1-17.9)	15.4 (13.7-17.1)	NR
DLQI	12.9 (8.6-17.2)	12.4 (4.6-20.2)	NR
Non-Naïve	43 (49.4)	44 (70.9)	0.014
Previous lines of treatment	1.4 ± 0.8	1.9 ± 0.9	NR

P values calculated using χ² test for categorical variables. DLQI: Dermatology life quality index; PASI: Psoriasis Areas and Severity Index, IQR: Inter-quartile range; NR: Not reported.

Regarding prior biologic exposure, 43 patients (49.4%) on secukinumab treatment had already received a previous biologic therapy compared to 44 patients (70.9%) with guselkumab. Patients treated with guselkumab had received a greater number of previous biologic therapies than patients treated with secukinumab, and a higher proportion of patients were biologic-experienced (70.9% vs 49.4%). The higher number of previous biologic lines in the guselkumab group may have influenced persistence outcomes and should be considered when interpreting between-group comparisons.

The most used prior biologic therapies among biologic-experienced patients were anti-tumor necrosis factor alpha (TNFα) agents (60.5%) and ustekinumab (20.9%) in the secukinumab group, while the most common prior treatments in the guselkumab group were ustekinumab (59.3%), anti-TNFα agents (52.6%), and IL-17 inhibitors (32.1%).

The overall median follow-up time for secukinumab was 24.0 months (IQR: 11.4-51.6 months) with a range between 1.2 months and 97.5 months. The overall median persistence of guselkumab was 19.8 months (IQR of 14.3 months to 32.6 months) with a range of 7.0 months to 55.3 months (Figure 1A). When comparing biologic-naïve and non-naïve patients, the median persistence for secukinumab was 25.1 months (IQR: 9.3-53.9 months) in biologic-naïve patients and 21.4 months (IQR: 11.8-49.6 months) in biologic-experienced patients, with no statistically significant difference between the subgroups (P = 0.843) (Figure 1B). For guselkumab, biologic-naïve patients had a median persistence of 16.3 months (IQR: 10.7-23.7 months), while biologic-experienced patients had a median persistence of 22.6 months (IQR: 15.5-34.1 months). Again, no significant difference was found between the two subgroups (P = 0.959) (Figure 1C).

Figure 1 Kaplan-Meier curves. A: Showing overall treatment persistence in patients with moderate-to-severe psoriasis treated with secukinumab or guselkumab during the study follow-up period; B: Showing treatment persistence with secukinumab according to prior biologic exposure, comparing biologic-naïve and biologic-experienced patients; C: Showing treatment persistence with guselkumab according to prior biologic exposure, comparing biologic-naïve and biologic-experienced patients.

Table 2 summarizes the survival functions for both biologic treatments. Guselkumab had the highest drug persistence rates during the study period. After 24 months of treatment, the cumulative probability of drug survival was 93.0% (95%CI: 85.2%-100%) for guselkumab compared to 75.3% (95%CI: 65.5%-85.0%) for secukinumab. These differences in treatment persistence between the two biologics remained evident at 36 and 48 months. Specifically, at 48 months, secukinumab persistence decreased to 57.3% (95%CI: 44.5%-70.0%) compared to guselkumab which maintained a survival function of 87.7% (95%CI: 79.5%-95.9%). At the 60-month follow-up, only data for secukinumab were available, revealing a survival function of 49.3% (95%CI: 35.5%-63.1%). Log-rank test analyses confirmed significant differences in drug persistence rates between the two treatment groups, favouring guselkumab (P = 0.003) (Figure 1A). The mean adherence rate was 83.1% ± 7.9 for secukinumab and 86.5% ± 8.9 for guselkumab.

Table 2 Survival function at years 1, 2, 3, 4 and 5 for patients receiving secukinumab and guselkumab.

Drug	Measure	12 months	24 months	36 months	48 months	60 months
Secukinumab (n = 87)	Patients on treatment/number of discontinuations	62/5	43/4	34/5	25/3	15/1
Secukinumab (n = 87)	Survival function (95%CI)	82.8 (74.6-91.0)	75.3 (65.5-85.0)	67.9 (56.7-79.0)	57.3 (44.5-70.0)	49.3 (35.5-63.1)
Guselkumab (n = 62)	Patients on treatment/number of discontinuations	50/2	23/1	11/0	3/0	-
Guselkumab (n = 62)	Survival function (95%CI)	98.2 (94.8-100)	93.0 (85.2-100)	87.7 (75.2-100)	87.7 (79.5-95.9)	-

A total of 18 patients (20.7%) receiving secukinumab treatment discontinued therapy during the study period. The main reasons for discontinuation were lack of effectiveness in 12 patients (13.8%), adverse effects in 4 patients (4.6%), and other reasons in 2 patients (2.3%). Three patients (4.8%) discontinued guselkumab therapy: 2 (3.2%) due to lack of efficacy and 1 (1.6%) due to adverse events. These results show a higher discontinuation rate for secukinumab than for guselkumab during the long-term follow-up period.

DISCUSSION

Persistence of biologic treatments for psoriasis is an important factor in long-term disease control. Low persistence rates can lead to suboptimal treatment outcomes and increased healthcare costs[14]. Given the lifelong nature of psoriasis treatment, improving therapy persistence remains a primary objective in managing the condition. In addition, an increasing number of biologics have become available, facilitating rapid switching between treatments. This highlights the importance of understanding the treatment persistence of each biologic. Our real-world data provide valuable insights into the drug survival rates of two widely used biologic targets for the treatment of plaque psoriasis in routine clinical practice. The overall median persistence for biologics in our cohort was approximately 2 years, with secukinumab showing a slightly longer persistence compared to guselkumab. In comparison, Yiu et al[4] reported similar findings, with secukinumab demonstrating a longer median persistence than guselkumab. However, the persistence data for guselkumab are lower than those for secukinumab due to the shorter period of follow-up for guselkumab. In our results, no significant differences were observed when comparing the persistence of biologic-naïve patients with those who were not, in both the secukinumab and guselkumab groups. These findings suggest that both secukinumab and guselkumab provide similar drug survival rates, regardless of prior biologic treatment experience. Although biologic-naïve patients are generally associated with improved drug survival, this trend was not observed in our cohort, likely due to the limited sample size. However, some studies, such as those by Mourad et al[15] and Langley et al[16], indicate that IL-23 inhibitors are less impacted by previous biologic treatments, which may explain the comparable persistence rates observed in our cohort. Kaplan-Meier analysis revealed higher persistence rates at 12 months, 24 months, and 48 months for guselkumab (98.2%, 93.0%, and 87.7%) than for secukinumab (82.8%, 75.3%, and 57.3%). Our results align with real-world data, showing that the differences in drug survival between secukinumab and guselkumab become more pronounced over time[4,11,17]. This trend aligns with findings from Torres et al[11], which reported similar survival rates of 92.0% for guselkumab and 78.0% for secukinumab. The divergence in persistence rates between the two agents increased progressively over time. At 48 months, guselkumab continued to show a numerically higher survival rate than secukinumab (87.7% vs 57.3%); however, this later comparison should be interpreted with caution because of the more limited follow-up maturity and smaller number of patients remaining under observation, particularly in the guselkumab group. The widening persistence gap over time in favor of guselkumab suggests a more favorable retention profile in this cohort; however, this observation should not be interpreted as proof of superior effectiveness, because persistence is influenced by multiple factors, including treatment era, prescribing patterns, prior biologic exposure, dosing convenience, and the non-randomized nature of the study. The higher persistence reported for anti-IL-23 agents compared with IL-17 inhibitors has been associated with factors such as effectiveness, dosing convenience, and sustained response after treatment discontinuation; however, definitive comparative conclusions regarding safety and efficacy cannot be drawn from the present study[18-20]. Molecularly, this can be explained by a greater reduction in levels of resident memory T cells in the skin and regulatory T cells[21]. Regarding treatment discontinuations, the results of our study correspond with the existing literature, showing higher discontinuation rates for secukinumab compared to guselkumab[22,23]. In terms of safety, treatment discontinuations due to adverse events were infrequent in both groups, making any comparative interpretation difficult, particularly given the very small number of events observed in the guselkumab cohort. However, according to Yiu et al[4], no significant differences in safety were observed between the two drugs. A strength of this study is that patients were considered adherent to guselkumab and secukinumab based on the MPR data. Our study has several limitations. First, the retrospective nature of the data collection may limit the internal validity of the findings. Additionally, the lack of randomization means that the groups are not comparable, limiting the conclusions that can be drawn. In particular, the guselkumab group had a higher burden of previous biologic exposure, as reflected by a greater number of prior biologic lines, which may have acted as a confounding factor in the observed persistence differences. Although baseline PASI and DLQI values were broadly similar, residual differences in baseline disease severity between groups cannot be excluded and may also have influenced treatment retention and clinical response. Moreover, no adjusted survival analysis was performed, as the limited number of discontinuation events relative to the sample size could have produced unreliable multivariable estimates; therefore, the between-group persistence comparison should be interpreted as descriptive and exploratory. Furthermore, each treatment was approved in different years, leading to a longer follow-up period for secukinumab compared to guselkumab. This unequal follow-up duration may have distorted the comparison of long-term persistence and limited the comparability of the estimated survival curves between treatment groups. Finally, the relatively small sample size may reduce the external validity and limit the generalizability of our results. Other potentially relevant confounding factors, including underlying comorbidities, BMI and concomitant systemic treatments, were not fully controlled for and may also have influenced the observed associations between treatment and persistence.

CONCLUSION

In conclusion, guselkumab was associated with higher long-term persistence than secukinumab in this real-world cohort of patients with moderate-to-severe psoriasis. These findings should be interpreted cautiously given the retrospective, non-randomized design of the study.