Introduction
Plaque psoriasis is a chronic, immune-mediated, inflammatory disease characterized by prominent skin lesions, which can be scaly, thick, and occasionally pruritic [
1], and a substantial disease burden impacting on patient quality of life (QoL) [
2,
3]. Psoriasis is additionally associated with increased risk of several comorbidities [
4].
Interleukin (IL)-17A and IL-17F play a central role in the pathogenesis of psoriasis and psoriatic arthritis [
5‐
7], and both are overexpressed in psoriatic lesional skin [
5,
7,
8]. IL-17A and IL-17F share ~50% structural similarity and form homo- and heterodimers, with overlapping proinflammatory functions [
9‐
11]. Biologic therapy, including treatments targeting the IL-17 pathway, are recommended by the Japanese Dermatological Association for patients with plaque-type psoriasis who have not adequately responded to standard systemic therapies and have ≥ 10% body surface area (BSA) affected, or who have refractory skin or joint symptoms intractable to systemic therapies and significantly impaired QoL [
12].
Common biologic therapies targeting the IL-17 pathway inhibit IL-17 or target the IL-17 receptor complex [
13‐
16]. Anti-IL-17A agents have demonstrated efficacy in treating patients with moderate-to-severe psoriasis; however, nearly one-third of patients have discontinued treatment within 5 years due to ineffectiveness, primary or secondary failure, infection, or other causes, and require additional treatment options [
17]. Additionally, other factors may affect patient preferences when choosing biologic therapy and patients may prioritize different factors. A survey of 395 Japanese patients with psoriasis reported patients preferred drugs with long-term and early-onset efficacy, sustained efficacy after drug withdrawal, and low risk of serious infection, among other factors [
18].
Bimekizumab is a humanized monoclonal immunoglobulin G1 antibody that selectively binds with high affinity to IL-17A and IL-17F, inhibiting downstream signaling [
19,
20]. In four phase 3/3b clinical trials, bimekizumab demonstrated clinical superiority over placebo, adalimumab, secukinumab, and ustekinumab in patients with moderate-to-severe plaque psoriasis [
21‐
24]. Recently, bimekizumab was approved in Japan for the treatment of plaque psoriasis, generalized pustular psoriasis, and psoriatic erythroderma in patients who are not sufficiently responding to existing treatments [
25].
Prevalence and severity of psoriasis can significantly vary between populations and countries due to genetic and environmental factors [
26‐
28]. A lower prevalence of psoriasis in all ages was reported in Japan (0.4%), compared with Europe (0.7–2.9%) and the USA (5.1%) [
26]. Additionally, psoriasis occurs predominantly in males in Japan [
29,
30], unlike the approximately equal distribution of males and females in Western countries [
28]. Higher expression of IL-17A and IL-17-regulated proinflammatory cytokines has been shown in Asian versus Western patients with plaque psoriasis [
27]. Asian patients also tend to have milder forms of psoriasis, characterized by lesions of less epidermal thickness and radial expansion, compared with Western patients [
27].
Absolute Psoriasis Area and Severity Index (PASI) thresholds represent relevant treatment targets in psoriasis and can supplement percentage PASI improvement when assessing treatment efficacy [
31]. Among Japanese patients with plaque psoriasis, absolute PASI values of ≤ 2 or ≤ 3 have been used to demonstrate the efficacy of biologics [
32,
33]. Absolute PASI values have also been shown to correlate with better QoL [or low Dermatology Life Quality Index (DLQI) values] [
34].
Given the differences in disease epidemiology and severity between Japanese versus Western patient populations, this analysis of the BE VIVID Japan patient subpopulation aimed to evaluate the efficacy of bimekizumab in these patients. Absolute PASI values are reported alongside percentage PASI improvement, and other efficacy and safety outcomes.
Discussion
In this phase 3 active comparator and placebo-controlled trial, bimekizumab demonstrated improved efficacy compared with ustekinumab and placebo for the treatment of adult patients with moderate-to-severe plaque psoriasis. Overall, the Japan patient subpopulation results were generally consistent with the global study population [
24]. These findings suggest bimekizumab may be a viable treatment option in Japan, and effectiveness of bimekizumab treatment and dosing regimens in Japanese patients may be approximated from observations in Western populations.
Bimekizumab showed a faster onset of clinical response among Japanese patients compared with ustekinumab. The rapid onset was comparable between patients who received bimekizumab from week 0 and those who switched from placebo to bimekizumab at week 16. A fast onset of effectiveness is relevant as the Japanese Dermatological Association views this as an important consideration when selecting biologic therapy for psoriatic patients in Japan [
12]. Japanese patients with psoriasis have also shown a preference for drugs with early-onset efficacy [
18].
Patients with chronic plaque psoriasis can lose treatment response over time [
12,
37], and may need to switch treatments to maintain high skin clearance levels [
12]. In this analysis, high proportions of bimekizumab-treated patients maintained good skin clearance through 52 weeks of treatment.
Additionally, more bimekizumab-treated patients reached absolute PASI thresholds versus ustekinumab or placebo. Absolute PASI has been used as an efficacy measure in Japanese clinics, as evidenced in a number of studies assessing absolute PASI responses in Japanese patients with moderate-to-severe psoriasis [
32‐
34].
As psoriasis often has a detrimental impact on patient QoL [
2], it is important that clinical improvements in skin clearance can be linked to QoL improvements. A correlation between absolute PASI and DLQI has been shown in a study of Japanese patients with moderate-to-severe plaque psoriasis: in those who experienced a relapse, a change in absolute PASI response correlated with a steeper increase in DLQI scores compared with baseline [
34]. As this analysis measured relative and absolute PASI responses, DLQI, PROs, and other clinical outcomes, it provides holistic insight—across clinical and QoL outcomes—of the clinical benefits of bimekizumab in Japanese patients with psoriasis.
Overall, safety results for Japanese patients were consistent with the BE VIVID global study population [
24], with a slightly higher incidence of TEAEs related to skin and subcutaneous disorders, in particular eczema and contact dermatitis. Over 52 weeks, the occurrence of common TEAEs was comparable between bimekizumab and ustekinumab, except for oral candidiasis. As the IL-17 pathway controls fungal infections of the oral mucosa, and is subject to heightened inhibition through bimekizumab’s inhibition of IL-17F and IL-17A [
38‐
42], oral candidiasis would be expected to be more common in bimekizumab- versus ustekinumab-treated patients. Moreover, the frequency of oral candiasis infections was similar to observations in previous bimekizumab trials [
19,
24,
43,
44], and was higher than observations with other IL-17 inhibitors [
13,
14]. This might result from bimekizumab’s inhibition of IL-17F and IL-17A; further investigations can confirm this. Finally, while there was a higher number of reported candidiasis cases among Japanese patients in weeks 0–16 than in weeks 16–52, the results should be interpreted with caution given the small number of patients.
Limitations
Inferential comparisons of the outcomes and calculation of p-values were not prespecified given the small patient numbers in this analysis. Therefore, p-values have not been reported as the interpretation of those results may be limited. Absolute numbers and percentages have instead been reported for the various outcomes. Nonetheless, the current analysis provides evidence of bimekizumab efficacy and safety in Japanese patients, whereby clinical response is consistent with the overall population.
Head-to-head comparator trials are important for comparing between treatments; studies comparing bimekizumab with IL-17A or TNFα inhibitors have been published previously [
22,
23]. These studies, together with the present analysis, contribute toward the wider program evaluating bimekizumab efficacy and safety in adults with moderate-to-severe plaque psoriasis.
Finally, long-term data on bimekizumab efficacy and safety will be available through the ongoing open-label extension study (BE BRIGHT), which has recruited patients from this analysis and others in the “bimekizumab for psoriasis” program. These data would allow patients and clinicians in Japan to make informed treatment decisions.
Acknowledgements
Author Contributions
Conceptualization: Maggie Wang; Data Curation: Maggie Wang; Formal analysis: Akihiko Asahina, Yukari Okubo, Akimichi Morita, Yayoi Tada, Atsuyuki Igarashi, Richard G. Langley, Delphine Deherder, Mizuho Matano, Veerle Vanvoorden, Maggie Wang, Mamitaro Ohtsuki, Hidemi Nakagawa; Funding Acquisition: Delphine Deherder, Mizuho Matano, Veerle Vanvoorden, Maggie Wang; Investigation: Delphine Deherder, Mizuho Matano, Veerle Vanvoorden, Maggie Wang; Methodology: Maggie Wang; Resources: Delphine Deherder, Mizuho Matano, Veerle Vanvoorden, Maggie Wang; Supervision: Veerle Vanvoorden; Validation: Delphine Deherder, Maggie Wang; Visualization: Akihiko Asahina, Yukari Okubo, Akimichi Morita, Yayoi Tada, Atsuyuki Igarashi, Richard G. Langley, Delphine Deherder, Mizuho Matano, Veerle Vanvoorden, Maggie Wang, Mamitaro Ohtsuki, Hidemi Nakagawa; Writing – Original Draft Preparation: Akihiko Asahina, Yukari Okubo, Akimichi Morita, Yayoi Tada, Atsuyuki Igarashi, Richard G. Langley, Delphine Deherder, Mizuho Matano, Veerle Vanvoorden, Maggie Wang, Mamitaro Ohtsuki, Hidemi Nakagawa; Writing – Review and Editing: Akihiko Asahina, Yukari Okubo, Akimichi Morita, Yayoi Tada, Atsuyuki Igarashi, Richard G. Langley, Delphine Deherder, Mizuho Matano, Veerle Vanvoorden, Maggie Wang, Mamitaro Ohtsuki, Hidemi Nakagawa.
Disclosures
Akihiko Asahina: Honoraria and/or research grants from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Eli Lilly, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, and UCB Pharma. Yukari Okubo: Research grants from Eisai, Maruho, Shiseido, and Torii Pharmaceutical; current consulting/advisory board agreements from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, and Sun Pharma; speakers bureau from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly, Janssen, Jimro, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Sanofi, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, and UCB Pharma; clinical trials sponsored by AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Maruho, Pfizer, Sun Pharma, and UCB Pharma. Akimichi Morita: Research grants, consulting fees, and/or speaker’s fees from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, Ushio, and UCB Pharma. Yayoi Tada: Honoraria and/or grants from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Eli Lilly, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, Novartis, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, and UCB Pharma. Atsuyuki Igarashi: Speaker honoraria from AbbVie, Celgene, Eisai, Eli Lilly, Janssen Pharmaceutical, Kyowa Kirin, Maruho, Novartis, and Torii Pharmaceutical; research grants from Amgen, AbbVie, Bristol Myers Squibb, Eli Lilly, and LEO Pharma. Richard G. Langley: Principal investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer, and UCB Pharma; served on scientific advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer, and UCB Pharma; provided lectures for AbbVie, Amgen, Celgene, LEO Pharma, Merck, Novartis, and Pfizer. Delphine Deherder, Veerle Vanvoorden, Maggie Wang: Employees and shareholders of UCB Pharma. Mizuho Matano: Employee of UCB Pharma. Mamitaro Ohtsuki: Honoraria and/or research grants from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, and UCB Pharma. Hidemi Nakagawa: Consulting fees, and/or speaker's fees from AbbVie, Janssen, Japan Tobacco Inc., Kyowa Hakko Kirin, LEO Pharma, Maruho, Taiho Pharmaceutical, Torii Pharmaceutical, and UCB Pharma.