Abstract
Objective
Assess long-term safety, tolerability and efficacy of bimekizumab in ankylosing spondylitis (radiographic axial spondyloarthritis (r-axSpA)).
Methods
Patients with active r-axSpA completing the dose-ranging 48-week randomised controlled trial could enrol in the open-label extension, where patients received bimekizumab 160 mg every 4 weeks. Safety (exposure-adjusted incidence rates/100 patient-years (EAIRs)) and efficacy outcomes (binary: non-responder imputation (NRI) and observed case (OC); continuous: multiple imputation (MI)) are presented through 256 weeks.
Results
From Weeks 0–256, 289/303 (95.4%) patients had ≥1 treatment-emergent adverse event (TEAE); most frequent were nasopharyngitis (21.8%) and upper respiratory tract infection (14.5%). The EAIR of fungal infections was 7.4 (Candida infections: 2.6; oral candidiasis: 2.2); none systemic. EAIR of serious infections was 1.4; no active tuberculosis was reported. Active inflammatory bowel disease and anterior uveitis EAIRs were 0.8 and 0.7, respectively. 202/303 (66.7%) patients completed Week 256. 42 (13.9%) patients discontinued treatment due to TEAEs.
Efficacy at Week 48 was maintained for 5 years. At Week 256, NRI analysis showed 49.7% (OC: 73.1%) and 41.6% (OC: 71.1%) of patients achieved Assessment of SpondyloArthritis International Society 40% (ASAS40) response and Axial Spondyloarthritis Disease Activity Score (ASDAS) low disease activity, respectively. Mean (SE; MI) ASDAS improved from 3.9 (0.1) at baseline to 2.1 (0.1) at Week 48, which was maintained to Week 256. Improvements in pain, fatigue, physical function and health-related quality of life were sustained.
Conclusions
The safety profile of bimekizumab after 5 years of treatment remained consistent with previous reports, with no new safety signals identified. 5-year efficacy was sustained in this r-axSpA population following robust disease control achieved at Week 48.
Trial registration numbers
Keywords: Spondylitis, Ankylosing; Axial Spondyloarthritis; Treatment; DMARD
WHAT IS ALREADY KNOWN ON THIS TOPIC.
WHAT THIS STUDY ADDS
Up to 5 years of treatment, bimekizumab continued to be well tolerated and delivered sustained, long-term efficacy, including improvements in disease activity, patient symptoms, inflammation, physical function and rates of disease remission, ultimately leading to increased quality of life. No new safety signals were identified.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Following its approval for the treatment of axSpA in the European Union and USA, the continued reporting of safety and efficacy data for bimekizumab adds to the growing evidence base to inform its use in daily practice.
Introduction
Ankylosing spondylitis (AS; ie, radiographic axial spondyloarthritis (r-axSpA))1 2 is a chronic, immune-mediated inflammatory disease that mainly affects the axial skeleton.3 4 In recent years, growing scientific consensus supports the interchangeability of the terminology AS and r-axSpA,1 with a shift towards using the latter term, in part as it acknowledges the wider axial spondyloarthritis (axSpA) spectrum comprising non-radiographic (nr-)axSpA and r-axSpA.2 5 In light of this, AS/r-axSpA is hereafter referred to as r-axSpA. Patients with r-axSpA exhibit definite structural damage to the sacroiliac joints on radiographs and the condition can result in chronic pain and functional impairment, reducing health-related quality of life.6,9
Interleukin (IL)-17A and IL-17F, both members of the IL-17 cytokine family, and tumour necrosis factor (TNF) are key mediators of inflammation in spondyloarthritis,10,12 while Janus kinases (JAKs) are signal transducers of various cytokines.13 IL-17A, TNF and JAK inhibitors are recommended as effective targeted therapies in patients with axSpA.14,16
Although these therapies have been shown to reduce r-axSpA disease activity and improve patient quality of life, some patients do not achieve adequate disease control or experience secondary failure and require alternative therapies. Real-world data indicate that the achievement of inactive disease for patients with axSpA who receive existing biological disease-modifying antirheumatic drugs (bDMARDs) could constitute an unmet need.17
Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A. It is the first monoclonal antibody targeting both IL-17A and IL-17F approved by both the European Medicines Agency and the US Food and Drug Administration in axSpA.18 19 Previous clinical studies have shown that the dual inhibition of IL-17A and IL-17F with bimekizumab results in rapid and lasting clinical improvements in patients across the full disease spectrum of axSpA.20,22
Previously published results from the phase 2b dose-ranging BE AGILE study of bimekizumab in adults with r-axSpA reported rapid and significant improvement in disease activity at Week 12, which was maintained to Week 48.20 Bimekizumab was well-tolerated in the study, and treatment resulted in improvements in patient-reported outcomes (PROs) and health-related quality of life.20 Data published up to 156 weeks (3 years) of bimekizumab treatment demonstrated sustained long-term efficacy and safety.21
The reporting of safety and efficacy data for bimekizumab in patients with r-axSpA for up to 5 years is important as these data can inform its use in daily clinical practice. Here, we report safety and efficacy data up to 256 weeks of bimekizumab treatment (final study time point) in patients with r-axSpA across the BE AGILE study and its open-label extension (OLE).
A graphical summary of the results is provided in online supplemental figure 1.
Methods
Study design and participants
As reported previously,20 21 BE AGILE (NCT02963506) was a 48-week randomised, parallel-group, phase 2b, dose-ranging study, double-blind to Week 12, then dose-blind to Week 48. Patients who completed 48 weeks of treatment were eligible to enter the OLE (NCT03355573) for a further 204 weeks of treatment, with a subsequent safety visit 20 weeks after the last dose (online supplemental figure 2).
Eligible patients were ≥18 years of age, had a diagnosis of axSpA, with ≥3 months of symptom duration, age of onset <45 years and active disease defined as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4 and spinal pain ≥4 on a 0–10 Numerical Rating Scale (from BASDAI question 2). All patients enrolled in the study fulfilled the modified New York criteria for AS (definite sacroiliitis from a central reading of radiographs).23 Other key inclusion and exclusion criteria have been reported previously, in addition to randomisation, blinding details and OLE enrolment criteria (online supplemental figure 2).20 21
All study time points are reported relative to baseline (Week 0) of the initial randomised, controlled study. Here, we report results up to Week 256 (final study time point—up to 5 years total treatment duration).
Study procedures
At the baseline of the BE AGILE study, patients were randomised 1:1:1:1:1 to receive subcutaneous bimekizumab 16 mg, 64 mg, 160 mg or 320 mg, or placebo every 4 weeks (Q4W) (online supplemental figure 2). At Week 12, patients initially randomised to bimekizumab 16 mg, 64 mg, or placebo were re-randomised 1:1 to bimekizumab 160 mg or 320 mg Q4W through to Week 48, while patients initially randomised to bimekizumab 160 mg or 320 mg continued their dosing to Week 48. Patients who completed 48 weeks of treatment were eligible to enrol in the OLE (NCT03355573) for an additional 204 weeks of treatment, with a subsequent safety visit 20 weeks after the last dose. All patients in the OLE received open-label bimekizumab 160 mg Q4W, regardless of prior dosing regimen.
Outcomes
The primary safety variables of BE AGILE included the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events. All TEAEs were classified using the Medical Dictionary for Regulatory Activities V.19.0. Secondary safety variables included study withdrawals due to TEAEs and adverse events of interest: infections (serious, opportunistic, fungal and tuberculosis), neutropenia, hypersensitivity, suicidal ideation and behaviour, depression, major adverse cardiovascular events (MACE), liver function test changes/enzyme elevations, malignancies and inflammatory bowel disease (IBD; with gastroenterology referral, as appropriate). Along with IBD, other extra-musculoskeletal manifestations of axSpA, uveitis (comprising the preferred terms of iritis, iridocyclitis and uveitis) and psoriasis, were also recorded as TEAEs.
Efficacy variables were the secondary objective and included Axial Spondyloarthritis Disease Activity Score (ASDAS) inactive disease (ASDAS-ID; <1.3), ASDAS low disease activity (LDA; <2.1), Assessment of SpondyloArthritis International Society (ASAS) partial remission (ASAS PR), ASAS 20% and 40% response (ASAS20 and ASAS40), ASDAS, ASDAS major improvement (ASDAS-MI; improvement of ≥2.0), ASDAS clinically important improvement (improvement of ≥1.1), BASDAI, BASDAI 50% response, Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), resolution of enthesitis, high sensitivity (hs)C-reactive protein (CRP), total spinal pain, fatigue (BASDAI Q1), neck, back or hip pain (BASDAI Q2), morning stiffness (mean of BASDAI Q5+Q6), Ankylosing Spondylitis Quality of Life (ASQoL), 36-item Short Form Survey (SF-36) physical component summary (PCS) and mental component summary (MCS) scores.
Within the OLE, safety was assessed at OLE entry (Week 48), then Q4W to Week 60, then every 12 weeks to Week 256. Most efficacy outcomes were assessed at OLE entry, then every 12 weeks to Week 256. MASES was assessed every 12 weeks from entry to the OLE, then every 24 weeks from Week 96. ASQoL and SF-36 were assessed every 12 weeks from entry to the OLE, then every 24 weeks from Week 144. BASMI was assessed on OLE entry and then every 48 weeks.
Statistical analysis
Safety analyses are presented for exposure to bimekizumab across the total treatment period (Weeks 0–256), as well as separately for Weeks 0–48 for the respective safety sets (patients who had ≥1 dose of bimekizumab in the relevant study period). Additionally, safety analyses are presented for exposure to bimekizumab across the total treatment period, split by year. Exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY) of exposure to bimekizumab are presented.
Unless stated otherwise, efficacy variables are reported for the dose-blind set (DBS; N=296) from baseline (Week 0), which consisted of all patients who started the dose-blind period and who received ≥1 dose of study drug during the dose-blind period, including the dose at Week 12. This was to ensure that a full treatment sequence was available for each patient, in line with the 3-year results previously presented.21 Responses and change from baseline were derived relative to efficacy measurements at baseline (Week 0). For binary outcomes, missing data were handled in the most conservative way, using non-responder imputation (NRI), in which patients who discontinued the study were considered non-responders, in addition to patients with missing data. For continuous outcomes, missing data were imputed using multiple imputation (MI) based on the assumption that data were missing at random and unless stated otherwise, are reported using mean (SE). Observed case (OC) data are also presented and unless stated otherwise, are reported using mean (SD). All statistical analyses were conducted in SAS (V.9.3 or later).
Results
Patient disposition and baseline characteristics
Patient demographics and disease characteristics at BE AGILE baseline are reported in table 1. There were no notable differences in patient demographics and disease characteristics between the randomised population and patients treated with bimekizumab in the OLE. Patient demographics and baseline characteristics for the initial treatment groups have been reported previously.20
Table 1. Demographics and disease characteristics at baseline.
| n (%) unless otherwise stated | Baseline | |
| OverallSafety set(N=303) | OLESafety set(N=255) | |
| Age, years, mean (SD) | 42.2 (11.8) | 41.8 (11.4) |
| Sex, male | 256 (84.5) | 217 (85.1) |
| HLA-B27 positive | 270 (89.1)* | 232 (91.0)† |
| Age at first diagnosis, years, mean (SD) | 34.8 (10.4) | 34.5 (10.2) |
| Symptom duration, years, median (min–max) | 12.3 (0.2–47.2) | 12.1 (0.2–47.2) |
| Time since diagnosis, years, median (min–max) | 4.6 (0.0–37.3) | 4.6 (0.0–37.3) |
| ASDAS, mean (SD)‡ | 3.9 (0.8)§ | 3.9 (0.8) |
| BASDAI (0–10), mean (SD) | 6.5 (1.4) | 6.4 (1.4) |
| BASFI (0–10), mean (SD) | 5.8 (2.0) | 5.7 (1.9) |
| BASMI (0–10), mean (SD) | 4.7 (1.7)‡‡ | 4.7 (1.7)¶ |
| Total spinal pain (0–10), mean (SD) | 7.1 (1.7) | 7.0 (1.8) |
| Morning stiffness (0–10; mean of BASDAI Q5&6), mean (SD) | 6.7 (2.0) | 6.6 (2.0) |
| PtGADA (0–10), mean (SD) | 7.0 (1.7) | 6.9 (1.7) |
| hs-CRP>5 mg/L | 225 (74.3) | 193 (75.7) |
| hs-CRP, mg/L | ||
| mean (SD) | 19.0 (20.9)** | 19.5 (21.5)†† |
| median (min–max) | 12.1 (0.3–130.1)** | 12.1 (0.3–130.1)†† |
| MASES>0 | 200 (66.0) | 169 (66.3) |
| SF-36 MCS (0–100), mean (SD) | 54.1 (8.3) | 54.3 (8.2) |
| SF-36 PCS (0–100), mean (SD) | 32.1 (7.7) | 32.4 (7.4) |
| ASQoL (0–18), mean (SD) | 8.7 (4.3) | 8.5 (4.3) |
| History of IBD | ||
| Crohn’s disease | 2 (0.7) | 1 (0.4) |
| Ulcerative colitis | 5 (1.7) | 4 (1.6) |
| Colitis | 1 (0.3) | 1 (0.4) |
| History of anterior uveitis | 46 (15.2) | 39 (15.3) |
| History of psoriasis | 9 (3.0) | 7 (2.7) |
| Prior TNF inhibitor therapy | 34 (11.2) | 29 (11.4) |
| Concomitant treatment | ||
| NSAIDs | 272 (89.8) | 232 (91.0) |
| csDMARDs | 79 (26.1) | 67 (26.3) |
| Corticosteroids | 26 (8.6) | 23 (9.0) |
Overall BE AGILE (N=303) and OLE (N=255) safety sets.
All data are reported for a double-blind period baseline (Week 0), not the start of the OLE (Week 48).
n=303 including six patients with missing results; .
n=255 including five patients with missing results;.
ASDAS-CRP; .
n=302; .
n=254; .
n=300; .
n=254.
n=301.
ASDAS, Ankylosing Spondylitis Disease Activity Score; ASQoL, Ankylosing Spondylitis Quality of Life; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Function Index; BASMI, Bath Ankylosing Spondylitis Metrology Index; csDMARD, conventional synthetic disease-modifying anti-rheumatic drug; HLA-B27, human leucocytel antigen-B27; hs-CRP, high sensitivity C-reactive protein; IBD, inflammatory bowel disease; MASES, Maastricht Ankylosing Spondylitis Enthesitis Score; NSAIDnon-steroidal anti-inflammatory drugOLE, open-label extension; PtGADA, Patient’s Global Assessment of Disease Activity; SF-36 MCS36-item Short-Form Survey, mental component summarySF-36 PCS36-item Short-Form Survey, physical component summaryTNF, tumour necrosis factor
Of the 303 patients randomised at BE AGILE baseline (comprising the BE AGILE full analysis set and safety set), 256/303 (84.5%) patients entered the OLE, in which all patients received bimekizumab 160 mg Q4W (online supplemental figure 2). 255 patients were included in the OLE safety set, as one patient enrolled in the OLE but did not subsequently receive bimekizumab. Patient retention was high during the OLE, with 202/255 (79.2%) patients remaining in the study up to Week 256; 66.7% of the 303 patients initially randomised in BE AGILE completed the study (online supplemental figure 3; online supplemental figure 4). Following 38/303 (12.5%) discontinuations to Week 48, there were 53/255 (20.8%) discontinuations during the OLE: 19 due to adverse events, 23 due to withdrawn consent, 2 due to lack of efficacy, 4 due to loss during follow-up and 5 due to other reasons.
Safety
Overview
Among all patients randomised at BE AGILE baseline, exposure to bimekizumab across the 256 weeks was 1231 PY, with exposure to bimekizumab across the OLE comprising 970 PY. Across 256 weeks, 289/303 (95.4%) patients had ≥1 TEAE (EAIR: 134.6/100 PY); 58/303 (19.1%) patients had ≥1 serious TEAE (EAIR: 5.2/100 PY; table 2). The most frequently reported TEAEs by preferred term included nasopharyngitis (21.8%), upper respiratory tract infection (14.5%), bronchitis (13.2%), severe acute respiratory syndrome (SARS-CoV-2; COVID-19) infection (10.9%; defined by the preferred term ‘corona virus infection’) and pharyngitis (10.6%; table 2). Across 256 weeks, 42 (13.9%) patients discontinued bimekizumab due to TEAEs, most commonly due to gastrointestinal disorders (4.3%) or infections and infestations (3.3%). No patient pregnancies were recorded during the study. Three patient deaths were reported (Week 0–48: one death due to cardio-respiratory arrest; Week 48–256: two deaths due to cardio-respiratory arrest and a road traffic incident, respectively); none were considered treatment-related by the investigators.
Table 2. Safety overview.
| n (%) (EAIR/100 PY) | Weeks 0–48 | Weeks 0–256 | ||
| BKZ 160 mg* (n=149; 129 PY) | BKZ 320 mg* (n=150; 132 PY) | Total (N=303; 261 PY) | Total (N=303; 1231 PY) | |
| Any TEAE | 108 (72.5) (162.4) | 124 (82.7) (206.2) | 235 (77.6) (186.2) | 289 (95.4) (134.6) |
| Most frequently reported TEAEs (≥10%) by preferred term | ||||
| Nasopharyngitis | 14 (9.4) (11.5) | 20 (13.3) (15.9) | 34 (11.2) (13.7) | 66 (21.8) (6.5) |
| Upper respiratory tract infection | 6 (4.0) (4.7) | 11 (7.3) (8.6) | 17 (5.6) (6.7) | 44 (14.5) (4.0) |
| Bronchitis | 6 (4.0) (4.8) | 12 (8.0) (9.4) | 18 (5.9) (7.1) | 40 (13.2) (3.6) |
| SARS-CoV-2 (COVID-19) infection† | – | – | – | 33 (10.9) (2.8) |
| Pharyngitis | 11 (7.4) (8.8) | 7 (4.7) (5.5) | 18 (5.9) (7.1) | 32 (10.6) (2.8) |
| Serious TEAEs | 5 (3.4) (3.9) | 7 (4.7) (5.4) | 13 (4.3) (5.1) | 58 (19.1) (5.2) |
| Treatment discontinuations due to TEAEs‡ | 7 (4.7) (5.5) | 11 (7.3) (8.7) | 20 (6.6) (7.9) | 42 (13.9) (3.5) |
| Drug-related TEAEs | 51 (34.2) (49.5) | 58 (38.7) (57.7) | 110 (36.3) (54.0) | 160 (52.8) (21.8) |
| Deaths | 1 (0.7) (0.8) | 0 | 1 (0.3) (0.4) | 3 (1.0) (0.2) |
| Adverse events of interest | ||||
| Serious infections | 3 (2.0) (2.3) | 1 (0.7) (0.8) | 4 (1.3) (1.5) | 17 (5.6) (1.4) |
| Opportunistic infections§¶ | 0 | 0 | 1 (0.3) (0.4) | 3 (1.0) (0.2) |
| Active tuberculosis | 0 | 0 | 0 | 0 |
| Fungal infections** | 20 (13.4) (16.5) | 24 (16.0) (19.8) | 44 (14.5) (18.1) | 74 (24.4) (7.4) |
| Candida infections | 10 (6.7) (8.0) | 9 (6.0) (7.1) | 19 (6.3) (7.5) | 30 (9.9) (2.6) |
| Oral candidiasis†† | 8 (5.4) (6.4) | 8 (5.3) (6.3) | 16 (5.3) (6.3) | 25 (8.3) (2.2) |
| Skin Candida | 0 | 1 (0.7) (0.8) | 1 (0.3) (0.4) | 4 (1.3) (0.3) |
| Vulvovaginal candidiasis | 2 (1.3) (1.6) | 0 | 2 (0.7) (0.8) | 2 (0.7) (0.2) |
| Oropharyngeal candidiasis | 0 | 0 | 0 | 1 (0.3) (0.1) |
| Candida infection (unspecified) | 0 | 0 | 0 | 1 (0.3) (0.1) |
| Fungal infections NEC | 10 (6.7) (7.9) | 14 (9.3) (11.1) | 24 (7.9) (9.5) | 43 (14.2) (3.9) |
| Oral fungal infection | 8 (5.4) (6.3) | 6 (4.0) (4.6) | 14 (4.6) (5.5) | 20 (6.6) (1.7) |
| Fungal skin infection | 1 (0.7) (0.8) | 6 (4.0) (4.6) | 7 (2.3) (2.7) | 14 (4.6) (1.2) |
| Tongue fungal infection | 0 | 3 (2.0) (2.3) | 3 (1.0) (1.2) | 7 (2.3) (0.6) |
| Onychomycosis | 0 | 0 | 0 | 7 (2.3) (0.6) |
| Ear infection fungal | 1 (0.7) (0.8) | 0 | 1 (0.3) (0.4) | 1 (0.3) (0.1) |
| Vulvovaginal mycotic infection | 0 | 1 (0.7) (0.8) | 1 (0.3) (0.4) | 1 (0.3) (0.1) |
| Otitis externa fungal | 0 | 0 | 0 | 1 (0.3) (0.1) |
| Fungal infection | 0 | 0 | 0 | 1 (0.3) (0.1) |
| Tinea infections | 1 (0.7) (0.8) | 2 (1.3) (1.5) | 3 (1.0) (1.2) | 8 (2.6) (0.7) |
| Tinea pedis | 1 (0.7) (0.8) | 2 (1.3) (1.5) | 3 (1.0) (1.2) | 6 (2.0) (0.5) |
| Body tinea | 0 | 0 | 0 | 1 (0.3) (0.1) |
| Tinea capitis | 0 | 0 | 0 | 1 (0.3) (0.1) |
| Neutropenia | 1 (0.7) (0.8) | 0 | 1 (0.3) (0.4) | 4 (1.3) (0.3) |
| Serious hypersensitivity reactions | 0 | 0 | 0 | 0 |
| Adjudicated suicidal ideation and behaviour | 0 | 0 | 0 | 1 (0.3) (0.1) |
| Adjudicated MACE | 2 (1.3) (1.8) | 0 | 2 (0.7) (0.8) | 4 (1.3) (0.3) |
| Liver function analyses‡‡ | 13 (8.7) (10.8) | 15 (10.0) (12.0) | 28 (9.2) (11.4) | 52 (17.2) (4.8) |
| ALT increased | 6 (4.0) (4.8) | 7 (4.7) (5.4) | 13 (4.3) (5.1) | 26 (8.6) (2.3) |
| AST increased | 4 (2.7) (3.2) | 5 (3.3) (3.9) | 9 (3.0) (3.5) | 19 (6.3) (1.6) |
| Hepatic enzyme increased | 2 (1.3) (1.6) | 4 (2.7) (3.1) | 6 (2.0) (2.3) | 15 (5.0) (1.3) |
| Malignancies | 0 | 0 | 0 | 3 (1.0) (0.2) |
| Adjudicated IBD – definite or probable§§ | 1 (0.7) (0.8) | 3 (2.0) (2.3) | 4 (1.3) (1.5) | 10 (3.3) (0.8) |
| Ulcerative colitis | 0 | 2 (1.3) (1.5) | 2 (0.7) (0.8) | 4 (1.3) (0.3) |
| With prior history of IBD | 0 | 1 | 1 | 2 (25.0) (6.6)¶¶ |
| Without prior history of IBD | 0 | 1 | 1 | 2 (0.7) (0.2)*** |
| Crohn’s disease | 1 (0.7) (0.8) | 1 (0.7) (0.8) | 2 (0.7) (0.8) | 5 (1.7) (0.4) |
| With prior history of IBD | 0 | 0 | 0 | 0¶¶ |
| Without prior history of IBD | 1 | 1 | 2 | 5 (1.7) (0.4)*** |
| Colitis | 0 | 0 | 0 | 1 (0.3) (0.1) |
| With prior history of IBD | 0 | 0 | 0 | 0¶¶ |
| Without prior history of IBD | 0 | 0 | 0 | 1 (0.3) (0.1)*** |
| Anterior uveitis§§††† | 1 (0.7) (0.9) | 1 (0.7) (0.8) | 2 (0.7) (0.8) | 9 (3.0) (0.7) |
| With prior history | 1 | 1 | 2 | 3 (7.5) (1.8)‡‡‡ |
| Without prior history | 0 | 0 | 0 | 6 (2.3) (0.6)§§§ |
| Psoriasis§§¶¶¶ | 0 | 0 | 0 | 13 (4.3) (1.1)**** |
| Injection site reactions | 0 | 3 (2.0) (2.3) | 3 (1.0) (1.2) | 5 (1.7) (0.4) |
TEAEs are reported for the BE AGILE safety set (patients who received ≥1 dose of BKZ within the study period). As safety events were recorded to study periods in an ongoing manner, selected individual events’ relationship to study periods have been consolidated and may differ tofrom previous BE AGILE publications.
Patients received the indicated dose during the dose-blind period (Weeks 12–48); .
Defined by the preferred term corona virus infection; .
Permanent withdrawal of study drug; .
All fungal infections were mild–moderate; none were systemic; Opportunistic infections are defined using UCB-defined search criteria.
All oral candidiasis TEAEs were mild–moderate, and there were no serious cases; In BE AGILE, one case of recurrent herpes zoster in Weeks 0–48 and one case of oropharyngeal candidiasis and herpes oesophagitis, respectively, in Weeks 48–256.
Includes the preferred terms ALT increased, AST increased, GGT increased, hepatic enzyme increased, blood bilirubin increased, transaminases increased, GGT decreased, and liver function test increased; All fungal infections were mild–moderate; none were systemic.
Inflammatory bowel disease, anterior uveitis, and psoriasis are musculoskeletal manifestations of axSpA; All oral candidiasis TEAEs were mild–moderate, and there were no serious cases.
Includes the preferred terms ALT increased, AST increased, GGT increased, hepatic enzyme increased, blood bilirubin increased, transaminases increased, GGT decreased and liver function test increased.
Inflammatory bowel disease, anterior uveitis and psoriasis are extra-musculoskeletal manifestations of axial spondyloarthritis.
n=8.
n=295.
Includes the preferred terms iritis, iridocyclitis and uveitis.
n=40.
n=263.
Includes the preferred term psoriasis.
One patient had a history of psoriasis, diagnosed by a dermatologist.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BKZ, bimekizumab; EAIR, exposure-adjusted incidence rate; GGT, gamma-glutamyltransferase; IBD, inflammatory bowel disease; MACE, major adverse cardiovascular events; NEC, not elsewhere classified; PY, patient-years; TEAE, treatment-emergent adverse event
Adverse events of interest
Across 256 weeks, EAIRs were 1.4/100 PY for serious infections and 0.2/100 PY for opportunistic infections. Expectedly, there were no cases of active tuberculosis. Among the 74 (24.4%) patients who had a fungal infection (EAIR: 7.4/100 PY), 30 (9.9%) reported a Candida infection (EAIR: 2.6/100 PY). Most Candida infections were oral candidiasis, which occurred in 25 (8.3%) patients. Other fungal infections reported are detailed in table 2. All fungal infections (including Candida infections) were mild–moderate, and none were systemic. The vast majority of fungal infections did not lead to study discontinuation (2 (0.7%) patients had fungal infections leading to study discontinuation across the study period). Across all study years, Year 1 had the highest proportion of patients presenting with fungal infections (figure 1), while fungal infection duration was varied with a similar proportion of incidences lasting ≤28 days or >28 days. The vast majority of fungal infections resolved, with the patient having received corrective treatment. To Week 256, 73 (24.1%) patients had recurrence of any fungal infection. Of these, patients most commonly had recurrence of oral candidiasis (12/73 patients (16.4%)). The majority of patients who had a fungal infection did not have recurrence (230 patients (75.9%)), while multiple instances of recurrence (≥3 fungal infections overall) were uncommon (17 patients had multiple instances of fungal infection recurrence (5.6%); online supplemental table 1).
Figure 1. Safety overview by study year. TEAEs are reported for the BE AGILE safety set (patients who received ≥1 dose of bimekizumab within the study period) and who were at risk at the start of the specified study period shown. TEAEs are defined according to Medical Dictionary for Regulatory Activities V.19.0. Year 1: >0 to 52 weeks (n=303; 289.1 PY), Year 2: >52 to 104 weeks (n=269; 245.9 PY), Year 3: >104 to 156 weeks (n=236; 228.8 PY), Year 4: >156 to 208 weeks (n=223; 217.7 PY), Year 5: >208 to 260 weeks (n=216; 208.8 PY). EAIR, exposure-adjusted incidence rate; PY, patient-years; TEAE, treatment-emergent adverse event.
Over 5 years, EAIRs of neutropenia (0.3/100 PY), serious hypersensitivity reactions (0), malignancies (0.2/100 PY), adjudicated suicidal ideation and behaviour (0.1/100 PY), depression (0.2/100 PY), adjudicated MACE (0.3/100 PY) and injection site reactions (0.4/100 PY) were low. EAIRs of liver function analyses TEAEs, encompassing increased alanine aminotransferase (2.3/100 PY), increased aspartate aminotransferase (1.6/100 PY) and increased hepatic enzymes (1.3/100 PY) were also low (table 2). Five (1.7%) patients with liver function analysis TEAEs permanently discontinued treatment with bimekizumab; there were no cases of confirmed Hy’s law.
Interval safety data
Across 256 weeks, analysis of safety data year-by-year demonstrated that long-term exposure to bimekizumab is not associated with a changing safety profile (figure 1; online supplemental table 2). In Years 3–5 of exposure to bimekizumab, rates of TEAEs remained low, including adverse events of interest.
Extra-musculoskeletal manifestations
Across 256 weeks, the EAIR of anterior uveitis was 0.7/100 PY. Of the 9 (3.0%) patients who experienced a uveitis flare, three had a prior history of uveitis. All cases were mild–moderate, and none led to permanent treatment discontinuation. 10 (3.3%) patients had adjudicated definite or probable IBD (EAIR: 0.8/100 PY—Crohn’s disease: five patients; ulcerative colitis: four patients; colitis: one patient); most cases were mild–moderate and did not lead to permanent treatment discontinuation (two patients had IBD classed as severe—Crohn’s disease: one, ulcerative colitis: one). Two of these patients had a prior history of IBD; both had ulcerative colitis. No patients presenting with active IBD had diabetes mellitus. Six patients with IBD presented within a year of treatment initiation, with three patients presenting beyond 3 years of exposure. Psoriasis was reported in 13 (4.3%) patients (EAIR: 1.1/100 PY), of which one patient had a history of psoriasis (the other 12 patients had de novo psoriasis); most cases were mild–moderate (one patient had psoriasis classed as severe). One patient permanently discontinued treatment due to psoriasis.
Efficacy
ASDAS-ID, ASDAS LDA, ASAS-PR demonstrated consistent improvements to Week 48 and were maintained to Week 256. As previously reported, over half of bimekizumab-treated patients achieved an ASAS40 response (DBS, as defined in the Methods section) at Week 48.21 After four further years of treatment, at Week 256 (DBS—NRI), rates of ASAS20 and ASAS40 were sustained, with 57.8% (OC: 85.1%) and 49.7% (OC: 73.1%) patients achieving these responses, respectively, compared with 65.9% (OC: 76.2%) and 51.7% (OC: 59.8%) at Week 48 (figure 2; table 3).
Figure 2. ASAS40, ASDAS LDA, ASDAS-ID and ASDAS-CII responses to Week 256 (NRI, MI, OC). BE AGILE FAS (all randomised patients who received ≥1 dose of BKZ and had a valid measurement of the ASAS components at baseline; N=303) for Weeks 0–12; unless otherwise stated, DBS (patients who started the dose-blind period at Week 12 and received ≥1 dose of BKZ during the dose-blind period, including the dose at Week 12; N=296) for Weeks 12–256. Data for OLE FAS are also reported (patients who entered the OLE and had ≥1 scheduled efficacy assessment at OLE entry; N=249 (248 patients included in the MI model)) for Weeks 48–256. Data reported as NRI, MI and OC as indicated. In the NRI analyses, patients who did not enter the OLE were considered non-responders from Week 48 onwards. ASAS40, Assessment of SpondyloArthritis international Society 40% response; ASDAS, Ankylosing Spondylitis Disease Activity Score; ASDAS-CII, ASDAS clinically important improvement; ASDAS-ID, ASDAS inactive disease; ASDAS LDA, ASDAS low disease activity; BKZ, bimekizumab; DBS, double-blind set; FAS, full analysis set; MI, multiple imputation; NRI, non-responder imputation; OC, observed case; OLE, open-label extension; Q4W, every 4 weeks.
Table 3. Efficacy outcomes to Week 256.
| N (%) unless otherwise stated | Total (n=296) | ||
| Imputed | OC | ||
| ASDAS-ID (NRI) | Wk 48 | 58 (19.6) | 58/256 (22.7) |
| Wk 256 | 52 (17.6) | 52/173 (30.1) | |
| ASDAS LDA (NRI) | Wk 48 | 146 (49.3) | 146/256 (57.0) |
| Wk 256 | 123 (41.6) | 123/173 (71.1) | |
| ASAS PR (NRI) | Wk 48 | 80 (27.0) | 80/256 (31.3) |
| Wk 256 | 83 (28.0) | 83/201 (41.3) | |
| ASAS20 (NRI) | Wk 48 | 195 (65.9) | 195/256 (76.2) |
| Wk 256 | 171 (57.8) | 171/201 (85.1) | |
| ASAS40 (NRI) | Wk 48 | 153 (51.7) | 153/256 (59.8) |
| Wk 256 | 147 (49.7) | 147/201 (73.1) | |
| ASDAS (MI) mean (SE (MI)/SD (OC)) | BL | 3.9 (0.1) | 3.9 (0.8) |
| Wk 48 | 2.1 (0.1) | 2.0 (0.9) | |
| Wk 256 | 2.1 (0.1) | 1.8 (0.8) | |
| ASDAS-MI (NRI) | Wk 48 | 115 (38.9) | 115/256 (44.9) |
| Wk 256 | 95 (32.1) | 95/173 (54.9) | |
| ASDAS-CII (NRI) | Wk 48 | 200 (67.6) | 200/256 (78.1) |
| Wk 256 | 149 (50.3) | 149/173 (86.1) | |
| BASDAI (MI)Mean (SE (MI)/SD (OC)) | BL | 6.5 (0.1) | 6.5 (1.4) |
| Wk 48 | 3.0 (0.1) | 2.8 (2.0) | |
| Wk 256 | 2.5 (0.2) | 2.2 (1.8) | |
| BASDAI50 (NRI) | Wk 48 | 149 (50.3) | 149/256 (58.2) |
| Wk 256 | 151 (51.0) | 151/201 (75.1) | |
| BASFI (MI) mean (SE (MI)/SD (OC)) | BL | 5.7 (0.1) | 5.7 (2.0) |
| Wk 48 | 3.1 (0.1) | 3.0 (2.2) | |
| Wk 256 | 2.7 (0.1) | 2.5 (2.1) | |
| BASMI (MI) mean (SE (MI)/SD (OC)) | BL | 4.7 (0.1) | 4.7 (1.7) |
| Wk 48 | 3.9 (0.1) | 4.0 (1.8) | |
| Wk 252 | 3.8 (0.1) | 3.9 (1.8) | |
| MASES (MI)* mean (SE (MI)/SD (OC)) | BL | 4.4 (0.2) | 4.4 (3.0) |
| Wk 48 | 0.9 (0.1) | 0.8 (1.7) | |
| Wk 256 | 0.7 (0.1) | 0.6 (1.9) | |
| Resolution of enthesitis (NRI)*† | Wk 48 | 120/194 (61.9) | 120/168 (71.4) |
| Wk 256 | 112/194 (57.7) | 112/132 (84.8) | |
| hs-CRP (MI) geometric mean (median) | BL | 10.7 (12.1) | 10.6 (12.0) |
| Wk 48 | 3.0 (3.6) | 3.1 (3.5) | |
| Wk 256 | 2.7 (3.2) | 2.6 (2.9) | |
| Total spinal pain (MI) mean (SE (MI)/SD (OC)) | BL | 7.1 (0.1) | 7.1 (1.8) |
| Wk 48 | 3.2 (0.1) | 3.0 (2.2) | |
| Wk 256 | 2.7 (0.1) | 2.4 (2.0) | |
| Fatigue (BASDAI Q1) (MI) mean (SE (MI)/SE (OC)) | BL | 6.7 (0.1) | 6.7 (0.1) |
| Wk 48 | 3.6 (0.1) | 3.5 (0.1) | |
| Wk 256 | 2.9 (0.2) | 2.6 (0.2) | |
| Neck, back or hip pain (BASDAI Q2) (MI) mean (SE (MI)/SE (OC)) | BL | 7.5 (0.1) | 7.5 (0.1) |
| Wk 48 | 3.4 (0.1) | 3.3 (0.2) | |
| Wk 256 | 2.8 (0.2) | 2.5 (0.2) | |
| Morning stiffness (mean BASDAI Q5+Q6) (MI) mean (SE (MI)/SE (OC)) | BL | 6.6 (0.1) | 6.6 (0.1) |
| Wk 48 | 2.8 (0.1) | 2.7 (0.1) | |
| Wk 256 | 2.4 (0.2) | 2.1 (0.1) | |
| ASQoL (MI) mean (SE (MI)/SD (OC)) | BL | 8.7 (0.3) | 8.7 (4.3) |
| Wk 48 | 3.7 (0.2) | 3.4 (3.9) | |
| Wk 256 | 3.0 (0.2) | 2.5 (3.3) | |
| SF-36 PCS (MI) mean (SE (MI)/SD (OC)) | BL | 32.3 (0.5) | 32.3 (7.7) |
| Wk 48 | 44.1 (0.5) | 44.6 (8.8) | |
| Wk 256 | 45.8 (0.6) | 46.5 (8.2) | |
| SF-36 MCS (MI) mean (SE (MI)/SD (OC)) | BL | 54.1 (0.5) | 54.1 (8.3) |
| Wk 48 | 56.6 (0.4) | 56.8 (7.0) | |
| Wk 256 | 56.1 (0.5) | 56.8 (6.9) | |
Dose-blind set (Nn=296). For multiple imputation (MI), SE is reported and for observed cases (OC) SD is reported.
Data are reported as imputed (MI, based on the missing at random assumption, or NRI) and OC. For continuous variables, the mean (SE) is reported for MI analyses and the mean (SD) is reported for OC analyses.
Analyses on patients who had MASES>0 at baseline: n=100 in the dose-blind BKZ 160 mg mg group and n=94 in the dose-blind BKZ 320 mg mg group, and n=194 in the DBS total population;
Resolution of enthesitis is defined by MASES=0.
ASAS20/40Assessment of SpondyloArthritis International Society 20/40% responseASAS PRASAS partial remissionASDAS, Ankylosing Spondylitis Disease Activity Score; ASDAS-CII, ASDAS clinically important improvement; ASDASID, ASDAS inactive disease; ASDAS-MI, ASDAS major improvement; ASQoL, Ankylosing Spondylitis Quality of Life; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASDAI50, BASDAI 50% response; BASFI, Bath Ankylosing Spondylitis Function Index; BASMI, Bath Ankylosing Spondylitis Metrology Index; BL, baseline; hs-CRP, high sensitivity C-reactive protein; LDA, low disease activity; MASES, Maastricht Ankylosing Spondylitis Enthesitis Score; NRI, non-responder imputation; SF-36 P/MCSShort-Form 36 physical/component mental summarywk, week
Mean (SE) ASDAS at BE AGILE baseline in the DBS was 3.9 (0.1); ASDAS (MI) was similarly improved through Week 48 (2.1 (0.1)) and was further maintained to Week 256 (2.1 (0.1)) (figure 3; table 3). This was mirrored by the number of patients achieving ASDAS-MI (online supplemental figure 5). Mean (SE) BASDAI at baseline was 6.5 (0.1), improved to Week 48 (3.0 (0.1); MI) and showed further improvement to Week 256 (2.5 (0.2)) (figure 3; table 3). Mean BASFI and BASMI were similarly improved to Week 48 and maintained to Week 256 and 252, respectively (the last BASMI assessment was at Week 252; figure 3; table 3).
Figure 3. ASDAS, BASDAI, BASFI and total spinal pain absolute values and change from baseline to Week 256 (MI). BE AGILE FAS (all randomised patients who received ≥1 dose of BKZ and had a valid measurement of the ASAS components at baseline; N=303) for Weeks 0–12; unless otherwise stated, DBS (patients who started the dose-blind period at Week 12 and received ≥1 dose of BKZ during the dose-blind period, including the dose at Week 12; N=296) for Weeks 12–256. Data for OLE FAS are also reported (patients who entered the OLE and had ≥1 scheduled efficacy assessment at OLE entry; N=249) for Weeks 48–256. Baseline ASDAS, BASDAI, BASFI and total spinal pain are shown for the DBS. Data reported as MI. ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; BKZ, bimekizumab; CfB, change from baseline; DBS, dose-blind set; FAS, full analysis set; MI, multiple imputation; OLE, open-label extension; Q4W, every 4 weeks.
Improvements in mean MASES to Week 48, which were maintained to Week 256, reflected decreased levels of enthesitis. At Week 48 (DBS—NRI), resolution of enthesitis was achieved by 61.9% of patients, which was also maintained to Week 256 (57.7%). As an objective sign of systemic inflammation, elevated baseline hs-CRP geometric mean levels were rapidly reduced and were maintained at low levels through Weeks 48 and 256 (table 3).
PROs measuring key patient symptoms like total spinal pain, fatigue and morning stiffness were similarly improved, demonstrating sustained efficacy over 5 years of bimekizumab treatment (figure 3; table 3).
Patient health-related quality of life outcomes displayed similar improvements. Mean scores at baseline for ASQoL and SF-36 PCS were indicative of impaired health-related quality of life in this patient population with long-standing disease. Mean scores (both OC and MI) improved to Week 48 and these improvements were maintained up to Week 256 (DBS; table 3; online supplemental figure 6). In contrast, the baseline SF-36 MCS score was indicative of non-impaired mental health; scores were maintained over 256 weeks of bimekizumab treatment (DBS; table 3).
Discussion
In the phase 2b BE AGILE study (Week 0–48) and its long-term OLE (to Week 256), bimekizumab was found to be well tolerated in patients with r-axSpA over 5 years of treatment. The long-term safety profile of bimekizumab in patients with r-axSpA was in line with previous observations.21 Following rapid improvements within the first 48 weeks of treatment with bimekizumab, all efficacy outcomes were maintained or continued to improve over 5 years.
The safety data presented here indicate that there are no additional safety concerns with increased cumulative bimekizumab exposure in patients with r-axSpA over 5 years. The most frequently reported TEAEs over 5 years were nasopharyngitis, upper respiratory tract infection, bronchitis, SARS-CoV-2 (COVID-19) infection and pharyngitis. With the exception of SARS-CoV-2 infection, this was in line with what was previously reported at 3 years.21 The frequency of oral candidiasis observed was expected given the reported link between IL-17 inhibition and the occurrence of oral candidiasis.24 It is important to note that Candida infections reported in this study were all mild–moderate and the vast majority of fungal infections did not lead to study discontinuation. Repeated fungal infections, most commonly oral candidiasis, were seen in a minority of patients. Additionally, due to the long-term nature of the study, the existing incidence of infection in the general population should also be considered, which is particularly relevant for common upper respiratory infections.25 Analysis of safety data year-by-year demonstrated that long-term exposure to bimekizumab was associated with a consistent safety profile.
Incidence rates of IBD remained low over 5 years of exposure to bimekizumab and were in line with expected background rates of the condition in axSpA. This is consistent with the findings of phase 3 studies of bimekizumab across the full disease spectrum of axSpA.22
Acute anterior uveitis is a known and common extra-musculoskeletal manifestation in patients with r-axSpA.26 As observed over 3 years of exposure to bimekizumab, the EAIR of uveitis remained low through 5 years of treatment in this study (0.7/100 PY). This is in line with the low rates of uveitis observed in bimekizumab-treated patients with r-axSpA and nr-axSpA compared with placebo-treated patients in parallel phase 3 trials.22
Real-world evidence of IL-17A and TNF inhibitor use indicates that a large proportion of patients (>40%) with axSpA do not remain on therapy 1–2 years post-initiation, indicating a need for novel and effective treatment options.27 28 Although not directly comparable, patient retention was high, with 66.7% of those initially randomised in BE AGILE completing to Week 256. Real-world events that should be considered in the interpretation of these patient retention data include the COVID-19 pandemic and the ongoing war in Ukraine.
As a long-term report of the safety and efficacy of dual IL-17A/IL-17F inhibitor treatment in r-axSpA up to 5 years, this study supports the use of bimekizumab to provide sustained improvements in the signs and symptoms of axSpA and systemic inflammation as well as mobility, physical function and health-related quality of life. The presentation of key efficacy data using NRI provides conservative insights into the potential real-world patient outcomes of treatment with bimekizumab, and probable treatment persistence. The improvements in efficacy outcomes observed in patients receiving bimekizumab over 48 weeks were maintained or continued to improve through 5 years of treatment. Improvements in both ASAS PR and ASDAS-ID reflect increasing numbers of patients who achieved clinical remission to Week 256. The proportion of patients who achieved ASDAS LDA was also maintained. Using NRI, an ASAS40 response rate of >50% was maintained at all time points from Week 48–256, while in the observed case analysis, 73.1% of patients achieved ASAS40 at Week 256. Substantial reductions across disease symptoms and disease activity (ASDAS, BASDAI) to Week 48 were maintained over the 5-year study period. An increased proportion of patients achieving resolution of enthesitis and decreases in hs-CRP levels demonstrate that treatment with bimekizumab is associated with reduced systemic inflammation and reduced inflammation of the entheses, respectively. Given that high levels of hs-CRP are a predictor of further structural damage, and are associated with an increased risk of cardiovascular events in patients with axSpA, this treatment effect of bimekizumab is relevant to daily clinical practice.29 30
The outcomes reported here align with the ASAS-OMERACT core domain set (disease activity, morning stiffness, pain, fatigue, overall health and functioning, physical functioning and adverse events (including death)), which identifies the most important health and well-being domains for both physicians and patients.31 While the ASAS-OMERACT core domain set for axSpA is now heavily influential in clinical trial design,31 32 this trial preceded its publication. Consequently, while all core domains were assessed in BE AGILE, this was not the case for all core set instruments (swollen joint count, tender joint count and ASAS Health Index scores were not collected).32 Additionally, extra-musculoskeletal manifestations were not collected according to ASAS-OMERACT core domain set recommendations.32
Another limitation of the present analysis relates to the lack of an active or placebo comparator for bimekizumab during the OLE. Placebo was only administered up to Week 12, after which all patients received bimekizumab 160 mg or 320 mg Q4W. Spinal X-rays were not collected in order to evaluate the impact of bimekizumab on spinal disease progression. Similarly, MRI was not employed in this study, limiting the ability to determine whether local inflammation is suppressed by bimekizumab. However, MRI and radiographic assessment of inflammation and structural damage are being investigated in two parallel phase 3 studies, BE MOBILE 1 and BE MOBILE 2, which include patients with nr-axSpA and r-axSpA, respectively.22 33 Data reported in these studies demonstrate that treatment with bimekizumab is associated with rapid reductions in objective signs of inflammation at Week 16, which are maintained until Week 52.33
A key strength of the BE AGILE long-term extension study was that the systematic monitoring, reporting and coding of safety events over a longer period of cumulative bimekizumab exposure in patients with r-axSpA significantly contributes to the growing evidence base for the safety and tolerability of bimekizumab in this patient population, previously reported for up to 156 weeks of treatment.20 21
This phase 2b study also provides the most comprehensive and long-term evidence to date of bimekizumab’s safety and efficacy in patients with r-axSpA. The reporting of efficacy outcomes using the most conservative approach to the handling of missing data (NRI) gives further credence to this study’s findings. To our knowledge, this is the first report of ASAS40 outcome data reported up to 5 years using NRI in patients with r-axSpA treated with a bDMARD.
In conclusion, this 5-year analysis of long-term safety and efficacy provides further evidence supporting bimekizumab as an effective treatment option for patients with r-axSpA. Bimekizumab continued to be well tolerated across 5 years of exposure, with no new safety signals being identified. Treatment with bimekizumab delivered sustained, long-term efficacy, including improvements in disease activity, patient symptoms, inflammation, physical function and rates of disease remission, ultimately leading to increased quality of life. To our knowledge, this is the first report of 5-year efficacy outcome data using NRI in patients with r-axSpA treated with a bDMARD. This work contributes to a growing evidence base for bimekizumab across the full disease spectrum of axSpA, with recent phase 3 results demonstrating its safety and efficacy in nr-axSpA and r-axSpA, alike.22
supplementary material
Acknowledgements
The authors thank the patients, the investigators and their teams who took part in this study. The authors also acknowledge Celia Menckeberg, PhD, UCB, for publication coordination and Hugh Osborne, PhD, and James Evry, MSc, Costello Medical, Cambridge, UK, for medical writing and editorial assistance based on the authors’ input and direction. This study was funded by UCB.
Footnotes
Funding: This article was based on the NCT02963506; NCT03355573 trials which were sponsored by UCB. Support for third‑party medical writing assistance for this article, provided by Hugh Osborne, PhD, and James Evry, MSc, Costello Medical, Cambridge, UK was funded by UCB in accordance with Good Publication Practice (GPP) 2022 guidelines (https://www.ismpp.org/gpp-2022).
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent for publication: Not applicable.
Ethics approval: BE AGILE and its OLE were conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Guidance for Good Clinical Practice. Ethical approval was obtained from the relevant institutional review boards at participating sites. All patients provided written informed consent in accordance with local requirements. All the results presented in this article are in aggregate form, and no personally identifiable information was used for this study.
Data availability free text: Underlying data from this manuscript may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after study completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, trial protocols, annotated case report forms, statistical analysis plans, dataset specifications, and clinical study reports. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password-protected portal.
Data availability statement
Data are available upon reasonable request.
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Data Availability Statement
Data are available upon reasonable request.