Review of the reasons for and effectiveness of switching biologics for psoriasis treatment in Korea

Plain Language Summary

Biologics have been used for the treatment of psoriasis in patients who do not response to conventional treatments. However, in clinical practice, switching of biologics has become common. We investigate the reasons and efficacy of switching biologics in Korean patients with moderate and severe plaque psoriasis. The most common reason for switching biologics in Korea was treatment inefficacy, especially secondary failure. Despite the inefficacy of previous biologics, switching to a different agent may be an efficacious treatment option.

Introduction

Psoriasis is an inflammatory skin disease characterised by papules and plaques with silvery white scales. Patients with psoriasis are less satisfied with their lives due to the condition,¹ and they are more likely to have accompanying systemic diseases such as cardiovascular disease and metabolic syndrome compared to people without psoriasis.^2,3 In recent decades, the immunological aetiology of psoriasis has been revealed, and various biologic agents have been developed to act on these immunological pathways.

In Korea, since 2011, biologic agents have been used for the treatment of psoriasis in patients who do not respond to conventional treatments. However, biologic agents do not consistently exhibit equivalent therapeutic effects in all patients, and some show insufficient treatment responses or adverse reactions. In these cases, switching biologic agents may be considered. However, few studies have reported the reasons and efficacy of switching biologic agents in psoriasis.

This study investigated the reasons and efficacy of switching biologic agents in Korean patients with moderate and severe plaque psoriasis.

Methods

Results

Therapeutic efficacy and reasons for switching biologics

Among the 35 patients who changed biologic agents, the psoriasis area and severity index scores before the administration of the first agent ranged from 10.2 to 32.5 (average, 19.9). The average psoriasis area and severity index score after 14–16 weeks of administration was 4.0, which indicated a statistically significant decrease (P < 0.05). The average duration of administration of the first biologic agent was 133.3 ± 88.6 weeks. The psoriasis area and severity index scores before administration of the second biologic agent ranged from 1.3 to 19.8 (average, 12.1). The average psoriasis area and severity index score after 14–16 weeks of administration was 3.4, which again indicated a statistically significant decrease (P < 0.05) [Figure 1]. The psoriasis area and severity index scores after 14–16 weeks of administration of each second agent are described in [Figure 2]. The proportions of patients who achieved PASI 75, PASI 90 and PASI 100 at 14–16 weeks after administration of the first biologic agent were 57.1, 17.1 and 2.9%, respectively, and 51.4, 14.3 and 2.9%, respectively, after administration of the second biologic agent.

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Figure 1

Mean PASI score at baseline of the first and second biologics and after 14–16 weeks of using the second biologics among patients who switched biologic agents (n = 35). PASI: Psoriasis Area and Severity Index

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Figure 2

PASI score at baseline of the first and second biologics and after 14–16 weeks of using the second biologics in each patients who switched biologics. Second biologics as follows: (a) secukinumab (n = 12), (b) ixekizumab (n = 9), (c) guselkumab (n = 14)

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Table 2 shows the number of patients and their reasons for switching biologic agent. Of the 35 patients who changed biologics, 28 (80.0%) did so due to secondary failure. Two (5.7%) patients had primary failure, and two (5.7%) patients changed biologics due to adverse events.

Table 2 Biological treatment characteristics of patients treated with the first biologics

Demographics	Total	Ustekinumab	Secukinumab	Adalimumab
No. of patients	162	91	59	12
No. of continuously treated patients, n (%)	118 (72.8)	64 (70.3)	46 (78.0)	10 (83.3)
No. of discontinued patients, n (%)	44 (27.2)	27 (29.7)	13 (22.0)	2 (16.7)
No. of switched patients, n (%)	35 (21.6)	23 (25.3)	10 (16.9)	2 (16.7)
To secukinumab	12	10	-	2
To ixekizumab	9	5	4	0
To guselkumab	14	8	6	0

Data are presented as n (%) or mean ± SD, as appropriate.

Discussion

Despite their benefits, some patients discontinue biologic treatment due to insufficient therapeutic effects or adverse reactions. Waren⁴ reported that one-third and nearly one-half of patients stopped treatment within 1 year and after 3 years, respectively, following the first use of biologics. In this study, 44 (27.2%) of the 162 patients discontinued their first biologics, 35 (21.6%) of whom switched to other biologic agents.

In this study, among the 35 patients who switched biologic agents, 79.9%, achieved psoriasis area and severity index reduction after 14–16 weeks of administration of the first biologic agent, and 72.1% achieved psoriasis area and severity index reduction after the administration of the second biologic agent. Compared to the first biologic agent, the slightly lower rate of psoriasis area and severity index reduction after the use of the second biologic agent is due to the lower psoriasis area and severity index score before the use of the second biologics than before the use of the first agent. However, patients who switched to a second biologic agent also showed significant decreases in the psoriasis area and severity index score (P < 0.05). In addition, the rates of achievement of PASI 75, PASI 90 and PASI 100 were similar after administration of the first and second biologic agents. This suggests that switching to other biologic agents may be a treatment option that could provide significant clinical improvement even if the previous biologic agents were insufficiently effective or if the medication could not be continued due to side effects.

In addition, to identify the clinical factors related to biologics discontinuation, the group of patients that continued biologic use and the group that discontinued the first biologics were compared. Only patients with high psoriasis area and severity index scores and psoriatic arthritis showed significant differences before biologics use. The clinical factors associated with the discontinuation of the first biologic agent may be related to a poor response. Because it is known that the higher the severity of psoriasis, the lower the response to biological agents,⁵ the association between high pre-treatment psoriasis area and severity index score and biologics discontinuation was assessed. Disease severity is also associated with the presence of psoriatic arthritis.^6,7 Therefore, patients with high psoriasis area and severity index scores or concomitant psoriatic arthritis before starting biologics tend to switch and the commonest reason for switching is secondary failure.

The most common reason for switching to biologics in this study too was secondary failure. Twenty-eight (80.0%) patients switched biologics due to a decrease in the efficacy of the initial biologic agent over time. The decrease in therapeutic effect is partly due to the generation of anti-drug antibodies against that biologic agent.⁸ Two patients (5.7%) switched due to adverse reactions (suspected injection site reaction and drug-induced lupus). Compared to previous reports,^9,10 most of the patients in this study switched biologics due to secondary failure, and the proportion of patients who changed biologics due to primary failure or adverse reactions was relatively low.

In this study, 21.6% of patients changed biologic agents, a rate similar to those reported previously (18.5–34%).^9,10 The efficacy of the switched biologics, that is, the reduction rate of the average psoriasis area and severity index score at 14–16 weeks after replacement, was 72.1%, which was higher than the previously reported 53.3%.⁹ In addition, the average duration of administration of the first biologics was 133.3 weeks, which was longer than that previously reported (47.6–94.1^9,10 weeks). These differences may be due to differences in demographic characteristics between studies. Because the participants in this study had a lower body mass index compared to those in the previous study¹⁰ (23.6 kg/m² vs. 27.1 kg/m²), they had a higher drug dose to body weight, even if they were administered the same dose of biologics; thus, the biologics showed a better effect. Previous studies on biological drugs such as ustekinumab,¹¹ secukinumab¹² and ixekizumab¹³ in Koreans have shown their superior therapeutic effects compared to those in foreign clinical studies. However, a study with a larger population and longer follow-up period is needed to confirm this finding.

One of the limitations of this study was that the total number of patients was smaller due to problems such as insurance coverage standards for biologics as well as high prices. In addition, as a retrospective study, there were limitations such as the absence of a placebo control group and that the time point of 14–16 weeks was somewhat early to judge the effect of the biologics. Another limitation is that the various biologics were approved during different times during the study period.

In conclusion, in this study, 21.6% of patients with moderate to severe plaque psoriasis who were administered biological agents replaced their initial agent. The main reason for replacement was a decreased therapeutic effect of the first biologic agent over time. Even if the previous biologics were insufficiently effective or the drug could not be continued due to side effects, significant clinical improvement was observed after replacement of the biologic agent. We suggest that switching to another biologic agent may be an effective method in the treatment of patients with plaque psoriasis who lack a response to previous treatment or cannot continue administration due to adverse reactions.