# Safety and efficacy of bimekizumab in patients with psoriatic arthritis: 2-year results from two phase 3 studies

Philip Mease, Joseph Merola, Yoshiya Tanaka, Laure Gossec, Iain Mcinnes, Christopher Ritchlin, Robert Landewé, Akihiko Asahina, Barbara Ink, Andrea Heinrichs, et al.

► To cite this version:

Philip Mease, Joseph Merola, Yoshiya Tanaka, Laure Gossec, Iain Mcinnes, et al. Safety and efficacy of bimekizumab in patients with psoriatic arthritis: 2-year results from two phase 3 studies. Rheumatology and Therapy, 2024, 11 (5), pp.1363-1382. 10.1007/s40744-024-00708-8. hal-05000611

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1 Safety and efficacy of bimekizumab in patients with
2 psoriatic arthritis: 2-year results from two phase 3 studies
3

4 Philip J. Mease (0000-0002-6620-0457),¹ Joseph F. Merola (0000-0001-6514-4353),²

5 Yoshiya Tanaka (0000-0002-0807-7139),³ Laure Gossec (0000-0002-4528-310X),⁴,⁵

6 Iain B. McInnes (0000-0002-6462-4280),⁶ Christopher T. Ritchlin (0000-0002-2602-1219),⁷ Robert B.M. Landewé (0000-0002-0577-6620),⁸ Akihiko Asahina,⁹ Barbara

8 Ink,¹⁰ Andrea Heinrichs,¹¹ Rajan Bajracharya,¹⁰ Vishvesh Shende,¹⁰ Jason Coarse,¹²

9 Laura C. Coates (0000-0002-4756-663X)¹³

10 1. Department of Rheumatology, Providence-Swedish Medical Center and University of Washington, Seattle, Washington, USA; 2. Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA; 3. The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan; 4. Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; 5. AP-HP, Pitié-Salpêtrière hospital, Rheumatology department, Paris, France; 6. College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK; 7.
11 Allergy, Immunology & Rheumatology Division, University of Rochester Medical School, Rochester, New York, USA; 8. Amsterdam Rheumatology & Clinical Immunology Center, Amsterdam, and Zuyderland
12 MC, Heerlen, The Netherlands; 9. Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan; 10. UCB Pharma, Slough, UK; 11. UCB Biosciences GmbH, Monheim, Germany; 12. UCB Pharma, Morrisville, North Carolina, USA; 13. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Diseases, University of Oxford and Oxford Biomedical Research Centre, Oxford
13 University Hospitals NHS Trust, Oxford, UK
14
15
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17
18
19
20
21
22

23

24 **Correspondence to:** Professor Philip J. Mease; pmease@philipmease.com

25 **Short title:** BE OPTIMAL & BE COMPLETE 2-Year Safety & Efficacy

26 **Trial registration:** BE OPTIMAL: [NCT03895203](NCT03895203); BE COMPLETE: [NCT03896581](NCT03896581); BE

27 VITAL: [NCT04009499](NCT04009499)

28 **Funding:** UCB Pharma

29
1 **ABSTRACT (300/300)**

2 **Introduction**

3 Psoriatic arthritis (PsA) is a chronic inflammatory disease requiring long-term

4 treatment. Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits

5 interleukin (IL)-17F in addition to IL-17A, has demonstrated tolerability and

6 sustained clinical efficacy up to 1 year for patients with PsA. Here, we report the

7 longer-term safety and efficacy of bimekizumab up to 2 years.

8 **Methods**

9 BE OPTIMAL (biologic disease-modifying antirheumatic drug [bDMARD]-naïve) and

10 BE COMPLETE (prior inadequate response/intolerance to tumour necrosis factor

11 inhibitors [TNFi-IR]) assessed subcutaneous bimekizumab 160 mg every 4 weeks in

12 patients with PsA. BE OPTIMAL included a reference arm (adalimumab 40 mg every

13 2 weeks); patients switched to bimekizumab at Week 52 with no washout between

14 treatments. BE OPTIMAL Week 52 and BE COMPLETE Week 16 completers were

15 eligible for the BE VITAL open-label extension. Efficacy outcomes are reported to

16 Week 104/100 (BE OPTIMAL/BE COMPLETE).

17 **Results**

18 A total of 710/852 (83.3%) bDMARD-naïve and 322/400 (80.5%) TNFi-IR patients

19 completed Week 104/100. Up to 104 weeks, patients treated with bimekizumab in

20 BE OPTIMAL and BE COMPLETE had treatment-emergent adverse event incidence

21 rates (exposure-adjusted incidence rate/100 patient-years) of 179.9 (95% CI 166.9,

22 193.7) and 100.3 (89.2, 112.4), respectively. The proportion of patients achieving

23 efficacy outcomes (≥50% improvement from baseline in American College of

24 Rheumatology [ACR] response criteria, 100% improvement from baseline in Psoriatic

25 Arthritis Severity Index [PASI], minimal disease activity [MDA]) was sustained in all

26 patients from Week 52 to Week 104/100.

27 **Conclusion**

28 Bimekizumab was well tolerated for up to 2 years of treatment and no new safety

29 signals were observed. Sustained clinical efficacy was observed up to 2 years in

30 bDMARD-naïve and TNFi-IR patients with active PsA. Patients switching from

31 adalimumab to bimekizumab demonstrated further improvement in skin and nail

32 symptoms, and sustained efficacy in joint symptoms.

33
1 **KEY SUMMARY POINTS**

2 **Why carry out this study?**

3. As psoriatic arthritis (PsA) is a chronic disease requiring long-term treatment, it is
4 important to assess the safety and efficacy of novel therapies for clinicians and
5 patients to decide upon the best treatment options.

6. Many patients with PsA cycle through various treatments due to loss of response over time. Therefore, therapies that demonstrate consistent efficacy between biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients and those who experience loss of response or intolerance to tumour necrosis factor inhibitors (TNFi-IR) are of clinical importance.

11. The safety and efficacy of bimekizumab, which inhibits both IL-17A and IL-17F, was assessed in this study up to 2 years from the BE OPTIMAL (bDMARD-naïve) and BE COMPLETE (TNFi-IR) studies and the BE VITAL open-label extension.

14. **What was learned from the study?**

15. The safety of bimekizumab to 2 years was consistent with previous studies
16. assessing bimekizumab in PsA and psoriasis; no new safety signals were
17. observed with longer-term follow up. Bimekizumab treatment resulted in
18. sustained efficacy response over 2 years in both bDMARD-naïve and TNFi-IR
19. patients.

20. Bimekizumab is an effective, long-term treatment option for patients with PsA, irrespective of their prior biologic use. The data reported here may assist clinicians and patients with shared decision making with respect to treatment.

23

24
# 1 INTRODUCTION

Psoriatic arthritis (PsA) is a chronic, inflammatory disease that affects multiple

domains such as joints, skin and nails.<sup>1-3</sup> The impact of PsA on these domains results

in impaired patient function and quality of life.<sup>4</sup> As PsA is a chronic condition, there is

a need for treatments that deliver long-term efficacy with an acceptable safety

profile.

Long-term studies in PsA show the cumulative benefit to patients of maintaining high

disease control over the long-term;<sup>5-8</sup> however, some patients may respond

inadequately or lose response, therefore switching or cycling between multiple

therapies becomes necessary.<sup>9</sup> Interleukin (IL)-17 family members and IL-23 are

pivotal cytokines in the chronic inflammation seen in PsA, and treatments inhibiting

IL-17A and IL-23 are used to treat patients with this condition.<sup>10</sup> IL-17A and IL-12/23

inhibitors have also demonstrated longer persistence than tumour necrosis factor

inhibitors (TNFis) or targeted synthetic disease-modifying antirheumatic drugs

(DMARDs), and similar persistence to one another.<sup>11</sup> However, approximately

20–50% of patients taking a biologic DMARD (bDMARD) change or discontinue

treatment within one year.<sup>12, 13</sup> Furthermore, whilst 40% of patients who switched

from a TNFi to another bDMARD remained on their initial treatment after 20 months,

the two-year survival rate for biologics in any treatment line was 31.9–41.7% and

decreased to 17.3–23.3% after five years.<sup>14</sup>

IL-17A and IL-17F have recently been identified as drivers of joint and skin

inflammation.<sup>2, 15, 16</sup> IL-17A and IL-17F share approximately 50% of their structural

homology and have overlap in their pro-inflammatory function. Given IL-17A and

IL-17F can promote pro-inflammatory signalling by acting as either homodimers

(IL-17A/IL-17A or IL-17F/IL-17F) or heterodimers (IL-17A/IL-17F),<sup>17</sup> inhibiting both

isoforms may provide greater disease control. Indeed, *in vitro* dual neutralisation of

both these interleukins is more potent than neutralisation of IL-17A or IL-17F

alone.<sup>16, 18</sup> Bimekizumab is a humanised, monoclonal IgG1 antibody that selectively

inhibits IL-17F in addition to IL-17A.<sup>17, 19</sup> In the phase 3 BE OPTIMAL and BE

COMPLETE (plus BE VITAL open-label extension [OLE]) studies, the efficacy and

safety of bimekizumab were demonstrated to one year in patients who were

bDMARD-naïve, or who experienced inadequate response or intolerance to TNFi

(TNFi-IR).<sup>20, 21</sup>

Long-term tolerability, sustained efficacy across impacted disease domains, and

maximising patients' health-related quality of life are important treatment goals of

patients with PsA.<sup>3, 22, 23</sup> Therefore, therapies that adequately address these areas

and reduce treatment cycling would provide a significant benefit to patients. Herein,

the 2-year clinical safety and efficacy of bimekizumab from the BE VITAL OLE study

are reported, including the 1-year efficacy of bimekizumab in patients who switched

from TNFi (adalimumab) in BE OPTIMAL.

# 41 METHODS

## 42 Study designs

Complete methodologies were reported to Week 16/24 in the primary publications of

BE OPTIMAL and BE COMPLETE,<sup>24, 25</sup> and further details can be found in the

subsequent 1-year publications.<sup>20, 21</sup> All studies assessed subcutaneous bimekizumab
1 160 mg every 4 weeks (Q4W) in patients with active PsA who met the CASPAR

2 criteria.²⁶

3 In brief, BE OPTIMAL (NCT03895203; ClinicalTrials.gov) was a 52-week, phase 3,

4 multicentre, randomised, double-blind, placebo-controlled, active reference study of

5 bDMARD-naïve patients with active PsA. The study comprised a 16-week

6 placebo-controlled, double-blind period followed by a 36-week active treatment-blind

7 period. A reference arm (adalimumab 40 mg every two weeks [Q2W]) was included

8 to provide a standard-of-care reference for bimekizumab treatment. Patients were

9 randomised 3:2:1 to bimekizumab 160 mg Q4W, placebo or reference (adalimumab

10 40 mg Q2W). From Week 16, placebo-randomised patients received bimekizumab

11 160 mg Q4W.

12 BE COMPLETE (NCT03896581; ClinicalTrials.gov) was a 16-week, phase 3,

13 multicentre, randomised, double-blind, placebo-controlled study of patients with

14 active PsA and prior TNFi-IR. Patients were randomised 2:1 to bimekizumab 160 mg

15 Q4W or placebo.

16 BE VITAL (NCT04009499; ClinicalTrials.gov) is a multicentre, OLE study of patients

17 with active PsA who completed Week 52 of BE OPTIMAL or Week 16 of BE

18 COMPLETE and met eligibility criteria. The study commenced on 13<sup>th</sup> August 2019

19 and is ongoing. All patients that entered the BE VITAL OLE received bimekizumab

20 160 mg Q4W, regardless of feeder study or prior randomisation. Patients randomised

21 to the reference arm in BE OPTIMAL switched to receive bimekizumab 160 mg Q4W

22 at Week 52 regardless of treatment response. There was no washout period for

23 patients randomised to adalimumab who switched to bimekizumab. The OLE

24 included up to 140 weeks of treatment (Treatment Period) for all subjects in all

25 countries. Following the completion of, or early withdrawal from the Treatment

26 Period, patients returned for a safety follow-up visit 20 weeks after their last dose of

27 bimekizumab. Study designs can be found in **Figure 1**.

28 Study visits occurred Q4W from the Entry Visit (Week 0 of the BE VITAL OLE) to

29 Week 12, then every 12 weeks thereafter up to Week 140. In some countries, this

30 was extended past Week 140. Bimekizumab could be self-administered after Week

31 12, as patients were required to attend study visits less frequently. Patients could

32 still attend Q4W to receive bimekizumab if self-administration was not possible;

33 study outcomes were not collected at these visits.

34 **Patients**

35 Inclusion and exclusion criteria for BE OPTIMAL and BE COMPLETE have been

36 reported previously.²⁴, ²⁵ Patients in both studies were recruited during the same

37 period of time at overlapping study sites and countries. In BE OPTIMAL, patients

38 with current or prior exposure to any biologics for the treatment of PsA or psoriasis

39 were excluded. In BE COMPLETE, patients were required to have had a prior

40 inadequate response or intolerance to one or two TNFis for either PsA or psoriasis;

41 patients with current or previous exposure to any other biologics were excluded.

42 Patients with a prior history of uveitis and/or inflammatory bowel disease were not

43 excluded from either study.

44 To be eligible for enrolment in the BE VITAL OLE, patients must have completed

45 either Week 52 of BE OPTIMAL or Week 16 of BE COMPLETE, been expected to
1 benefit from the OLE per the investigator's discretion, not met any withdrawal

2 criteria in either feeder study, and provided separate informed consent for the OLE.

3 Studies were conducted in accordance with the Declaration of Helsinki and the

4 International Conference on Harmonization guidance for Good Clinical Practice.

5 Ethical approval was obtained from the relevant institutional review boards at

6 participating sites, and all patients provided written informed consent in accordance

7 with local requirements. Local institutional review board information can be found in

8 **Supplementary Appendix S1.**

9 **Outcomes**

10 The primary objective of the BE VITAL OLE was to assess the long-term safety and

11 tolerability of bimekizumab in adult patients with PsA over a period of up to 140

12 weeks. The secondary objective was to assess the long-term efficacy of bimekizumab.

13 Safety and efficacy outcomes are reported as the number of weeks from baseline of

14 BE OPTIMAL and BE COMPLETE. Safety outcomes are presented by treatment group

15 and by study period (Week 0–52 or Week 52–104), and efficacy outcomes are

16 presented by randomisation group (placebo-randomised, bimekizumab-randomised,

17 and reference (adalimumab)-randomised [BE OPTIMAL only]). Results are reported

18 by study; results for patients originally enrolled in BE OPTIMAL or BE COMPLETE are

19 hereafter referred to as 'BE OPTIMAL' or 'BE COMPLETE', respectively.

20 Safety outcomes, reported from Week 0 to 52 and Week 52 to Week 104, include

21 treatment-emergent adverse events (TEAEs), serious TEAEs, and study

22 discontinuations due to TEAEs. Other safety results reported include drug-related

23 TEAEs, severe TEAEs, deaths, and other safety topics of interest (major adverse

24 cardiovascular events [MACE], neutropenia, serious infections, fungal infections,

25 hypersensitivity, injection site reactions, suicidal ideation and behaviour,

26 malignancies, inflammatory bowel disease [IBD] and liver function test

27 changes/enzyme elevations). A serious adverse event must meet one or more of the

28 following criteria: death, life-threatening event, significant or persistent

29 disability/incapacity, congenital anomaly/birth defect (including that occurring in a

30 foetus), initial inpatient hospitalisation or prolongation of hospitalisation, or an

31 important medical event that (based on appropriate medical judgement) may

32 jeopardise the patient and may require surgical intervention to prevent one of the

33 other outcomes listed. A severe TEAE relates to the intensity of a TEAE, which are

34 reported as either mild, moderate or severe based on clinical classification. A TEAE

35 can be severe, but not considered a serious TEAE if it does not meet any of the

36 abovementioned criteria. MACE, suicidal ideation and behaviour, hepatic events and

37 IBD events were adjudicated by an external committee.

38 Clinical efficacy outcomes, assessed through Week 104/100 (BE OPTIMAL/BE

39 COMPLETE), included improvements from baseline of ≥20%, ≥50%, and ≥70% in

40 the American College of Rheumatology response criteria (ACR20/50/70),²⁷

41 improvements from baseline of ≥75%, ≥90%, and 100% in the Psoriasis Area and

42 Severity Index (PASI75/90/100, in patients with psoriasis affecting ≥3% body

43 surface area [BSA])²⁸ and ACR50+PASI100 (in patients with psoriasis affecting ≥3%

44 BSA).
1 Achievement of minimal and very low disease activity (MDA, VLDA; achievement of
2 ≥5/7 or 7/7, respectively, of the following criteria: tender joint count [TJC] ≤1,
3 swollen joint count [SJC] ≤1, either PASI ≤1 or BSA ≤3%, Patients' Assessment of
4 Arthritis Pain visual analogue scale [Pain VAS] ≤15, Patient's Global Assessment of
5 PsA [PGA-PsA-VAS] ≤20, Health Assessment Questionnaire-Disability Index [HAQ-DI]
6 ≤0.5,²⁹ and tender enthesal points ≤1 [measured with the Leeds Enthesitis Index,
7 LEI]),³⁰ as well as resolution of TJC, SJC, enthesitis (LEI=0), dactylitis (Leeds
8 Dactylitis Index [LDI]=0)³¹ and nail psoriasis (modified Nail Psoriasis Severity Index
9 [mNAPSI]=0) were also assessed to Week 104/100. Other assessed efficacy
10 outcomes were PASI ≤1 responders, Disease Activity Index for Psoriatic Arthritis
11 (DAPSA) high disease activity (HDA), moderate disease activity (MoDA), low disease
12 activity (LDA) and remission (REM),³² and Psoriatic Arthritis Disease Activity Score
13 (PASDAS) REM and LDA.³³

14 Patient-reported outcomes (PROs) assessed through Week 104/88 include the HAQ-DI change from baseline (CfB) and minimal clinically important difference (MCID; decrease from baseline of ≥0.35 in patients with baseline score of ≥0.35), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) total score CfB, the Pain VAS CfB and ≥30/50% improvement thresholds, the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire total score CfB and MCID (decrease from baseline ≥3 in patients with PsAID-12 at ≥3 baseline), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) CfB and MCID (CfB ≥4 in patients with FACIT-Fatigue subscale ≤48 at baseline) and the Short-Form 36-item Health Survey Physical Component Summary (SF-36 PCS) CfB.

24 Statistical analysis

Statistical powering and sample size determination for BE OPTIMAL and BE
25 COMPLETE were reported in the primary publications.²⁴, ²⁵ There was no formal
26 sample size for the BE VITAL OLE, as it was determined by the number of patients
27 eligible for entry to the study.
28

29 Descriptive statistics are used to provide an overview of the safety and efficacy
30 results. Baseline values for efficacy variables were determined from baseline values
31 of the respective feeder studies (Week 0), as per the EULAR guidance for reporting
32 clinical trial extension data.³⁴

33 The Safety Set consisted of all randomised patients who received at least one dose
34 of bimekizumab. Safety variables were analysed for all patients in the Safety Set.
35 Adverse events were coded according to the Medical Dictionary for Regulatory
36 Activities (MedDRA version 19.0). Safety outcomes are reported as
37 exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY) of exposure,
38 with associated 95% confidence intervals (95% CI).

39 The Randomised Set consisted of all enrolled patients randomised in either feeder
40 study. Efficacy variables were analysed for all patients in the Randomised Set and
41 reported here by treatment group at initial randomisation.

42 Non-responder imputation (NRI) was used to impute missing data for binary
43 outcomes and multiple imputation was used to impute missing data for continuous
44 outcomes. For categorical data, worst-category imputation was used. Data were
45 imputed using baseline patient numbers from randomisation of the feeder studies.
46 Any patients that did not enter the BE VITAL OLE were imputed as non-responders,
1 as per the EULAR guidance for reporting clinical trial extension data.³⁴ Observed case

2 (OC) data are also reported for binary outcomes. All analyses were done with SAS,

3 version 9.3 or higher.

4 RESULTS

5 Patient disposition and baseline characteristics

6 Patient disposition from baseline is provided in **Supplementary Figure S1**. Of

7 patients who were randomised in BE OPTIMAL at Week 0, 90.4% (254/281) of

8 placebo-randomised patients, 87.9% (379/431) of bimekizumab-randomised patients

9 and 86.4% (121/140) of reference (adalimumab)-randomised patients entered the

10 BE VITAL OLE. Of patients who were randomised in BE OPTIMAL, 85.1% (239)

11 placebo-randomised, 83.3% (359) bimekizumab-randomised and 80.0% (112)

12 reference (adalimumab)-randomised patients completed Week 104.

13 Of patients who were randomised in BE COMPLETE, 91.0% (121/133) of

14 placebo-randomised patients and 95.9% (256/267) of bimekizumab-randomised

15 patients entered the BE VITAL OLE. Of patients that were randomised in BE

16 COMPLETE, 80.5% (107) of placebo-randomised patients and 80.5% (215)

17 bimekizumab-randomised patients completed Week 100.

18 Patient demographics and baseline characteristics have been reported previously and

19 were representative of patients with long-standing moderate-to-severe PsA.²⁰, ²¹, ²⁴, ²⁵

20 Treatment arms were generally comparable within each trial (Supplementary

21 Table S1).

22 Safety

23 Generally, incidence rates of TEAEs and other safety events remained consistent

24 from Week 0–52 to Week 52–104. Safety data from baseline to Week 52 can be

25 found in Table 1, Supplementary Tables S2–S6 and the 1-year reports for BE

26 OPTIMAL and BE COMPLETE.²⁰, ²¹ After Week 52 and up to Week 104, patients

27 treated with bimekizumab in BE OPTIMAL (n=773), including patients who had

28 switched from the reference treatment (adalimumab) to bimekizumab at Week 52,

29 had a TEAE incidence rate (EAIR/100 PY) of 152.2 (95% CI 139.6, 165.5). From

30 Week 52 to 104, patients in BE COMPLETE (n=361) had a TEAE incidence rate of

31 87.3 (75.3, 100.6; Table 1). The incidence rates of serious TEAEs were 8.2 (6.2,

32 10.6) and 4.9 (2.8, 7.9) in BE OPTIMAL and BE COMPLETE, respectively. The

33 incidence rates of study discontinuations due to TEAEs were similar between trials;

34 3.0 (1.9, 4.6) in BE OPTIMAL and 1.8 (0.7, 3.9) in BE COMPLETE. From Week 52 and

35 104, the incidence rate of deaths for patients treated with bimekizumab was 0.1 (0.0,

36 0.8) in BE OPTIMAL and 0 in BE COMPLETE. In BE OPTIMAL, 1 death occurred

37 between Week 52 and Week 104 in a 51-year-old female patient who switched from

38 the reference treatment at Week 52. The death was due to an acute myocardial

39 infarction and was deemed unrelated to study treatment by the investigator. The

40 patient had a history of cardiovascular risk factors.

41 The three most common TEAEs for Week 52–104 in BE OPTIMAL were SARS-CoV-2

42 (COVID-19) infection (18.6 [15.4, 22.1]), upper respiratory tract infection (6.3 [4.6,

43 8.4]) and oral candidiasis (5.5 [3.9, 7.5]). In BE COMPLETE, the three most common

44 TEAEs were SARS-CoV-2 (COVID-19) infection (7.4 [4.7, 10.9]), upper respiratory

45 tract infection (4.6 [2.6, 7.6] and nasopharyngitis (4.3 [2.3, 7.2]); Table 1).
1 The incidence rates of fungal infections reported by the investigators from Week 52
2 to Week 104 were 10.5 (8.3, 13.2) in BE OPTIMAL and 4.6 (2.6, 7.5) in BE
3 COMPLETE (Table 1). The rates of Candida infections were 6.5 (4.8, 8.7) and 3.3
4 (1.7, 5.9) in BE OPTIMAL and BE COMPLETE, respectively (Supplementary Table
5 S2). Most cases were oral candidiasis (BE OPTIMAL: 5.5 [3.9, 7.5]; BE
6 COMPLETE: 3.3 [1.7, 5.9]), the next most frequent was vulvovaginal candidiasis (BE
7 OPTIMAL: 0.8 [0.3, 1.8]; BE COMPLETE: 0). There was one serious case of
8 oropharyngeal candidiasis in BE OPTIMAL, and no serious Candida infections in BE
9 COMPLETE. There were no systemic Candida infections in either study. Further
10 breakdown of fungal infections can be found in Supplementary Table S2.

11 In BE OPTIMAL from Week 0–104, 89.3% (735) of patients did not report a Candida
12 infection, 6.4% (53) patients reported one Candida infection and 4.3% (35) of
13 patients reported two or more Candida infections. In BE COMPLETE, 92.0% (357) of
14 patients did not report a Candida infection, 5.9% (23) reported one Candida
15 infection and 2.1% (8) reported two or more.

16 The incidence rates of fungal infections leading to patient discontinuation between
17 Week 52 and Week 104 were low in both studies (all oral candidiasis; BE
18 OPTIMAL: 0.5 [0.1, 1.4]; BE COMPLETE: 0.6 [0.1, 2.1]). There were no documented
19 cases of patient discontinuation due to recurrent fungal infections.

20 The incidence rate of malignancies (excluding nonmelanoma skin cancer) between
21 Week 52 and Week 104 was similar between studies (BE OPTIMAL: 0.4 [0.1, 1.2];
22 BE COMPLETE: 0.6 [0.1, 2.2]); a further breakdown of malignancies can be found in
23 Supplementary Table S3).

24 Incidence rates from Week 52 to Week 104 were similar between studies for events
25 adjudicated as MACE (BE OPTIMAL: 0.4 [0.1, 1.2]; BE COMPLETE: 0;
26 Supplementary Table S4), neutropenia (BE OPTIMAL: 1.2 [0.6, 2.3]; BE
27 COMPLETE: 1.8 [0.7, 3.9]) and injection site reactions (BE OPTIMAL: 1.8 [1.0, 3.1];
28 BE COMPLETE: 0.3 [0.0, 1.7]). Incidence rates of thromboembolism were low in
29 BKZ-treated patients (Supplementary Table S5). The incidence rate for
30 hypersensitivity was 6.9 (5.1, 9.1) in BE OPTIMAL and 3.6 (1.9, 6.4) in BE
31 COMPLETE; the majority of these were dermatitis and eczema (BE OPTIMAL: 3.6
32 [2.4, 5.3]; BE COMPLETE: 1.2 [0.3, 3.1]). There were low incidence rates of events
33 adjudicated as suicidal ideation and behaviour (BE OPTIMAL: 0.1 [0.0, 0.8]; BE
34 COMPLETE: 0; Supplementary Table S6) and definite or probable IBD (BE
35 OPTIMAL: 0.4 [0.1, 1.2]; BE COMPLETE: 0). There were no reported cases of uveitis
36 in either study.
1 **Efficacy**

2 ACR50 response rates with bimekizumab treatment were sustained from Week 52 to
3 Week 104/100 in both the BE OPTIMAL and BE COMPLETE studies (Figure 2). In BE
4 OPTIMAL, 51.5% of bimekizumab-randomised patients, 50.5% of placebo-
5 randomised patients, and 50.7% of reference (adalimumab)-randomised patients
6 achieved ACR50 at Week 104, respectively. In BE COMPLETE at Week 100, ACR50
7 responses were 50.6% of bimekizumab-randomised patients and 48.1% of
8 placebo-randomised patients, respectively (Figure 2). ACR20 and ACR70 responses
9 were also sustained during the OLE in both patient populations (Figure 2; OC data
10 also shown).

11 The proportion of patients achieving complete skin clearance (PASI100) was
12 sustained from Week 52 to Week 104/100 in bimekizumab-randomised and
13 placebo-randomised patients with ≥3% BSA affected by psoriasis at baseline
14 (Figure 3). An increase in the proportion of patients achieving PASI100 occurred in
15 reference (adalimumab)-randomised patients following the switch to bimekizumab.
16 In BE OPTIMAL, 59.4% of bimekizumab-randomised patients and 60.0% of
17 placebo-randomised patients achieved PASI100 at Week 104. The proportion of
18 reference (adalimumab)-randomised patients that achieved PASI100 increased from
19 48.5% at Week 52 to 60.3% at Week 104. In BE COMPLETE, 63.1% of
20 bimekizumab-randomised patients and 65.9% of placebo-randomised patients
21 achieved PASI100 at Week 100, respectively (Figure 3). PASI75 and PASI90
22 responses were also sustained to Week 104/100 between trials (Figure 3; OC data
23 also shown).

24 The proportion of patients achieving MDA was similarly sustained in all patients from
25 Week 52 to Week 104/100 (Figure 4). In BE OPTIMAL, 52.4% of
26 bimekizumab-randomised patients, 49.8% of placebo-randomised patients, 50.7% of
27 reference (adalimumab)-randomised patients were judged to be in MDA at Week 104.
28 In BE COMPLETE, 44.9% of bimekizumab-randomised patients and 46.6% of
29 placebo-randomised patients achieved MDA at Week 100 (Figure 4). VLDA and
30 ACR50+PASI100 responses were also sustained to Week 104/100 between trials
31 (Figure 4; OC data also shown).

32 Also sustained from Week 52 to Week 104/100 was the proportion of patients
33 achieving resolution of SJC (SJC=0), an objective measure of inflammation. In BE
34 OPTIMAL, 60.6% of bimekizumab-randomised patients, 58.0% of
35 placebo-randomised patients, and 56.4% of reference (adalimumab)-randomised
36 patients achieved SJC resolution at Week 104. In BE COMPLETE, 53.6% of
37 bimekizumab-randomised patients and 60.9% of placebo-randomised patients
38 achieved SJC resolution at Week 100 (Figure 5I). Resolution of TJC (TJC=0), as
39 well as change from baseline in SJC and TJC values were also sustained to Week
40 104/100 between trials (Figure 5II; OC data also shown for resolution data).

41 Results were similar for enthesitis (Figure 6) at Week 104, where of patients that
42 had enthesitis at baseline (LEI >0), 53.8% of bimekizumab-randomised, 67.1% of
43 placebo-randomised, and 55.6% of reference (adalimumab)-randomised patients in
44 BE OPTIMAL achieved resolution (LEI=0), along with 53.8% of
45 bimekizumab-randomised and 50.0% of placebo-randomised patients in BE
46 COMPLETE. Dactylitis resolution (LDI=0) and nail psoriasis resolution (mNAPSI=0)
47 are also reported in Figure 6.
1 Patient-reported outcomes are also reported at 2 years (Table 2). DAPSA disease

2 states (Supplementary Figure S2) and nail psoriasis CfB (Supplementary

3 **Figure S3) data can be found in the supplement.**

4 DISCUSSION

5 Results from the BE VITAL OLE demonstrated that bimekizumab maintained a

6 tolerable safety profile, whilst sustaining efficacy seen at one year up to two years in

7 patients with active PsA who were bDMARD-naïve or TNFi-IR. The safety profile was

8 consistent with that observed to one year.²⁰,²¹ Efficacy up to two years, for patients

9 treated with bimekizumab from baseline or Week 16, was sustained from Week 52

10 across a range of PsA domains, including joints, skin and nails and reflected in

11 composite outcomes such as MDA. For patients in BE OPTIMAL who switched from

12 the reference treatment (adalimumab) to bimekizumab at Week 52, efficacy was

13 generally sustained through two years, with further improvements in skin and nails,

14 following the switch and with no washout between treatments.

15 The long-term safety profile, observed up to two years, was generally consistent

16 between bDMARD-naïve and TNFi-IR patients. Bimekizumab was well tolerated in

17 patients with PsA; no new safety signals were observed with long-term treatment.²⁰,

18 ²¹ No additional safety signals were observed following direct switch from reference

19 (adalimumab) treatment to bimekizumab without a washout. Incidence rates of

20 TEAEs did not increase with exposure, and incidence rates for adverse events of

21 interest were low, such as suicidal ideation and behaviour, uveitis, MACE, IBD and

22 hypersensitivity.

23 The majority of fungal infections were mild or moderate, and none were systemic;

24 the incidence of fungal infections did not increase with long-term therapy. Most

25 fungal infections resolved with standard antifungal therapy. Given that fungal

26 infections were categorised at the discretion of the investigator, some *Candida*

27 infections may have been reported as a fungal infection "not elsewhere classified".

28 All fungal infections are reported in **Supplementary Table S2**. There were low

29 numbers of recurrent *Candida* infections, low incidence rates of patient

30 discontinuation due to fungal infections, and no instances of patients discontinuing

31 after fungal infection recurrence.

32 Treatment with bimekizumab demonstrated consistent sustained clinical efficacy to

33 two years in bDMARD-naïve and TNFi-IR patients with active PsA. The majority of

34 improvements across domains observed at one year were sustained at similar levels

35 for up to two years. TNFi-naïve and TNFi-experienced patients alike have been

36 shown to switch to a new biologic over their treatment period,³⁵ however, patients

37 switching from a TNFi to another bDMARD often experience reduced persistence of

38 the second agent.¹⁴ Time to discontinuation has been shown to be shorter in TNFi-

39 experienced patients, who are more likely to discontinue or switch.³⁵ The long-term

40 efficacy demonstrated in these trials suggests that bimekizumab can provide lasting

41 benefit in the clinical management of patients with PsA, who require lifelong

42 treatment. bDMARD-naïve patients switching from reference (adalimumab)

43 treatment to bimekizumab at Week 52 showed sustained efficacy in joint symptoms

44 after the switch; further improvement in skin and nail responses were observed

45 following switch to bimekizumab and were sustained to Week 104.
1 A strength of this analysis was the high proportion of patients remaining in both

2 studies for two years. Another strength was that response data were imputed using

3 NRI from baseline of BE OPTIMAL and BE COMPLETE, and were not modified at any

4 later timepoint. Additionally, there were similar long-term responses between the

5 two study populations. In BE OPTIMAL, the reference treatment to bimekizumab

6 switch demonstrated that a direct switch without washout is possible without an

7 increased risk of adverse events.

8 A limitation of the BE VITAL OLE study is that it was not designed to compare

9 treatment groups from BE OPTIMAL and BE COMPLETE. Additionally, in BE OPTIMAL,

10 there was not an early visit that assessed efficacy outcomes after the switch from

11 reference treatment to bimekizumab. Therefore, the impact of receiving two

12 biologics without a washout period between them could not be evaluated at an early

13 timepoint. Also, in BE OPTIMAL, caution is needed when evaluating the reference

14 (adalimumab)/bimekizumab treatment arm, as the switch took place regardless of

15 treatment response. This may not be applicable to what is seen in the clinic. In BE

16 COMPLETE, as it was open-label following Week 16 (versus BE OPTIMAL, which was

17 open-label following Week 52), patients received a greater duration of open-label

18 treatment.

19 Further long-term efficacy and safety data are being collected and will be reported at

20 3 years when available. Additionally, further evaluation of subgroups for responses

21 and parameters key for long-term responses will be assessed. The authors also

22 acknowledge the need for real-world data for bimekizumab in patients with a wider

23 range of inclusion criteria.

24 CONCLUSIONS

25 Bimekizumab was well tolerated, with a safety profile consistent with that previously

26 observed in studies of bimekizumab in PsA during phase 2b and 3 studies.

27 Bimekizumab treatment resulted in a sustained high level of efficacy response over 2

28 years in both bDMARD-naïve and TNFi-IR patients. Responses were consistent across

29 these populations. Efficacy outcomes in the reference (adalimumab) arm following

30 switch to bimekizumab were sustained to 2 years, with a further increase in efficacy

31 observed in skin and nail outcomes.
1 ACKNOWLEDGEMENTS AND AFFILIATIONS

2 The authors thank the patients, the investigators and their teams who took part in
3 this study. The authors also acknowledge Heather Edens, PhD, UCB Pharma, Smyrna,
4 GA, USA, for publication coordination and editorial contribution and Laura Mawdsley,
5 MSc, Costello Medical, Cambridge, UK for medical writing and editorial assistance
6 based on the authors' input and direction. This study was funded by UCB.

7 AUTHORS' CONTRIBUTIONS

8 **Substantial contributions to study conception and design:** Philip J. Mease,
9 Joseph F. Merola, Yoshiya Tanaka, Laure Gossec, Iain B. McInnes, Christopher T.
10 Ritchlin, Robert B.M. Landewé, Akihiko Asahina, Barbara Ink, Andrea Heinrichs,
11 Rajan Bajracharya, Vishvesh Shende, Jason Coarse, Laura C. Coates; **substantial
12 contributions to analysis and interpretation of the data:** Philip J. Mease,
13 Joseph F. Merola, Yoshiya Tanaka, Laure Gossec, Iain B. McInnes, Christopher T.
14 Ritchlin, Robert B.M. Landewé, Akihiko Asahina, Barbara Ink, Andrea Heinrichs,
15 Rajan Bajracharya, Vishvesh Shende, Jason Coarse, Laura C. Coates; **drafting the
16 article or revising it critically for important intellectual content:** Philip J.
17 Mease, Joseph F. Merola, Yoshiya Tanaka, Laure Gossec, Iain B. McInnes,
18 Christopher T. Ritchlin, Robert B.M. Landewé, Akihiko Asahina, Barbara Ink, Andrea
19 Heinrichs, Rajan Bajracharya, Vishvesh Shende, Jason Coarse, Laura C. Coates; **final
20 approval of the version of the article to be published:** Philip J. Mease, Joseph
21 F. Merola, Yoshiya Tanaka, Laure Gossec, Iain B. McInnes, Christopher T. Ritchlin,
22 Robert B.M. Landewé, Akihiko Asahina, Barbara Ink, Andrea Heinrichs, Rajan
23 Bajracharya, Vishvesh Shende, Jason Coarse, Laura C. Coates.

24 FUNDING

25 This study was sponsored by UCB Pharma. Support for third-party writing assistance
26 for this article, provided by Laura Mawdsley, MSc, Costello Medical, Cambridge, UK,
27 was funded by UCB Pharma in accordance with [Good Publication Practice (GPP 2022)](https://wwwGoodPublicationPracticeGPP2022 guidelines). The journal's Rapid Service Fee was funded by UCB Pharma.

29 MEDICAL WRITING/EDITORIAL ASSISTANCE

30 Support for third-party writing assistance for this article, provided by Laura Mawdsley,
31 MSc, Costello Medical, Cambridge, UK, was funded by UCB Pharma in accordance
32 with [Good Publication Practice (GPP 2022) guidelines](https://wwwGoodPublicationPracticeGPP2022 guidelines).

33 DATA AVAILABILITY

34 Data from this manuscript may be requested by qualified researchers six months
35 after product approval in the US and/or Europe, or global development is
36 discontinued, and 18 months after trial completion. Investigators may request access
37 to anonymised individual patient data and redacted study documents which may
38 include: raw datasets, analysis-ready datasets, study protocol, blank case report
39 form, annotated case report form, statistical analysis plan, dataset specifications and
40 clinical study report. Prior to use of the data, proposals need to be approved by an
41 independent review panel at [www.Vivli.org](https://www.Vivli.org) and a signed data sharing agreement will
42 need to be executed. All documents are available in English only, for a prespecified
43 time, typically 12 months, on a password protected portal.

44 ETHICAL APPROVAL

45 Studies were conducted in accordance with the Declaration of Helsinki and the
46 International Conference on Harmonization guidance for Good Clinical Practice.
47 Ethical approval was obtained from the relevant institutional review boards at
1 participating sites, and all patients provided written informed consent in accordance

2 with local requirements.

3 CONFLICT OF INTEREST

4 Philip J. Mease: Received research grants from AbbVie, Acelyrin, Amgen, BMS, Eli

5 Lilly, Janssen, Novartis, Pfizer and UCB Pharma; consulting fees from AbbVie,

6 Acelyrin, Aclaris, Alumis, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Inmagene,

7 Janssen, Moonlake Pharma, Novartis, Pfizer, Takeda, UCB Pharma and Ventyx;

8 speakers bureau fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and

9 UCB Pharma; data safety and advisory board for Genascence.

10 Joseph F. Merola: Is a consultant and/or investigator for AbbVie, Amgen,

11 AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli

12 Lilly, Incyte, Janssen, LEO Pharma, MoonLake Immunotherapeutics, Novartis, Pfizer,

13 Sanofi-Regeneron, Sun Pharma and UCB Pharma. Joseph F. Merola's current

14 affiliation is "Department of Dermatology and Department of Medicine, Division of

15 Rheumatology, UT Southwestern Medical Center, Dallas, Texas, USA".

16 Yoshiya Tanaka: Speaker fees and/or honoraria from: AbbVie, Asahi-kasei, Astellas,

17 AstraZeneca, Behringer-Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead,

18 GlaxoSmithKline, Pfizer, Taisho, UCB Pharma; received grants from: Behringer-

19 Ingelheim, Chugai, Taisho. Yoshiya Tanaka is an Editorial Board member of

20 Rheumatology & Therapy. Yoshiya Tanaka was not involved in the selection of peer

21 reviewers for the manuscript nor any of the subsequent editorial decisions.

22 Laure Gossec: Grants or contracts from AbbVie, Biogen, Eli Lilly, Novartis and UCB

23 Pharma; consulting fees from AbbVie, BMS, Celltrion, Janssen, Novartis, Pfizer and

24 UCB Pharma; honoraria for lectures from AbbVie, Amgen, BMS, Celltrion, Janssen, Eli

25 Lilly, MSD, Novartis, Pfizer, Stada and UCB Pharma; has received support for

26 attending meetings and/or travel from MSD, Novartis, Pfizer; has received medical

27 writing support from AbbVie, Amgen, Galapagos, Janssen, Pfizer and UCB Pharma.

28 Membership on an entity's Board of Directors or advisory committees: EULAR

29 Treasurer.

30 Iain B. McInnes: Consulting fees and honoraria from AbbVie, AstraZeneca, BMS,

31 Boehringer Ingelheim, Cabaletta, Causeway Therapeutics, Celgene, Evelo, Janssen,

32 Eli Lilly, Moonlake Immunotherapeutics, Novartis and UCB Pharma; Research support

33 from BMS, Boehringer Ingelheim, Celgene, Janssen, Novartis, and UCB Pharma.

34 Christopher T. Ritchlin: Research for AbbVie; consultant for Amgen, AbbVie, BMS,

35 Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, Solarea and UCB Pharma.

36 Robert B. M. Landewé: Consultancy fees from AbbVie, AstraZeneca, BMS, Novartis,

37 Pfizer, Eli Lilly, and UCB Pharma; research grants from AbbVie, Pfizer, Novartis, and

38 UCB Pharma; owner of Rheumatology Consultancy BV, an AMS company under

39 Dutch law.

40 Akihiko Asahina: Honoraria and/or research grants from AbbVie, Amgen, Bristol

41 Myers Squibb, Boehringer Ingelheim, Eisai, Eli Lilly, Janssen, Kyowa Kirin, LEO

42 Pharma, Maruho, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Sun Pharma, Taiho

43 Pharma, Torii Pharmaceutical Co., and UCB Pharma.
1 **Barbara Ink**: Employee of UCB Pharma, shareholder of AbbVie, GSK and UCB

2 Pharma.

3 **Andrea Heinrichs, Vishvesh Shende**: Employees of UCB Pharma.

4 **Rajan Bajracharya, Jason Coarse**: Employees and shareholders of UCB Pharma.

5 **Laura C. Coates**: Grants/research support from AbbVie, Amgen, Celgene, Eli Lilly,

6 Gilead, Janssen, Novartis, Pfizer and UCB Pharma; consultant for AbbVie, Amgen,

7 BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen,

8 Moonlake Immunotherapeutics, Novartis, Pfizer, and UCB Pharma; speaking fees

9 from AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen,

10 medac, Novartis, Pfizer, and UCB Pharma. Laura C. Coates is an Editorial Board

11 member of Rheumatology & Therapy. Laura C. Coates was not involved in the

12 selection of peer reviewers for the manuscript nor any of the subsequent editorial

13 decisions.

14 **CONSENT FOR PUBLICATION**

15 All the results presented in this article are in aggregate form, and no personally

16 identifiable information was used for this study.
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10

11

12
1 TABLES AND FIGURES

2 **Figure 1.** BE OPTIMAL and BE COMPLETE study designs

3

4 The ADA 40 mg Q2W treatment arm served as an active reference. The BE OPTIMAL study was not powered for statistical comparisons of ADA to BKZ or PBO. Completion

5 rates include patients that completed to Week 52/104 in BE OPTIMAL and Week 52/100 in BE COMPLETE not on randomised treatment (BE OPTIMAL Week 52: 8 [1.0%],

6 Week 104: 8 [0.9%]; BE COMPLETE Week 52: 4 [1.0%], Week 100: 2 [0.5%]). ACR50: ≥50% improvement in American College of Rheumatology response criteria;

7 ADA: adalimumab; bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; OLE: open-label extension; PBO: placebo; TNFi-IR: prior inadequate response

8 or intolerance to tumour necrosis factor inhibitors.

9
<table><caption>1 Table 1. Safety for Week 0–52 and Week 52–104</caption><thead><tr><th rowspan="3">EAIR (95% CI) /100 PY</th><th colspan="4">BE OPTIMAL<br>(bDMARD-naïve)</th><th colspan="2">BE COMPLETE<br>(TNFi-IR)</th></tr><tr><th colspan="2">Week 0–52</th><th colspan="2">Week 52–104</th><th colspan="2">Week 0–52</th></tr><tr><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=702<br>595.6 PY</th><th>ADA 40 mg<br>Q2W<br>n=140<br>136.8 PY</th><th>ADA → BKZ<br>160 mg Q4W<br>n=121<br>117.2 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=773<br>738.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=388<br>340.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=361<br>335.2 PY</th></tr></thead><tbody><tr><td>TEAEs</td><td>223.0<br>(204.8, 242.3)</td><td>209.4<br>(172.6, 251.7)</td><td>164.5<br>(132.1, 202.4)</td><td>152.2<br>(139.6, 165.5)</td><td>125.2<br>(110.0, 142.0)</td><td>87.3<br>(75.3, 100.6)</td></tr><tr><td>Serious TEAEs</td><td>7.8<br>(5.7, 10.4)</td><td>7.5<br>(3.6, 13.9)</td><td>4.3<br>(1.4, 10.1)</td><td>8.2<br>(6.2, 10.6)</td><td>7.0<br>(4.4, 10.4)</td><td>4.9<br>(2.8, 7.9)</td></tr><tr><td>Study discontinuation due to TEAEs</td><td>4.1<br>(2.6, 6.1)</td><td>5.2<br>(2.1, 10.8)</td><td>3.4<br>(0.9, 8.8)</td><td>3.0<br>(1.9, 4.6)</td><td>5.1<br>(3.0, 8.1)</td><td>1.8<br>(0.7, 3.9)</td></tr><tr><td>Drug-related TEAEs</td><td>47.8<br>(41.7, 54.5)</td><td>53.6<br>(40.3, 69.9)</td><td>36.0<br>(24.9, 50.2)</td><td>29.7<br>(25.5, 34.3)</td><td>29.8<br>(23.9, 36.9)</td><td>16.6<br>(12.3, 21.8)</td></tr><tr><td>Severe TEAEs</td><td>3.9<br>(2.5, 5.9)</td><td>6.8<br>(3.1, 12.9)</td><td>3.4<br>(0.9, 8.8)</td><td>3.8<br>(2.6, 5.6)</td><td>4.8<br>(2.7, 7.8)</td><td>2.7<br>(1.2, 5.1)</td></tr><tr><td>Deaths</td><td>0.2<br>(0.0, 0.9)<sup>b</sup></td><td>0</td><td>0.9<br>(0.0, 4.8)<sup>c</sup></td><td>0.1<br>(0.0, 0.8)<sup>c</sup></td><td>0.3<br>(0.0, 1.6)<sup>d</sup></td><td>0</td></tr><tr><td>Most frequent TEAEs<sup>e</sup></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>SARS-CoV-2 (COVID-19) infection<sup>f</sup></td><td>3.4<br>(2.1, 5.2)</td><td>2.9<br>(0.8, 7.5)</td><td>18.9<br>(11.6, 29.2)</td><td>18.6<br>(15.4, 22.1)</td><td>8.5<br>(5.6, 12.3)</td><td>7.4<br>(4.7, 10.9)</td></tr><tr><td>Nasopharyngitis</td><td>15.4<br>(12.3, 19.1)</td><td>9.4<br>(4.8, 16.3)</td><td>5.3<br>(1.9, 11.5)</td><td>5.3<br>(3.7, 7.2)</td><td>7.0<br>(4.5, 10.6)</td><td>4.3<br>(2.3, 7.2)</td></tr><tr><td>Upper respiratory tract infection</td><td>8.8<br>(6.6, 11.6)</td><td>6.1<br>(2.6, 12.0)</td><td>6.2<br>(2.5, 12.7)</td><td>6.3<br>(4.6, 8.4)</td><td>3.6<br>(1.9, 6.3)</td><td>4.6<br>(2.6, 7.6)</td></tr><tr><td>Oral candidiasis<sup>g</sup></td><td>6.7<br>(4.8, 9.2)</td><td>0.7<br>(0.0, 4.1)</td><td>4.4<br>(1.4, 10.2)</td><td>5.5<br>(3.9, 7.5)</td><td>7.6<br>(4.9, 11.3)</td><td>3.3<br>(1.7, 5.9)</td></tr><tr><td>Urinary tract infection</td><td>7.3<br>(5.2, 9.8)</td><td>3.7<br>(1.2, 8.7)</td><td>4.4<br>(1.4, 10.3)</td><td>4.2<br>(2.8, 6.0)</td><td>7.0<br>(4.5, 10.5)</td><td>4.0<br>(2.1, 6.8)</td></tr><tr><td>Adjudicated MACE<sup>h</sup></td><td>0.7<br>(0.2, 1.7)</td><td>0</td><td>1.7<br>(0.2, 6.2)</td><td>0.4<br>(0.1, 1.2)</td><td>0.6<br>(0.1, 2.1)</td><td>0</td></tr><tr><td>Neutropenia<sup>i</sup></td><td>1.7<br>(0.8, 3.1)</td><td>1.5<br>(0.2, 5.3)</td><td>0</td><td>1.2<br>(0.6, 2.3)</td><td>1.8<br>(0.7, 3.9)</td><td>1.8<br>(0.7, 3.9)</td></tr><tr><td>Serious infections</td><td>1.0<sup>j</sup></td><td>1.5<sup>j</sup></td><td>1.7</td><td>1.8</td><td>2.1</td><td>0.6</td></tr></tbody></table>
<table><thead><tr><th rowspan="3">EAIR (95% CI) /100 PY</th><th colspan="4">BE OPTIMAL<br>(bDMARD-naïve)</th><th colspan="2">BE COMPLETE<br>(TNFi-IR)</th></tr><tr><th colspan="2">Week 0–52</th><th>Week 52–104</th><th>Week 52–104</th><th colspan="2">Week 0–52</th></tr><tr><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=702<br>595.6 PY</th><th>ADA 40 mg<br>Q2W<br>n=140<br>136.8 PY</th><th>ADA → BKZ<br>160 mg Q4W<br>n=121<br>117.2 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=773<br>738.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=388<br>340.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=361<br>335.2 PY</th></tr></thead><tbody><tr><td></td><td>(0.4, 2.2)</td><td>(0.2, 5.3)</td><td>(0.2, 6.2)</td><td>(0.9, 3.0)</td><td>(0.8, 4.3)</td><td>(0.1, 2.2)</td></tr><tr><td>Fungal infections</td><td>15.3<br>(12.2, 18.9)</td><td>1.5<br>(0.2, 5.3)</td><td>12.0<br>(6.4, 20.4)</td><td>10.5<br>(8.3, 13.2)</td><td>12.2<br>(8.7, 16.7)</td><td>4.6<br>(2.6, 7.5)</td></tr><tr><td>Candida infections</td><td>9.8<br>(7.4, 12.7)</td><td>0.7<br>(0.0, 4.1)</td><td>4.4<br>(1.4, 10.2)</td><td>6.5<br>(4.8, 8.7)</td><td>8.0<br>(5.2, 11.7)</td><td>3.3<br>(1.7, 5.9)</td></tr><tr><td>Hypersensitivity</td><td>10.4<br>(7.9, 13.4)</td><td>5.3<br>(2.1, 10.9)</td><td>9.0<br>(4.3, 16.5)</td><td>6.9<br>(5.1, 9.1)</td><td>5.8<br>(3.5, 9.0)</td><td>3.6<br>(1.9, 6.4)</td></tr><tr><td>Dermatitis and eczema</td><td>4.1<br>(2.6, 6.1)</td><td>1.5<br>(0.2, 5.3)</td><td>4.4<br>(1.4, 10.3)</td><td>3.6<br>(2.4, 5.3)</td><td>2.4<br>(1.0, 4.7)</td><td>1.2<br>(0.3, 3.1)</td></tr><tr><td>Serious hypersensitivity</td><td>0.2<br>(0.0, 0.9)<sup>k</sup></td><td>0</td><td>0</td><td>0.1<br>(0.0, 0.8)<sup>k</sup></td><td>0</td><td>0.3<sup>l</sup><br>(0.0, 1.7)</td></tr><tr><td>Injection site reactions</td><td>2.7<br>(1.6, 4.4)</td><td>10.2<br>(5.4, 17.4)</td><td>2.6 (0.5, 7.6)</td><td>1.8 (1.0, 3.1)</td><td>1.8<br>(0.7, 3.9)</td><td>0.3<br>(0.0, 1.7)</td></tr><tr><td>Adjudicated suicidal ideation and<br>behaviour</td><td>0</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr><tr><td>Malignancies excluding non-melanoma<br>skin cancer</td><td>0.5<br>(0.1, 1.5)</td><td>0</td><td>0</td><td>0.4 (0.1, 1.2)</td><td>0.9<br>(0.2, 2.6)</td><td>0.6<br>(0.1, 2.2)</td></tr><tr><td>Adjudicated IBD<sup>m</sup></td><td>0.7<br>(0.2, 1.7)</td><td>0</td><td>1.7 (0.2, 6.2)</td><td>0.4 (0.1, 1.2)</td><td>0</td><td>0</td></tr><tr><td>Uveitis</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Elevated liver function, n/N (%)</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>ALT >3 × ULN</td><td>13/701 (1.9)</td><td>7/139 (5.0)</td><td>2/121 (1.7)</td><td>8/764 (1.0)</td><td>7/388 (1.8)</td><td>4/354 (1.1)</td></tr><tr><td>AST or ALT >3 × ULN</td><td>21/701 (3.0)</td><td>9/139 (6.5)</td><td>4/121 (3.3)</td><td>15/764 (2.0)</td><td>11/388 (2.8)</td><td>8/354 (2.3)</td></tr></tbody></table>

1 Safety set. [a] BKZ groups include PBO/BKZ Week 16 switchers (for both BE OPTIMAL and BE COMPLETE), includes events after switch only; BE OPTIMAL Weeks 52–104 also includes ADA/BKZ switchers in addition to PBO- and BKZ-randomised patients, events after switch only; [b] One death due to a motorcycle accident; [c] One death due to acute myocardial infarction, reported as unrelated to the study drug; [d] Sudden death in 54-year old patient with a history of hypertension, aortic regurgitation and electrocardiogram changes of coronary artery disease; no further information available as no autopsy was performed; [e] Five most common TEAEs in any BKZ-treated group at the Week 104 data cut; [f] All COVID-19 infections were mild or moderate, none were severe; [g] All infections were mild or moderate and none were serious, nine patients discontinued the study after an oral candidiasis event whilst receiving BKZ (one in BE OPTIMAL and two in BE COMPLETE during Week 0–52, four in BE OPTIMAL and two in BE COMPLETE during Week 52–104).

2 includes ADA/BKZ switchers in addition to PBO- and BKZ-randomised patients, events after switch only; [b] One death due to a motorcycle accident; [c] One death due to acute myocardial infarction, reported as unrelated to the study drug; [d] Sudden death in 54-year old patient with a history of hypertension, aortic regurgitation and electrocardiogram changes of coronary artery disease; no further information available as no autopsy was performed; [e] Five most common TEAEs in any BKZ-treated group at the Week 104 data cut; [f] All COVID-19 infections were mild or moderate, none were severe; [g] All infections were mild or moderate and none were serious, nine patients discontinued the study after an oral candidiasis event whilst receiving BKZ (one in BE OPTIMAL and two in BE COMPLETE during Week 0–52, four in BE OPTIMAL and two in BE COMPLETE during Week 52–104).

3 acute myocardial infarction, reported as unrelated to the study drug; [d] Sudden death in 54-year old patient with a history of hypertension, aortic regurgitation and electrocardiogram changes of coronary artery disease; no further information available as no autopsy was performed; [e] Five most common TEAEs in any BKZ-treated group at the Week 104 data cut; [f] All COVID-19 infections were mild or moderate, none were severe; [g] All infections were mild or moderate and none were serious, nine patients discontinued the study after an oral candidiasis event whilst receiving BKZ (one in BE OPTIMAL and two in BE COMPLETE during Week 0–52, four in BE OPTIMAL and two in BE COMPLETE during Week 52–104).

4 electrocardiogram changes of coronary artery disease; no further information available as no autopsy was performed; [e] Five most common TEAEs in any BKZ-treated group at the Week 104 data cut; [f] All COVID-19 infections were mild or moderate, none were severe; [g] All infections were mild or moderate and none were serious, nine patients discontinued the study after an oral candidiasis event whilst receiving BKZ (one in BE OPTIMAL and two in BE COMPLETE during Week 0–52, four in BE OPTIMAL and two in BE COMPLETE during Week 52–104).

5 at the Week 104 data cut; [f] All COVID-19 infections were mild or moderate, none were severe; [g] All infections were mild or moderate and none were serious, nine patients discontinued the study after an oral candidiasis event whilst receiving BKZ (one in BE OPTIMAL and two in BE COMPLETE during Week 0–52, four in BE OPTIMAL and two in BE COMPLETE during Week 52–104).

6 discontinued the study after an oral candidiasis event whilst receiving BKZ (one in BE OPTIMAL and two in BE COMPLETE during Week 0–52, four in BE OPTIMAL and two in BE COMPLETE during Week 52–104).
1. BE COMPLETE during Week 52–104); [h] Events whilst receiving BKZ: one case each of acute myocardial infarction, cerebrovascular accident, ischaemic stroke and thrombotic

2. cerebral infarction during Week 0–52 of BE OPTIMAL; two cases of acute myocardial infarction and one case of ischaemic stroke (deemed by the investigator to be related to

3. study medication) during Week 52–104 of BE OPTIMAL; one case of cerebral haemorrhage and one sudden death during Week 0–52 of BE COMPLETE; no MACE events during

4. Week 52–104 of BE COMPLETE; [i] BE OPTIMAL: nine neutropenia, 1 neutrophil count decreased in BKZ Total and two neutropenia in ADA treatment arms during Week 0–52,

5. eight neutropenia, one neutrophil count decreased in BKZ Total treatment arm during Week 52–104; BE COMPLETE: five neutropenia, one neutrophil count decreased Week

6. 0–52, three neutropenia, four neutrophil count decreased during Week 52–104; [j] Six serious infections were reported on the BKZ treatment arm: one cellulitis, one

7. gangrene, one pneumonia, one upper respiratory tract infection, one cystitis and one urinary tract infection. Two ADA-treated patients reported serious infections: one otitis

8. media and one reported both herpes zoster and atypical pneumonia; [k] One serious face swelling event; [l] One serious hypersensitivity event (dermatitis); [m] Cases

9. deemed definite or probable IBD by the investigator. ADA: adalimumab; ALT: alanine aminotransferase; AST: aspartate aminotransferase; bDMARD: biologic disease-modifying

10. antirheumatic drug; BKZ: bimekizumab; CI: confidence interval; EAIR: exposure-adjusted incidence rate; IBD: inflammatory bowel disease; MACE: major adverse

11. cardiovascular event; PBO: placebo; PYs: patient-years; Q2W: every two weeks; Q4W: every four weeks; TEAE: treatment-emergent adverse event; TNFi-IR: prior inadequate

12. response or intolerance to tumour necrosis factor inhibitors; ULN: upper limit of normal.
1 **Figure 2.** ACR20/50/70 responses to Week 104/100 (NRI, OC)

2

3 Randomised set. In BE OPTIMAL, patients randomised to ADA at baseline switched to BKZ 160 mg Q4W at Week 52. [a] Reference arm; study not powered for statistical

4 comparisons between ADA and BKZ or PBO. ACR20/50/70: ≥20/50/70% improvement from baseline in American College of Rheumatology response criteria;

5 ADA: adalimumab; bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; NRI: non-responder imputation; OC: observed case; PBO: placebo;

6 Q4W: every 4 weeks; TNFi-IR: prior inadequate response or intolerance to tumour necrosis factor inhibitors.
1 **Figure 3.** PASI75/90/100 responses to Week 104/100 (NRI, OC)

2

3 Randomised set, in patients with ≥3% body surface area affected by psoriasis at baseline. In BE OPTIMAL, patients randomised to ADA at baseline switched to BKZ 160 mg

4 Q4W at Week 52. [a] Reference arm; study not powered for statistical comparisons between ADA and BKZ or PBO. ADA: adalimumab; bDMARD: biologic disease-modifying

5 antirheumatic drug; BKZ: bimekizumab; NRI: non-responder imputation; OC: observed case, PASI75/90/100: ≥75/90/100% improvement from baseline in Psoriasis Area and

6 Severity Index; PBO: placebo; Q4W: every 4 weeks; TNFi-IR: prior inadequate response or intolerance to tumour necrosis factor inhibitors.
1 **Figure 4.** MDA, VLDA and ACR50+PASI100 responses to Week 104/100 (NRI, OC)

2

3 Randomised set. In BE OPTIMAL, patients randomised to ADA at baseline switched to BKZ 160 mg Q4W at Week 52. [a] In patients with psoriasis body surface area ≥3% at baseline. BE OPTIMAL: 140 PBO/BKZ, 217 BKZ, 68 ADA/BKZ; BE COMPLETE: 88 PBO/BKZ, 176 BKZ; [b] Reference arm; study not powered for statistical comparisons between

4
5 ADA and BKZ or PBO. ACR50+PASI100: Achievement of both ≥50% improvement in American College of Rheumatology response criteria and 100% improvement in Psoriasis Area and Severity Index; ADA: adalimumab; bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; MDA: minimal disease activity; NRI: non-responder

6
7 Area and Severity Index; ADA: adalimumab; bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; MDA: minimal disease activity; NRI: non-responder imputation; OC: observed case; PBO: placebo; Q4W: every 4 weeks; TNFi-IR: prior inadequate response or intolerance to tumour necrosis factor inhibitors; VLDA: very low disease activity.

8 disease activity.

imputation; OC: observed case; PBO: placebo; Q4W: every 4 weeks; TNFi-IR: prior inadequate response or intolerance to tumour necrosis factor inhibitors; VLDA: very low

8 disease activity.
1 **Figure 5.** SJC (I) and TJC (II) resolution and change from baseline to Week 104/100

2 I.

3

4 II.

5

6 Randomised set. In BE OPTIMAL, patients randomised to ADA at baseline switched to BKZ 160 mg Q4W at Week 52. Error bars represent standard errors. [a] Reference arm;

7 study not powered for statistical comparisons between ADA and BKZ or PBO. ADA: adalimumab; bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab;

8 Cfb: change from baseline; MI: multiple imputation; NRI: non-responder imputation; OC: observed case; PBO: placebo; Q4W: every 4 weeks; SJC: swollen joint count;

9 TJC: tender joint count; TNFi-IR: prior inadequate response or intolerance to tumour necrosis factor inhibitors.

10
1 **Figure 6.** Enthesitis, dactylitis and nail psoriasis resolution to Week 104/100 (NRI, OC)

2

3 Randomised set. In BE OPTIMAL, patients randomised to ADA at baseline switched to BKZ 160 mg Q4W at Week 52. [a] In patients with enthesitis at baseline (LEI >0; BE

4 OPTIMAL: 70 PBO/BKZ, 143 BKZ, 36 ADA/BKZ; BE COMPLETE: 36 PBO/BKZ, 106 BKZ); [b] In patients with dactylitis at baseline (LDI >0; BE OPTIMAL: 33 PBO/BKZ, 56 BKZ,

5 11 ADA/BKZ; BE COMPLETE: 14 PBO/BKZ, 34 BKZ); [c] In patients with nail psoriasis at baseline (mNAPSI >0; BE OPTIMAL: 156 PBO/BKZ, 244 BKZ, 75 ADA/BKZ; BE

6 COMPLETE: 83 PBO/BKZ, 159 BKZ); [d] Reference arm; study not powered for statistical comparisons between ADA and BKZ or PBO. ADA: adalimumab; bDMARD: biologic

7 disease-modifying antirheumatic drug; BKZ: bimekizumab; LDI: Leeds Dactylitis Index; LEI: Leeds Enthesitis Index; mNAPSI: modified Nail Psoriasis Severity Index;

8 NRI: non-responder imputation; OC: observed case; PBO: placebo; Q4W: every 4 weeks; TNFi-IR: prior inadequate response or intolerance to tumour necrosis factor

9 inhibitors.
<table><caption>1 Table 2. Additional efficacy outcomes (Week 104/100) and patient reported outcomes (Week 104/88)</caption><thead><tr><th rowspan="3"></th><th colspan="4">BE OPTIMAL<br>(bDMARD-naïve)</th><th colspan="4">BE COMPLETE<br>(TNFi-IR)</th></tr><tr><th colspan="2">PBO → BKZ<br>160 mg Q4W<br>n=281</th><th colspan="2">BKZ 160 mg Q4W<br>n=431</th><th colspan="2">ADA → BKZ<br>160 mg Q4W<sup>a</sup><br>n=140</th><th colspan="2">PBO → BKZ<br>160 mg Q4W<br>n=133</th></tr><tr><th>NRI<br>n (%)</th><th>OC<br>n/N (%)</th><th>NRI<br>n (%)</th><th>OC<br>n/N (%)</th><th>NRI<br>n (%)</th><th>OC<br>n/N (%)</th><th>NRI<br>n (%)</th><th>OC<br>n/N (%)</th></tr></thead><tbody><tr><td>PASI ≤1<sup>b</sup> or<br>BSA ≤3%</td><td>258 (91.8)</td><td>258/262 (98.5)</td><td>384 (89.1)</td><td>384/391 (98.2)</td><td>124 (88.6)</td><td>124/124 (100)</td><td>111 (83.5)</td><td>111/112 (99.1)</td><td>234 (87.6)</td><td>234/237 (98.7)</td></tr><tr><td>DAPSA<sup>c</sup></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>LDA+REM</td><td>141 (50.2)</td><td>141/226 (62.4)</td><td>228 (52.9)</td><td>228/349 (65.3)</td><td>77 (55.0)</td><td>77/107 (72.0)</td><td>71 (53.4)</td><td>71/101 (70.3)</td><td>123 (46.1)</td><td>123/204 (60.3)</td></tr><tr><td>REM</td><td>56 (19.9)</td><td>56/226 (24.8)</td><td>102 (23.7)</td><td>102/349 (29.2)</td><td>39 (27.9)</td><td>39/107 (36.4)</td><td>22 (16.5)</td><td>22/101 (21.8)</td><td>42 (15.7)</td><td>42/204 (20.6)</td></tr><tr><td>PASDAS<sup>c</sup></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>LDA+REM</td><td>151 (53.7)</td><td>151/218 (69.3)</td><td>234 (54.3)</td><td>234/334 (70.1)</td><td>79 (56.4)</td><td>79/103 (76.7)</td><td>64 (48.1)</td><td>64/90 (71.1)</td><td>133 (49.8)</td><td>133/191 (69.6)</td></tr><tr><td>REM</td><td>83 (29.5)</td><td>83/218 (38.1)</td><td>138 (32.0)</td><td>138/334 (41.3)</td><td>45 (32.1)</td><td>45/103 (43.7)</td><td>20 (15.0)</td><td>20/90 (22.2)</td><td>71 (26.6)</td><td>71/191 (37.2)</td></tr><tr><td>HAQ-DI MCID<sup>d</sup></td><td>118 (53.4)</td><td>118/184 (64.1)</td><td>167 (52.5)</td><td>167/257 (65.0)</td><td>58 (50.4)</td><td>58/88 (65.9)</td><td>57 (51.8)</td><td>57/84 (67.9)</td><td>121 (52.4)</td><td>121/183 (66.1)</td></tr><tr><td>Pain VAS<sup>e</sup><br>≥30%<br>improvement</td><td>172 (61.2)</td><td>172/232 (74.1)</td><td>246 (57.1)</td><td>246/350 (70.3)</td><td>77 (55.0)</td><td>77/109 (70.6)</td><td>81 (60.9)</td><td>81/104 (77.9)</td><td>167 (62.5)</td><td>167/212 (78.8)</td></tr><tr><td>Pain VAS<sup>e</sup><br>≥50%<br>improvement</td><td>154 (54.8)</td><td>154/232 (66.4)</td><td>222 (51.5)</td><td>222/350 (63.4)</td><td>68 (48.6)</td><td>68/109 (62.4)</td><td>65 (48.9)</td><td>65/104 (62.5)</td><td>150 (56.2)</td><td>150/212 (70.8)</td></tr><tr><td>PsAID-12 total<br>score MCID<sup>f</sup></td><td>80 (40.4)</td><td>80/162 (49.4)</td><td>133 (44.9)</td><td>133/243 (54.7)</td><td>51 (45.9)</td><td>51/88 (58.0)</td><td>44 (43.6)</td><td>44/77 (57.1)</td><td>103 (52.0)</td><td>103/161 (64.0)</td></tr><tr><td>FACIT-Fatigue<br>MCID<sup>g</sup></td><td>127 (49.0)</td><td>127/210 (60.5)</td><td>192 (50.0)</td><td>192/310 (61.9)</td><td>56 (42.4)</td><td>56/102 (54.9)</td><td>55 (45.5)</td><td>55/95 (57.9)</td><td>131 (52.4)</td><td>131/202 (64.9)</td></tr><tr><td></td><th colspan="4">MI, mean (SE)</th><th colspan="4">MI, mean (SE)</th></tr><tr><td>HAQ-DI CfB</td><td>-0.37 (0.03)</td><td></td><td>-0.34 (0.02)</td><td></td><td>-0.37 (0.05)</td><td></td><td>-0.36 (0.06)</td><td></td><td>-0.39 (0.03)</td><td></td></tr><tr><td>BASDAI total<br>score CfB<sup>h</sup></td><td>-3.0 (0.2)</td><td></td><td>-3.2 (0.1)</td><td></td><td>-3.1 (0.2)</td><td></td><td>-3.3 (0.3)</td><td></td><td>-3.1 (0.2)</td><td></td></tr><tr><td>Pain VAS CfB<sup>e</sup></td><td>-31.1 (1.9)</td><td></td><td>-29.2 (1.5)</td><td></td><td>-32.3 (2.5)</td><td></td><td>-34.6 (2.7)</td><td></td><td>-33.9 (1.8)</td><td></td></tr></tbody></table>
<table><thead><tr><th rowspan="2"></th><th colspan="3">BE OPTIMAL<br>(bDMARD-naïve)</th><th colspan="2">BE COMPLETE<br>(TNFi-IR)</th></tr><tr><th>PBO → BKZ<br>160 mg Q4W<br>n=281</th><th>BKZ 160 mg Q4W<br>n=431</th><th>ADA → BKZ<br>160 mg Q4W<sup>a</sup><br>n=140</th><th>PBO → BKZ<br>160 mg Q4W<br>n=133</th><th>BKZ 160 mg Q4W<br>n=267</th></tr></thead><tbody><tr><td>PsAID-12 total score CfB<sup>1</sup></td><td>-2.3 (0.1)</td><td>-2.2 (0.1)</td><td>-2.5 (0.2)</td><td>-2.1 (0.2)</td><td>-2.5 (0.1)</td></tr><tr><td>FACIT-Fatigue CfB<sup>1</sup></td><td>5.0 (0.6)</td><td>4.7 (0.4)</td><td>5.1 (0.8)</td><td>4.7 (0.8)</td><td>5.8 (0.6)</td></tr><tr><td>SF-36 PCS CfB<sup>1</sup></td><td>8.8 (0.6)</td><td>8.4 (0.5)</td><td>9.3 (0.9)</td><td>8.3 (0.9)</td><td>8.9 (0.6)</td></tr></tbody></table>

Randomised set. Data reported at Week 104 in BE OPTIMAL and Week 100 in BE COMPLETE. [a] Reference arm: study not powered for statistical comparisons of ADA to BKZ or PBO; [b] In patients with psoriasis affecting ≥3% body surface area at baseline; [c] Missing DAPSA and PASDAS data were imputed using worst-category imputation.

DAPSA REM defined as a DAPSA score of ≤4, REM+LDA defined as a DAPSA score of ≤14. PASDAS REM defined as a PASDAS score of <1.9, PASDAD REM+LDA defined as a

PASDAS score of <3.2. PASDAS reported to Week 88 in BE COMPLETE; [d] HAQ-DI MCID defined as decrease from baseline ≥0.35 in patients with HAQ-DI ≥0.35 at baseline

(BE OPTIMAL PBO/BKZ: n=221, BKZ n=318, ADA/BKZ=115; BE COMPLETE PBO/BKZ n=110, BKZ n=231); [e] Pain VAS assessed using the Patient's Assessment of Arthritis

Pain VAS which ranges from 0 to 100, 0 representing 'no pain' and 100 'most severe pain': Pain VAS ≥30% and ≥50% represent a moderate and substantial improvement in patient-reported pain, respectively; [f] PsAID-12 MCID defined as decrease from baseline ≥3 in patients with PsAID-12 at ≥3 baseline. Reported to Week 88 in BE COMPLETE;

[g] FACIT-Fatigue MCID defined as CfB ≥4 in patients with FACIT-Fatigue subscale ≤48 at baseline (BE OPTIMAL PBO/BKZ: n=259, BKZ n=384, ADA/BKZ=132; BE COMPLETE

PBO/BKZ n=121, BKZ n=250); Reported to Week 88 in BE COMPLETE; [h] BASDAI ≥4 at baseline (BE OPTIMAL PBO/BKZ: n=213, BKZ n=311, ADA/BKZ=107; BE COMPLETE PBO/BKZ n=96, BKZ n=204); [i] Reported to Week 88 in BE COMPLETE. ADA: adalimumab; bDMARD: biologic disease-modifying antirheumatic drug; BASDAI: Bath Ankylosing

Spondylitis Disease Activity Index; BKZ: bimekizumab; CfB: change from baseline; DAPSA: Disease Activity in Psoriatic Arthritis; FACIT-Fatigue: Functional Assessment of

Chronic Illness Therapy-Fatigue; HAQ-DI: Health Assessment Questionnaire-Disability Index; LDA; low disease activity; MCID: minimal clinically important difference;

MI: multiple imputation; mNAPSI: modified Nail Psoriasis Severity Index; NRI: non-responder imputation; OC: observed case; PASDAS: Psoriatic Arthritis Disease Activity

Score; PASI: Psoriasis Area and Severity Index; PBO: placebo; PsAID-12: 12-item Psoriatic Arthritis Impact of Disease questionnaire; Q4W: every 4 weeks; REM: remission;

SD: standard deviation; SF-36 PCS: Short-Form 36-item Health Survey Physical Component Summary; TNFi-IR: prior inadequate response or intolerance to tumour necrosis

factor inhibitors; VAS: visual analogue scale.
1 **SUPPLEMENTARY APPENDIX**

2 **Supplementary Figure S1.** Patient disposition in BE OPTIMAL and BE COMPLETE

3 I. BE OPTIMAL

<figure><img src="image_2.png" /></figure>
1

2 II. BE COMPLETE

<figure><img src="image_3.png" /></figure>

3

4 Patients completing safety follow-up period: BE OPTIMAL PBO (n=19, 45.2%), BKZ (n=38, 52.8%), ADA (n=17, 60.7%); BE COMPLETE PBO (n=12, 42.9%); BKZ (n=28,

5 53.8%). Safety reported to Week 104 in BE COMPLETE. [a] Patients who withdrew from the study medication but returned for the final visit (Week 52 or Week 104) were
1 considered as having completed the treatment period not on randomised treatment; [b] 2 patients classified as ongoing as they did not have a visit for Week 52 but no formal

2 discontinuation reason was reported; [d] Ongoing includes patients who did not have a Week 100 visit and no visits after in the BE VITAL OLE but have not discontinued

3 within the timeframe. ADA: adalimumab; BKZ: bimekizumab; OLE: open-label extension; PBO: placebo.

4
<table><caption>1 Supplementary Table S1. Baseline demographics and disease characteristics</caption><thead><tr><th rowspan="2"></th><th colspan="3">BE OPTIMAL<br>(bDMARD-naïve)</th><th colspan="2">BE COMPLETE<br>(TNFi-IR)</th></tr><tr><th>PBO → BKZ<br>160 mg Q4W<br>n=281</th><th>BKZ 160 mg Q4W<br>n=431</th><th>ADA → BKZ<br>160 mg Q4W<sup>a</sup><br>n=140</th><th>PBO → BKZ<br>160 mg Q4W<br>n=133</th><th>BKZ 160 mg Q4W<br>n=267</th></tr></thead><tbody><tr><td>Age, years, mean (SD)</td><td>48.7 (11.7)</td><td>48.5 (12.6)</td><td>49.0 (12.8)</td><td>51.3 (12.9)</td><td>50.1 (12.4)</td></tr><tr><td>Sex, male, n (%)</td><td>127 (45.2)</td><td>201 (46.6)</td><td>71 (50.7)</td><td>60 (45.1)</td><td>130 (48.7)</td></tr><tr><td>BMI, kg/m<sup>2</sup>, mean (SD)</td><td>29.6 (6.1)</td><td>29.2 (6.8)</td><td>28.4 (5.9)</td><td>29.0 (5.4)</td><td>30.1 (6.5)</td></tr><tr><td>Time since PsA diagnosis,<sup>b</sup><br>years, mean (SD)</td><td>5.6 (6.5)</td><td>6.0 (7.3)</td><td>6.1 (6.8)</td><td>9.2 (8.1)</td><td>9.6 (9.9)</td></tr><tr><td>Any csDMARD at baseline</td><td>194 (69.0)</td><td>301 (69.8)</td><td>99 (70.7)</td><td>63 (47.4)</td><td>139 (52.1)</td></tr><tr><td>Concomitant methotrexate, n (%)</td><td>163 (58.0)</td><td>252 (58.5)</td><td>82 (58.6)</td><td>51 (38.3)</td><td>119 (44.6)</td></tr><tr><td>Prior TNFi exposure, n (%)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Inadequate response to 1 TNFi</td><td>–</td><td>–</td><td>–</td><td>103 (77.4)</td><td>203 (76.0)</td></tr><tr><td>Inadequate response to 2 TNFi</td><td>–</td><td>–</td><td>–</td><td>15 (11.3)</td><td>30 (11.2)</td></tr><tr><td>Intolerance to TNFi</td><td>–</td><td>–</td><td>–</td><td>15 (11.3)</td><td>34 (12.7)</td></tr><tr><td>TJC (of 68 joints), mean (SD)</td><td>17.1 (12.5)</td><td>16.8 (11.8)</td><td>17.5 (13.1)</td><td>19.3 (14.2)</td><td>18.4 (13.5)</td></tr><tr><td>SJC (of 66 joints), mean (SD)</td><td>9.5 (7.3)</td><td>9.0 (6.2)</td><td>9.6 (7.1)</td><td>10.3 (8.2)</td><td>9.7 (7.5)</td></tr><tr><td>hs-CRP ≥6 mg/L, n (%)</td><td>121 (43.1)</td><td>158 (36.7)</td><td>44 (31.4)</td><td>59 (44.4)</td><td>118 (44.2)</td></tr><tr><td>Affected BSA ≥3%, n (%)</td><td>140 (49.8)</td><td>217 (50.3)</td><td>68 (48.6)</td><td>88 (66.2)</td><td>176 (65.9)</td></tr><tr><td>PASI score,<sup>c</sup> mean (SD)</td><td>7.9 (5.6)</td><td>8.2 (6.8)</td><td>8.5 (7.6)</td><td>8.5 (6.6)</td><td>10.1 (9.1)</td></tr><tr><td>Enthesitis (LEI >0),<sup>d</sup> n (%)</td><td>70 (24.9)</td><td>143 (33.2)</td><td>36 (25.7)</td><td>36 (27.1)</td><td>106 (39.7)</td></tr><tr><td>LEI score,<sup>e</sup> mean (SD)</td><td>2.9 (1.5)</td><td>2.5 (1.5)</td><td>2.3 (1.6)</td><td>2.9 (1.6)</td><td>2.6 (1.5)</td></tr><tr><td>Dactylitis (LDI >0),<sup>f</sup> n (%)</td><td>33 (11.7)</td><td>56 (13.0)</td><td>11 (7.9)</td><td>14 (10.5)</td><td>34 (12.7)</td></tr><tr><td>LDI score,<sup>g</sup> mean (SD)</td><td>47.3 (41.1)</td><td>46.7 (54.3)</td><td>49.7 (31.9)</td><td>66.4 (127.6)</td><td>72.7 (114.4)</td></tr></tbody></table>
<table><thead><tr><th rowspan="2"></th><th colspan="3">BE OPTIMAL<br>(bDMARD-naïve)</th><th colspan="2">BE COMPLETE<br>(TNFi-IR)</th></tr><tr><th>PBO → BKZ<br>160 mg Q4W<br>n=281</th><th>BKZ 160 mg Q4W<br>n=431</th><th>ADA → BKZ<br>160 mg Q4W<sup>a</sup><br>n=140</th><th>PBO → BKZ<br>160 mg Q4W<br>n=133</th><th>BKZ 160 mg Q4W<br>n=267</th></tr></thead><tbody><tr><td>Nail psoriasis (mNAPSI >0),<sup>h</sup> n (%)</td><td>156 (55.5)</td><td>244 (56.6)</td><td>75 (53.6)</td><td>83 (62.4)</td><td>159 (59.6)</td></tr><tr><td>mNAPSI score,<sup>i</sup> mean (SD)</td><td>4.0 (2.1)</td><td>4.1 (2.5)</td><td>3.7 (2.3)</td><td>4.5 (2.8)</td><td>4.3 (2.8)</td></tr><tr><td>HAQ-DI score,<sup>j</sup> mean (SD)</td><td>0.89 (0.61)</td><td>0.82 (0.59)</td><td>0.86 (0.54)</td><td>1.04 (0.69)</td><td>0.97 (0.59)</td></tr><tr><td>BASDAI total score,<sup>k</sup> mean (SD)</td><td>6.2 (1.3)</td><td>6.1 (1.3)</td><td>6.1 (1.3)</td><td>6.5 (1.3)</td><td>6.2 (1.3)</td></tr></tbody></table>

Randomised set. [a] Reference arm: study not powered for statistical comparisons of ADA to BKZ or PBO; [b] BE OPTIMAL: Data missing for two PBO patients, eight BKZ patients and one ADA patient; BE COMPLETE: Data missing for one PBO patient and one BKZ patient; [c] In patients with ≥3% BSA with psoriasis at baseline; [d] BE

OPTIMAL: data missing for six BKZ patients and one ADA patient, BE COMPLETE: data missing for one PBO patient; [e] In patients with enthesitis at baseline; [f] BE

OPTIMAL: data missing for seven BKZ patients and one ADA patient, BE COMPLETE: data missing for one PBO patient; [g] In patients with dactylitis at baseline; [h] Data

missing for seven BKZ patients in BE OPTIMAL and one PBO patient in BE COMPLETE; [i] In patients with nail psoriasis at baseline; [j] Data missing for one BKZ patient in BE

OPTIMAL; [k] In patients with a BASDAI total score >4 at baseline (BE OPTIMAL: 213 PBO, 311 BKZ, 107 ADA; BE COMPLETE: 96 PBO, 204 BKZ). ADA: adalimumab;

BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; BSA: body surface area; BMI: body

mass index; csDMARD: conventional synthetic disease-modifying antirheumatic drug; HAQ-DI: Health Assessment Questionnaire-Disability Index; hs-CRP: high sensitivity

C-reactive protein; LDI: Leeds Dactylitis Index; LEI: Leeds Enthesitis Index; mNAPSI: modified nail psoriasis severity index; PASI: Psoriasis Area and Severity Index;

PBO: placebo; PsA: psoriatic arthritis; Q2W: every 2 weeks; Q4W: every 4 weeks; SD: standard deviation; SJC: swollen joint count; TJC: tender joint count; TNFi: tumour

necrosis factor inhibitors; TNFi-IR: prior inadequate response or intolerance to TNFi.

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<table><caption>1 Supplementary Table S2. Fungal events of interest from Week 0–52 and Week 52–104</caption><thead><tr><th rowspan="3">EAIR (95% CI) /100 PY</th><th colspan="4">BE OPTIMAL<br>(bDMARD-naïve)</th><th colspan="2">BE COMPLETE<br>(TNFi-IR)</th></tr><tr><th colspan="2">Week 0–52</th><th colspan="2">Week 52–104</th><th rowspan="2">Week 0–52</th><th rowspan="2">Week 52–104</th></tr><tr><th>BKZ 160 mg Q4W Total<sup>a</sup><br>n=702<br>595.6 PY</th><th>ADA 40 mg Q2W<br>n=140<br>136.8 PY</th><th>ADA → BKZ<br>160 mg Q4W<br>n=121<br>117.2 PY</th><th>BKZ 160 mg Q4W Total<sup>a</sup><br>n=773<br>738.0 PY</th><th>BKZ 160 mg Q4W Total<sup>a</sup><br>n=388<br>340.0 PY</th><th>BKZ 160 mg Q4W Total<sup>a</sup><br>n=361<br>335.2 PY</th></tr></thead><tbody><tr><td>Fungal infections</td><td>15.3<br>(12.2, 18.9)</td><td>1.5 (0.2, 5.3)</td><td>12.0 (6.4, 20.4)</td><td>10.5 (8.3, 13.2)</td><td>12.2 (8.7, 16.7)</td><td>4.6 (2.6, 7.5)</td></tr><tr><td>Candida infections</td><td>9.8 (7.4, 12.7)</td><td>0.7 (0.0, 4.1)</td><td>4.4 (1.4, 10.2)</td><td>6.5 (4.8, 8.7)</td><td>8.0 (5.2, 11.7)</td><td>3.3 (1.7, 5.9)</td></tr><tr><td>Oral candidiasis</td><td>6.7 (4.8, 9.2)</td><td>0.7 (0.0, 4.1)</td><td>4.4 (1.4, 10.2)</td><td>5.5 (3.9, 7.5)</td><td>7.6 (4.9, 11.3)</td><td>3.3 (1.7, 5.9)</td></tr><tr><td>Vulvovaginal candidiasis</td><td>1.4 (0.6, 2.7)</td><td>0</td><td>0</td><td>0.8 (0.3, 1.8)</td><td>0</td><td>0</td></tr><tr><td>Oesophageal candidiasis</td><td>0.7 (0.2, 1.7)</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0.6 (0.1, 2.1)</td><td>0</td></tr><tr><td>Skin candida</td><td>0.7 (0.2, 1.7)</td><td>0</td><td>0</td><td>0.3 (0.0, 1.0)</td><td>0</td><td>0</td></tr><tr><td>Oropharyngeal candidiasis</td><td>0.3 (0.0, 1.2)</td><td>0</td><td>0</td><td>0.3 (0.0, 1.0)</td><td>0</td><td>0</td></tr><tr><td>Candida infection</td><td>0</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr><tr><td>Otitis externa candida</td><td>0</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr><tr><td>Fungal infections NEC</td><td>5.2 (3.5, 7.4)</td><td>0</td><td>8.1 (3.7, 15.4)</td><td>4.0 (2.7, 5.8)</td><td>3.6 (1.9, 6.3)</td><td>0.9 (0.2, 2.6)</td></tr><tr><td>Fungal skin infection</td><td>1.9 (0.9, 3.3)</td><td>0</td><td>2.6 (0.5, 7.6)</td><td>1.0 (0.4, 2.0)</td><td>1.2 (0.3, 3.0)</td><td>0.6 (0.1, 2.2)</td></tr><tr><td>Vulvovaginal mycotic infection</td><td>1.2 (0.5, 2.4)</td><td>0</td><td>0.9 (0.0, 4.8)</td><td>0.1 (0.0, 0.8)</td><td>1.2 (0.3, 3.0)</td><td>0</td></tr><tr><td>Oral fungal infection</td><td>1.7 (0.8, 3.1)</td><td>0</td><td>4.4 (1.4, 10.3)</td><td>1.9 (1.1, 3.2)</td><td>0.3 (0.0, 1.6)</td><td>0.3 (0.0, 1.7)</td></tr><tr><td>Eye infection, fungal</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0.3 (0.0, 1.6)</td><td>0</td></tr><tr><td>Tongue fungal infection</td><td>0.5 (0.1, 1.5)</td><td>0</td><td>0</td><td>0.3 (0.0, 1.0)</td><td>0.6 (0.1, 2.1)</td><td>0</td></tr><tr><td>Fungal oesophagitis</td><td>0.2 (0.0, 0.9)</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr><tr><td>Gastrointestinal fungal infection</td><td>0</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr><tr><td>Oropharyngitis fungal</td><td>0</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr><tr><td>Otitis media fungal</td><td>0</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr><tr><td>Laryngitis fungal</td><td>0.2 (0.0, 0.9)</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr></tbody></table>
<table><thead><tr><th rowspan="3">EAIR (95% CI) /100 PY</th><th colspan="4">BE OPTIMAL<br>(bDMARD-naïve)</th><th colspan="2">BE COMPLETE<br>(TNFi-IR)</th></tr><tr><th colspan="2">Week 0–52</th><th colspan="2">Week 52–104</th><th rowspan="2">Week 0–52</th><th rowspan="2">Week 52–104</th></tr><tr><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=702<br>595.6 PY</th><th>ADA 40 mg<br>Q2W<br>n=140<br>136.8 PY</th><th>ADA → BKZ<br>160 mg Q4W<br>n=121<br>117.2 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=773<br>738.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=388<br>340.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=361<br>335.2 PY</th></tr></thead><tbody><tr><td>Onychomycosis</td><td>0.2 (0.0, 0.9)</td><td>0</td><td>0.9 (0.0, 4.8)</td><td>0.3 (0.0, 1.0)</td><td>0</td><td>0</td></tr><tr><td>Upper respiratory fungal<br>infection</td><td>0.2 (0.0, 0.9)</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Tinea infections</td><td>1.2 (0.5, 2.4)</td><td>0.7 (0.0, 4.1)</td><td>0</td><td>0.5 (0.1, 1.4)</td><td>1.5 (0.5, 3.5)</td><td>0.3 (0.0, 1.7)</td></tr><tr><td>Tinea versicolour</td><td>0.5 (0.1, 1.5)</td><td>0.7 (0.0, 4.1)</td><td>0</td><td>0</td><td>0.3 (0.0, 1.6)</td><td>0</td></tr><tr><td>Tinea capitis</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0.3 (0.0, 1.6)</td><td>0</td></tr><tr><td>Body tinea</td><td>0.2 (0.0, 0.9)</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0.3 (0.0, 1.6)</td><td>0</td></tr><tr><td>Tinea infection</td><td>0.2 (0.0, 0.9)</td><td>0</td><td>0</td><td>0</td><td>0.3 (0.0, 1.6)</td><td>0</td></tr><tr><td>Tinea pedis</td><td>0.3 (0.0, 1.2)</td><td>0</td><td>0</td><td>0.3 (0.0, 1.0)</td><td>0.3 (0.0, 1.6)</td><td>0.3 (0.0, 1.7)</td></tr><tr><td>Tinea cruris</td><td>0</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0.3 (0.0, 1.6)</td><td>0</td></tr><tr><td>Serious fungal infections</td><td>0</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr><tr><td>Fungal infections leading to patient<br>discontinuation<sup>b</sup></td><td>0.5 (0.1, 1.5)</td><td>0</td><td>0</td><td>0.5 (0.1, 1.4)</td><td>0.6 (0.1, 2.1)</td><td>0.6 (0.1, 2.1)</td></tr></tbody></table>

Safety set. [a] BKZ groups include PBO/BKZ Week 16 switchers, includes events after switch only; BE OPTIMAL Weeks 52–104 also includes ADA/BKZ switchers, events after switch only; [b] There were no documented cases of recurrent fungal infections leading to discontinuation. ADA: adalimumab; bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; CI: confidence interval; EAIR: exposure-adjusted incidence rate; NEC: not elsewhere classified; PBO: placebo; PYs: patient-years; Q2W: every 2 weeks; Q4W: every 4 weeks; TNFi-IR: prior inadequate response or intolerance to tumour necrosis factor inhibitors.

1
2
3
4
5
<table><caption>1 Supplementary Table S3. Malignancies from Week 0–52 and Week 52–104</caption><thead><tr><th rowspan="3">EAIR (95% CI) /100 PY</th><th colspan="4">BE OPTIMAL<br>(bDMARD-naïve)</th><th colspan="2">BE COMPLETE<br>(TNFi-IR)</th></tr><tr><th colspan="2">Week 0–52</th><th colspan="2">Week 52–104</th><th rowspan="2">Week 0–52</th><th rowspan="2">Week 52–104</th></tr><tr><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=702<br>595.6 PY</th><th>ADA 40 mg<br>Q2W<br>n=140<br>136.8 PY</th><th>ADA → BKZ<br>160 mg Q4W<br>n=121<br>117.2 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=773<br>738.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=388<br>340.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=361<br>335.2 PY</th></tr></thead><tbody><tr><td>Malignancies excluding nonmelanoma<br>skin cancer</td><td>0.5 (0.1, 1.5)</td><td>0</td><td>0</td><td>0.4 (0.1, 1.2)</td><td>0.9 (0.2, 2.6)</td><td>0.6 (0.1, 2.2)<sup>b</sup></td></tr><tr><td>Breast cancer stage 1</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Breast cancer</td><td>0</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0.3 (0.0, 1.7)</td></tr><tr><td>Colon cancer</td><td>0.2 (0.0, 0.9)</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Chronic lymphocytic leukaemia stage<br>0</td><td>0.2 (0.0, 0.9)</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Papillary thyroid cancer</td><td>0.2 (0.0, 0.9)</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Ovarian cancer</td><td>0</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr><tr><td>Bone cancer metastatic</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0.3 (0.0, 1.7)</td></tr><tr><td>Endometrial cancer stage 1</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0.3 (0.0, 1.6)</td><td>0</td></tr><tr><td>Gastric cancer</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0.3 (0.0, 1.7)</td></tr><tr><td>Gastric cancer recurrent</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0.3 (0.0, 1.6)</td><td>0</td></tr><tr><td>Prostate cancer</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0.3 (0.0, 1.6)</td><td>0</td></tr><tr><td>Uterine cancer</td><td>0</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr></tbody></table>

Safety set. [a] BKZ groups include PBO/BKZ Week 16 switchers (for both BE OPTIMAL and BE COMPLETE), includes events after switch only; BE OPTIMAL Weeks 52–104 also includes ADA/BKZ switchers, events after switch only; [b] One patient had both bone cancer and breast cancer. ADA: adalimumab; bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; CI: confidence interval; EAIR: exposure-adjusted incidence rate; PBO: placebo; PYs: patient-years; Q2W: every 2 weeks; Q4W: every 4 weeks; TNFi-IR: prior inadequate response or intolerance to tumour necrosis factor inhibitors.

2

3

4

5

6
<table><caption>1 Supplementary Table S4. Adjudicated major adverse cardiovascular events from Week 0–52 and Week 52–104</caption><thead><tr><th rowspan="3">EAIR (95% CI) /100 PY</th><th colspan="4">BE OPTIMAL<br>(bDMARD-naïve)</th><th colspan="2">BE COMPLETE<br>(TNFi-IR)</th></tr><tr><th colspan="2">Week 0–52</th><th colspan="2">Week 52–104</th><th rowspan="2">Week 0–52</th><th rowspan="2">Week 52–104</th></tr><tr><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=702<br>595.6 PY</th><th>ADA 40 mg<br>Q2W<br>n=140<br>136.8 PY</th><th>ADA → BKZ<br>160 mg Q4W<br>n=121<br>117.2 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=773<br>738.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=388<br>340.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=361<br>335.2 PY</th></tr></thead><tbody><tr><td>Total</td><td>0.7 (0.2, 1.7)</td><td>0</td><td>1.7 (0.2, 6.2)</td><td>0.4 (0.1, 1.2)</td><td>0.6 (0.1, 2.1)</td><td>0</td></tr><tr><td>Acute myocardial infarction</td><td>0</td><td>0</td><td>0.9 (0.0, 4.8)</td><td>0.3 (0.0, 1.0)</td><td>0</td><td>0</td></tr><tr><td>Cerebrovascular accident</td><td>0.2 (0.0, 0.9)</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Ischaemic stroke</td><td>0.2 (0.0, 0.9)</td><td>0</td><td>0.9 (0.0, 4.8)</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr><tr><td>Myocardial infarction</td><td>0.2 (0.0, 0.9)</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Thrombotic cerebral infarction</td><td>0.2 (0.0, 0.9)</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Cerebral haemorrhage</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0.3 (0.0, 1.6)</td><td>0</td></tr><tr><td>Sudden death</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0.3 (0.0, 1.6)</td><td>0</td></tr></tbody></table>

2 Safety set. [a] BKZ groups include PBO/BKZ Week 16 switchers (for both BE OPTIMAL and BE COMPLETE), includes events after switch only; BE OPTIMAL Weeks 52–104 also

3 includes ADA/BKZ switchers, events after switch only. ADA: adalimumab; bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; CI: confidence interval;

4 EAIR: exposure-adjusted incidence rate; PBO: placebo; PYs: patient-years; Q2W: every 2 weeks; Q4W: every 4 weeks; TNFi-IR: prior inadequate response or intolerance to

5 tumour necrosis factor inhibitors.

6
<table><caption>1 **Supplementary Table S5.** Venous thromboembolism events from Week 0–52 and Week 52–104</caption><thead><tr><th rowspan="3">n (%)<br>EAIR [95% CI] /100 PY</th><th colspan="4">BE OPTIMAL<br>(bDMARD-naïve)</th><th colspan="2">BE COMPLETE<br>(TNFi-IR)</th></tr><tr><th colspan="2">Week 0–52</th><th>Week 52–104</th><th>Week 52–104</th><th colspan="2">Week 0–52</th></tr><tr><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=702<br>595.6 PY</th><th>ADA 40 mg<br>Q2W<br>n=140<br>136.8 PY</th><th>ADA → BKZ<br>160 mg Q4W<br>n=121<br>117.2 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=773<br>738.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=388<br>340.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=361<br>335.2 PY</th></tr></thead><tbody><tr><td>Pulmonary embolism</td><td>0</td><td>0</td><td>0</td><td>1 (0.1)<br>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr><tr><td>Deep vein thrombosis</td><td>1 (0.1)<br>0.2 (0.0, 0.9)</td><td>0</td><td>0</td><td>3 (0.4)<br>0.4 (0.1, 1.2)</td><td>0</td><td>0</td></tr></tbody></table>

2 Safety set. Events reported by event type. [a] BKZ groups include PBO/BKZ Week 16 switchers (for both BE OPTIMAL and BE COMPLETE), includes events after switch only;

3 BE OPTIMAL Weeks 52–104 also includes ADA/BKZ switchers in addition to PBO- and BKZ-randomised patients, events after switch only. bDMARD: biologic disease-modifying

4 antirheumatic drug; ADA: adalimumab; BKZ: bimekizumab; CI: confidence interval; EAIR: exposure-adjusted incidence rate; PBO: placebo; PYs: patient-years; Q2W: every

5 two weeks; Q4W: every four weeks; TNFi-IR: prior inadequate response or intolerance to tumour necrosis factor inhibitors.

6
<table><caption>1 Supplementary Table S6. Adjudicated suicidal ideation and behaviour events from Week 0–52 and Week 52–104</caption><thead><tr><th rowspan="3">EAIR (95% CI) /100 PY</th><th colspan="4">BE OPTIMAL<br>(bDMARD-naïve)</th><th colspan="2">BE COMPLETE<br>(TNFi-IR)</th></tr><tr><th colspan="2">Week 0–52</th><th>Week 52–104</th><th>Week 52–104</th><th colspan="2">Week 0–52</th></tr><tr><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=702<br>595.6 PY</th><th>ADA 40 mg<br>Q2W<br>n=140<br>136.8 PY</th><th>ADA → BKZ<br>160 mg Q4W<br>n=121<br>117.2 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=773<br>738.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=388<br>340.0 PY</th><th>BKZ 160 mg<br>Q4W Total<sup>a</sup><br>n=361<br>335.2 PY</th></tr></thead><tbody><tr><td>Total</td><td>0</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr><tr><td>Psychiatric evaluation abnormal</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Suicidal behaviour</td><td>0</td><td>0</td><td>0</td><td>0.1 (0.0, 0.8)</td><td>0</td><td>0</td></tr></tbody></table>

2 Safety set. [a] BKZ groups include PBO/BKZ Week 16 switchers (for both BE OPTIMAL and BE COMPLETE), includes events after switch only; BE OPTIMAL Weeks 52–104 also

3 includes ADA/BKZ switchers, events after switch only. ADA: adalimumab; bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; CI: confidence interval;

4 EAIR: exposure-adjusted incidence rate; PBO: placebo; PYs: patient-years; Q2W: every 2 weeks; Q4W: every 4 weeks; TNFi-IR: prior inadequate response or intolerance to

5 tumour necrosis factor inhibitors.

6
<figure><img src="image_4.png" /><figcaption>1 **Supplementary Figure S2.** DAPSA disease states to Week 104/100 (WCI)</figcaption></figure>

3 Randomised set. In BE OPTIMAL, patients on ADA switched to BKZ 160 mg Q4W at Week 52. [a] Reference arm; study not powered for statistical comparisons between ADA

and BKZ or PBO. ADA: adalimumab; bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; BL: baseline; DAPSA: Disease Activity Index for Psoriatic

Arthritis; HDA: high disease activity; LDA: low disease activity; MoDA: moderate disease activity; PBO: placebo; Q2W: every 2 weeks; Q4W: every 4 weeks; REM: remission;

TNFi-IR: prior inadequate response or intolerance to tumour necrosis factor inhibitors; WCI: worst category imputation.
<figure><img src="image_5.png" /><figcaption>1 **Supplementary Figure S3.** Nail psoriasis change from baseline to Week 104/100 (MI)</figcaption></figure>

2 Randomised set, in patients with mNAPSI >0 at baseline. In BE OPTIMAL, patients on ADA switched to BKZ 160 mg Q4W at Week 52. [a] Reference arm; study not powered

3 for statistical comparisons between ADA and BKZ or PBO. ADA: adalimumab; bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; CfB: change from

4 baseline; mNAPSI: modified Nail Psoriasis Severity Index; NRI: non-responder imputation; OC: observed case; PBO: placebo; Q2W: every 2 weeks; Q4W: every 4 weeks;

5 TNFi-IR: prior inadequate response or intolerance to tumour necrosis factor inhibitors.

6
1 Supplementary Appendix S1. Local institutional review board and independent ethics committee names for BE OPTIMAL and BE COMPLETE

<table><thead><tr><th>BE OPTIMAL</th><th>BE COMPLETE</th></tr></thead><tbody><tr><td><strong>Australia</strong><br>Monash Medical Center<br>246 Clayton Road<br>Level 4 Block<br>3168 Clayton<br>Victoria<br>Australia<br>Site: 30002</td><td>CALHN Research Office - SA Health Government<br>Level 3, Roma Mitchell House<br>136 North Terrace<br>South Australia<br>Site: 30006</td></tr><tr><td>CALHN Research Office - SA Health Government<br>Level 3, Roma Mitchell House<br>136 North Terrace<br>South Australia<br>Site: 30006</td><td>Bellberry Limited<br>123 Glen Osmond Road<br>Eastwood<br>5063 South Australia<br>Sites: 30007, 30005</td></tr><tr><td>Bellberry Limited<br>123 Glen Osmond Road<br>Eastwood 5063<br>South Australia<br>Site 30003</td><td>-</td></tr><tr><td>Bellberry Limited<br>123 Glen Osmond Road<br>Eastwood 5063<br>South Australia<br>Site 30005</td><td>-</td></tr><tr><td>Bellberry Limited<br>123 Glen Osmond Road<br>Eastwood 5063<br>South Australia<br>Site 30007</td><td>-</td></tr></tbody></table>
<table><tr><td>Bellberry Limited<br>123 Glen Osmond Road<br>Eastwood 5063<br>South Australia<br>Site 30008</td><td>-</td></tr></table>

Belgium

UZ Leuven - Campus Gasthuisberg
Ethische Commissie Onderzoek UZ/KU Leuven
Herestraat 49
3000 Leuven
Belgium
Site: 40002

-

CHU Ambroise Paré
Comité d'éthique
Boulevard Kennedy 2
7000 Mons
Belgium
Site: 40059

-

CHU de Liège – Sart Tilman
Comité d'éthique Hospitalo-Facultaire Universitaire de
Liège
Domaine Universitaire du Sart Tilman, Bâtiment B35
4000 Liège
Belgium
Sites: 40060, 40003

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Canada

Advarra
372 Hollandview Trail Suite 300
Ontario L4G 0A5 Aurora
Canada

Advarra
372 Hollandview Trail Suite 300
Ontario L4G 0A5 Aurora
Canada
<table><tr><td>Sites: 50041, 50042, 50044<br/>Nova Scotia Health Authority Research Ethics Board<br/>5790 University Avenue Room 118<br/>Nova Scotia B3H 1V7 Halifax<br/>Canada<br/>Site: 50043</td><td>Sites: 50042, 50044<br/>Nova Scotia Health Authority Research Ethics Board<br/>5790 University Avenue Room 118<br/>Nova Scotia B3H 1V7 Halifax<br/>Canada<br/>Site: 50043</td></tr><tr><td colspan="2"><strong>Czech Republic</strong></td></tr><tr><td>CTCenter MaVe s.r.o.<br/>Eticka komise<br/>Na Sibeniku 914/1 779 00 Olomouc<br/>Czech Republic<br/>Site: 40064</td><td>Fakultni nemocnice v Motole<br/>Eticka komise (Central Ethic Committee)<br/>V Uvalu 84 Praha 5 150 06 Praha 5<br/>Czech Republic<br/>Sites: 40009, 40012, 40063, 40066</td></tr><tr><td>Fakultni nemocnice v Motole<br/>Eticka komise<br/>V Uvalu 84 Praha 5 150 06 Praha 5<br/>Czech Republic<br/>Sites: 40009, 40010, 40012, 40013, 40014, 40015,<br/>40061, 40062, 40063, 40064, 40065, 40066</td><td>Revmatologicky ustav<br/>Eticka komise<br/>Na Slupi 4 128 50 Praha 2<br/>Czech Republic<br/>Site: 40066</td></tr><tr><td>Revmatologicky ustav<br/>Eticka komise<br/>Na Slupi 4 128 50 Praha 2<br/>Czech Republic<br/>Site: 40066</td><td>-</td></tr><tr><td colspan="2"><strong>France</strong></td></tr><tr><td>CPP Sud Est III<br/>Bâtiment Pinel (Central Ethic Committee)<br/>59 Boulevard Pinel<br/>Bron 69500<br/>France<br/>Sites: 40019, 40067, 40068, 40069, 40070</td><td>-</td></tr></table>
<table><tr><td><strong>Germany</strong><br>Ethikkommission an der Medizinischen Fakultät der<br>Universität Leipzig<br>Ethic Committee<br>Käthe-Kollwitz-Straße 82 Karl-Sudhoff-Institut Sachsen<br>4109 Leipzig<br>Germany<br>Site: 40078</td><td>Ethikkommission an der Medizinischen Fakultät der<br>Universität Leipzig<br>Ethic Committee<br>Käthe-Kollwitz-Straße 82 Karl-Sudhoff-Institut Sachsen<br>4109 Leipzig<br>Germany<br>Site: 40078</td></tr><tr><td>Ethikkommission der Ärztekammer Hamburg Ethic<br>Committee<br>Weidestraße 122b Hamburg 22083 Hamburg<br>Germany<br>Sites: 40029, 40071</td><td>Ethikkommission der Ärztekammer Hamburg Ethic<br>Committee<br>Weidestraße 122b Hamburg 22083 Hamburg<br>Germany<br>Sites: 40029, 40071</td></tr><tr><td>Ethikkommission an der Medizinischen Fakultät Ernst-<br>Moritz-Arndt-Universität Greifswald<br>Institut für Pharmakologie<br>Felix-Hausdorff-Str. 3 Mecklenburg-Vorpommern<br>17487 Greifswald<br>Germany<br>Site: 40074</td><td>Ethikkommission der Ärztekammer Nordrhein Ethics<br>Committee<br>Tersteegenstraße 9 Nordrhein-Westfalen 40474<br>Düsseldorf<br>Germany<br>Site: 40026</td></tr><tr><td>Ethikkommission der Ärztekammer Nordrhein Ethics<br>Committee<br>Tersteegenstraße 9 Nordrhein-Westfalen 40474<br>Düsseldorf<br>Germany<br>Site: 40026<br>Ethikkommission der Ärztekammer Westfalen-Lippe<br>und der medizinischen Fakultät der WWU Münster<br>Ethics Committee<br>Gartenstr. 210 - 214 Nordrhein-Westfalen 48147<br>Münster</td><td>Ethikkommission der Medizinischen Fakultät der<br>Friedrich-Alexander-Universität Erlangen-Nürnberg<br>Krankenhausstraße 12 Bayern 91054 Erlangen<br>Germany<br>Sites: 40023, Central EC</td></tr></table>
<table><tr><td>Germany<br>Site: 40027</td><td>Ethikkommission der Ärztekammer Sachsen-Anhalt -<br>IRB/IEC<br>IRB/IEC<br>Am Kirchtor 9 Sachsen-Anhalt 06108 Halle (Saale)<br>Germany<br>Site: 40348</td><td>Ethikkommission der Landesärztekammer<br>Brandenburg<br>Dreifertstraße 12 03044 Cottbus<br>Germany<br>Site: 40076</td></tr><tr><td>Ethikkommission der Medizinischen Fakultät der<br>Friedrich-Alexander-Universität Erlangen-Nürnberg<br>Krankenhausstraße 12 Bayern 91054 Erlangen<br>Germany<br>Site: 40023 (Central EC)</td><td>Ethikkommission des Fachbereichs Medizin der<br>Goethe-<br>Universität<br>Ethic Committee<br>Theodor-Stern-Kai 7 Haus 1, 2. OG, Zi. 207 Hessen<br>60596 Frankfurt am Main<br>Germany<br>Site: 40117</td><td></td></tr><tr><td>Ethikkommission der Landesärztekammer<br>Brandenburg<br>Dreifertstraße 12 03044 Cottbus<br>Germany<br>Site: 40076</td><td></td><td>-</td></tr><tr><td>Ethikkommission des Landes Berlin, Landesamt für<br>Gesundheit und Soziales<br>Ethics Committee<br>Turmstraße 21 Haus A Berlin 10559 Berlin<br>Germany<br>Sites: 40025, 40028</td><td></td><td>-</td></tr><tr><td>Ethikkommission des Fachbereichs Medizin der<br>Goethe-Universität<br>Ethic Committee</td><td></td><td>-</td></tr></table>
<table><tr><td>Theodor-Stern-Kai 7 Haus 1, 2. OG, Zi. 207 Hessen<br>60596 Frankfurt am Main<br>Germany<br>Site: 40117</td><td></td></tr><tr><td colspan="2"><b>Hungary</b></td></tr><tr><td>Debreceni Egyetem Klinikai Központ, Regionális<br>Intézményi és Kutatásetikai Bizottság<br>40332 Debrecen Nagyerdei krt. 98. Pf. 34.<br>Hungary<br>Site: 40032</td><td>Csongrád Megyei Dr. Bugyi István Kórház<br>Mozgasszervi<br>Rehabil. Osztaly<br>Sima F. u. 44-58 Csongrád 6600 Szentes<br>Hungary<br>Site: 40079</td></tr><tr><td>Csongrád Megyei Dr. Bugyi István Kórház<br>Mozgasszervi Rehabil. Osztaly<br>Sima F. u. 44-58 Csongrád 6600 Szentes<br>Hungary<br>Site: 40079</td><td>Markhot Ferenc Oktatokorhaz es Rendelointezet -<br>Rheumatology<br>Rheumatology<br>Furdo u. 4. Heves 3300 Eger<br>Hungary<br>Site: 40030</td></tr><tr><td>Markhot Ferenc Oktatokorhaz es Rendelointezet -<br>Rheumatology<br>Rheumatology<br>Furdo u. 4. Heves 3300 Eger<br>Hungary<br>Site: 40030</td><td>Pest Megyei Flór Ferenc Kórház Intézményi,<br>Kutatásetikai<br>Bizottság2143, Kistarcsa Semmelweis tér 1.<br>Hungary<br>Site: 40082</td></tr><tr><td>Vasútegészségügyi Kft. Intézeti Kutatásetikai Bizottság<br>1062 Budapest<br>Podmaniczky utca 109<br>Hungary<br>Site: 40080</td><td>–</td></tr><tr><td>Fejér Megyei Szent György Egyetemi Oktató Kórház,<br>Kutatásetikai Bizottság,</td><td>–</td></tr></table>
<table><tr><td>8000, Szekesfehervar<br>Seregelyesi ut 3<br>Hungary<br>Site: 40033</td><td></td></tr><tr><td>Pest Megyei Flór Ferenc Kórház Intézményi,<br>Kutatásetikai Bizottság 2143<br>Kistarcsa Semmelweis tér 1<br>Hungary<br>Site: 40082</td><td>-</td></tr><tr><td>Medical Research Council Ethics Committee for Clinical<br>Pharm<br>Alkotmány u. 25. Budapest<br>1054 Budapest<br>Hungary<br>Sites: 40081, 40083</td><td>-</td></tr><tr><td colspan="2" style="text-align: center; font-weight: bold;">Italy</td></tr><tr><td>Comitato Etico Catania 1 (Central Ethics Committee)<br>A.O.U. Policlinico Vittorio Emanuele Di Catania Via<br>Santa Sofia, 78<br>95123 Catania<br>Italy<br>Site: 40084</td><td>Comitato Etico Catania 1 (Central Ethic Committee)<br>A.O.U. Policlinico Vittorio Emanuele Di Catania Via<br>Santa Sofia, 78<br>95123 Catania<br>Italy<br>Site: 40084</td></tr><tr><td>COMITATO ETICO DELL'AREA VASTA EMILIA NORD -<br>Segreteria Locale di Reggio Emila<br>c/o AUSL - IRCCS di Reggio Emilia Edificio Spallanzani<br>Viale Umberto I, 50<br>42100 Reggio Emilia<br>Italy<br>Site: 40086</td><td>COMITATO ETICO DELL'AREA VASTA EMILIA<br>NORD - Segreteria Locale di Reggio Emila<br>c/o AUSL - IRCCS di Reggio Emilia Edificio Spallanzani<br>Viale Umberto I, 50<br>42100 Reggio Emilia<br>Italy<br>Site: 40086</td></tr><tr><td>Comitato Etico Area 1</td><td>Comitato Etico Area 1</td></tr></table>
<table><tr><td>ASST Fatebenefratelli Sacco<br/>Via GB Grassi 74<br/>20157 Milano<br/>Italy<br/>Site: 40087</td><td>ASST Fatebenefratelli Sacco, Via GB Grassi 74<br/>20157 Milano<br/>Italy<br/>Site: 40087</td></tr><tr><td colspan="2"><b>Japan</b></td></tr><tr><td>Hokkaido University Hospital Institutional Review Board<br/>Kita 14, Nishi 5, Kita-ku<br/>Sapporo, Hokkaido, 060-8648<br/>Japan<br/>Site: 20031</td><td>Hokkaido University Hospital Institutional Review Board<br/>Kita 14, Nishi 5, Kita-ku<br/>Sapporo, Hokkaido, 060-8648<br/>Japan<br/>Site: 20031</td></tr><tr><td>Nagoya City University Institutional Review Board<br/>1 Kawasumi, Mizuhocho, Mizuho-ku<br/>Nagoya, Aichi, 467-8602<br/>Japan<br/>Site: 20033</td><td>Nagoya City University Institutional Review Board<br/>1 Kawasumi, Mizuhocho, Mizuho-ku<br/>Nagoya, Aichi, 467-8602,<br/>Japan<br/>Site: 20033</td></tr><tr><td>Juntendo University Hospital Institutional Review Board<br/>3-1-3, Hongo<br/>Bunkyo-ku, Tokyo, 113-8431<br/>Japan<br/>Site: 20035</td><td>Saitama medical University Hospital Institutional Review Board<br/>38 Morohongo, Moroyama-machi,<br/>Iruma-gun, Saitama, 350-0495,<br/>Japan<br/>Site: 20039</td></tr><tr><td>Kochi Medical School Hospital Institutional Review Board<br/>185-1 Kohasu, Oko-cho<br/>Nankoku-shi, Kochi, 783-8505<br/>Japan<br/>Site: 20038</td><td>Kochi Medical School Hospital Institutional Review Board<br/>185-1 Kohasu, Oko-cho,<br/>Nankoku-shi, Kochi, 783-8505<br/>Japan<br/>Site: 20038</td></tr></table>
<table><tr><td>Kagawa University Hospital Institutional Review Board<br>1750-1 Ikenobe, Miki-cho<br>Kita-gun, Kagawa, 761-0793<br>Japan<br>Site: 20045</td><td>Kagawa University Hospital Institutional Review Board<br>1750-1 Ikenobe, Miki-cho<br>Kita-gun, Kagawa, 761-0793<br>Japan<br>Site: 20045</td></tr><tr><td>Jichi Medical University Saitama Medical Center<br>Institutional Review Board<br>1-847, Amanumacho, Omiya-ku<br>Saitama, Saitama, 330-8503<br>Japan<br>Site: 20048</td><td>Jichi Medical University Saitama Medical Center<br>Institutional Review Board<br>1-847, Amanumacho, Omiya-ku,<br>Saitama, Saitama, 330-8503,<br>Japan<br>Site: 20048</td></tr><tr><td>Hospital of the University of Occupational and<br>Environmental Health, Japan Institutional Review<br>Board<br>1-1 Iseigaoka, Yahatanishi-ku<br>Kitakyushu, Fukuoka, 807-8556<br>Japan<br>Site: 20049</td><td>Hospital of the University of Occupational and<br>Environmental Health, Japan Institutional Review<br>Board<br>1-1 Iseigaoka, Yahatanishi-ku,<br>Kitakyushu, Fukuoka, 807-8556<br>Japan<br>Site: 20049</td></tr><tr><td>St. Luke's International Hospital Institutional Review<br>Board<br>9-1 Akashicho<br>Chuo-ku, Tokyo, 104-8560<br>Japan<br>Site: 20030</td><td>St. Luke's International Hospital Institutional Review<br>Board<br>9-1 Akashicho,<br>Chuo-ku, Tokyo, 104-8560<br>Japan<br>Site: 20030</td></tr><tr><td>Osaka University Hospital Institutional Review Board<br>2-15 Yamadaoka<br>Suita, Osaka, 565-0871<br>Japan<br>Site: 20032</td><td>Osaka University Hospital Institutional Review Board<br>2-15 Yamadaoka,<br>Suita, Osaka, 565-0871,<br>Japan<br>Site: 20032</td></tr><tr><td>National Hospital Organization Osaka Minami Medical</td><td>National Hospital Organization Osaka Minami Medical</td></tr></table>
<table><tr><td>Center Institutional Review Board<br>2-1 Kidohigashimachi<br>Kawachinagano, Osaka, 586-8521<br>Japan<br>Site: 20036</td><td>Center Institutional Review Board<br>2-1 Kidohigashimachi,<br>Kawachinagano, Osaka, 586-8521,<br>Japan<br>Site: 20036</td></tr><tr><td>Osaka City University Hospital Institutional Review Board<br>1-5-7 Asahimachi, Abeno-ku<br>Osaka, Osaka, 545-8586<br>Japan<br>Site: 20041</td><td>Osaka Metropolitan University Hospital Institutional Review Board<br>1-5-7 Asahimachi, Abeno-ku<br>Osaka, Osaka, 545-8586,<br>Japan<br>Site: 20041</td></tr><tr><td>Sasebo Chuo Hospital Institutional Review Board<br>15 Yamato-cho<br>Sasebo, Nagasaki, 857-1195<br>Japan<br>Site: 20042</td><td>Sasebo Chuo Hospital Institutional Review Board<br>15 Yamato-cho,<br>Sasebo, Nagasaki, 857-1195,<br>Japan<br>Site: 20042</td></tr><tr><td>Nihon University Hospital's Joint Institutional Review Board<br>30-1 Oyaguchi, Kami-cho<br>Itabashi-ku, Tokyo, 173-8610<br>Japan<br>Site: 20043</td><td>Nihon University Hospital's Joint Institutional Review Board<br>30-1 Oyaguchi, Kami-cho<br>Itabashi-ku, Tokyo, 173-8610,<br>Japan<br>Site: 20043</td></tr><tr><td>The Jikei University Hospital Institutional Review Board<br>3-19-18, Nishi-Shinbashi,<br>Minato-ku, Tokyo, 105-8471<br>Japan<br>Site: 20044</td><td>The Jikei University Hospital Institutional Review Board<br>3-19-18, Nishi-Shinbashi,<br>Minato-ku, Tokyo, 105-8471,<br>Japan<br>Site: 20044</td></tr><tr><td>Nippon Life Hospital Institutional Review Board<br>2-1-54 Enokojima, Nishi-ku</td><td>Nippon Life Hospital Institutional Review Board<br>2-1-54 Enokojima, Nishi-ku,</td></tr></table>
Osaka, Osaka, 550-0006
Japan
Site: 20046

Osaka, Osaka, 550-0006,
Japan
Site: 20046

Poland

Komisja Bioetyczna przy Okregowej Radzie Lekarskiej
Wielkopolskiej Izby Lekarskiej
Ul. Nowowiejskiego 51
61-734 Poznan
Poland
Sites: 40037, 40038, 40039, 40041, 40042, 40043,
40044, 40088, 40090, 40091, 40092, 40093, 40094,
40095, 40096, 40097, 40098, 40118, 40119

Komisja Bioetyczna przy Okregowej Radzie Lekarskiej
Wielkopolskiej Izby Lekarskiej
Ul. Nowowiejskiego 51
61-734 Poznan
Poland
Sites: 40037, 40038, 40039, 40041, 40043, 40044,
40090,
40091, 40097, 40098, 40118, 40119

Russian Federation

Leningrad Regional Clinical Hospital
Ethics Committe
45-49 Prospect Lunacharskogo
194291 Saint-Petersburg
Russian Federation
Site: 20001

Leningrad Regional Clinical Hospital
Ethics Committe
45-49 Prospect Lunacharskogo
194291 Saint-Petersburg
Russian Federation
Site: 20001

Clinical Rheumatological Hospital #25
Ethics Committe
Liter A, 30 Bolshaya Podyacheskaya Ulitsa
190068 Saint-Petersburg
Russian Federation
Site: 20003

Independent Ethics Committee "Pharmexpert"
8/2, prospekt Nauki
Sankt-Peterburg
195257 Saint-Petersburg
Russian Federation
Site: 20004

Independent Ethics Committee "Pharmexpert"
8/2, prospekt Nauki
Sankt-Peterburg
195257 Saint-Petersburg
Russian Federation

LLC Family Outpatient Clinic 4
Local Ethic Committee
33, Stantsionnaya st
141060 Korolev
Russian Federation
<table><tr><td>Site: 20004<br>LLC Family Outpatient Clinic 4<br>Local Ethic Committee<br>33, Stantsionnaya str<br>141060 Korolev<br>Russian Federation<br>Site: 20005</td><td>Site: 20005<br>LLC "BioMed" - Administration<br>Administration<br>6, Nikitina street 600005 Vladimir<br>Russian Federation<br>Site: 20006</td></tr><tr><td>LLC "BioMed" - Administration<br>Administration<br>6, Nikitina street 600005 Vladimir<br>Russian Federation<br>Site: 20006</td><td>LLC Clinic of private security guards and detectives<br>84, Borovaya str<br>Sankt-Peterburg<br>192007 Saint Petersburg<br>Russian Federation<br>Site: 20009</td></tr><tr><td>LLC Clinic of private security guards and detectives<br>84, Borovaya str<br>Sankt-Peterburg<br>192007 Saint Petersburg<br>Russian Federation<br>Site: 20009</td><td>City Clinical Hospital # 1 n.a. N.I. Pirogov<br>Ethics Committee<br>8, Leninsky Prospect<br>Moskva 119049<br>Moscow<br>Russian Federation<br>Site: 20010</td></tr><tr><td>City Clinical Hospital # 1 n.a. N.I. Pirogov<br>Ethics Committee<br>8, Leninsky Prospect<br>Moskva 119049<br>Moscow<br>Russian Federation<br>Site: 20010</td><td>Clinical Hospital Of Emergency Care N.V. Soloviev<br>Ethics Committee<br>11 Ulitsa Zagorodnyj Sad<br>150003 Yaroslavl<br>Russian Federation<br>Site: 20015</td></tr><tr><td>Clinical Hospital of Emergency Care N.V. Soloviev<br>Ethics Committee<br>11 Ulitsa Zagorodnyj Sad</td><td>Rheumatology Research Institute Of Russian Academy<br>Of<br>Medica</td></tr></table>
<table><tr><td>150003 Yaroslavl<br/>Russian Federation<br/>Site: 20015</td><td>Ethics Committee<br/>Kashirskoe Shosse, 34<br/>115522 Moscow<br/>Russian Federation<br/>Sites: 20002</td></tr><tr><td>Rheumatology Research Institute of Russian Academy<br/>of Medica<br/>Ethics Committee<br/>Kashirskoe Shosse, 34<br/>115522 Moscow<br/>Russian Federation<br/>Sites: 20002, 20017</td><td>Saratov Regional Clinical Hospital<br/>rheumatology<br/>1, Smirnovskoe uschelye<br/>Saratovskaya oblast'<br/>410053 Saratov<br/>Russian Federation<br/>Site: 20007</td></tr><tr><td>Saratov Regional Clinical Hospital<br/>Rheumatology<br/>1, Smirnovskoe uschelye<br/>Saratovskaya oblast<br/>410053 Saratov<br/>Russian Federation<br/>Site: 20007</td><td>SBHI of Yaroslavl Region "Clinical Hospital n.a. N.A.<br/>Semashko"<br/>12, Gagarina street<br/>Yaroslavskaya oblast'<br/>150023 Yaroslavl<br/>Russian Federation<br/>Site: 20008</td></tr><tr><td>SBHI of Yaroslavl Region "Clinical Hospital n.a. N.A.<br/>Semashko<br/>12, Gagarina street<br/>Yaroslavskaya oblast<br/>150023 Yaroslavl<br/>Russian Federation<br/>Site: 20008</td><td>The Republican Hospital N.A. V.A. Baranov<br/>Ethics Committee<br/>3 Ulitsa Pirogova<br/>185019 Petrozavodsk<br/>Russian Federation<br/>Site: 20013</td></tr><tr><td>Ryazan State Medical University I.P. Pavlov<br/>Ethics Committee<br/>9, Vysokovoltnaya Ulitsa<br/>390026 Ryazan<br/>Russian Federation</td><td>Ulyanovsk Regional Clinical Hospital<br/>Rheumatology<br/>7, Tretyego Internatsionala ul.<br/>432063 Ulyanovsk<br/>Russian Federation</td></tr></table>
<table><thead><tr><th>Site: 20012</th><th>Site: 20014</th></tr></thead><tbody><tr><td>The Republican Hospital N.A. V.A. Baranov<br>Ethics Committee<br>3 Ulitsa Pirogova<br>185019 Petrozavodsk<br>Russian Federation<br>Site: 20013</td><td>-</td></tr><tr><td>Ulyanovsk Regional Clinical Hospital<br>Rheumatology<br>7, Tretyego Internatsionala ul.<br>432063 Ulyanovsk<br>Russian Federation<br>Site: 20014</td><td>-</td></tr><tr><td>Ryazan Regional Clinical Cardiological Dispensary<br>Local Ethics Committee<br>96 Stroikova Ulitsa<br>390026 Ryazan<br>Russian Federation<br>Site: 20016</td><td>-</td></tr><tr><td>The Llc Institute of Medical Trials<br>Lec<br>25 Koli Tomchaka Ul. Liter A3<br>196084 Saint-Petersburg<br>Russian Federation<br>Site: 20083</td><td>-</td></tr><tr><td colspan="2" style="text-align: center; font-weight: bold;">Spain</td></tr><tr><td>CEIC Corporació Sanitària Parc Taulí Fundació Parc<br>Taulí<br>Edifici Santa Fe Ala izquierda, 2ª planta C/ Parc Taulí,<br>1 Barcelona 08208</td><td>-</td></tr></tbody></table>
Sabadell
Spain
Sites: 40045, 40049, 40099, 40101, 40102, 40103, 40104, 40105, 40106

United Kingdom

New Cross hospital
Rheumatology
New Cross hospital
Wolverhampton WV10 0QP
Wolverhampton
United Kingdom
Site: 40107

Nuffield Orthopaedic Centre
ND07, NDORMS Windmill Road, Headington
Oxfordshire
OX3 7HE
Oxford
United Kingdom
Site: 40109

Nuffield Orthopaedic Centre
ND07, NDORMS Windmill Road, Headington
Oxfordshire
OX3 7HE
Oxford
United Kingdom
Site: 40109

Bradford Royal Infirmary
Rheumatology
Duckworth Lane
BD9 6RJ
Bradford
United Kingdom
Site: 40111

Royal Cornwall Hospital
Treliske Truro
Cornwall
TR1 3LJ
Cornwall
United Kingdom
Site: 40112

Stamford and Rutland hospital
Ryhall Road
PE9 1UA
Stamford
United Kingdom
Site: 40116

Barnsley Hospital NHS Foundation Trust
Gawber Road
S75 2EP
Barnsley

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<table><tr><td>United Kingdom<br>Site: 40115</td><td><strong>United States</strong></td></tr><tr><td>Advarra<br>IRB/IEC<br>6100 Merriweather Drive, Suite 600<br>Maryland 21044<br>Columbia<br>United States<br>Sites: 50001, 50002, 50004, 50006, 50007, 50008,<br>50009, 50012, 50015, 50016, 50017, 50020, 50028,<br>50029, 50033, 50035, 50036, 50037, 50039, 50040,<br>50049, 50050, 50051, 50125</td><td>Advarra<br>IRB/IEC<br>6100 Merriweather Drive, Suite 600<br>Maryland 21044<br>Columbia<br>United States<br>Sites: 50001, 50002, 50004, 50005, 50006, 50008,<br>50009,<br>50011 50012, 50015, 50016, 50017, 50019, 50020,<br>50021, 50024, 50026, 50028, 50029, 50031, 50033,<br>50034, 50035, 50036, 50037, 50039, 50040, 50047<br>50050, 50064, 50125</td></tr><tr><td>WCG IRB<br>IRB/EC<br>1019 39th Avenue SE Suite 120<br>Washington 98374<br>Puyallup<br>United States<br>Site: 50010</td><td>WCG IRB<br>IRB/EC<br>1019 39th Avenue SE Suite 120<br>Washington 98374<br>Puyallup<br>United States<br>Site: 50010</td></tr><tr><td>-</td><td>Ochsner Institutional Review Board<br>Institutional Review Board<br>1514 Jefferson Highway<br>Louisiana 70121<br>New Orleans<br>UNITED STATES<br>Site: 50023</td></tr></table>