Bimekizumab Complete Clearance of Both Skin and Nail Psoriasis: Comparative Efficacy in Phase III/IIIb Studies

Abstract

Background

Nail psoriasis can have a substantial negative impact on both the physical and emotional well-being of patients, and is a risk factor for psoriatic arthritis. Achieving complete clearance of nails in addition to skin is therefore an important treatment goal.

Objectives

We aimed to evaluate concurrent complete skin and nail clearance in patients with moderate-to-severe plaque psoriasis treated with bimekizumab or active comparators.

Methods

Data were analyzed from the BE SURE and BE VIVID phase III trials, their open-label extension BE BRIGHT, and the BE RADIANT phase IIIb trial and its open-label extension. Included patients had baseline modified Nail Psoriasis Severity Index (mNAPSI) >0 and entered their respective open-label extension. Proportions of patients achieving complete skin (PASI 100; 100% improvement from baseline in Psoriasis Area and Severity Index) and nail (mNAPSI 0) clearance at the same time are reported for bimekizumab- and active comparator-treated patients during controlled trial periods, and in the long term for continuous bimekizumab-treated patients and those switching from comparators. Data are reported using modified non-responder imputation.

Results

At the end of comparator-controlled periods, 45.8% of bimekizumab (N = 151) versus 18.3% of adalimumab (N = 91) patients (BE SURE week 24), 51.1% of bimekizumab (N = 169) versus 26.5% of ustekinumab (N = 92) patients (BE VIVID week 52), and 63.3% of bimekizumab (N = 182) versus 36.1% of secukinumab (N = 155) patients (BE RADIANT week 48) achieved PASI 100 and mNAPSI 0. Following long-term treatment, 57.7% of adalimumab switchers/49.1% of continuous bimekizumab patients (BE SURE/BE BRIGHT year 4), 52.2% of ustekinumab switchers/48.3% of continuous bimekizumab patients (BE VIVID/BE BRIGHT year 4), and 51.9% of secukinumab switchers/57.4% of continuous bimekizumab patients (BE RADIANT year 3) achieved PASI 100 and mNAPSI 0.

Conclusions

Numerically higher proportions of bimekizumab-treated patients achieved concurrent complete skin and nail clearance versus adalimumab, ustekinumab, and secukinumab. Clearance rates increased following switch to bimekizumab, and were sustained long-term in both switchers to bimekizumab and continuous bimekizumab-treated patients. [Graphical abstract available.]

Clinical Trial Registration

NCT03412747, NCT03370133, NCT03598790, NCT03536884.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at 10.1007/s40257-025-00968-2.

Plain Language Summary

An investigation of how well bimekizumab works in completely clearing skin and nail psoriasis together.

What is psoriasis?

Psoriasis is a long-lasting disease that can cause red, scaly patches on the skin, and it can cause symptoms in other parts of the body because it affects more than just one area. These patches can flake, itch, and hurt. The nails are also affected in up to six out of ten people living with psoriasis, causing discomfort and impacting quality of life, even though nails are small. Nail psoriasis takes longer to treat than skin psoriasis. It is associated with the development of psoriatic arthritis, which causes joint pain, swelling, and stiffness, and can cause permanent changes to the joints. Many people with psoriasis therefore want treatments that can clear both skin and nail symptoms.

What did we do?

In this global study, we looked at how well bimekizumab, a psoriasis medication, works to clear both skin and nail psoriasis at the same time. We analyzed how many patients treated with bimekizumab had achieved completely clear skin and nails after up to 1 year compared with other medications (adalimumab, ustekinumab, and secukinumab). We also looked over the long term in patients receiving bimekizumab throughout or those switching from other medications to bimekizumab.

What did we find?

More patients treated with bimekizumab achieved completely clear skin and nails compared with other medications. Similar numbers of bimekizumab-treated patients maintained completely clear skin and nails through up to 4 years, including those switching from other medications. These results suggest bimekizumab helps improve different areas of psoriasis that affect patients.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40257-025-00968-2.

Key Points

Nail psoriasis can impair quality of life and is an independent risk factor for psoriatic arthritis, with approximately one third of patients with psoriasis progressing to psoriatic arthritis over the course of their disease.

Higher proportions of bimekizumab-treated patients with moderate-to-severe plaque psoriasis achieved complete skin and nail clearance, both individually and at the same time, during head-to-head phase III trials versus adalimumab, ustekinumab, and secukinumab.

In patients switching from comparators to bimekizumab, clearance rates increased and were sustained in the long term at levels similar to those continuously treated with bimekizumab.

These analyses demonstrate a long-lasting complete clearance of skin and nail psoriasis by bimekizumab, reflecting its ability to treat multiple domains of psoriatic disease, which may be beneficial to patients with psoriasis who are candidates for systemic therapy.

Introduction

Complete skin clearance, or 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100), is becoming an increasingly achievable treatment goal with new biologics for patients with plaque psoriasis [1–4]. However, the PASI does not include an assessment of nail psoriasis clearance [5]. Importantly, psoriasis of the nails is highly visible and can have a substantial negative impact on both the physical and emotional well-being of patients, relative to the small area of the body affected [6]. Moreover, compared to patients without, patients with nail involvement have higher work absence, more healthcare resource use, higher stress, and a lower health-related quality of life [6, 7].

In patients with psoriasis, nail involvement has a prevalence of approximately 40–60% and, across their lifetime, an estimated 80–90% of patients with plaque psoriasis will experience nail involvement [5, 8]. The nail is connected to underlying bone in the finger through an enthesis network fused with the extensor tendon, which crosses the distal interphalangeal joint [9]. As a result of the anatomical connection between the nail and the musculoskeletal system, nail psoriasis can be an early indicator and independent risk factor for psoriatic arthritis (PsA); therefore, patients with psoriasis who experience nail involvement are three times more likely to develop PsA [9]. Considering prevalence and that approximately one third of patients with psoriasis progress to PsA over the course of their disease [10], there is a need for awareness and understanding of nail disease among healthcare professionals to improve the identification and early management of patients at high risk of progression to PsA [11].

Systemic treatment, including biologic therapies, is recommended for nail psoriasis when it is severe (sometimes defined as involvement on four or more fingernails, or onycholysis/onychodystrophy affecting at least two fingernails) or when there is a large impact on patient health-related quality of life [12–15]. However, because of their structure and growth rate, nails are often more difficult to treat than skin and can take 6–9 months to completely regrow [5, 16]. Complete resolution of multiple domains of psoriatic disease beyond skin has become an increasingly important treatment goal in patients with psoriasis, as highlighted by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) [11]. Therapies that can effectively treat these domains of psoriatic disease at the same time, including resolving an independent risk factor and controlling underlying inflammation associated with disease progression to PsA, are therefore highly desirable.

Bimekizumab is a monoclonal immunoglobulin G1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A [17], and has previously demonstrated superior rates of complete skin clearance versus adalimumab, ustekinumab, and secukinumab in comparator-controlled periods of phase III trials [1, 3, 4]. Treatment with bimekizumab has been reported to lead to up to 76.2% of patients achieving PASI 100 and 63.4% of patients achieving mNAPSI 0 (modified Nail Psoriasis Severity Index 0) after 1 year [18–20].

To evaluate the efficacy of bimekizumab in different domains of psoriatic disease at the same time, we assessed concurrent clearance of both skin and nails at any given timepoint post hoc in patients with moderate-to-severe plaque psoriasis treated with bimekizumab versus adalimumab, ustekinumab, and secukinumab during head-to-head phase III trials. We also report long-term efficacy of bimekizumab in these two domains, including in patients who switched to bimekizumab from comparators.

Methods

Study Design and Participants

Data for this post hoc analysis were included from: BE SURE (NCT03412747), a 56-week trial comparing bimekizumab to adalimumab; BE VIVID (NCT03370133), a 52-week trial comparing bimekizumab to ustekinumab; 3 years of their common open-label extension (OLE) BE BRIGHT (4 years’ total treatment; NCT03598790); and BE RADIANT, a 48-week trial comparing bimekizumab to secukinumab and 2 years of its OLE (3 years’ total treatment; NCT03536884).

Eligible patients were adults (≥18 years of age) with moderate-to-severe plaque psoriasis, with a baseline PASI ≥12, ≥10% body surface area affected by psoriasis, and an Investigator’s Global Assessment score ≥3 on a 5-point scale. Study designs have been reported in full previously [1, 3, 4, 21, 22]. Briefly, in BE SURE, patients were randomized 1:1:1 to bimekizumab 320 mg every 4 weeks (Q4W), bimekizumab Q4W to week 16 followed by bimekizumab every 8 weeks (Q8W), or adalimumab 80 mg at baseline, 40 mg at week 1 then every 2 weeks to week 24 followed by switch to bimekizumab Q4W for the remainder of the trial. In BE VIVID, patients were randomized 2:4:1 to ustekinumab 45 mg or 90 mg at baseline (weight-dependent dosing) and week 4 then every 12 weeks, bimekizumab Q4W, or placebo to week 16 followed by bimekizumab Q4W. In BE RADIANT, patients were randomized 1:1 to bimekizumab Q4W to week 16 (followed by 1:2 re-randomization to bimekizumab Q4W or Q8W to week 48), or secukinumab 300 mg weekly to week 4 followed by Q4W.

Upon completion of BE SURE or BE VIVID, eligible patients could enroll into the BE BRIGHT OLE. All patients received open-label bimekizumab Q4W or Q8W, depending on prior treatment, dose, and response at the end of the initial trial [21]. At OLE week 24, patients receiving bimekizumab Q4W who had achieved a ≥90% improvement from baseline in PASI (PASI 90) could switch to bimekizumab Q8W at the investigator’s discretion. All remaining bimekizumab Q4W patients were switched to bimekizumab Q8W at OLE week 48 or their next scheduled clinic visit.

At the end of the BE RADIANT comparator-controlled period, patients could enroll into the BE RADIANT OLE. Upon OLE entry, patients received bimekizumab Q4W or Q8W depending on prior treatment, dose, and response at the end of the comparator-controlled period. Following protocol amendment, all patients switched to bimekizumab Q8W at OLE week 16 or the next scheduled clinic visit [22]. A summary of the studies included in this analysis is provided in Fig. 1 of the Electronic Supplementary Material (ESM)

Fig. 1.

Complete skin clearance, nail clearance, and concurrent skin and nail clearance in comparator-controlled trial periods (modified non-responder imputation [mNRI]). a BE SURE week 24; b over 24 weeks in BE SURE; c BE VIVID week 52; d over 52 weeks in BE VIVID; e BE RADIANT week 48; f over 48 weeks in BE RADIANT. Bimekizumab (BKZ) Total represents all BKZ dose groups combined for patients in BE SURE and BE RADIANT. In BE VIVID, patients in the BKZ Total group received BKZ every 4 weeks (Q4W) only during the first year of treatment according to study design. Only patients with nail involvement (modified Nail Psoriasis Severity Index [mNAPSI] >0) at baseline who entered the open-label extensions were included in the analysis. ADA adalimumab, PASI 100 100% improvement from baseline in Psoriasis Area and Severity Index, Q8W every 8 weeks, SEC secukinumab, UST ustekinumab

Outcomes

The mNAPSI assesses the severity of nail psoriasis. Specifically, the mNAPSI evaluates psoriasis of the nail matrix through: nail pitting (0–3), nail plate crumbling (0–3), leukonychia (0/1), and red spots in the lunula (0/1); and evaluates psoriasis of the nail bed through: onycholysis/oil drop dyschromia (0–3), splinter hemorrhages (0/1), and nail-bed hyperkeratosis (0/1) [23]. The range of scores is 0–13 for each fingernail, totaling to a maximum score of 130 for all fingernails [9]. A total mNAPSI score of 0 indicates completely clear nails.

The PASI evaluates the severity of psoriatic skin lesions (scored 0–4 for increasing severity) weighted by the percentage of skin affected across the head, trunk, upper limbs, and lower limbs [ 24 ]. The total PASI score ranges, and lower limbs [24]. The total PASI score ranges from 0 to 72 [23]. A PASI 100 response indicates a 100% improvement from baseline in PASI, equating to complete skin clearance [24].

Statistical Analysis

All included patients had fingernail involvement at baseline, defined as mNAPSI >0, and entered their respective OLE. Bimekizumab dose groups were combined (bimekizumab Total), and results are also reported for the subset who received the dosing regimen approved for the majority of patients with moderate-to-severe plaque psoriasis (bimekizumab Q4W/Q8W) where available (BE SURE and BE RADIANT only; there was no bimekizumab Q4W/Q8W group in BE VIVID because of the study design).

Proportions of patients who achieved complete clearance of skin (PASI 100), complete clearance of nails (mNAPSI 0), and complete clearance of both skin and nails (PASI 100 and mNAPSI 0) at the same visit are reported in bimekizumab-treated and adalimumab-, ustekinumab-, and secukinumab-treated patients during comparator-controlled trial periods (BE SURE: bimekizumab Total versus adalimumab to week 24; BE VIVID: bimekizumab Q4W versus ustekinumab to week 52; BE RADIANT: bimekizumab Total versus secukinumab to week 48). Proportions of patients who achieved concurrent absolute PASI ≤1 and mNAPSI 0, or concurrent body surface area ≤1% (National Psoriasis Foundation-defined target outcome) [25] and mNAPSI 0, are reported in the ESM.

Proportions of continuously bimekizumab-treated patients, as well as adalimumab-, ustekinumab-, and secukinumab-treated patients who switched to bimekizumab at the end of comparator-controlled periods, who achieved these outcomes are also reported through the long term (3 or 4 years of total treatment depending on the trial). Data are reported using modified non-responder imputation (mNRI) and observed case (OC). For mNRI, patients who discontinued because of lack of efficacy or treatment-related adverse events were considered non‑responders at subsequent timepoints; multiple imputation was used for all other missing data. The statistical analysis methods presented here refer to all outcomes, including those presented in the ESM. For all outcomes, descriptive statistics were used to summarize the results. No statistical hypothesis testing was performed on these post hoc analyses.

Results

Patient Disposition and Baseline Characteristics

In BE SURE, 91 and 151 patients with mNAPSI >0 at baseline were randomized to adalimumab and bimekizumab, respectively, and entered the BE BRIGHT OLE. Of the bimekizumab-randomized patients, 60 received bimekizumab Q4W/Q8W. In BE VIVID, 92 and 169 patients with mNAPSI >0 at baseline were randomized to ustekinumab and bimekizumab, respectively, and entered the BE BRIGHT OLE. There was no bimekizumab Q4W/Q8W group in BE VIVID.

In BE RADIANT, 155 and 182 patients with mNAPSI >0 at baseline were randomized to secukinumab and bimekizumab, respectively, and entered the BE RADIANT OLE. Of the bimekizumab-randomized patients, 100 received bimekizumab Q4W/Q8W.

Across all trials and arms included in these post hoc analyses, over half of patients had mNAPSI >10 and over 70% of patients had nail involvement on four or more nails at baseline. The mean mNAPSI score was consistent between arms, with a range of 18.3–21.0, and most patients had both nail matrix and nail bed involvement, with a range of 67.0–76.7% (Table 1).

Table 1.

Demographics and clinical characteristics of patients with nail involvement (mNAPSI >0) at baseline and who entered their respective open-label extensions

	BE SURE			BE VIVID		BE RADIANT
	BKZ Total (N = 151)	BKZ Q4W/Q8W (N = 60)	ADA/BKZ (N = 91)	BKZ Total (N = 169)	UST/BKZ (N = 92)	BKZ Total (N = 182)	BKZ Q4W/Q8W (N = 100)	SEC/BKZ (N = 155)
Age (years), mean (SD)	45.8 (12.3)	45.7 (11.9)	45.6 (14.0)	45.4 (13.7)	47.9 (12.9)	46.1 (14.6)	45.6 (15.0)	45.4 (12.9)
Male, n (%)	116 (76.8)	46 (76.7)	69 (75.8)	144 (85.2)	75 (81.5)	135 (74.2)	73 (73.0)	124 (80.0)
White, n (%)	132 (87.4)	52 (86.7)	82 (90.1)	122 (72.2)	68 (73.9)	167 (91.8)	95 (95.0)	153 (98.7)
Weight (kg), mean (SD)	92.9 (22.3)	92.3 (24.5)	90.5 (20.9)	91.5 (22.1)	89.5 (20.4)	91.3 (20.2)	92.5 (21.3)	92.2 (18.0)
BMI (kg/m2), mean (SD)	30.8 (7.0)	30.6 (7.0)	29.7 (6.3)	29.9 (6.5)	29.6 (6.1)	30.1 (6.1)	30.5 (6.3)	29.9 (5.4)
Duration of psoriasis (years), mean (SD)	20.0 (11.9)	18.3 (10.5)	16.1 (10.7)	16.8 (10.9)	18.9 (11.4)	19.1 (13.6)	19.8 (13.7)	18.0 (11.5)
PASI, mean (SD)	21.0 (7.1)	20.4 (6.4)	19.2 (6.1)	22.9 (8.4)	21.2 (8.6)	21.3 (8.7)	21.5 (9.1)	19.7 (6.1)
BSA (%), mean (SD)	28.0 (15.7)	25.9 (12.3)	25.5 (15.6)	30.0 (17.5)	26.5 (17.1)	26.8 (17.7)	26.0 (15.8)	22.3 (12.4)
IGA, n (%)
3: moderate	94 (62.3)	36 (60.0)	65 (71.4)	101 (59.8)a	55 (59.8)	107 (58.8)a	58 (58.0)a	111 (71.6)
4: severe	57 (37.7)	24 (40.0)	26 (28.6)	67 (39.6)	37 (40.2)	74 (40.7)	41 (41.0)	44 (28.4)
DLQI total score, mean (SD)	11.4 (6.3)	11.9 (5.6)	10.9 (7.6)	9.8 (6.3)	11.0 (7.0)	11.0 (6.8)	10.9 (7.0)	11.8 (7.4)
mNAPSI, mean (SD)	21.0 (20.5)	19.1 (15.9)	18.3 (18.3)	20.8 (20.5)	21.0 (19.9)	18.4 (18.1)	18.4 (17.2)	18.8 (18.6)
mNAPSI >10, n (%)	90 (59.6)	35 (58.3)	51 (56.0)	100 (59.2)	53 (57.6)	107 (58.8)	62 (62.0)	88 (56.8)
Patients with ≥4 nails involved, n (%)	111 (73.5)	46 (76.7)	72 (79.1)	122 (72.2)	71 (77.2)	133 (73.1)	75 (75.0)	112 (72.3)
Location of psoriasis on fingernails, n (%)
Only nail matrix psoriasisb	21 (13.9)	8 (13.3)	15 (16.5)	32 (18.9)	15 (16.3)	25 (13.7)	10 (10.0)	25 (16.1)
Only nail bed psoriasisc	20 (13.2)	6 (10.0)	15 (16.5)	17 (10.1)	9 (9.8)	32 (17.6)	15 (15.0)	16 (10.3)
Both nail bed and matrix psoriasisd	110 (72.8)	46 (76.7)	61 (67.0)	120 (71.0)	68 (73.9)	125 (68.7)	75 (75.0)	114 (73.5)
PsA, n (%)e	23 (15.2)	6 (10.0)	15 (16.5)	33 (19.5)	18 (19.6)	32 (17.6)	19 (19.0)	40 (25.8)
Any prior systemic therapy, n (%)	105 (69.5)	40 (66.7)	69 (75.8)	145 (85.8)	78 (84.8)	135 (74.2)	76 (76.0)	120 (77.4)
Any prior biologic therapy, n (%)	48 (31.8)	16 (26.7)	32 (35.2)	70 (41.4)	34 (37.0)	66 (36.3)	32 (32.0)	59 (38.1)

ADA adalimumab, BKZ bimekizumab, BMI body mass index, BSA body surface area, DLQI Dermatology Life Quality Index, IGA Investigator's Global Assessment, mNAPSI modified Nail Psoriasis Severity Index, PASE Psoriatic Arthritis Screening and Evaluation, PASI Psoriasis Area and Severity Index, PsA psoriatic arthritis, Q4W every 4 weeks, Q8W every 8 weeks, SD standard deviation, SEC secukinumab, UST ustekinumab

^aOne additional patient had an IGA of 2 (mild)

^bOnly nail matrix psoriasis: patients with a score >0 for at least one nail of any of the following: pitting, nail plate crumbling, leukonychia, red spots in the lunula and no scores >0 for onycholysis/oil drop dyschromia, splinter hemorrhages, nail bed hyperkeratosis on any nails

^cOnly nail bed psoriasis: patients with a score >0 for at least one nail of any of the following: onycholysis/oil drop dyschromia, splinter hemorrhages, nail bed hyperkeratosis and no scores >0 for pitting, nail plate crumbling, leukonychia, red spots in the lunula on any nails

^dBoth nail matrix and nail bed psoriasis: patients with a score >0 for nail matrix sub-scores on one or more nails and with a score >0 for nail bed sub-scores on one or more nails (can be across different nails)

^eMedical history of PsA or PASE >47. BKZ Total represents all bimekizumab dose groups combined

Complete Skin Clearance

Numerically higher proportions of bimekizumab-treated patients achieved complete skin clearance (PASI 100) versus comparators across all three head-to-head studies (Fig. 1; mNRI). At the end of comparator-controlled periods, 73.2% of all bimekizumab-treated versus 34.9% of adalimumab-treated patients in BE SURE (week 24; Fig. 1a), 70.1% of all bimekizumab-treated versus 40.7% of ustekinumab-treated patients in BE VIVID (week 52; Fig. 1c), and 75.7% of all bimekizumab-treated versus 48.4% of secukinumab-treated patients in BE RADIANT (week 48; Fig. 1e) achieved PASI 100 (mNRI).

Complete skin clearance was maintained in continuously bimekizumab-treated patients in the long term (Fig. 2). In patients who switched from comparators to bimekizumab, levels of complete skin clearance increased to similar levels to those treated continuously with bimekizumab by the end of each OLE (Fig. 2). Following completion of BE SURE and entry into BE BRIGHT, 73.2% of patients who switched from adalimumab to bimekizumab at week 24 achieved complete skin clearance at year 4 versus 62.9% of continuously bimekizumab-treated patients (Fig. 2a; mNRI). Following completion of BE VIVID and entry into BE BRIGHT, 65.7% of ustekinumab switchers and 59.9% of continuously bimekizumab-treated patients achieved complete skin clearance at year 4 (Fig. 2c; mNRI). Following entry into the BE RADIANT OLE, 67.9% of secukinumab switchers and 72.8% of continuously bimekizumab-treated patients achieved complete skin clearance at year 3 (Fig. 2e; mNRI).

Fig. 2.

Long-term complete skin clearance, nail clearance, and concurrent skin and nail clearance, including among switchers to bimekizumab (BKZ) (modified non-responder imputation [mNRI], observed case [OC]). a BE SURE/BE BRIGHT week 200; b over 4 years in BE SURE/BE BRIGHT; c BE VIVID/BE BRIGHT week 196; d over 4 years in BE VIVID/BE BRIGHT; e BE RADIANT week 144; f over 3 years in BE RADIANT. Kinetic plots and bar charts report mNRI. The tables report OC. BKZ Total represents all bimekizumab dose groups combined. Only patients with nail involvement (modified Nail Psoriasis Severity Index [mNAPSI] >0) at baseline who entered the open-label extensions were included in the analysis. ADA adalimumab, PASI 100 100% improvement from baseline in the Psoriasis Area and Severity Index, Q4W every 4 weeks, Q8W every 8 weeks, SEC secukinumab, UST ustekinumab

Complete Nail Clearance

Across all three head-to-head studies, higher proportions of bimekizumab-treated patients achieved complete nail clearance than patients treated with comparators (Fig. 1). After 24 weeks of treatment in BE SURE, 57.8% of all bimekizumab-treated patients achieved mNAPSI 0 versus 41.6% of adalimumab-treated patients (Fig. 1a; mNRI). After 52 weeks of treatment in BE VIVID, 69.0% of all bimekizumab- versus 48.7% of ustekinumab-treated patients achieved mNAPSI 0 (Fig. 1c; mNRI). After 48 weeks of treatment in BE RADIANT, 79.2% of all bimekizumab- versus 68.6% of secukinumab-treated patients achieved mNAPSI 0 (Fig. 1e; mNRI).

Following the switch to bimekizumab, levels of complete nail clearance increased in patients treated with comparators and were maintained by the end of the OLEs in both switchers and in continuously bimekizumab-treated patients (Fig. 2). At year 4, 72.3% of adalimumab switchers achieved complete nail clearance versus 67.9% of continuous bimekizumab-treated patients (BE BRIGHT; Fig. 2a; mNRI). Similarly, at year 4, 69.1% of ustekinumab switchers achieved complete nail clearance versus 67.3% of continuous bimekizumab-treated patients (BE BRIGHT; Fig. 2c; mNRI). Finally, at year 3, 72.2% of secukinumab switchers versus 71.2% of continuous bimekizumab-treated patients achieved complete nail clearance (BE RADIANT; Fig. 2e; mNRI).

Concurrent Complete Skin and Nail Clearance

Numerically higher proportions of all bimekizumab-treated patients achieved concurrent skin and nail clearance (PASI 100 and mNAPSI 0) when compared with adalimumab, ustekinumab, and secukinumab (Fig. 1). At the end of comparator-controlled periods, 45.8% of all bimekizumab-treated versus 18.3% of adalimumab-treated patients in BE SURE (week 24; Fig. 1a, b), 51.1% of all bimekizumab-treated versus 26.5% of ustekinumab-treated patients in BE VIVID (week 52; Fig. 1c, d), and 63.3% of all bimekizumab-treated versus 36.1% of secukinumab-treated patients in BE RADIANT (week 48; Fig. 1e, f) achieved concurrent complete skin and nail clearance (mNRI). Results for the approved bimekizumab dosing regimen (bimekizumab Q4W/Q8W) groups in BE SURE (Fig. 1b) and BE RADIANT (Fig. 1f) were consistent with the overall bimekizumab-treated populations (all dose regimens combined).

Levels of concurrent complete skin and nail clearance were maintained in continuously bimekizumab-treated patients and increased to similar levels in those patients who switched to bimekizumab. Following completion of BE SURE and entry into BE BRIGHT, 57.7% of adalimumab switchers and 49.1% of continuously bimekizumab-treated patients achieved concurrent complete skin and nail clearance at year 4 (Fig. 2a, b; mNRI). Following completion of BE VIVID and entry into BE BRIGHT, 52.2% of ustekinumab switchers and 48.3% of continuously bimekizumab-treated patients achieved concurrent complete skin and nail clearance at year 4 (Fig. 2c, d; mNRI). Following entry into BE RADIANT OLE, 51.9% of secukinumab switchers and 57.4% of continuously bimekizumab-treated patients achieved concurrent complete skin and nail clearance at year 3 (Fig. 2e, f; mNRI).

Similar results were observed when different treatment goals were used to classify skin outcomes (body surface area ≤1% and mNAPSI 0 [Fig. 2 of the ESM] or PASI ≤1 and mNAPSI 0 [Fig. 3 of the ESM]), with numerically higher proportions of bimekizumab-treated patients achieving these outcomes than patients treated with comparators.

Discussion

In these analyses, numerically higher proportions of bimekizumab-treated patients achieved complete skin clearance, complete nail clearance, and clearance of skin and nail psoriasis at the same time versus adalimumab, ustekinumab, and secukinumab, during comparator-controlled study periods of three phase III/IIIb trials. In the long term, levels of concurrent skin and nail clearance were maintained in patients continuously treated with bimekizumab. Following the switch from adalimumab, ustekinumab, or secukinumab to bimekizumab, rates of concurrent clearance of skin and nail psoriasis increased to similar levels to those treated continuously with bimekizumab from study entry, and were maintained through 3 (BE RADIANT) and 4 (BE BRIGHT) years. These results demonstrate high levels of long-lasting efficacy with bimekizumab across skin and nails individually, as well as in both of these GRAPPA-defined domains of psoriatic disease at the same time [11].

Although this analysis did not assess progression to PsA directly, nail involvement as well as severe skin involvement, among other clinical features reported in the published literature, have been shown to be associated with an increased medium-to-long-term risk of developing PsA in patients with psoriasis [5, 26–28]. The long-lasting complete clearance of nail and skin psoriasis by bimekizumab, as demonstrated here, may reflect its ability to resolve these factors that put patients at a higher risk for progression to PsA, and control underlying inflammation to lower progression to PsA. These findings also suggest that bimekizumab could serve as a surrogate marker for broader improvements in psoriatic disease, including potential benefits in PsA. In addition, achieving the threshold of complete skin clearance, as shown here, includes resolution of scalp psoriasis, further reflecting the efficacy of bimekizumab across multiple aspects of psoriasis [29]. Bimekizumab treatment has previously demonstrated complete and sustained clearance of the scalp in patients with moderate-to-severe scalp psoriasis, which has also been described as a clinical feature that may be associated with higher risk for PsA [19, 29]. Prospective studies are needed to determine whether resolution of risk factors for PsA, and sustained control of skin and nail inflammation, could influence patients’ disease trajectories from psoriasis to PsA.

The efficacy of bimekizumab across PsA disease domains, including joint, enthesitis, and dactylitis outcomes, has been demonstrated in the BE OPTIMAL and BE COMPLETE phase III trials [30, 31]. Additionally, the efficacy of bimekizumab in the axial domain and its related peripheral extra-musculoskeletal and peripheral manifestations, such as entheseal involvement, has been demonstrated in the BE MOBILE 1 and 2 phase III trials in the treatment of non-radiographic and radiographic axial ankylosing spondyloarthritis, respectively [32]. Moreover, bimekizumab has demonstrated consistent efficacy in the treatment of PsA and axial ankylosing spondyloarthritis irrespective of patients’ prior biologic exposure, including tumor necrosis factor inhibitors. Along with the results presented here in skin and nails, this demonstrates that bimekizumab provides durable complete resolution of inflammation across the spectrum of psoriatic disease domains [11]. As psoriasis is a systemic disease, with several identified metabolic, cardiovascular, and arthritic comorbidities, it is important to recognize the need for consistent cross-functional care across healthcare professionals to enable early detection and effective management across all domains of the disease [11, 33].

To the best of our knowledge, rates of concurrent clearance of skin and nail psoriasis have not been extensively analyzed among biologics, except for ixekizumab [34, 35]. Data shown here with bimekizumab were generally similar to or numerically higher than those in a similar analysis of patients treated with ixekizumab, an IL-17A inhibitor reported in one recent network meta-analysis to be the most effective therapy for nail psoriasis [34, 35]. In patients with moderate-to-severe nail psoriasis at baseline, treatment with ixekizumab across phase III trials in psoriasis resulted in concurrent clearance of skin and nails in 6.8–10.5% of patients at week 12 and 28.6–37.9% of patients at week 24, whilst 40.5% achieved both outcomes at week 52 (NRI) [34]. Here, treatment with bimekizumab resulted in 13.2–17.9% of patients at week 12 in BE SURE and BE VIVID, 45.8% of patients at week 24 in BE SURE, and 51.1–63.3% of patients across all included studies achieving both PASI 100 and mNAPSI 0 at Year 1 (week 48/52/56; mNRI).

One strength of these analyses is the direct head-to-head nature of the comparison during comparator-controlled periods, rather than being an indirect or mixed treatment comparison such as a network meta-analysis. Meanwhile, a limitation of these analyses is the inclusion of patients that entered the OLE only, rather than all randomized patients, which may bias results shown for comparator-controlled periods as only patients who completed the first year of treatment were included. However, the number of bimekizumab-randomized patients with nail involvement who discontinued treatment prior to entering the OLEs was low, with a range of 10.8–16.6% across included studies, and so this is not expected to have had a large impact on the results presented here.

Conclusions

Bimekizumab treatment resulted in numerically higher proportions of patients achieving complete clearance of psoriasis across both skin and nails, compared with adalimumab, ustekinumab, and secukinumab, in patients with nail psoriasis at baseline. Patients switching from comparators to bimekizumab demonstrated further improvement in skin and nail symptoms, and sustained complete clearance of both in the long term, similar to those continuously treated with bimekizumab. The ability of bimekizumab to treat multiple domains of psoriatic disease could be highly advantageous to patients with psoriasis who are candidates for systemic therapy.

Supplementary Information

Below is the link to the electronic supplementary material.

Declarations

Funding

This study was sponsored by UCB. This article, and its associated graphical abstract, were based on the original studies BE VIVID (NCT03370133), BE SURE (NCT03412747), BE BRIGHT (NCT03598790), and BE RADIANT (NCT03536884), sponsored by UCB. Support for third-party writing assistance for this article and its associated graphical abstract, provided by Michael Haycox, PhD, Alexa Holland, MSc, and Ria Gill, BSc, Costello Medical, UK, was funded by UCB in accordance with Good Publication Practice (GPP 2022) guidelines (https://www.ismpp.org/gpp-2022).

Conflicts of Interest/Competing Interests

Joseph F. Merola: consultant and/or investigator for AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Dermavant, Eli Lilly and Company, Incyte, Janssen, LEO Pharma, MoonLake Immunotherapeutics, Novartis, Pfizer, Sanofi-Regeneron, Sun Pharma, and UCB. Richard B. Warren: consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DICE Therapeutics, Eli Lilly and Company, GSK, Janssen, LEO Pharma, Meiji Pharma, Novartis, Pfizer, RAPT Therapeutics, Sanofi, Sun Pharma, UCB, and Union; research grants to his institution from AbbVie, Almirall, Amgen, Celgene, Eli Lilly and Company, Janssen, LEO Pharma, Novartis, Pfizer, and UCB; honoraria from AbbVie, Almirall, Bristol Myers Squibb, Eli Lilly and Company, Galderma, Janssen, and Novartis. Diamant Thaçi: investigator and/or consultant/advisor for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Galderma, Johnson & Johnson, Kyowa Kirin, LEO Pharma, L’Oreal, New Bridge, Novartis, Pfizer, Regeneron, Samsung, Sanofi, Takeda, Target-RWE, UCB, and Vichy; received grants from AbbVie, LEO Pharma, and Novartis. Kenneth B. Gordon: received consulting fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly and Company, Janssen, Novartis, Pfizer, Sun Pharma, and UCB; research support from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, and UCB. Emi Nishida: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly and Company, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, Taiho, Torii, and UCB. Bruce Strober: consultant (honoraria) for AbbVie, Alumis, Almirall, Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Capital One, CorEvitas, Dermavant, Janssen, LEO Pharma, Eli Lilly and Company, Maruho, Oruka, Meiji Seika Pharma, Protagonist, Takeda, Novartis, Pfizer, UCB, Rapt, Regeneron, Sanofi-Genzyme, and Union Therapeutics; stock options from Connect Biopharma and Mindera Health; speaker for AbbVie, Arcutis, Dermavant, Eli Lilly and Company, Incyte, Janssen, Regeneron, and Sanofi Genzyme; scientific co-director (consulting fee): CorEvitas Psoriasis Registry; investigator for CorEvitas Psoriasis Registry; editor-in-chief (honorarium): Journal of Psoriasis and Psoriatic Arthritis. Curdin Conrad: consultant and/or principal investigator in clinical trials for AbbVie, Actelion, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galderma, Incyte, Johnson & Johnson, LEO Pharma, MSD, Novartis, Pfizer, Samsung, Sanofi, Takeda, and UCB. Sarah Kavanagh: consultant for Aclipse Therapeutics, Aliada Therapeutics, Allay Therapeutics, Autobahn Therapeutics, Cognition Therapeutics, Colorado Prevention Center, Karuna Therapeutics, Kisbee Therapeutics, LB Pharmaceuticals, Nesos, Novartis, Onward Medical, PharPoint Research, Summit Analytical, Tonix Pharmaceuticals, Tornado Therapeutics, UCB, Whitsell Innovations, Worldwide Clinical Trials, and Zosano Pharma. José Manuel López Pinto, Bengt Hoepken: employees and shareholders of UCB. Paolo Gisondi: consultant for AbbVie, Abiogen, Almirall, Celgene, Eli Lilly and Company, Janssen, LEO Pharma, Merck, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Sanofi, and UCB.

Ethics Approval

Studies were conducted in accordance with the principles of the Declaration of Helsinki and approved by an independent review board and independent ethics committee.

Consent to Participate

All participants provided informed written consent documented in accordance with local regulations.

Consent for Publication

All the results presented in this article are in aggregate form, and no personally identifiable information was used for this study.

Availability of Data and Material

Underlying data from this article may be requested by qualified researchers 6 months after product approval in the USA and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents, which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of these data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password-protected portal.

Code Availability

Not applicable.

Authors’ Contributions

Substantial contributions to study conception and design: JFM, RBW, DT, KBG, EN, BS, CC, SK, JMLP, BH, PG; substantial contributions to analysis and interpretation of the data: JFM, RBW, DT, KBG, EN, BS, CC, SK, JMLP, BH, PG; drafting the article or revising it critically for important intellectual content: JFM, RBW, DT, KBG, EN, BS, CC, SK, JMLP, BH, PG; final approval of the version of the article to be published: JFM, RBW, DT, KBG, EN, BS, CC, SK, JMLP, BH, PG.