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1 Bimekizumab efficacy and safety in patients with moderate to severe
2 plaque psoriasis who switched from adalimumab, ustekinumab, or

3 secukinumab: Results from phase 3/3b trials
4 Running head: Switching to Bimekizumab in Plaque Psoriasis
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Downloaded from https://academic.oup.com/bjd/advance-article/doi/10.1093/bjd/ljac089/6850554 by guest on 03 December 2022
5 Georgios Kokolakis,1 Richard B. Warren,2 Bruce Strober,3,4 Andrew Blauvelt,5 Luis Puig,6
6 Akimichi Morita,7 Melinda Gooderham,8,9 Andreas Körber,10 Veerle Vanvoorden,11 Maggie
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7 Wang,12 Dirk de Cuyper,11 Cynthia Madden,12 Natalie Nunez Gomez13 and Mark
8 Lebwohl14
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1
9 Psoriasis Research and Treatment Center, Department of Dermatology, Venereology
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10 and Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie
11 Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; 2Dermatology
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Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research
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13 Centre, The University of Manchester, Manchester, UK; 3Yale University, New Haven, CT,
14 USA; 4Central Connecticut Dermatology Research, Cromwell, CT, USA; 5Oregon Medical
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15 Research Center, Portland, OR, USA; 6Hospital de la Santa Creu i Sant Pau, Universitat
16 Autònoma de Barcelona, Barcelona, Spain; 7Nagoya City University Graduate School of
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17 Medical Sciences, Nagoya, Japan; 8SKiN Centre for Dermatology, Probity Medical
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18 Research, Peterborough, ON, Canada; 9Queen’s University, Kingston, ON, Canada;

10 11 12
19 HautaerzteRue143, Essen, Germany; UCB Pharma, Brussels, Belgium; UCB Pharma,
13 14
20 Morrisville, NC, USA; UCB Pharma, Monheim, Germany; Icahn School of Medicine at
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21 Mount Sinai, New York, NY, USA

22
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23 Correspondence: Dr Georgios Kokolakis

24 Email: [email protected]
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25
26
© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of
Dermatologists. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse,
distribution, and reproduction in any medium, provided the original work is properly cited. 1
1 ABSTRACT
2 Background: Discontinuation of biologics is common among patients with psoriasis due

3 to treatment failure or adverse events. To achieve improvements in disease
4 management, patients and clinicians may choose to switch biologics.
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Objective: Evaluate the efficacy and safety of switching to bimekizumab from
adalimumab, ustekinumab, and secukinumab.
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5 Methods: Data are reported for up to 80 weeks after patients switched to bimekizumab
6 from adalimumab at Week 24 in BE SURE, ustekinumab at Week 52 in BE VIVID (upon
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7 entry into the BE BRIGHT OLE), and secukinumab at Week 48 in BE RADIANT (upon
8 entry into the BE RADIANT OLE).
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9 Efficacy outcomes are reported by number of weeks after switching to bimekizumab and
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were split based on whether patients had achieved a 90% reduction from baseline in
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11 Psoriasis Area and Severity Index (PASI 90) at the time of switch. Treatment-emergent
adverse events (TEAEs) are reported using exposure-adjusted incidence rates (EAIRs)
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12
13 per 100 patient-years.
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14 Results: Rapid and durable improvements in clinical responses and benefits in health-
related quality of life were observed among PASI 90 non-responders who switched to
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15
16 bimekizumab. Most PASI 90 non-responders achieved PASI 90 four weeks after
17 switching to bimekizumab from adalimumab (66.7%), ustekinumab (79.1%), and
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18 secukinumab (52.5%). After 48 weeks of bimekizumab, 90.7%, 89.5%, and 79.2% of

19 PASI 90 non-responders had achieved PASI 90 after switching from adalimumab,
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20 ustekinumab, or secukinumab, respectively. Durable improvements were also observed

21 for PASI 100, Investigator’s Global Assessment score (IGA) 0/1, body surface area
22 affected by psoriasis (BSA) ≤1%, absolute PASI ≤2, and Dermatology Life Quality Index
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23 (DLQI) 0/1. Among PASI 90 responders, existing treatment responses were maintained
24 or improved after switching to bimekizumab.
25 The majority of TEAEs were mild or moderate. EAIRs were generally similar between
26 active-comparator treatment periods and after switching to bimekizumab. EAIRs typically
27 decreased with a longer duration of bimekizumab exposure.
2
1 Conclusions: High proportions of patients who did not adequately respond to
2 adalimumab, ustekinumab, or secukinumab, achieved high levels of skin clearance after
3 switching to bimekizumab. Bimekizumab was well-tolerated and there were no new
4 safety findings.
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Trial Registration: BE SURE (NCT03412747), BE VIVID (NCT03370133), BE BRIGHT

5
6 (NCT03598790), BE RADIANT (NCT03536884).
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7 INTRODUCTION
8 The introduction of biologic agents has substantially improved clinical outcomes for
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9 patients with moderate to severe plaque psoriasis.1,2 Despite this, real-world data
10 indicate that discontinuation of biologics is common with the most prevalent reasons
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11 being primary failure, secondary failure, and adverse events.3 As a result, many patients
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and clinicians choose to switch biologics in an attempt to achieve improvements in
disease management and clinical outcomes.4,5 This applies to patients seeking to
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14 improve upon an existing treatment response and patients with an inadequate response
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15 to initial biologics.4
16 Biologic therapies for the treatment of psoriasis inhibit specific proinflammatory

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17 cytokines implicated in psoriasis pathophysiology, including tumor necrosis factor-alpha

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18 (TNF-α), interleukin (IL)‑17, and IL-12 and/or IL-23.1,6 Due to the availability of low-cost
19 biosimilars, many biologic experienced patients receive first-line treatment with
adalimumab (TNF-α inhibitor).7,8 Furthermore, due to their earlier availability, many
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20
21 patients are initially treated with ustekinumab (IL-12/23 inhibitor) or secukinumab (IL-
22 17A inhibitor).9,10 Findings of a recent network meta‑analysis suggested that prior
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23 biologic use may be a risk factor for future biologic failure in patients with moderate to
24 severe plaque psoriasis.11 Therefore, for patients and clinicians to make informed
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25 treatment decisions, it is important to directly assess the efficacy and safety of switching
26 from common biologics.5
27 Bimekizumab is a monoclonal IgG1 antibody that inhibits both IL-17A and IL-17F.12 IL-
28 17F, which shares 50% homology with IL-17A, is elevated in psoriatic lesions and
29 demonstrates proinflammatory functions, similar to IL-17A.12,13 In the BE SURE,
3
1 BE VIVID, and BE RADIANT phase 3/3b trials, treatment with bimekizumab led to rapid
2 and substantial clinical improvements in patients with moderate to severe plaque
3 psoriasis.14-16 In BE RADIANT, greater proportions of patients achieved complete skin
4 clearance with bimekizumab over 16 and 48 weeks vs. secukinumab, which may reflect
5 the increased anti-inflammatory effect associated with dual inhibition of IL‑17A and IL-
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6 17F compared with IL-17A inhibition alone.13,16
7 In addition to improvements in clinical outcomes, the safety profile of switching biologics
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8 is an important consideration for clinicians and patients. The overall incidence of
9 treatment emergent adverse events (TEAEs) with bimekizumab was comparable to
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10 adalimumab in BE SURE, ustekinumab in BE VIVID, and secukinumab in BE RADIANT,
11 with the exception of an increased incidence of mild to moderate oral candidiasis, which
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12 did not lead to increased rates of treatment discontinuation.14-16 Here, we report efficacy
and safety data through two years of treatment among patients who switched to
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bimekizumab from adalimumab at Week 24 in BE SURE, ustekinumab at Week 52 in BE
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15 VIVID (upon entry into the BE BRIGHT open-label extension [OLE]), and secukinumab at
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16 Week 48 in BE RADIANT (upon entry into the BE RADIANT OLE).
17 PATIENTS and METHODS

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Patient population
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18
19 Data are reported from three active comparator-controlled phase 3/3b trials and their
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20 OLEs (BE SURE [NCT03412747], BE VIVID [NCT03370133], BE BRIGHT [NCT03598790],

21 and BE RADIANT [NCT03536884]).14-16 Full inclusion and exclusion criteria have been
described.14-16 All trials enrolled patients with moderate to severe plaque psoriasis, with
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22
23 a baseline Psoriasis Area and Severity Index (PASI) ≥12, ≥10% body surface area (BSA)
24 affected by psoriasis, and an Investigator’s Global Assessment (IGA) score ≥3 on a 5-
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25 point scale, who were eligible for systemic psoriasis therapy and/or phototherapy. All
26 patients entering the trials provided written informed consent, obtained and documented
27 in accordance with local regulations and ethical principles originating from the
28 Declaration of Helsinki.
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1 Study design
2 Full study designs for BE SURE, BE VIVID, and the 48-week double-blinded period of BE
3 RADIANT have been reported.14-16 Study designs for the patients included in these
4 analyses are presented in Figure 1.
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The 56-week BE SURE trial randomized patients in a 1:1:1 ratio to adalimumab or two

5
6 bimekizumab dosing schedules. Adalimumab-randomized patients received 80 mg at
7 baseline, 40 mg at week 1, then 40 mg every 2 weeks (Q2W). At Week 24, all
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8 adalimumab-randomized patients were switched to bimekizumab 320 mg every 4 weeks
9 (Q4W) for the remainder of the trial. The 52‑week BE VIVID trial randomized patients in
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10 a 2:4:1 ratio to ustekinumab, bimekizumab, or placebo. Ustekinumab-randomized
11 patients received 45 mg or 90 mg at baseline, Week 4, then every 12 weeks (Q12W).
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12 Dosing was 45 mg for patients ≤100 kg and 90 mg for patients >100 kg at baseline.
Eligible patients who completed BE SURE and BE VIVID could enroll in the BE BRIGHT
13
14 OLE.
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In BE BRIGHT, patients received bimekizumab 320 mg Q4W or Q8W, depending on
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15
16 treatment and PASI 90 response at the end of the feeder trials. Patients receiving
17 bimekizumab 320 mg Q4W at the end of BE SURE, with a Week 56 PASI 90 response
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18 (PASI 90 responders), were randomized 4:1 to bimekizumab 320 mg Q4W or Q8W.

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19 Patients who did not achieve a Week 56 PASI 90 response (PASI 90 non-responders)
20 continued to receive bimekizumab 320 mg Q4W upon entry into BE BRIGHT.
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21 Ustekinumab-randomized Week 52 PASI 90 responders in BE VIVID were randomized

22 1:1 to bimekizumab 320 mg Q4W or Q8W upon entry into BE BRIGHT; Week 52 PASI 90
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23 non-responders received bimekizumab 320 mg Q4W upon entry into BE BRIGHT. At

24 Week 24 of BE BRIGHT, patients receiving bimekizumab 320 mg Q4W who achieved
25 PASI 90 could switch to bimekizumab 320 mg Q8W at the investigator’s discretion.
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26 In BE RADIANT, patients were randomized to secukinumab 300 mg weekly to Week 4

27 then Q4W (in a 1:1 ratio with bimekizumab). Eligible patients who completed the 48-
28 week double-blinded period could enroll in the BE RADIANT OLE. On entering the OLE,
29 patients initially randomized to secukinumab received bimekizumab 320 mg Q4W or
30 Q8W, depending on Week 48 PASI 90 response. Secukinumab-randomized Week 48
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1 PASI 90 responders were randomized 1:1 to bimekizumab 320 mg Q4W or Q8W; Week
2 48 PASI 90 non‑responders received bimekizumab 320 mg Q4W. During the BE
3 RADIANT OLE, patients switched from bimekizumab 320 mg Q4W to Q8W at Week 64
4 (OLE Week 16), or at the next scheduled clinic visit if the patient had already completed
5 Week 64, after the implementation of a protocol amendment.
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6
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7
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8 Efficacy outcomes
9 Proportions of patients who achieved PASI 90, PASI 100, IGA 0/1, BSA ≤1%, PASI ≤2,
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10 and Dermatology Life Quality Index (DLQI) 0/1 are reported by the number of weeks
11 after switching to bimekizumab from adalimumab, ustekinumab, and secukinumab,
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regardless of bimekizumab dosing (bimekizumab total). Efficacy outcomes are reported
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13 by PASI 90 response status at the time of switch.
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14 Safety outcomes
15 TEAEs, TEAEs leading to discontinuation, and serious adverse events (SAEs) are
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16 reported during treatment with adalimumab, ustekinumab, or secukinumab, and after

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17 switching to bimekizumab. To cover the half-life of each comparator biologic and

18 capture TEAEs when both biologics were present, bimekizumab safety data were split by
≤6 months and >6 months after receiving the first bimekizumab dose. TEAEs are
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19
20 reported through to Week 48 of the OLEs.
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21 TEAEs were defined as AEs that occurred during exposure to treatment and up to 140
22 days after the last dose of bimekizumab. TEAEs were coded according to the Medical
23 Dictionary for Regulatory Activities (MedDRA) version 19.0. The intensity of TEAEs was
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24 recorded by the investigator as mild, moderate, or severe. Safety topics of interest were
25 infections (serious, opportunistic, tuberculosis, and fungal), malignancies, major adverse
26 cardiac events (MACE), neutropenia, suicidal ideation and behavior (SIB), inflammatory
27 bowel disease (IBD), and hypersensitivity. Elevated liver enzyme TEAEs and laboratory
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1 elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) are
2 also reported.
3 Statistical analysis
4 Comparisons of efficacy and safety outcomes were not pre-specified in these analyses,
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5 therefore inferential statistical comparisons were not performed. Missing data were
6 accounted for using modified non-responder imputation (mNRI). For mNRI, patients
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7 with missing data following treatment discontinuation due to lack of efficacy were
8 considered non-responders, whereas all other missing data were imputed using multiple
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9 imputation. NRI and observed case (OC) are also reported in the Supplement. TEAEs
10 were evaluated based on exposure-adjusted incidence rates (EAIRs) per 100
11 patient-years with associated 95% confidence intervals. The percentage of patients who
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12 experienced TEAEs are reported in the Supplement.
13 RESULTS
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14 Patient population
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15 In BE SURE, 159 patients were randomized to adalimumab; 149 switched to
16 bimekizumab 320 mg Q4W at Week 24; 129 completed the trial to Week 56 and entered
the BE BRIGHT OLE (Figure S1). In BE VIVID, 163 patients were randomized to
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18 ustekinumab; 136 completed the trial to Week 52 and switched to bimekizumab upon
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19 entry into the BE BRIGHT OLE (Figure S2). In BE RADIANT, 370 patients were
20 randomized to secukinumab; 309 completed the 48‑week double-blinded treatment
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21 period and switched to bimekizumab upon entry into the BE RADIANT OLE (Figure S3).
22 Demographics and baseline characteristics were representative of a patient population

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23 with moderate to severe plaque psoriasis eligible for biologic therapy (Table 1).
24 Baseline characteristics were generally similar between PASI 90 responders and PASI 90
non-responders within each trial.
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1 Efficacy
2 Efficacy outcomes in PASI 90 non-responders
3 A total of 54/159 (34.0%) adalimumab-randomized, 44/163 (27.0%)

4 ustekinumab-randomized, and 53/370 (14.3%) secukinumab‑randomized patients who
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5 did not achieve PASI 90 at the end of the active-comparator treatment period entered
6 the OLEs (Figures S1–S3).
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7 Among the PASI 90 non-responders, 66.7% (adalimumab/bimekizumab), 79.1%
8 (ustekinumab/bimekizumab), and 52.5% (secukinumab/bimekizumab) achieved PASI 90
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9 four weeks after one dose of bimekizumab (Figure 2A). Furthermore, 33.3%
10 (adalimumab/bimekizumab), 41.9% (ustekinumab/bimekizumab), and 20.9%
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11 (secukinumab/bimekizumab) of the PASI 90 non-responders achieved PASI 100 four
12 weeks after switching (Figure 2B).
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13 Among adalimumab, ustekinumab, and secukinumab PASI 90 non-responders, clinical
responses continued to improve after switching to bimekizumab; 48 weeks after switch,
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15 90.7% (adalimumab/bimekizumab), 89.5% (ustekinumab/bimekizumab), and 79.2%
16 (secukinumab/bimekizumab) of patients achieved PASI 90 (Figure 2A). Meanwhile,
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17 70.1% (adalimumab/bimekizumab), 58.1% (ustekinumab/bimekizumab), and 50.9%

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18 (secukinumab/bimekizumab) of patients achieved PASI 100 (Figure 2B). After switching

19 to bimekizumab, a similar pattern of rapid and durable response was reported for
IGA 0/1 (Figure 2C), BSA ≤1% (Figure 2D), and PASI ≤2 (Table S1). Improvements
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20
21 in clinical responses in PASI 90 non‑responders were comparable using mNRI, NRI and
22 OC (Figures S4–S5, Table S1).
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23 Benefits in health-related quality of life (HRQoL) were observed with bimekizumab; 24

24 weeks after switching, DLQI 0/1 response rates increased from 29.6% to 80.7%
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25 (adalimumab/bimekizumab), 48.8% to 81.4% (ustekinumab/bimekizumab), and 51.0%

26 to 85.7% (secukinumab/bimekizumab), these were maintained for at least 48 weeks
27 post-switch (Table 2). Similar improvements in DLQI 0/1 were observed using mNRI,
28 NRI and OC (Table S2).
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1 Efficacy outcomes in PASI 90 responders
2 A total of 75/159 (47.2%) adalimumab-randomized, 92/163 (56.4%)

3 ustekinumab-randomized, and 256/370 (69.2%) secukinumab‑randomized patients who
4 achieved PASI 90 at the end of the active-comparator treatment period entered the
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OLEs (Figures S1–S3).

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6 Among adalimumab, ustekinumab, and secukinumab PASI 90 responders, clinical
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7 responses were maintained or improved following switch to bimekizumab; 48 weeks
8 after switch, 96.0% (adalimumab/bimekizumab), 100% (ustekinumab/bimekizumab),
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9 and 95.2% (secukinumab/bimekizumab) of patients maintained PASI 90 (Figure 3A).
10 Furthermore, 48 weeks after switching to bimekizumab, proportions of PASI 90
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11 responders who achieved PASI 100 increased from 58.7% to 82.7%
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to 79.9% (secukinumab/bimekizumab) (Figure 3B). Among PASI 90 responders, the
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14 high level of IGA 0/1, BSA ≤1%, and PASI ≤2 responses at the time of switch were
maintained with bimekizumab treatment (Figures 3C–3D, Table S1). The pattern of
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16 clinical responses after switching to bimekizumab was similar using mNRI, NRI and OC
17 (Figures S6–S7, Table S1).
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DLQI 0/1 response rates at the time of switching were 69.3%

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19 (adalimumab/bimekizumab), 85.8% (ustekinumab/bimekizumab), and 87.5%
20 (secukinumab/bimekizumab) (Table 2). After 24 weeks of bimekizumab treatment,
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21 DLQI 0/1 response rates were comparable between all groups (range: 86.6%–88.1%)
22 and maintained for at least 48 weeks after switching (Table 2). Proportions of PASI 90
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23 responders who achieved DLQI 0/1 were similar using mNRI, NRI and OC (Table S2).
24 Safety
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25 In the first 6 months after receiving the first bimekizumab dose, TEAEs occurred at an
26 EAIR of 256.7/100 PY, 258.0/100 PY, and 200.1/100 PY for patients who had switched
27 from adalimumab, ustekinumab, or secukinumab, respectively (Table 3). The majority
28 of TEAEs were mild or moderate (Table 3). EAIRs did not increase with longer duration
29 of bimekizumab exposure (Tables 3–4).
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1 The most common TEAEs after switching to bimekizumab were nasopharyngitis, oral
2 candidiasis, upper respiratory tract infection, and urinary tract infection (Table 4).
3 Overall, the EAIR of serious infections remained low after patients switched to
4 bimekizumab (Table 4). The EAIR of oral candidiasis increased during the first 6 months
5 after switching to bimekizumab. Although EAIRs generally decreased with a longer
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6 duration of bimekizumab exposure, the EAIR remained higher than active comparators
7 >6 months after the first bimekizumab dose. In the first 6 months after switching to
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8 bimekizumab from adalimumab or secukinumab, the EAIR of nasopharyngitis decreased
9 and the EAIR of urinary tract infection remained similar, whereas both increased after
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10 switching to bimekizumab from ustekinumab (Table 4). The EAIR of upper respiratory
11 tract infection decreased after switching to bimekizumab (Table 4).
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12 The EAIR of elevated liver enzymes did not increase in patients who switched to
bimekizumab from adalimumab, ustekinumab, or secukinumab. Elevations in AST or ALT
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14
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were generally similar to active comparators in the first 6 months after switching to
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15 bimekizumab and did not increase following a longer duration of bimekizumab exposure
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16 (Table 4). EAIRs of IBD, malignancies, MACE, and serious hypersensitivity reactions
17 were low during the active-comparator treatment periods and remained low after
switching to bimekizumab (Table 4). Similarly, the EAIR of neutropenia remained low
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19 after switching to bimekizumab from ustekinumab or secukinumab, and decreased in
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20 patients who switched from adalimumab (Table 4). There were no incidences of
21 adjudicated SIB after switching to bimekizumab (Table 4).
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22 DISCUSSION
In these analyses, we report clinical responses among patients who switched to

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23
24 bimekizumab from adalimumab, ustekinumab, or secukinumab in BE SURE/BE BRIGHT,
25 BE VIVID/BE BRIGHT, and BE RADIANT/BE RADIANT OLE.14-16 Most PASI 90 non-
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26 responders (at the time of switching to bimekizumab from an active-comparator)

27 achieved PASI 90 within four weeks of bimekizumab treatment, and high levels of
28 responses were observed for at least 48 weeks of bimekizumab treatment. Over 95% of
29 PASI 90 responders (at the time of switching to bimekizumab from an active-
30 comparator) maintained this response through 48 weeks of bimekizumab, and the
31 proportion of PASI 90 responders who achieved PASI 100 increased after switching.
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1 These data demonstrate that high proportions of patients can either maintain or achieve
2 complete and/or near complete skin clearance after switching to bimekizumab from a
3 prior biologic therapy.
4 Given the availability of lower cost biosimilars and health care coverage preferences in
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numerous countries, treatment guidelines often recommend adalimumab as the first-line

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6 biologic therapy for the treatment of psoriasis.7,8 In these analyses, rapid and substantial
7 improvements in clinical and HRQoL outcomes were demonstrated in patients who
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8 switched to bimekizumab after an inadequate response to 24 weeks of adalimumab
9 treatment. These responses were maintained for up to 80 weeks after switching to
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10 bimekizumab, an important consideration given that secondary failure is a common
11 reason for discontinuing biologics.3
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12 Four weeks after switching to bimekizumab, higher levels of response were observed in
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PASI 90 non-responders who switched from ustekinumab (IL-12/23 inhibitor) vs.
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14 secukinumab (IL-17A inhibitor). IL-17 is a key effector cytokine in psoriasis
pathophysiology and the earlier response in ustekinumab switchers may relate to
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16 bimekizumab inhibiting IL-12/23 independent sources of IL-17.13 Nevertheless, over
17 50% of PASI 90 non-responders achieved PASI 90 four weeks after switching from
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18 secukinumab to bimekizumab, which increased to 79.2% after 48 weeks of

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19 bimekizumab. This supports previous observations of successful intra-class switching

20 among anti-IL‑17 biologics and highlights the benefit of dual inhibition of IL-17A and IL-
21 17F.17,18
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22 In PASI 90 responders at switch, rates of complete skin clearance (PASI 100) after 48
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23 weeks of bimekizumab treatment increased from 58.7% to 82.7%

25 to 79.9% (secukinumab/bimekizumab). PASI 100 is associated with improved HRQoL vs.
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26 PASI 90 in patients with psoriasis.19 In these analyses, in addition to improvements in

27 skin clearance, increased rates of DLQI 0/1 were observed after switching to
28 bimekizumab.
29 It is important to evaluate the safety of switching between biologic treatments. In these

30 analyses, switching from adalimumab, ustekinumab, or secukinumab to bimekizumab
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1 was well-tolerated and there were no new safety findings. Overall, safety data were
2 comparable to those previously reported in phase 3/3b bimekizumab clinical trials in
3 plaque psoriasis.14-16,20 In line with the mechanism of action of bimekizumab, and the
4 contribution of IL-17A and IL-17F to host protection against oral mucosal fungal
5 infection,21,22 the incidence of oral candidiasis increased after switching to bimekizumab.
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6 Most oral candidiasis cases were mild to moderate and assessed as treatment-related.
7 Consistent with previous reports, the vast majority of cases did not lead to treatment
discontinuation.14-16,20
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8
9 In these trials, the time between the last dose of active comparator and first dose of
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10 bimekizumab was limited, which may be more reflective of patients switching biologics
11 in clinical practice. All data were reported through to Week 48 of the OLEs and included
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12 data for up to 80 weeks post‑switch; this is a key strength and ensured that the
longer-term efficacy and safety of switching to bimekizumab were evaluated. In
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14
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addition, the similarity between results using three methods of data imputation (mNRI,
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15 NRI, OC) demonstrate the robustness of the data.
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17 Given that patients switched to bimekizumab at different time points in each of the
18 trials, bimekizumab efficacy data were not available for the same time periods for all
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19 patients. Furthermore, since bimekizumab dosing could change (from Q4W to Q8W) in
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20 the OLEs per study design, the ability to draw conclusions on different bimekizumab
21 maintenance dosing regimens is limited. As Q8W bimekizumab dosing has been
22 associated with lower EAIRs of TEAEs versus Q4W,20 this may have contributed to the
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23 reduction in TEAEs observed with a longer duration of bimekizumab exposure. Of note,

24 similar and high levels of efficacy have previously been demonstrated with both Q4W
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25 and Q8W bimekizumab dosing regimens.14-16
26 In summary, we demonstrate that patients who do not adequately respond to treatment

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27 with adalimumab, ustekinumab, or secukinumab can achieve rapid and high levels of
28 clinical responses and HRQoL benefit after switching to bimekizumab. Furthermore,
29 clinical responses were maintained or improved in patients with an existing treatment
30 response on a prior biologic. The benefits of switching to bimekizumab likely reflect the
31 increased anti-inflammatory effect associated with dual inhibition of IL-17A and IL-17F.
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1 Overall, switching to bimekizumab was well‑tolerated and there were no new safety
2 findings.
3 ACKNOWLEDGEMENTS
4 The authors thank the patients, the investigators and their teams who took part in this
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5 study. The authors also acknowledge Susanne Wiegratz, MSc, UCB Pharma, Monheim,
6 Germany, for publication coordination and Robert Jones, PhD, and Claire Hews, PhD,
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7 from Costello Medical, UK, for medical writing and editorial assistance based on the
8 authors’ input and direction. This study was funded by UCB Pharma. Richard B. Warren
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9 is supported by the Manchester NIHR Biomedical Research Centre.
10 Funding: These studies were sponsored by UCB Pharma. Support for third-party writing
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11 assistance for this article, provided by Robert Jones, PhD, and Claire Hews, PhD,
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13
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Costello Medical, UK, was funded by UCB Pharma in accordance with Good Publication
Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).
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14 Conflicts of interest: GK: Received travel grants or honoraria, or has been a
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15 consultant member of advisory boards and speaker bureaus or has served as

16 investigator for AbbVie, Actelion, Almirall, Amgen, Basilea, Biogen, Boehringer
Ingelheim, Bristol Myers Squibb, Celgene, Hexal-Sandoz, Janssen-Cilag, LEO Pharma, Eli
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17
18 Lilly, MSD, Novartis, Pfizer, Sanofi, and UCB Pharma. RBW: Consulting fees from
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19 AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Bristol Myers Squibb,
20 Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer,
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21 Sanofi, and UCB Pharma; research grants to his institution from AbbVie, Almirall,
22 Janssen, LEO Pharma, Novartis, and UCB Pharma; honoraria from Astellas, DiCE, GSK,
and Union. BS: Consultant (honoraria) for AbbVie, Almirall, Amgen, Arcutis, Arena,
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23
24 Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Connect Biopharma,
25 Dermavant, Eli Lilly, EPI Health, Evelo Biosciences, Immunic Therapeutics Janssen, LEO
A
26 Pharma, Maruho, Meiji Seika Pharma, Mindera Health, Novartis, Ono, Pfizer, Regeneron,
27 Sanofi Genzyme, Sun Pharma, UCB Pharma, Union Therapeutics, Ventyxbio, and vTv
28 Therapeutics; stock options for Connect Biopharma and Minder Health; speaker for
29 AbbVie, Eli Lilly, Incyte, Janssen, Regeneron, and Sanofi Genzyme; scientific co-director
30 (consulting fee) for CorEvitas (formerly Corrona) Psoriasis Registry; investigator for
31 AbbVie, Cara, CorEvitas Psoriasis Registry, Dermavant, Dermira, and Novartis; editor-in-
13
1 chief (honoraria) for the Journal of Psoriasis and Psoriatic Arthritis. AB: Has served as a
2 speaker/received honoraria from AbbVie, Eli Lilly and Company, and UCB; served as a
3 scientific adviser/received honoraria from AbbVie, Abcentra, Affibody, Aligos, Almirall,
4 Alumis, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim,
5 Bristol Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly and Company,
PT
6 Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, Janssen,
7 Landos, LEO Pharma, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme,
RI
8 Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB Pharma,
9 Vibliome, and Xencor; acted as a clinical study investigator/institution has received
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10 clinical study funds from AbbVie, Acelyrin, Amgen, Arcutis, Athenex, Boehringer
11 Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Evelo, Galderma,
12 Incyte, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB
U
13 Pharma. LP: Received consultancy/speaker’s honoraria from and/or participated in trials
14
N
sponsored by AbbVie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene,
Eli Lilly, Gebro, Janssen, JS BIOCAD, LEO Pharma, Merck-Serono, MSD, Mylan, Novartis,
A
15
16 Pfizer, Regeneron, Roche, Samsung-Bioepis, Sandoz, Sanofi Genzyme, and UCB Pharma.
M
17 AM: Received research grants, consulting fees, and/or speaker’s fees from AbbVie,
18 Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Eisai, Janssen, Kyowa
D
19 Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko, Nippon Kayaku,
20 Novartis, Pfizer, Sun Pharma, Taiho Pharma, Torii Pharma, Ushio, and UCB Pharma. MG:
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21 Investigator, speaker, consultant or advisory board member for AbbVie, Akros, Amgen,
22 AnaptysBio, Arcutis, Aslan, Bausch Health, Bristol Myers Squibb, Boehringer Ingelheim,
EP
23 Celgene, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Incyte, Janssen, Kyowa Kirin,
24 MedImmune, Meiji, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma,
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25 and UCB Pharma. AK: Speaker (honoraria) or consulting fees from: Abbvie, Almirall,
26 Beiersdorf, Biogen-Idec, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Hexal,
27 Janssen-Cilag, LEO Pharma, Eli Lilly, MSD, Novartis, Pfizer, Sanofi, and UCB Pharma. VV,
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28 CM, DdC, MW: Employees and shareholders of UCB Pharma. NNG: Former employee
29 of UCB Pharma. ML: Employee of Mount Sinai and receives research funds from AbbVie,
30 Amgen, Arcutis, Avotres Therapeutics, Boehringer Ingelheim, Dermavant, Eli Lilly,
31 Incyte, Janssen, LLC, Ortho Dermatologics, Regeneron, and UCB Pharma; consultant for
32 Aditum Bio, Almirall, AltruBio, AnaptysBio, Arcutis, Aristea Therapeutics, Arrive
14
1 Technologies, Avotres Therapeutics, BiomX, Boehringer Ingelheim, Bristol Myers Squibb,
2 Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Dr. Reddy’s
3 Laboratories, Evelo Biosciences, Evommune, Facilitation of International Dermatology
4 Education, Forte Biosciences, Foundation for Research and Education in Dermatology,
5 Helsinn Therapeutics, Hexima, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer,
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6 Seanergy, and Verrica.
7 Data availability: Underlying data from this manuscript may be requested by qualified
RI
8 researchers 6 months after product approval in the US and/or Europe, or global
9 development is discontinued, and 18 months after trial completion. Investigators may
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10 request access to anonymized individual patient-level data and redacted trial documents,
11 which may include analysis-ready datasets, study protocol, annotated case report form,
12 statistical analysis plan, dataset specifications, and clinical study report. Prior to use of
U
13 the data, proposals need to be approved by an independent review panel at
14
N
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
15
16 a password protected portal.
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17 Ethics statement: All patients entering the trials provided written informed consent,
18 obtained and documented in accordance with local regulations and ethical principles
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19 originating from the Declaration of Helsinki.

20
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21 What is already known about the topic?

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22  Biologic agents have substantially improved clinical outcomes for patients with
23 moderate to severe plaque psoriasis. Patients who are not adequately responding
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24 to their current biologic therapy may decide, with their clinician, to switch
25 biologics. However, prior biologic use may be a risk factor for future biologic
failure. Therefore, for patients and clinicians to make informed treatment
A
26
27 decisions, it is important to directly assess the efficacy and safety of switching
28 biologics.
15
1 What does this study add?
2  High proportions of patients can either achieve or maintain complete and/or near
3 complete skin clearance after switching to bimekizumab from adalimumab,
4 ustekinumab, or secukinumab. Switching to bimekizumab was well-tolerated and
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there were no new safety findings. There was a limited time between the last

5
6 dose of active-comparator and switching to bimekizumab, thus the results are
7 likely to be relevant for patients and may help to support clinical decision
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8 making.
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9
10 REFERENCES
U
11 1. Mahil SK, Smith CH. Psoriasis biologics: a new era of choice. The Lancet 2019;
12
13
394: 807-8.
2. N
Sbidian E, Chaimani A, Afach S, et al. Systemic pharmacological treatments for
chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev 2020;
A
14
15 1: Cd011535.
3. Gulliver SR, Gulliver W. Investigation of prevalence of biologic use and
M
16
17 discontinuation rates in moderate-to-severe psoriasis patients in Newfoundland and
18 Labrador using real-world data. Dermatol Ther 2021; 34: e14944.
19 4. Hu Y, Chen Z, Gong Y, et al. A review of switching biologic agents in the
D
20 treatment of moderate-to-severe plaque psoriasis. Clin Drug Investig 2018; 38: 191‑9.
21 5. Honda H, Umezawa Y, Kikuchi S, et al. Switching of biologics in psoriasis:
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22 Reasons and results. J Dermatol 2017; 44: 1015-9.

23 6. Ghoreschi K, Balato A, Enerbäck C, et al. Therapeutics targeting the IL-23 and
24 IL-17 pathway in psoriasis. Lancet 2021; 397: 754-66.
25 7. Bellinvia S, Cummings JRF, Ardern-Jones MR, et al. Adalimumab biosimilars in
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26 Europe: An overview of the clinical evidence. BioDrugs 2019; 33: 241-53.

27 8. Sator P. Safety and tolerability of adalimumab for the treatment of psoriasis: a
28 review summarizing 15 years of real-life experience. Ther Adv Chronic Dis 2018; 9: 147-
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29 58.
30 9. European Medicines Agency. Cosentyx (secukinumab) summary of product
31 characteristics. 2022. Available at: https://www.ema.europa.eu/en/documents/product-
32 information/cosentyx-epar-product-information_en.pdf (last accessed 14 March 2022).
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33 10. European Medicines Agency. Stelara (ustekinumab) summary of product

34 characteristics. 2021. Available at: https://www.ema.europa.eu/en/documents/product-
35 information/stelara-epar-product-information_en.pdf (last accessed 14 March 2022).
36 11. Wade R, Sharif-Hurst S, Smith C, et al. Characteristics modifying response to
37 biological treatments for psoriasis: considering subgroups in network meta-analysis. Br J
38 Dermatol 2021; 184: 358-9.
39 12. Glatt S, Baeten D, Baker T, et al. Dual IL-17A and IL-17F neutralisation by
40 bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a
16
1 randomised placebo-controlled clinical trial that IL-17F contributes to human chronic
2 tissue inflammation. Ann Rheum Dis 2018; 77: 523.
3 13. Blauvelt A, Chiricozzi A. The immunologic role of IL-17 in psoriasis and psoriatic
4 arthritis pathogenesis. Clin Rev Allergy Immunol 2018; 55: 379-90.
5 14. Warren RB, Blauvelt A, Bagel J, et al. Bimekizumab versus adalimumab in plaque
6 psoriasis. N Engl J Med 2021; 385: 130-41.
7 15. Reich K, Papp KA, Blauvelt A, et al. Bimekizumab versus ustekinumab for the
treatment of moderate to severe plaque psoriasis (BE VIVID): efficacy and safety from a
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8
9 52-week, multicentre, double-blind, active comparator and placebo controlled phase 3
10 trial. The Lancet 2021; 397: 487-98.
11 16. Reich K, Warren RB, Lebwohl M, et al. Bimekizumab versus secukinumab in
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12 plaque psoriasis. N Engl J Med 2021; 385: 142-52.
13 17. Gasslitter I, Kirsten N, Augustin M, et al. Successful intra-class switching among
14 IL-17 antagonists: a multicentre, multinational, retrospective study. Arch Dermatol Res
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15 2019; 311: 421-4.
16 18. Georgakopoulos JR, Phung M, Ighani A, et al. Efficacy and safety of switching to
17 ixekizumab in secukinumab nonresponders with plaque psoriasis: A multicenter
retrospective study of interleukin 17A antagonist therapies. J Am Acad Dermatol 2018;
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18
19 79: 155-7.
19. Strober B, Papp KA, Lebwohl M, et al. Clinical meaningfulness of complete skin
20
21
20.
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clearance in psoriasis. J Am Acad Dermatol 2016; 75: 77-82.e7.
Gordon KB, Langley RG, Warren RB, et al. Bimekizumab safety in patients with
A
22
23 moderate to severe plaque psoriasis: Pooled results from phase 2 and phase 3
24 randomized clinical trials. JAMA Dermatol 2022; 158: 735-44.
M
25 21. Gladiator A, Wangler N, Trautwein-Weidner K, et al. Cutting edge: IL-17–

26 secreting innate lymphoid cells are essential for host defense against fungal infection. J
27 Immunol 2013; 190: 521.
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28 22. Trautwein-Weidner K, Gladiator A, Nur S, et al. IL-17-mediated antifungal

29 defense in the oral mucosa is independent of neutrophils. Mucosal Immunol 2015; 8:
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30 221-31.
31
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32 SUPPORTING INFORMATION
33 Please see file under ‘Supplementary file for review’.

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34 FIGURE LEGENDS
35 Figure 1. Study overview for patients included in the switching analyses. Only the
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36 treatment arms for the active-comparator treatment groups in the BE SURE, BE VIVID
37 and BE RADIANT trials are shown. In the 56-week BE SURE trial, patients randomized to
38 adalimumab switched to BKZ Q4W at Week 24. On completion of BE SURE or BE VIVID,
39 patients could enroll in the BE BRIGHT OLE and received BKZ Q4W or Q8W, depending
40 on PASI response on completion of the feeder trial. At Week 24 of BE BRIGHT, patients
17
1 receiving BKZ 320 mg Q4W who achieved PASI 90 were eligible to switch to BKZ 320 mg
2 Q8W, at the discretion of the investigator. In BE RADIANT, patients who completed the
3 48‑week double-blinded treatment period entered the OLE and received BKZ Q4W or
4 Q8W, depending on PASI response at Week 48. The duration between the last dose of
5 active comparator and first dose of bimekizumab was: 2 weeks for adalimumab
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6 switchers, 4 weeks for secukinumab switchers and 12 weeks for ustekinumab switchers.
7 [a] Following a protocol amendment, all patients receiving BKZ 320 mg Q4W in the
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8 open-label extension period were switched to BKZ 320 mg Q8W at the next scheduled
9 clinic visit on or after the Week 64 visit. BKZ: bimekizumab; PASI 90: ≥90% reduction
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10 from baseline in Psoriasis Area and Severity Index; Q2W: every 2 weeks; Q4W: every 4
11 weeks; Q8W: every 8 weeks; Q12W: every 12 weeks.
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12 Figure 2. Clinical responses in PASI 90 non-responders initially treated with
adalimumab, ustekinumab, or secukinumab who switched to bimekizumab (mNRI). In
13
14
N
BE SURE, patients switched from ADA to BKZ at Week 24. In BE VIVID, patients
A
15 switched from UST to BKZ upon entry to the BE BRIGHT OLE at Week 52. In BE
M
16 RADIANT, patients switched from SEC to BKZ upon entry to the BE RADIANT OLE at
17 Week 48. On entering the OLEs, PASI 90 non-responders received BKZ 320 mg Q4W,
and could switch to Q8W during the OLEs according to the study designs shown in
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18
19 Figure 1. For mNRI, patients with missing data following treatment discontinuation due
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20 to lack of efficacy were considered non-responders, whereas all other missing data were
21 imputed using multiple imputation. ADA: adalimumab; BKZ: bimekizumab; BSA ≤1%:
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22 body surface area affected by psoriasis ≤1%; IGA 0/1: score of 0 (clear) or 1 (almost
23 clear) with ≥2‑category improvement relative to baseline in Investigator's Global
Assessment, scored on a 5-point scale; mNRI: modified non-responder imputation; OLE:
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24
25 open-label extension; PASI 90/100: ≥90%/100% improvement from baseline in
26 Psoriasis Area and Severity Index; Q4W: every 4 weeks; SEC: secukinumab;
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27 UST: ustekinumab.
28 Figure 3. Clinical responses in PASI 90 responders initially treated with adalimumab,

29 ustekinumab, or secukinumab who switched to bimekizumab (mNRI). In BE SURE,
30 patients switched from ADA to BKZ at Week 24. In BE VIVID, patients switched from
31 UST to BKZ upon entry to the BE BRIGHT OLE at Week 52. In BE RADIANT, patients
18
1 switched from SEC to BKZ upon entry to the BE RADIANT OLE at Week 48. On entering
2 the OLEs, PASI 90 responders were randomized to receive BKZ 320 mg Q4W or Q8W
3 dosing (4:1 in BE SURE/BE BRIGHT, 1:1 in BE VIVID/BE BRIGHT, 1:1 in BE RADIANT).
4 Patients receiving Q4W dosing could switch to Q8W during the OLEs according to the
5 study designs shown in Figure 1. For mNRI, patients with missing data following
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6 treatment discontinuation due to lack of efficacy were considered non responders,
7 whereas all other missing data were imputed using multiple imputation. [a] Four
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8 patients included in the UST/BKZ group did not demonstrate a PASI 90 response at
9 Week 52 of BE VIVID but were re-randomized as PASI 90 responders at OLE entry. ADA:
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10 adalimumab; BKZ: bimekizumab; BSA ≤1%: body surface area affected by psoriasis
11 ≤1%; IGA 0/1: score of 0 (clear) or 1 (almost clear) with ≥2-category improvement
12 relative to baseline in Investigator's Global Assessment, scored on a 5-point scale;
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13 mNRI: modified non-responder imputation; OLE: open-label extension; PASI 90/100:
14
every 4 weeks; SEC: secukinumab; UST: ustekinumab.
N
≥90%/100% improvement from baseline in Psoriasis Area and Severity Index; Q4W:
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15
16
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17 Table 1. Demographics and baseline characteristics by PASI 90 response status

BE SURE/BE BRIGHT BE VIVID/BE BRIGHT BE RADIANT/BE
OLEa OLEb RADIANT OLEc
D
ADA/BKZ UST/BKZ SEC/BKZ

Week 24 Week 52 Week 48
Week 24 Week 52 Week 48
TE
PASI 90 PASI 90 PASI 90

PASI 90 PASI 90 PASI 90
Non- Non- Non-
Responder Responder Responder
Responder Responder Responder
N=75 N=92d N=256
N=54 N=44 N=53
Age (years),
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45.7 ± 14.0 45.3 ± 14.4 51.3 ± 11.6 44.7 ± 13.6 46.4 ± 13.0 44.1 ± 14.7
mean ± SD
Male, n (%) 41 (75.9) 53 (70.7) 29 (65.9) 68 (73.9) 34 (64.2) 170 (66.4)
Caucasian, n
48 (88.9) 68 (90.7) 31 (70.5) 73 (79.3) 50 (94.3) 242 (94.5)
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(%)
Weight (kg),
96.6 ± 20.3 85.4 ± 18.5 89.1 ± 21.5 86.6 ± 21.0 95.7 ± 20.0 88.1 ± 19.0
mean ± SD
Disease
duration
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15.4 ± 11.3 17.7 ± 12.5 21.0 ± 12.7 17.3 ± 11.4 18.7 ± 11.4 17.1 ± 12.1
(years), mean ±
SD
Prior biologic
21 (38.9) 26 (34.7) 19 (43.2) 32 (34.8) 22 (41.5) 82 (32.0)
exposure, n (%)
Prior anti-TNF
4 (7.4) 8 (10.7) 6 (13.6) 12 (13.0) 12 (22.6) 49 (19.1)
therapy, n (%)
Prior anti-IL-17
17 (31.5) 15 (20.0) 11 (25.0) 21 (22.8) 9 (17.0) 38 (14.8)
exposure, n (%)
Prior systemic
34 (63.0) 59 (78.7) 37 (84.1) 73 (79.3) 44 (83.0) 187 (73.0)
therapy, n (%)
19
BSA (%), mean
26.3 ± 17.1 25.3 ± 13.8 26.4 ± 20.6 27.6 ± 15.2 21.0 ± 13.5 23.6 ± 13.4
± SD
PASI, mean ±
19.5 ± 6.1 19.1 ± 5.9 20.3 ± 8.3 21.6 ± 8.4 18.1 ± 4.9 19.8 ± 6.3
SD
IGA
3
(moderate),
n (%)
4 (severe), n 35 (64.8) 55 (73.3) 26 (59.1) 57 (62.0) 37 (69.8) 190 (74.2)
PT
(%) 19 (35.2) 20 (26.7) 18 (40.9) 35 (38.0) 16 (30.2) 66 (25.8)
DLQI, mean ± e
11.9 ± 7.5 9.7 ± 7.0 11.0 ± 5.9 10.8 ± 7.3 11.2 ± 7.7 11.2 ± 7.2
SD
1 [a] In BE SURE, patients switched from ADA to BKZ at Week 24; [b] In BE VIVID, patients switched from
RI
2 UST to BKZ upon entry to the BE BRIGHT OLE at Week 52; [c] In BE RADIANT, patients switched from SEC
3 to BKZ upon entry to the BE RADIANT OLE at Week 48; [d] Four patients included in the UST/BKZ group did
4 not demonstrate a PASI 90 response at Week 52 of BE VIVID but were re-randomized as PASI 90
5 responders at OLE entry; [e] N=43. ADA: adalimumab; BKZ: bimekizumab; BSA: body surface area; DLQI:
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6 Dermatology Life Quality Index; IGA: Investigator’s Global Assessment; IL: interleukin; PASI: Psoriasis Area
7 and Severity Index; PASI 90: ≥90% reduction from baseline in Psoriasis Area and Severity Index;
8 SEC: secukinumab; SD: standard deviation; TNF: tumor necrosis factor; UST: ustekinumab.
9
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10 Table 2. DLQI 0/1 response rate in PASI 90 non-responders and PASI 90 responders at
11 the time of switching to bimekizumab from adalimumab, ustekinumab, or secukinumab
12 (mNRI) N
A
Weeks DLQI 0/1 in PASI 90 non-responders at DLQI 0/1 in PASI 90 responders at
M
since switch switch
switch to ADA/BKZ UST/BKZ SEC/BKZ ADA/BKZ UST/BKZ SEC/BKZ
a
BKZ (N=54) (N=44) (N=53) (N=75) (N=92) (N=256)
D
Week 0 29.6% 48.8% 51.0% 69.3% 85.8% 87.5%

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Week 24b 80.7% 81.4% 85.7% 86.6% 87.0% 88.1%
Week
84.2% 88.4% 73.6% 89.0% 89.1% 84.0%
48/56c
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Week 80d 88.9% - - 88.0% - -
13 [a] Four patients included in the UST/BKZ group did not demonstrate a PASI 90 response at Week 52 of BE
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14 VIVID but were re-randomized as PASI 90 responders at OLE entry; [b] Due to differences in scheduling,
15 the first common visit at which DLQI was assessed was 24 weeks after switch in all trials; [c] Due to
16 differences in scheduling, assessments were performed 48 weeks after switch in BE RADIANT and BE
17 VIVID/BE BRIGHT, and 56 weeks after switch in BE SURE/BE BRIGHT; [d] Long-term data up to 80 weeks
18 after switch from UST and SEC to BKZ are still pending. For mNRI, patients with missing data following
A
19 treatment discontinuation due to lack of efficacy were considered non‑responders, whereas all other missing
20 data were imputed using multiple imputation. ADA: adalimumab; BKZ: bimekizumab; DLQI: Dermatology
21 Life Quality Index; mNRI: modified non-responder imputation; PASI 90: ≥90% reduction from baseline in
22 Psoriasis Area and Severity Index; SEC: secukinumab; UST: ustekinumab.
23
20
P
RI
SC

1 Table 3. Overview of TEAEs among patients who switched to bimekizumab from adalimumab, ustekinumab, or secukinumab
2
BE SURE/BE BRIGHT OLE BE VIVID/BE BRIGHT OLE BE RADIANT/BE RADIANT OLE
U
≤6 months >6 months ≤6 months >6 months ≤6 months >6 months
after first after first after first after first after first after first
N
BKZ dosea BKZ dosec BKZ dose BKZ dosec BKZ dose BKZ dosec
ADA Q2W BKZ Q4Wb BKZ total UST Q12W BKZ total BKZ total SEC Q4W BKZ total BKZ total
A
N=159 N=149 N=131 N=163 N=136 N=135 N=370 N=318 N=310
BE BRIGHT BE BRIGHT BE BRIGHT BE RADIANT BE RADIANT
M
Trial / weeks BE SURE BE SURE OLE BE VIVID OLE OLE BE RADIANT OLE OLE
Week 0–24 Week 24–56 Week 0–48 Week 0–52 Week 0–24 Week 24–48 Week 0–48 Week 0–24 Week 24–48
Total exposure, PY 72 90 119 158 67 57 333 157 129
D
Summary of TEAEs, EAIR/100 PY (95% CI)
297.5 256.7 202.5 189.2 258.0 197.0 229.8 200.1 127.3
Any TEAEs (244.8, (211.1, (165.0, (158.1, (208.2, (154.4, (204.5, (172.9, (106.1,
TE
358.3) 309.1) 246.1) 224.6) 316.1) 247.7) 257.2) 230.4) 151.5)
7.0 8.0 5.1 5.8 4.5 3.5 4.6 4.5 6.3
Severe TEAEs
(2.3, 16.3) (3.2, 16.5) (1.9, 11.2) (2.7, 11.1) (0.9, 13.1) (0.4, 12.7) (2.6, 7.5) (1.8, 9.3) (2.7, 12.4)
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TEAEs leading to 7.0 5.6 1.7 4.5 1.5 5.3 3.0 3.2 2.3
discontinuation (2.3, 16.3) (1.8, 13.1) (0.2, 6.1) (1.8. 9.2) (0.0, 8.3) (1.1, 15.4) (1.5, 5.6) (1.0, 7.5) (0.5, 6.9)
Treatment-related 62.0 63.0 37.7 24.4 66.3 51.4 44.5 43.0 28.3
CC
TEAEs (43.9, 85.1) (45.9, 84.2) (26.4, 52.3) (16.8, 34.2) (46.7, 91.3) (33.6, 75.3) (36.8, 53.3) (32.8, 55.3) (19.6, 39.5)
7.0 10.4 5.1 8.6 6.0 5.3 6.4 6.5 3.9

Serious TEAEs
(2.3, 16.3) (4.7, 19.6) (1.9, 11.2) (4.6, 14.7) (1.6, 15.4) (1.1, 15.4) (4.0, 9.9) (3.1, 11.9) (1.3, 9.1)
A
1.4 0.0 0.0 0.6 0.0 0.0 0.3 0.6 0.0

TEAEs leading to death
(0.0, 7.7) (0.0, 0.0) (0.0, 0.0) (0.0, 3.5) (0.0, 0.0) (0.0, 0.0) (0.0, 1.7) (0.0, 3.6) (0.0, 0.0)
3 The data cut-off for all trials was OLE Week 48. [a] Due to differences in study designs, data are reported for 32 weeks (approximately 8 months) after first BKZ
4 dose; [b] All adalimumab-randomized patients were switched to BKZ 320 mg Q4W dosing at Week 24 of BE SURE; [c] Data correspond to 48 weeks of treatment
5 in BE SURE/BE BRIGHT OLE, 24 weeks of treatment in BE VIVID/BE BRIGHT OLE and 24 weeks of treatment in the BE RADIANT OLE. ADA: adalimumab; BKZ:
6 bimekizumab; BKZ total: data from BKZ 320 mg Q4W and BKZ 320 mg Q8W dosing were combined; CI: confidence interval; EAIR: exposure-adjusted incidence
7 rate; OLE: open-label extension; PY: patient-years; Q2W: every 2 weeks; Q4W: every 4 weeks; Q12W: every 12 weeks; SEC: secukinumab;
8 TEAE: treatment-emergent adverse event; UST: ustekinumab.
21
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RI
SC

1 Table 4. Most common TEAEs and TEAEs of interest among patients who switched to bimekizumab from adalimumab, ustekinumab,
2 or secukinumab
U
N
A
N=159 N=149 N=131 N=163 N=136 N=135 N=370 N=318 N=310
M
BE BRIGHT BE BRIGHT BE BRIGHT BE RADIANT BE RADIANT
Trial / weeks BE SURE BE SURE OLE BE VIVID OLE Week 0– OLE BE RADIANT OLE OLE
Week 0–24 Week 24–56 Week 0–48 Week 0–52 24 Week 24–48 Week 0–48 Week 0–24 Week 24–48
Most common TEAEs, EAIR/100 PY (95% CI)d
D
60.2 24.8 21.0 26.3 40.1 16.4 36.9 19.8 8.7
Nasopharyngitis
(42.6, 82.6) (15.1, 38.3) (13.1, 31.8) (18.4, 36.4) (25.7, 59.7) (7.5, 31.1) (30.1, 44.8) (13.3, 28.4) (4.3, 15.6)
TE
0.0 32.4 13.6 0.6 18.7 23.7 3.4 16.5 9.5
Oral candidiasis
(0.0, 0.0) (21.2, 47.5) (7.6, 22.4) (0.0, 3.6) (9.7, 32.7) (12.6, 40.6) (1.7, 6.0) (10.7, 24.4) (4.9, 16.7)
Upper respiratory tract 22.0 10.4 8.9 12.1 10.6 7.1 11.5 5.8 1.6
infection (12.3, 36.2) (4.8, 19.8) (4.3, 16.3) (7.2, 19.2) (4.3, 21.9) (1.9, 18.1) (8.0, 15.9) (2.7, 11.1) (0.2, 5.6)
EP
7.0 6.9 8.8 4.6 10.7 5.3 6.8 9.2 4.7

UTI
(2.3, 16.2) (2.5, 14.9) (4.2, 16.1) (1.8, 9.4) (4.3, 22.0) (1.1, 15.4) (4.3, 10.3) (5.0, 15.4) (1.7, 10.3)
TEAEs of interest, EAIR/100 PY (95% CI)
1.4 4.5 0.0 2.6 1.5 0.0 2.4 1.9 2.3
CC
Serious infections
(0.0, 7.7) (1.2, 11.5) (0.0, 0.0) (0.7, 6.6) (0.0, 8.3) (0.0, 0.0) (1.0, 4.8) (0.4, 5.6) (0.5, 6.8)
0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
Active tuberculosis
(0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0)
1.4 45.2 23.9 2.6 28.8 31.4 11.1 27.9 23.0
A
Fungal infections
(0.0, 7.7) (31.5, 62.9) (15.5, 35.3) (0.7, 6.6) (17.1, 45.5) (18.3, 50.3) (7.7, 15.5) (20.0, 37.8) (15.3, 33.2)
0.0 33.7 17.7 0.6 23.8 23.7 5.2 20.7 15.3
Candida infections
(0.0, 0.0) (22.2, 49.0) (10.6, 27.6) (0.0, 3.6) (13.3, 39.2) (12.6, 40.6) (3.1, 8.4) (14.1, 29.4) (9.2, 23.9)
0.0 32.4 13.6 0.6 18.7 23.7 3.4 16.5 9.5
Oral candidiasis
(0.0, 0.0) (21.2, 47.5) (7.6, 22.4) (0.0, 3.6) (9.7, 32.7) (12.6, 40.6) (1.7, 6.0) (10.7, 24.4) (4.9, 16.7)
1.4 1.1 0.8 0.6 1.5 1.8 3.1 1.9 3.1
Tinea infections
(0.0, 7.7) (0.0, 6.2) (0.0, 4.7) (0.0, 3.5) (0.0, 8.3) (0.0, 9.7) (1.5, 5.6) (0.4, 5.7) (0.9, 8.0)
22
P
RI
SC

U
N
N=159 N=149 N=131 N=163 N=136 N=135 N=370 N=318 N=310
Fungal infections 0.0 11.6 5.1 1.3 4.5 7.1 3.0 5.2 6.3
A
NEC (0.0, 0.0) (5.5, 21.2) (1.9, 11.2) (0.2, 4.6) (0.9, 13.2) (1.9, 18.1) (1.5, 5.6) (2.2, 10.2) (2.7, 12.5)
Inflammatory bowel 0.0 0.0 0.0 0.0 0.0 0.0 0.3 0.0 0.0
M
disease (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 1.7) (0.0, 0.0) (0.0, 0.0)
0.0 0.0 0.8 0.0 0.0 0.0 0.6 0.6 0.8
Adjudicated MACE
(0.0, 0.0) (0.0, 0.0) (0.0, 4.7) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.1, 2.2) (0.0, 3.6) (0.0, 4.3)
1.4 1.1 0.0 0.6 0.0 1.7 0.9 0.6 0.0
Malignancies D
(0.0, 7.7) (0.0, 6.2) (0.0, 0.0) (0.0, 3.5) (0.0, 0.0) (0.0, 9.7) (0.2, 2.7) (0.0, 3.6) (0.0, 0.0)
0.0 1.1 0.0 0.6 0.0 1.7 0.9 0.6 0.0
NMSC
(0.0, 0.0) (0.0, 6.2) (0.0, 0.0) (0.0, 3.5) (0.0, 0.0) (0.0, 9.7) (0.2, 2.7) (0.0, 3.6) (0.0, 0.0)
TE
0.0 0.0 0.0 0.6 0.0 0.0 0.0 0.0 0.0
Adjudicated SIB
(0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 3.5) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0)
5.6 0.0 0.8 0.6 0.0 0.0 0.9 0.0 0.0
Neutropenia
(1.5, 14.4) (0.0, 0.0) (0.0, 4.7) (0.0, 3.6) (0.0, 0.0) (0.0, 0.0) (0.2, 2.7) (0.0, 0.0) (0.0, 0.0)
EP
Elevated liver 15.8 6.9 6.1 2.6 1.5 1.7 5.9 3.2 1.6
enzymese (7.9, 28.3) (2.5, 15.0) (2.4, 12.5) (0.7, 6.6) (0.0, 8.3) (0.0, 9.7) (3.5, 9.2) (1.0, 7.5) (0.2, 5.6)
AST or ALT
elevationsf
CC
>x3 upper limit of

5.6 5.5 4.3 2.6 3.0 1.7 4.6 3.2 0.0
normal
(1.5, 14.4) (1.8, 12.9) (1.4, 10.0) (0.7, 6.5) (0.4, 10.8) (0.0, 9.7) (2.6, 7.6) (1.0, 7.5) (0.0, 0.0)
0.0 2.2 0.9 0.6 0.0 0.0 0.9 0.6 0.0
>x5 upper limit of
(0.0, 0.0) (0.3, 8.0) (0.0, 4.7) (0.0, 3.5) (0.0, 0.0) (0.0, 0.0) (0.2, 2.6) (0.0, 3.6) (0.0, 0.0)
normal
A
Serious
0.0 0.0 0.8 0.0 0.0 0.0 0.0 0.6 0.0
hypersensitivity
(0.0, 0.0) (0.0, 0.0) (0.0, 4.7) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 3.6) (0.0, 0.0)
reactions
Injection site 5.6 1.1 0.8 0.6 3.0 1.7 2.1 3.9 1.6
reactionsg (1.5, 14.4) (0.0, 6.2) (0.0, 4.7) (0.0, 3.6) (0.4, 10.8) (0.0, 9.7) (0.9, 4.4) (1.4, 8.5) (0.2, 5.6)
1 The data cut-off for all trials was OLE Week 48. [a] Due to differences in study designs, data are reported for 32 weeks (approximately 8 months) after first BKZ
2 dose; [b] All adalimumab-randomized patients were switched to BKZ 320 mg Q4W dosing at Week 24 of BE SURE; [c] Data correspond to 48 weeks of treatment
23
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RI
SC

1 in BE SURE/BE BRIGHT OLE, 24 weeks of treatment in BE VIVID/BE BRIGHT OLE and 24 weeks of treatment in the BE RADIANT OLE; [d] Most common TEAEs
2 are reported for events with an EAIR >5.0/100 PY in any treatment group; [e] Liver function tests included the following preferred terms reported as adverse
3 events: increased hepatic enzyme, AST, gamma‑glutamyltransferase, ALT, liver function test, transaminases, blood bilirubin, and abnormal liver function test; [f]
U
4 Not all hepatic laboratory parameter elevations were reported as adverse events; [g] Includes events reported under the high level term of injection site reactions.
5 ADA: adalimumab; AST: aspartate aminotransferase; ALT: alanine aminotransferase; BKZ: bimekizumab; BKZ total: data from BKZ 320 mg Q4W and BKZ 320 mg
6 Q8W dosing were combined; CI: confidence interval; EAIR: exposure-adjusted incidence rate; MACE: major adverse cardiac event; NEC: not elsewhere classified;
N
7 NMSC: non-melanoma skin cancer; OLE: open-label extension; PY: patient-years; Q2W: every 2 weeks; Q4W: every 4 weeks; Q12W: every 12 weeks; SEC:
8 secukinumab; SIB: suicidal ideation and behavior; TEAE: treatment-emergent adverse event; UST: ustekinumab; UTI: urinary tract infection.
A
M
D
TE
EP
CC
A
24
PT
25
RI
SC
U 246x139 mm (6.9 x DPI)
190x98 mm (6.9 x DPI)

N
Figure 2A
Figure 1
A
M
D
TE
EP
CC
A
6
PT
26
RI
SC
U 172x89 mm (6.9 x DPI)
173x90 mm (6.9 x DPI)

N Figure 2B
A
Figure 2C
M
D
TE
EP
CC
A
6
PT
27
RI
SC
U 172x89 mm (6.9 x DPI)
194x98 mm (6.9 x DPI)

N Figure 2D
Figure 3A
A
M
D
TE
EP
CC
A
6
PT
28
RI
SC
U 169x89 mm (6.9 x DPI)
173x89 mm (6.9 x DPI)

N Figure 3B
A
Figure 3C
M
D
TE
EP
CC
A
6
PT
29
RI
SC
U 173x88 mm (6.9 x DPI)
N Figure 3D
A
M
D
TE
EP
CC
A

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1 Bimekizumab efficacy and safety in patients with moderate to severe

2 plaque psoriasis who switched from adalimumab, ustekinumab, or

4 Running head: Switching to Bimekizumab in Plaque Psoriasis

18 Research, Peterborough, ON, Canada; 9Queen’s University, Kingston, ON, Canada;

21 Mount Sinai, New York, NY, USA

23 Correspondence: Dr Georgios Kokolakis

2 Background: Discontinuation of biologics is common among patients with psoriasis due

18 secukinumab (52.5%). After 48 weeks of bimekizumab, 90.7%, 89.5%, and 79.2% of

20 ustekinumab, or secukinumab, respectively. Durable improvements were also observed

Downloaded from https://academic.oup.com/bjd/advance-article/doi/10.1093/bjd/ljac089/6850554 by guest on 03 December 2022

16 Biologic therapies for the treatment of psoriasis inhibit specific proinflammatory

17 cytokines implicated in psoriasis pathophysiology, including tumor necrosis factor-alpha

7 In addition to improvements in clinical outcomes, the safety profile of switching biologics

17 PATIENTS and METHODS

20 OLEs (BE SURE [NCT03412747], BE VIVID [NCT03370133], BE BRIGHT [NCT03598790],

Downloaded from https://academic.oup.com/bjd/advance-article/doi/10.1093/bjd/ljac089/6850554 by guest on 03 December 2022

18 (PASI 90 responders), were randomized 4:1 to bimekizumab 320 mg Q4W or Q8W.

21 Ustekinumab-randomized Week 52 PASI 90 responders in BE VIVID were randomized

23 non-responders received bimekizumab 320 mg Q4W upon entry into BE BRIGHT. At

26 In BE RADIANT, patients were randomized to secukinumab 300 mg weekly to Week 4

16 reported during treatment with adalimumab, ustekinumab, or secukinumab, and after

17 switching to bimekizumab. To cover the half-life of each comparator biologic and

22 Demographics and baseline characteristics were representative of a patient population

2 Efficacy outcomes in PASI 90 non-responders

3 A total of 54/159 (34.0%) adalimumab-randomized, 44/163 (27.0%)

17 70.1% (adalimumab/bimekizumab), 58.1% (ustekinumab/bimekizumab), and 50.9%

18 (secukinumab/bimekizumab) of patients achieved PASI 100 (Figure 2B). After switching

23 Benefits in health-related quality of life (HRQoL) were observed with bimekizumab; 24

25 (adalimumab/bimekizumab), 48.8% to 81.4% (ustekinumab/bimekizumab), and 51.0%

2 A total of 75/159 (47.2%) adalimumab-randomized, 92/163 (56.4%)

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6 Among adalimumab, ustekinumab, and secukinumab PASI 90 responders, clinical

DLQI 0/1 response rates at the time of switching were 69.3%

In these analyses, we report clinical responses among patients who switched to

26 responders (at the time of switching to bimekizumab from an active-comparator)

Downloaded from https://academic.oup.com/bjd/advance-article/doi/10.1093/bjd/ljac089/6850554 by guest on 03 December 2022

18 secukinumab to bimekizumab, which increased to 79.2% after 48 weeks of

19 bimekizumab. This supports previous observations of successful intra-class switching

23 weeks of bimekizumab treatment increased from 58.7% to 82.7%

26 PASI 90 in patients with psoriasis.19 In these analyses, in addition to improvements in

29 It is important to evaluate the safety of switching between biologic treatments. In these

23 reduction in TEAEs observed with a longer duration of bimekizumab exposure. Of note,

25 and Q8W bimekizumab dosing regimens.14-16

26 In summary, we demonstrate that patients who do not adequately respond to treatment

15 consultant member of advisory boards and speaker bureaus or has served as

19 originating from the Declaration of Helsinki.

21 What is already known about the topic?

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22 Reasons and results. J Dermatol 2017; 44: 1015-9.

26 Europe: An overview of the clinical evidence. BioDrugs 2019; 33: 241-53.

33 10. European Medicines Agency. Stelara (ustekinumab) summary of product

25 21. Gladiator A, Wangler N, Trautwein-Weidner K, et al. Cutting edge: IL-17–

28 22. Trautwein-Weidner K, Gladiator A, Nur S, et al. IL-17-mediated antifungal

33 Please see file under ‘Supplementary file for review’.

28 Figure 3. Clinical responses in PASI 90 responders initially treated with adalimumab,

17 Table 1. Demographics and baseline characteristics by PASI 90 response status

ADA/BKZ UST/BKZ SEC/BKZ

PASI 90 PASI 90 PASI 90

Week 0 29.6% 48.8% 51.0% 69.3% 85.8% 87.5%

Week 24b 80.7% 81.4% 85.7% 86.6% 87.0% 88.1%

18 (PASI 90 responders), were randomized 4:1 to bimekizumab 320 mg Q4W or Q8W.