Article Text
PDF
Abstract
Objectives To assess impact of bimekizumab treatment on patient-reported outcomes and health-related quality of life (HRQoL) in patients with active psoriatic arthritis (PsA), using 16-week data from two phase 3 studies.
Methods BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug (bDMARD)-naïve) and BE COMPLETE (NCT03896581; tumour necrosis factor inhibitor inadequate response/intolerance (TNFi-IR)) are phase 3 studies of subcutaneous bimekizumab 160 mg Q4W; both were double-blind and placebo-controlled to 16 weeks. Patients were randomised 3:2:1 to bimekizumab, placebo or reference (subcutaneous adalimumab 40 mg Q2W) in BE OPTIMAL; 2:1 to bimekizumab or placebo in BE COMPLETE. Patient-reported outcomes for pain, fatigue, physical function and HRQoL are reported to week 16 using pooled and individual study data for bimekizumab and placebo patients.
Results 1073/1112 (96.5%) patients completed week 16 (bimekizumab: 677/698 [97.0%]; placebo: 396/414 [95.7%]). Bimekizumab-treated patients achieved rapid improvements vs placebo in pain, fatigue, physical function and HRQoL by week 4, after a single dose. Improvements continued to week 16 for all patient-reported outcomes, including Pain Visual Analogue Scale (VAS; mean (95% CI) change from baseline: bimekizumab: –25.2 [–27.2, –23.1]; placebo: –5.7 [–8.2, –3.3]) and FACIT-Fatigue (bimekizumab: 4.5 [3.9, 5.1]; placebo: 1.1 [0.3, 2.0]); both nominal p<0.001. Greater proportions of bimekizumab-treated patients achieved minimal clinically important differences for patient-reported symptoms vs placebo, including FACIT-Fatigue (bimekizumab: 53.1%; placebo: 36.3%) and HAQ-DI (bimekizumab: 53.0%; placebo: 28.7%); both nominal p<0.001.
Conclusion Bimekizumab treatment demonstrated rapid and greater improvements in patient-reported pain, fatigue, physical function and HRQoL to week 16 vs placebo in bDMARD-naïve and TNFi-IR patients.
Trial registration number ClinicalTrials.gov: NCT03895203; NCT03896581.
- arthritis, psoriatic
- biological therapy
- patient reported outcome measures
- health-related quality of life
Data availability statement
Data are available upon reasonable request. Data from this manuscript may be requested by qualified researchers 6 months after product approval in the USA and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymised individual patient data and redacted study documents, which may include raw datasets, analysis-ready datasets, study protocols, blank case report forms, 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 prespecified time, typically 12 months, on a password-protected portal.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
- arthritis, psoriatic
- biological therapy
- patient reported outcome measures
- health-related quality of life
WHAT IS ALREADY KNOWN ON THIS TOPIC
Some patients with psoriatic arthritis (PsA) may not respond to treatment or may experience persistent symptoms, such as pain and fatigue, and suboptimal health-related quality of life; additional treatment options with rapid and sustained efficacy across these symptoms are required.
Primary efficacy and safety data from the first 16/24 weeks of the phase 3 BE OPTIMAL and BE COMPLETE studies of bimekizumab (BKZ) treatment in PsA demonstrated the therapeutic benefit of inhibition of interleukin (IL)-17F in addition to IL-17A when treating patients with PsA.
WHAT THIS STUDY ADDS
This post hoc study of patients who were biologic disease-modifying antirheumatic drug (bDMARD)-naïve (BE OPTIMAL) or had tumour necrosis factor inhibitor inadequate response/intolerance (TNFi-IR; BE COMPLETE) showed that treatment with BKZ resulted in rapid and distinct improvements vs placebo in patient-reported pain, fatigue and health-related quality of life as early as week 4 and up to week 16.
The use of pooled data and a breadth of generic and PsA-specific or arthritis-specific patient-reported outcome measures provides a robust analysis of a larger group of patients across the PsA spectrum during the initial treatment period.
HOW THIS STUDY MIGHT AFFECT RESEARCH PRACTICE OR POLICY
The results presented here demonstrate rapid, clinically meaningful improvements in patient-reported pain, fatigue and health-related quality of life with BKZ treatment among patients with PsA who were bDMARD-naïve or TNFi-IR, providing evidence for the efficacy of BKZ across clinical and patient-reported symptoms of PsA.
Introduction
Psoriatic arthritis (PsA) is a chronic, inflammatory, musculoskeletal disease that develops in approximately 30% of patients with psoriasis.1–4 Patients with PsA report pain as one of the symptoms causing the greatest disturbance to their lives, alongside skin manifestations, joint stiffness and swelling, and fatigue. These substantially impact patients’ quality of life, reduce their ability to engage in activities of daily living and have a profound effect on their social and emotional well-being.2 3
The European Alliance of Associations for Rheumatology (EULAR) treatment recommendations for PsA state that the main goal is to maximise quality of life through control of symptoms, prevention of structural damage and normalisation of physical and social function.5 Patient-reported symptom measures are a key component of assessing treatments for a condition with heterogeneous clinical presentation such as PsA.6 They are used in clinical trials and routine clinical practice to comprehensively evaluate features of the disease, including joint and skin symptoms and disease impact.6
Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. In patients with active PsA, improvements in patient-reported symptoms up to 3 years in the phase 2b study BE ACTIVE and its open-label extension (OLE) have been reported.7 In the phase 3 studies, BE OPTIMAL (biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients) and BE COMPLETE (patients with inadequate response or intolerance to tumour necrosis factor inhibitor (TNFi-IR)), bimekizumab has also demonstrated rapid and clinically meaningful improvements in joint and skin outcomes (including ≥50% improvement from baseline in American College of Rheumatology response criteria (ACR50) and complete skin clearance, assessed using 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100)) to 16 weeks vs placebo.8 9 The safety profile was consistent with observations in psoriasis and axial spondyloarthritis.10–15
Top-line patient-reported outcome data were reported in the primary manuscripts, including change from baseline (CfB) to week 16 in the Physical Component Summary score of the Short Form 36-item Health Survey (SF-36 PCS), Health Assessment Questionnaire-Disability Index (HAQ-DI), Psoriatic Arthritis Impact of Disease 12-item questionnaire (PsAID-12), Patient’s Assessment of Arthritis Pain (PtAAP) and Functional Assessment of Chronic Illness Therapy-Fatigue subscale (FACIT-Fatigue). This post hoc analysis reports the impact of subcutaneous bimekizumab on the patient-reported symptoms and health-related quality of life (HRQoL) of patients with active PsA up to 16 weeks, using a broad range of clinically relevant patient-reported symptom measures in a pooled population of patients who were bDMARD-naïve or TNFi-IR.
Methods
Study design and participants
Full details of the methods of the BE OPTIMAL (NCT03895203) and BE COMPLETE (NCT03896581) studies have been reported in the primary manuscripts.8 9 To summarise, BE OPTIMAL and BE COMPLETE were two phase 3, multicentre trials assessing bimekizumab in bDMARD-naïve (no current or prior exposure to any biologics for the treatment of PsA or psoriasis) or TNFi-IR (history of inadequate response or intolerance to treatment with one or two tumour necrosis factor inhibitors for psoriasis or PsA) patients with active PsA, respectively.
Both studies were double-blind and placebo-controlled to 16 weeks. Patients in BE OPTIMAL were randomised 3:2:1 (stratified by region and bone erosion [0, ≥1]) to receive either subcutaneous bimekizumab 160 mg every 4 weeks (Q4W), placebo or reference (subcutaneous adalimumab 40 mg Q2W, included as a reference to standard of care; data not reported here). At week 16, patients receiving placebo switched to receive bimekizumab 160 mg Q4W. Those who had been receiving bimekizumab or adalimumab continued their dosing until week 52. Patients in BE COMPLETE were randomised 2:1 to subcutaneous bimekizumab 160 mg Q4W or placebo. Patients who completed week 52 of BE OPTIMAL or week 16 of BE COMPLETE were eligible to enter an open-label extension, BE VITAL (NCT04009499; results not reported here), in which all patients received bimekizumab 160 mg Q4W.
Key inclusion and exclusion criteria have been reported previously.8 9 For both studies, eligible patients were ≥18 years and had a documented diagnosis of adult-onset PsA meeting the Classification Criteria for Psoriatic Arthritis for ≥6 months prior to screening. Patients had active PsA with a tender joint count (TJC) ≥3 (of 68), swollen joint count (SJC) ≥3 (of 66) and ≥1 active psoriatic lesion and/or a documented psoriasis history.
Both studies were conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation guidance for Good Clinical Practice.
In this post hoc analysis, we report pooled results for patients receiving bimekizumab or placebo during the placebo-controlled phase to week 16 in BE OPTIMAL and BE COMPLETE.
Patient-reported outcome measures
Patient-reported symptoms are reported to week 16 and include measures of pain and fatigue, physical function and HRQoL. Patient-reported outcome measures were completed electronically prior to any interventions or dosing on that day.
Arthritis pain was assessed using the PtAAP 100 mm Visual Analogue Scale (VAS), referred to as Pain VAS hereafter, which is part of the ACR core set of measures in arthritis; the score ranges from 0–100, where 0 is ‘no pain’ and 100 is ‘most severe pain’.16 Fatigue was assessed using the 13-item FACIT-Fatigue, which has been validated in patients with PsA to assess self-reported fatigue and its impact on daily activities and function.17 The FACIT-Fatigue subscale score ranges from 0–52, with higher scores representing lower levels of fatigue.
Physical function was assessed using the HAQ-DI, a 20-item questionnaire measuring specific daily living activities, including dressing, rising, eating and walking, which also accounts for any aids or devices used. The HAQ-DI score ranges from 0 to 3, with lower HAQ-DI scores indicating better physical function.18
HRQoL was assessed using both disease-specific measures, the PsAID-12 and Psoriatic Arthritis Quality of Life (PsAQoL) questionnaires, and generic measures, the EQ-5D-3L and SF-36.
The PsAID-12 questionnaire assesses the impact of PsA on 12 physical, social and psychological domains, each by use of a single question with a 0–10 numerical rating scale. The total score is calculated by multiplying the domain scores by a patient-derived weighting factor to reflect the importance and relevance of each question to patients, before summing the domain scores; higher total scores indicate worse status.19 PsAID-12 total scores are reported here; full results, including analyses of single-item domain scores, have been reported in a separate, dedicated manuscript.20
The PsAQoL questionnaire includes 20 items answered as ‘true’ or ‘not true’; the PsAQoL score ranges from 0–20, with higher scores indicating worse HRQoL.21
For the EQ-5D-3L VAS, the patient rates their health status on a scale of 0–100 (0 and 100 representing the worst and best imaginable health status, respectively).22 For the EQ-5D-3L Utility (UK tariff), the patient assesses their health across five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). This is used to generate a health state profile ranging from less than 0 (0 is a health state equivalent to death; negative values are valued as worse than death) to 1 (perfect health).22
The SF-36 is a 36-item HRQoL instrument that groups items into eight domains (physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role and mental health). Physical and Mental Component Summary scores (PCS, MCS) are calculated from the eight domains. Component and domain scores are standardised, with a mean of 50 and SD of 10 in the US population; higher scores indicate better HRQoL.23
Results from planned analyses of CfB in patient-reported symptoms at week 16 are reported, along with post hoc responder analyses.
Schedule of assessments
Patient-reported symptoms in BE OPTIMAL were completed electronically at baseline and weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 44 and 52 (HAQ-DI and Pain VAS), or baseline followed by weeks 4, 16, 24, 36 and 52 (PsAQoL, PsAID-12, FACIT-Fatigue, SF-36 and EQ-5D-3L). Results of assessments up to week 16 are reported here.
Patient-reported symptoms in BE COMPLETE were completed electronically at baseline and weeks 4, 8, 12 and 16 (HAQ-DI and Pain VAS) or baseline followed by weeks 4, 12 and 16 (PsAQoL, PsAID-12, FACIT-Fatigue, SF-36 and EQ-5D-3L).
Statistical analysis
Statistical powering and sample size determination are reported in the primary manuscripts.8 9 Both studies were powered to compare bimekizumab with placebo for the primary endpoint of ACR50 response and key secondary endpoints at week 16; the primary endpoint and secondary endpoints were met in both studies.8 9 BE OPTIMAL was not powered for statistical comparisons of adalimumab to bimekizumab or placebo. The controlled testing procedure and related p values can be found in the primary manuscripts.8 9 Data for endpoints related to resolution of enthesitis or dactylitis were pooled across BE OPTIMAL and BE COMPLETE at week 16, as pre-specified in the BE OPTIMAL statistical testing hierarchy. All other endpoints in the pooled analysis were not statistically powered for comparison; as a post hoc analysis, all p values reported here were therefore not pre-specified, powered or controlled for multiplicity and should be considered nominal for purposes of interpretation.8 9
All outcomes reported in this manuscript are from the pooled population of both bDMARD-naïve (BE OPTIMAL) and TNFi-IR (BE COMPLETE) patients for common visits. All patients randomised to bimekizumab or placebo were included in the analysis; therefore, results from the BE OPTIMAL reference arm are not included here and are instead presented in the online supplemental file. Results for the individual studies are provided in the online supplemental file.
Supplemental material
Supplemental material
Non-responder imputation (NRI) was used for missing binary variables and multiple imputation (MI) for missing continuous variables. 39 (3.5%) patients did not complete the 16-week double-blind period (placebo: 18 [4.3%]; bimekizumab: 21 [3.0%]); patient dispositions by study are reported elsewhere.8 9 Predictors in the MI model included region and bone erosions for BE OPTIMAL, region and prior TNFi exposure for BE COMPLETE, and region and study ID for the pooled analysis. P values for responder variables were created using logistic regression and p values for continuous variables were created using ANCOVA.
Per the Initiative on Methods, Measurement and Pain Assessment in Clinical Trials recommendations, post hoc analyses of patients who reported improvement in Pain VAS of ≥30% and ≥50% from baseline were carried out, as these are considered clinically important thresholds of ‘moderately important’ and ‘substantial’ improvement, respectively.24 25 The proportions of patients with ≥70% improvement from baseline in Pain VAS are also reported.
FACIT-Fatigue minimal clinically important difference (MCID) was defined as an increase of ≥4 points in patients with a score of ≤48 at baseline.17 HAQ-DI MCID was defined as a decrease of ≥0.35 points from baseline in patients with HAQ-DI ≥0.35 at baseline.26 Normative state was defined as HAQ-DI ≤0.5.27
PsAID-12 clinically meaningful within-patient improvement was defined as a decrease of ≥3 points from baseline in patients with baseline scores ≥3.19 PsAID-12 PASS was defined as achievement of a score of ≤4.
The SF-36 PCS MCID threshold was defined as a ≥5-point increase.
Role of the funding source
UCB contributed to study design, participated in data collection, completed the data analysis and participated in data interpretation. UCB also participated in writing, review and approval of the manuscript. All authors had full access to the data, reviewed and approved the final version, and were responsible for the decision to submit for publication. A medical writing agency, employed by UCB, assisted with manuscript preparation under the authors’ direction.
Results
Patient disposition and baseline characteristics
Across both studies, 1112 patients were randomised to placebo or bimekizumab; 414 to placebo and 698 to bimekizumab. Of those, 1073 (96.5%) completed the 16-week double-blind period (placebo: 396 [95.7%]; bimekizumab: 677 [97.0%]).
Baseline patient demographics and disease characteristics were comparable between treatment groups in the pooled analysis set (table 1). Baseline characteristics for each study are reported in the primary manuscripts; while generally comparable across the studies, BE COMPLETE comprised TNFi-IR patients who were slightly older with longer duration since PsA diagnosis, higher baseline TJC, higher Pain VAS scores and a greater proportion of patients with ≥3% body surface area (BSA) affected by psoriasis compared with bDMARD-naïve patients in BE OPTIMAL.8 9
Pooled baseline patient characteristics, disease activity and patient-reported outcomes from BE OPTIMAL and BE COMPLETE
Patient-reported symptoms
All outcomes reported here are from the pooled population of bDMARD-naïve (BE OPTIMAL) and TNFi-IR (BE COMPLETE) patients; results for the individual studies and BE OPTIMAL adalimumab reference arm are provided in the Supplement (online supplemental tables S2–S5 and figures S2–S8).
Supplemental material
Pain
For patients treated with bimekizumab, numerically greater reductions in Pain VAS score from baseline were observed vs placebo by week 4; these improvements continued to week 16 (p<0.001 at all timepoints; figure 1A). The proportion of responders with ≥30%, ≥50% or≥70% improvement in Pain VAS increased rapidly by week 4 for bimekizumab patients vs placebo (bimekizumab: 305/698 [43.7%], 213/698 [30.5%] and 125/698 [17.9%] vs placebo: 85/414 [20.5%], 42/414 [10.1%] and 20/414 [4.8%]; p<0.001 for all levels of improvement) (figure 1B, online supplemental table S1) and continued to increase to week 16 (bimekizumab: 421/698 [60.3%], 346/698 [49.6%] and 246/698 [35.2%] vs placebo: 105/414 [25.4%], 72/414 [17.4%] and 38/414 [9.2%]; p<0.001 for all levels of improvement). Median time to ≥30% and ≥50% improvement in Pain VAS was 7.9 and 9.1 weeks for bimekizumab-treated patients, respectively (table 2). Median time to ≥70% improvement for both bimekizumab and placebo, along with median time to ≥30% and ≥50% improvement for placebo, were not evaluable, as the number of patients achieving these thresholds to week 16 was too few for analysis.
Pooled study outcomes at week 16
Pain VAS values to week 16 (pooled analysis). Randomised set. Nominal p values reported; analyses were not adjusted for multiplicity. *** denotes nominal p<0.001. Pain VAS score ranges from 0 to 100, higher scores indicate worse status. CfB: change from baseline; MI: multiple imputation; NRI: non-responder imputation; Q4W: every 4 weeks; VAS: Visual Analogue Scale.
Fatigue
Improvements in FACIT-Fatigue score among bimekizumab-treated patients were also observed by week 4: mean (95% CI) CfB was higher in bimekizumab patients vs placebo (bimekizumab: 3.0 [2.5, 3.5], n=698 vs placebo: 1.0 [0.4, 1.7], n=414; p<0.001) (online supplemental table 1); this trend continued to week 16 (bimekizumab: 4.5 [3.9, 5.1] vs placebo: 1.1 [0.3, 2.0]; p<0.001) (figure 2A; table 2). Similarly, of patients with FACIT-Fatigue ≤48 at baseline, the proportion of bimekizumab-treated patients achieving FACIT-Fatigue MCID was higher than placebo at week 4 (bimekizumab: 278/633 [43.9%] vs placebo: 129/380 [33.9%]; p=0.002) (online supplemental table 1) and week 16 (bimekizumab: 336/633 [53.1%] vs placebo: 138/380 [36.3%]; p<0.001) (figure 2B).
FACIT-Fatigue scores to week 16 (pooled analysis). Randomised set. Nominal p values reported; analyses were not adjusted for multiplicity. *** denotes nominal p<0.001; ** denotes nominal p<0.01. FACIT-Fatigue scores range from 0 to 52, higher scores indicate lower levels of fatigue. CfB: change from baseline; FACIT: Functional Assessment of Chronic Illness Therapy; MCID: minimal clinically important difference; MI: multiple imputation; NRI: non-responder imputation; Q4W: every 4 weeks.
Physical function
Patients receiving bimekizumab demonstrated numerically greater improvements in physical function, assessed using mean (95% CI) CfB in HAQ-DI score, compared with placebo by week 4 (bimekizumab: −0.20 [–0.23, –0.17] vs placebo: −0.08 [–0.11, –0.04]; p<0.001) (online supplemental table 1). These improvements continued to week 16 (bimekizumab: −0.30 [–0.34, –0.27] vs placebo: −0.08 [–0.12, –0.04]; p<0.001) (figure 3A; table 2). Similarly, the proportion of bimekizumab-treated patients with HAQ-DI ≥0.35 at baseline achieving HAQ-DI MCID was numerically greater by week 4 vs placebo (bimekizumab: 222/549 [40.4%] vs placebo: 78/331 [23.6%]; p<0.001) and improvements continued to week 16 (bimekizumab: 291/549 [53.0%] vs placebo: 95/331 [28.7%]; p<0.001) (figure 3B; table 2). The proportion of all bimekizumab-treated patients achieving normative value response was numerically greater by week 4 vs placebo (bimekizumab: 346/698 [49.6%] vs placebo: 161/414 [38.9%]; p<0.001) (online supplemental table 1) and patients demonstrated improvement to week 16 (bimekizumab: 398/698 [57.0%] vs placebo: 153/414 [37.0%]; p<0.001) (figure 3C; table 2).
Physical function and HRQoL to week 16 (pooled analysis). Randomised set. Nominal p values reported; analyses were not adjusted for multiplicity. ***denotes nominal p<0.001. HAQ-DI score ranges from 0 to 3, lower scores indicate better physical function. PsAID-12 score ranges from 0 to 10, higher scores indicate worse status. CfB: change from baseline; HAQ-DI: Health Assessment Questionnaire-Disability Index; HRQoL: health-related quality of life; MCID: minimal clinically important difference; MI: multiple imputation; NRI: non-responder imputation; PsAID-12: Psoriatic Arthritis Impact of Disease-12; Q4W: every 4 weeks.
HRQoL
Patients receiving bimekizumab showed numerically greater improvements in PsAID-12 total score vs placebo patients by week 4, demonstrated by greater mean (95% CI) CfB (bimekizumab: –1.3 [–1.4, –1.2] vs placebo: –0.2 [–0.3, 0.0]; p<0.001) (online supplemental table 1); these improvements continued to week 16 (bimekizumab: −2.0 [–2.1, –1.8] vs placebo: −0.5 [–0.7, –0.3]; p<0.001), respectively (figure 3D; table 2). A greater number of bimekizumab-treated patients with a PsAID-12 score of ≥3 at baseline achieved a clinically meaningful response in PsAID-12 total score at week 16 vs placebo: 206/494 (41.7%) vs 25/299 (8.4%), respectively (p<0.001) (figure 3E; table 2).
PsAQoL total score showed rapid numerically greater improvements in bimekizumab-treated patients vs placebo, with a greater mean (95% CI) CfB at week 4 (bimekizumab: −1.4 [–1.7, –1.2] vs placebo: −0.3 [–0.6, 0.0]; p<0.001) (online supplemental table 1). Improvements in PsAQoL scores continued to week 16 on bimekizumab treatment (bimekizumab: −2.1 [–2.5, –1.8] vs placebo: −0.2 [–0.6, 0.2]; p<0.001) (figure 4; table 2).
PsAQoL values to week 16 (pooled analysis). Randomised set. Nominal p values reported; analyses were not adjusted for multiplicity. *** denotes p<0.001. PsAQoL score ranges from 0 to 20, higher scores indicate worse HRQoL. CfB: change from baseline; HRQoL: health-related quality of life; MI: multiple imputation; OC: observed case; PsAQoL: Psoriatic Arthritis Quality of Life; Q4W: every 4 weeks.
In bimekizumab-treated patients, there were numerically greater mean (95% CI) improvements from baseline in EQ-5D-3L VAS values compared with placebo at week 4 (bimekizumab: 6.6 [5.1, 8.2] vs placebo: 0.8 [–1.4, 3.0]; p<0.001) (online supplemental table S1), which continued to improve to week 16 (bimekizumab: 11.5 [9.7, 13.3] vs placebo: 1.7 [–0.7, 4.1]; p<0.001) (table 2). Similar trends were observed for EQ-5D-3L Utility (UK tariff) scores; bimekizumab-treated patients demonstrated numerically greater mean (95% CI) improvements from baseline compared with placebo at week 4 (bimekizumab: 0.10 [0.08, 0.12] vs placebo: 0.03 [0.01, 0.05]) (online supplemental table S1) and week 16 (bimekizumab: 0.16 [0.14, 0.17] vs placebo: 0.03 [0.01, 0.06]) (table 2).
Greater mean (95% CI) improvements from baseline in SF-36 PCS score were observed as early as week 4 in bimekizumab-treated patients vs placebo (bimekizumab: 4.3 [3.8, 4.8] vs placebo: 1.9 [1.3, 2.6]; p<0.001) (online supplemental table S1), and these improvements continued to week 16 (bimekizumab: 6.7 [6.1, 7.3] vs placebo: 2.1 [1.3, 2.8]; p<0.001) (table 2). Additionally, greater proportions of bimekizumab-treated patients vs placebo achieved SF-36 PCS MCID as early as week 4 (online supplemental table S1) (bimekizumab: 282/698 [40.4%] vs placebo: 115/414 [27.8%]; p<0.001), and this trend continued to week 16 (bimekizumab: 368/698 [52.7%] vs placebo: 129/414 [31.2%]; p<0.001) (table 2).
The high mean (SD) SF-36 MCS scores (indicating better mental health) observed at baseline for both bimekizumab and placebo patients (bimekizumab: 54.4 [9.0]; placebo: 54.7 [9.2]) were maintained to week 16, with very small mean (95% CI) CfB observed at both week 4 (bimekizumab: 0.4 [–0.1, 0.9] vs placebo: –0.8 [–1.5, –0.2]; p=0.003) (online supplemental table S1) and week 16 (bimekizumab: 0.7 [0.1, 1.3] vs placebo: −0.8 [–1.6, –0.1]; p=0.002) (table 2).
Among SF-36 individual domain scores, physical functioning, physical role and bodily pain demonstrated the greatest numerical improvements at week 16 among bimekizumab-treated patients (online supplemental figure S4). Improvements were also seen across the other domains (general health, vitality, social functioning, emotional role and mental health), although to a lesser extent due to high baseline scores, which allowed less room for improvement.
Discussion
This study evaluated the short-term impact of bimekizumab, following first dose of treatment and up to 16 weeks of therapy, on patient-reported pain, fatigue and HRQoL in patients with active PsA who were bDMARD-naïve or TNFi-IR. To week 16, bimekizumab treatment demonstrated numerically greater improvements in patient-reported symptoms compared with placebo, including in the aspects of disease that are most important to patients with PsA.2
At week 4, after a single dose of bimekizumab during either phase 3 study, rapid and numerically greater improvements vs placebo in all patient-reported symptoms were observed in both the pooled population and in individual bDMARD-naïve and TNFi-IR patient populations. These improvements continued to week 16 and are consistent with published improvements in clinical and composite measures of overall efficacy and tolerability demonstrated by bimekizumab in patients with PsA.8 9
Patients with PsA have identified pain and fatigue as being notably burdensome features of the disease, so it is important that new treatments address these aspects of patients’ disease.2 Bimekizumab-treated patients demonstrated clinically relevant improvements in both pain and fatigue to week 16, as assessed by ≥30/50/70% improvement in Pain VAS, and FACIT-Fatigue MCID. Achievement of these outcomes was observed rapidly after treatment was initiated, with 53.9% bimekizumab-treated patients achieving ≥30% improvement in Pain VAS, considered a palpable improvement, by 8 weeks of treatment.24 By week 16, 49.6% bimekizumab-treated patients had achieved ≥50% improvement in Pain VAS. These results demonstrate considerable efficacy in this important symptom. These trends in pain and fatigue response were further supported by improvements in the SF-36 bodily pain and vitality domain scores at week 16 compared with baseline.
The HAQ-DI questionnaire has been provisionally endorsed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) as a measure of physical function in PsA trials.28 Greater improvements with bimekizumab treatment compared with placebo were shown in HAQ-DI outcomes, suggesting that bimekizumab treatment is associated with a better ability to undertake normal activities of daily living.3 These results are further supported by the improvements exhibited by bimekizumab-treated patients in individual items of the PsAQoL, a validated quality of life instrument specific to PsA.21
Mean SF-36 scores also improved to a greater extent in bimekizumab-treated vs placebo patients. The high mean SF-36 MCS scores at baseline, indicating good mental well-being, may be in part due to the exclusion criteria for BE OPTIMAL and BE COMPLETE, which excluded patients with suicidal ideation, positive suicide behaviour or severe depression.8 9 Mean SF-36 MCS scores remained high throughout the duration of the studies, indicating mental well-being was not negatively impacted. The SF-36 PCS results support the findings from HAQ-DI outcome measures, that bimekizumab is associated with improved ability to undergo activities of daily living.
Evaluations of HRQoL using PsAID-12 and PsAQoL, as well as EQ-5D-3L and SF-36, demonstrated a reduced impact of PsA on HRQoL in patients receiving bimekizumab, beyond clinical features and across all facets of HRQoL. Full PsAID-12 results, including analyses of individual domain scores, have been reported in a separate, dedicated manuscript.20
Strengths
A key strength of this post hoc analysis is the inclusion of a large, pooled patient population of both bDMARD-naïve and TNFi-IR patients, making these results relevant to patients across the PsA spectrum. The similarity of responses between bDMARD-naïve and TNFi-IR patients suggests that these data can validly be pooled to increase the sample size despite minor differences in baseline characteristics. Further, as many PsA trials enrol both bDMARD-naïve and TNFi-IR patient populations, pooling data from studies enrolling these patient populations separately puts these results into context with other trials in PsA.
This study comprised a breadth of generic and PsA-specific or arthritis-specific patient-reported outcome measures, ensuring comprehensive capture of concepts that are important to patients with PsA, as reflected in the PsA Core Domain Set that lists pain, fatigue, physical function and HRQoL as core domains to be captured in clinical studies.29 As many of the included outcomes were reported at 4-week intervals, improvements were observed as early as week 4—and as early as week 2 where assessed in BE OPTIMAL—and consistent improvements were observed over several timepoints to week 16.
Limitations
In the context of a chronic disease requiring lifelong treatment, the findings from this 16-week analysis of bimekizumab vs placebo in two randomised controlled trials will require confirmation with longer-term data to assess whether these improvements are sustained. Future publications will report further patient-reported symptom and HRQoL results up to 1 year and beyond.
Additionally, baseline demographics and disease characteristics, such as weight and gender, have been reported to impact treatment efficacy30 31; it is therefore important to assess this in the context of bimekizumab, to ensure consistent efficacy across all subgroups of patients. As this is beyond the scope of this manuscript, such subgroup analyses will be explored in future publications. Furthermore, although predictive modelling was not undertaken in the current study, analysing predictors of response at week 16 and up to 1 year could be an avenue for future research. Future work could also seek to identify the role of pain as an indicator of inflammation through evaluating the association between improvements in pain and SJC.
Conclusions
Overall, treatment of active PsA with subcutaneous bimekizumab during two phase 3 studies demonstrated rapid improvements in the patient-reported symptoms and HRQoL of bDMARD-naïve and TNFi-IR patients up to 16 weeks. The patient-reported improvements in pain, fatigue, HRQoL and impact of disease in this study provide further evidence of the efficacy of bimekizumab in patients with PsA alongside improvements in clinical measures previously reported8 9; future studies will evaluate these outcomes using longer-term data.10 11
Data availability statement
Data are available upon reasonable request. Data from this manuscript may be requested by qualified researchers 6 months after product approval in the USA and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymised individual patient data and redacted study documents, which may include raw datasets, analysis-ready datasets, study protocols, blank case report forms, 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 prespecified time, typically 12 months, on a password-protected portal.
Ethics statements
Patient consent for publication
Ethics approval
BE OPTIMAL and BE COMPLETE 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, and all patients provided written informed consent in accordance with local requirements. Participants gave informed consent to participate in the study before taking part.
Acknowledgments
The authors thank the patients, the investigators and their teams who took part in this study. The authors also acknowledge Heather Edens, PhD, UCB, Smyrna, GA, USA, for publication coordination and editorial assistance, and Emma Lockyer, MChem, Lucy Berry, MBBS, both of Costello Medical, Cambridge, UK, and Sona Popat, BA, and Aditi Mehta, MSc, both of Costello Medical, London, UK, for medical writing and editorial assistance based on the authors’ input and direction. This research was funded by UCB.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors Substantial contributions to study conception and design: MEH, PJM, JFM, WT, NG, BI, JC, JL, VT and DDG; substantial contributions to analysis and interpretation of the data: MEH, PJM, JFM, WT, NG, BI, JC, JL, VT and DDG; drafting the article or reviewing it critically for important intellectual content: MEH, PJM, JFM, WT, NG, BI, JC, JL, VT and DDG; final approval of the version of the article to be published: MEH, PJM, JFM, WT, NG, BI, JC, JL, VT and DDG; manuscript guarantor: JL.
Funding This study was sponsored by UCB. Support for third-party writing assistance for this article, provided by Emma Lockyer, MChem, Lucy Berry, MBBS, both of Costello Medical, Cambridge, UK, and Sona Popat, BA, and Aditi Mehta, MSc, both of Costello Medical, London, UK, was funded by UCB in accordance with Good Publication Practice (GPP 2022) guidelines.
Competing interests MEH: Advisory board member and consultant for AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer and UCB. PJM: Research grants from AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB; consultancy fees from AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma and UCB; speakers’ bureau for AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB. JFM: Affiliated with Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA at time of analysis; currently affiliated with UT Southwestern Medical Center, Dallas, TX, USA; consultant and/or investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Pfizer, Novartis, Regeneron, Sanofi, Sun Pharma and UCB. WT: Research grants, consulting fees, speaking fees, and/or honoraria from AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ovo Pharma, Pfizer and UCB. NG, JC, JL: Employees and shareholders of UCB. BI: Employee of UCB; shareholder of AbbVie, GSK and UCB. VT: Employee of UCB. DDG: Consultant and/or received grant support from Abbvie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.