Abstract
Objective To assess the longer-term effect of bimekizumab up to 1 year on patient-reported symptoms, health-related quality of life (HRQOL), and work productivity in patients with active PsA who were biologic disease-modifying antirheumatic drug (bDMARD)-naïve or had inadequate response/intolerance to tumor necrosis factor inhibitors (TNFi-IR).
Methods BE OPTIMAL (ClinicalTrials.gov: NCT03895203; bDMARD-naïve patients) and BE COMPLETE (NCT03896581; TNFi-IR patients) are phase III studies of subcutaneous bimekizumab 160 mg every 4 weeks. Both studies were double-blind and placebo-controlled to 16 weeks. Patients who completed week 52 of BE OPTIMAL or week 16 of BE COMPLETE were eligible for the open-label extension, BE VITAL (NCT04009499), during which all patients received bimekizumab. Patient-reported pain, fatigue, physical function, HRQOL, and work productivity are reported to week 52 or 40 (52/40) using individual study data for bimekizumab and placebo treatment arms.
Results Bimekizumab-randomized patients demonstrated sustained mean improvements from baseline in patient-reported outcomes to week 52/40, including pain (visual analog scale [0-100 mm]: bDMARD-naïve −30.5; TNFi-IR −31.8), fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue scale [0-52]: bDMARD-naïve 5.3; TNFi-IR 6.0), physical function (Health Assessment Questionnaire–Disability Index [0-3]: bDMARD-naïve −0.34; TNFi-IR −0.39), and HRQOL (36-item Short Form Health Survey, physical component summary: bDMARD-naïve 8.1; TNFi-IR 8.4); placebo patients who switched to bimekizumab at week 16 demonstrated comparable levels of improvement from week 16 to week 52/40. Improvements in overall work impairment were sustained among bimekizumab-randomized patients to week 52. Similar trends were observed for absenteeism, presenteeism, and activity impairment.
Conclusion Bimekizumab treatment resulted in sustained improvements in patient-reported symptoms, HRQOL, and work productivity up to 1 year in bDMARD-naïve and TNFi-IR patients with active PsA.
Visual Plain Language Summary
Psoriatic arthritis (PsA) is a chronic, inflammatory disease occurring in up to 30% of patients with psoriasis. It can present as skin manifestations, joint swelling, dactylitis, enthesitis, and axial disease, and may cause irreversible structural damage.1-4 As well as these clinical features, patients with PsA often experience severe functional impairment and physical health effects, including pain and fatigue.2 These disease manifestations negatively affect health-related quality of life (HRQOL) and productivity in the workplace and at home,2-4 contributing to higher rates of unemployment and sickness absence among patients with PsA compared with the general population.5-7
The importance of assessing the effect of PsA on HRQOL from a patient perspective has been acknowledged by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) working group, as evidenced by the inclusion of pain and fatigue in the PsA Core Domain Set.8 Further, recommendations published by the European Alliance of Associations for Rheumatology (EULAR) for the management of PsA with pharmacological therapies include maximizing HRQOL as a main treatment goal for patients.9 As patients who have received treatment can often experience residual symptoms, including joint and skin disease, pain, fatigue, and disability,10 it is necessary to assess the long-term outcomes of new therapies, including clinical response and control of the effects of disease on patients’ lives, as well as physician-assessed clinical symptoms.
Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. Bimekizumab has demonstrated rapid and clinical improvements in joint and skin efficacy outcomes to 52 weeks, with high levels of response observed among patients with active PsA who were biologic disease-modifying antirheumatic drug (bDMARD)-naïve or had inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR).11,12 Bimekizumab has also demonstrated rapid and clinically meaningful improvements in patient-reported outcomes (PROs) and HRQOL outcomes to 16 weeks vs placebo.13
The objective of this study was to assess the longer-term effect of bimekizumab treatment up to 1 year on PROs, HRQOL, and, for the first time, work productivity in patients with active PsA who were bDMARD-naïve or TNFi-IR.
METHODS
Study design and participants. Full methodological details of BE OPTIMAL (ClinicalTrials.gov: NCT03895203) and BE COMPLETE (NCT03896581) are reported in the primary manuscripts, including key inclusion and exclusion criteria.14,15 In brief, both were phase III multicenter trials, double-blind and placebo-controlled to 16 weeks, assessing the efficacy and safety of bimekizumab in patients with active PsA who were bDMARD-naïve or TNFi-IR.
Patients in BE OPTIMAL were randomized 3:2:1 to receive subcutaneous (SC) bimekizumab 160 mg every 4 weeks (Q4W), placebo, or the reference biologic (SC adalimumab [ADA] 40 mg Q2W). The reference arm was included to assess the risk-benefit profile of bimekizumab against a commonly used standard of care treatment. At week 16, patients receiving placebo switched to receive bimekizumab (placebo/bimekizumab group). Those who were randomized to bimekizumab or ADA continued their dosing until week 52 (Supplementary Figure S1, available with the online version of this article). Patients in BE COMPLETE were randomized 2:1 to SC bimekizumab 160 mg Q4W or placebo (Supplementary Figure S1). Patients who completed week 52 of BE OPTIMAL or week 16 of BE COMPLETE were eligible to enter BE VITAL (open-label extension; NCT04009499), in which all patients received bimekizumab (Supplementary Figure S1). Data are reported here to 52 weeks.
PRO measures. Change from baseline (CFB) and responders in patient-reported symptoms, including pain and fatigue, physical function, HRQOL, and work productivity, are reported.
Pain was assessed using the patient’s assessment of arthritis pain on a 100-mm visual analog scale (pain VAS), which ranges from 0 (no pain) to 100 (most severe pain).16 Post hoc analyses of patients who reported clinically important reductions in pain VAS ≥ 30% (moderate improvement) and ≥ 50% (substantial improvement) were carried out.17,18 Additionally, the proportions of patients with ≥ 70% improvement in pain VAS are reported.
Fatigue was assessed using the 13-item Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale (0-52, with lower scores representing higher levels of fatigue).19 FACIT-Fatigue minimal clinically important difference (MCID) was defined as a ≥ 4-point increase in patients with a baseline score ≤ 48.19
Physical functioning was assessed using the Health Assessment Questionnaire–Disability Index (HAQ-DI), a 20-item questionnaire measuring the level of difficulty patients experience with activities across 8 categories, including dressing, rising, eating, and walking. The score ranges from 0 to 3, with lower scores indicating better physical function.20 HAQ-DI MCID was defined as a ≥ 0.35-point decrease from baseline in patients with baseline HAQ-DI ≥ 0.35.21 Normative state was defined as HAQ-DI ≤ 0.5.22
HRQOL was assessed using a combination of disease- and nondisease-specific measures. The 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) assesses the effect of PsA on 12 physical, social, and psychological domains. Single-item domain and total scores range from 0 to 10; higher total scores indicate worse status. Detailed PsAID-12 results to 1 year, including responder analyses, have been reported in full elsewhere.23
The PsA-specific QOL (PsAQOL) questionnaire includes 20 items, giving a total score on a 0-20 scale, with higher scores indicating worse HRQOL.
The 6-item Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questionnaire assesses the severity of subjective symptoms—including fatigue; peripheral arthritis; neck, back, and hip pain; and morning stiffness and duration—on a 0-10 scale. Although originally designed for axial spondyloarthritis (axSpA), the BASDAI questionnaire has been found to correlate with overall disease activity in PsA.24
The 36-item Short Form Health Survey (SF-36; version 2, standard recall) is a generic HRQOL instrument. Items are distributed across 8 subscales, reported as individual scores. In addition, the physical component summary (PCS) and mental component summary (MCS) scores were calculated. Norm-based T-scores, standardized by setting the general US population to a mean score of 50 and an SD of 10, are presented here.25 Higher scores indicate a better HRQOL. As per the user manual, the MCID thresholds for SF-36 PCS and MCS are 3.8-point and 4.6-point increases, respectively.25 However, a more stringent approach was taken in the current manuscript, and the MCID threshold for both component summaries was defined as a ≥ 5-point increase.
For the EQ-5D-5L VAS, the patient rates their health status on a 0-100 scale (0 and 100 representing the worst and best imaginable health status, respectively). For the EQ-5D-3L utility (UK tariff), the patient assesses their health across 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). This is used to generate a health state profile ranging from < 0 (0 is a health state equivalent to death; negative values are valued as worse than death) to 1 (perfect health).26,27
Work productivity was assessed using the Work Productivity and Activity Impairment–Specific Health Problem (WPAI-SHP) questionnaire (v2.0), adapted for PsA.28 The WPAI-SHP consists of 6 questions, of which 5 are regrouped into 4 subdomains. The subdomains assessed in all employed patients include work time missed (absenteeism), impairment while working (presenteeism), and overall work impairment (sum of absenteeism and presenteeism). Activity impairment attributable to PsA was assessed in all patients. Scores are expressed as percentages, where higher numbers indicate greater impairment and lower productivity; improvement is reported as absolute percentage reduction from baseline. The proportion of patients who gained employment was assessed in patients who were unemployed at baseline.
The schedule of assessments is presented in Supplementary Table S1 (available with the online version of this article).
Statistical analysis. Statistical powering and sample size determination are reported in the primary manuscripts.14,15 Data reported here are beyond week 16 and include exploratory endpoints.
Both studies were powered to compare bimekizumab with placebo at week 16 for the primary endpoint, American College of Rheumatology (ACR) response criteria ≥ 50% improvement, and key secondary endpoints. Nonresponder imputation (NRI) was used for missing binary variables, and multiple imputation (MI) for missing continuous variables. For efficacy data, 95% CI are reported.
BE OPTIMAL was not powered for statistical comparisons of ADA to bimekizumab or placebo; results for patients randomized to ADA are provided in Supplementary Tables S2-4 (available with the online version of this article).
RESULTS
Patient disposition and baseline characteristics. Of the 852 bDMARD-naïve patients randomized in BE OPTIMAL (281 placebo, 431 bimekizumab, and 140 ADA reference arm), 770 (90.4%) patients completed week 52, including 9 patients not on randomized treatment.
Of the 400 TNFi-IR patients randomized in BE COMPLETE (133 placebo, 267 bimekizumab), 388 (97%) patients completed week 16 and 377 (94.3%) entered the open-label extension (BE VITAL). In total, 360 (90%) and 347 (86.8%) patients remained in the study at weeks 40 and 52, respectively, including 4 patients at each timepoint not on randomized treatment.
Baseline patient demographics and clinical disease characteristics were reported in the primary manuscripts (Supplementary Table S2, available with the online version of this article).14,15
In general, patient-reported baseline disease characteristics were comparable across studies and treatment arms. Pain VAS and WPAI-SHP subdomain values were numerically higher among the TNFi-IR population at baseline compared with the bDMARD-naïve population (Table 1).
Individual study outcomes at week 52/40.
PROs.
• Pain. Reductions from baseline in pain VAS at week 16 were sustained or continued to improve to week 52 for bimekizumab-randomized bDMARD-naïve and TNFi-IR patients; those who switched from placebo to bimekizumab at week 16 demonstrated similar reductions in pain VAS by week 52 (Figure 1A).
(A) Pain VAS CfB (MI) and (B) improvements of ≥ 30/50/70% in pain VAS (NRI). Randomized set. Pain VAS ranges from 0 (no pain) to 100 (most severe pain). Improvements of 30%, 50%, and 70% (pain VAS 30/50/70) are considered clinically important improvements in patient-reported pain.16-18 bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; CfB: change from baseline; MI: multiple imputation; NRI: nonresponder imputation; PBO: placebo; Q4W: every 4 weeks; TNFi-IR: inadequate response or intolerance to tumor necrosis factor inhibitor; VAS: visual analog scale.
For bimekizumab-randomized patients, the proportions of responders reporting a meaningful improvement in pain (≥ 50% improvement from baseline) at week 16 were sustained or continued to improve to week 52 (bDMARD-naïve: 243/431 [56.4%]; TNFi-IR: 152/267 [56.9%]). For placebo/bimekizumab switchers, the proportion of responders improved to week 52 (bDMARD-naïve: 158/281 [56.2%]; TNFi-IR: 56/133 [42.1%]). Similar trends were seen for ≥ 30% and ≥ 70% improvements in pain VAS (Figure 1B).
• Fatigue. Among bimekizumab-randomized patients, clinically meaningful improvements in fatigue at week 16 were sustained up to 1 year among both bDMARD-naïve and TNFi-IR patients. For bDMARD-naïve placebo/bimekizumab switchers, similar improvements in fatigue were reported at week 52 to bimekizumab-randomized patients; for TNFi-IR placebo patients who switched to bimekizumab at week 16, mean fatigue CFB was nearing that seen in bimekizumab-randomized patients at week 40 (Figure 2A).
(A) FACIT-Fatigue CfB (MI) and (B) FACIT-Fatigue MCID (increase from baseline ≥ 4a; NRI). Randomized set. FACIT-Fatigue score ranges from 0 to 52, with 52 being the best possible score. For BE COMPLETE, FACIT-Fatigue values were not collected at week 52, only collected to week 40. a FACIT-Fatigue MCID defined as score increase from baseline ≥ 4 in patients with FACIT-Fatigue ≤ 48 at baseline. bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; CfB: change from baseline; FACIT-Fatigue: Functional Assessment of Chronic Illness Therapy–Fatigue; MCID: minimal clinically important difference; MI: multiple imputation; NRI: nonresponder imputation; PBO: placebo; Q4W: every 4 weeks; TNFi-IR: inadequate response or intolerance to tumor necrosis factor inhibitor.
Similarly, the proportion of bimekizumab-randomized patients attaining FACIT-Fatigue MCID at week 16 was sustained or improved through 1 year (bDMARD-naïve: 207/384 [53.9%] at week 52; TNFi-IR: 146/250 [58.4%] at week 40). Among bDMARD-naïve patients, the proportion of placebo/bimekizumab patients attaining FACIT-Fatigue MCID at week 16 improved to a similar level as bimekizumab-randomized patients by week 52 (139/259 [53.7%]); attainment also improved among TNFi-IR patients by week 40 (54/121 [44.6%]; Figure 2B).
• Physical function. Improvements in physical functioning with bimekizumab treatment observed at week 16 were sustained or improved up to week 52 in both the bDMARD-naïve and TNFi-IR populations when assessed using mean CFB in HAQ-DI score. For placebo/bimekizumab switchers, similar CFB in HAQ-DI scores to bimekizumab-randomized patients were reported by week 52 in both populations (Figure 3A).
(A) HAQ-DI CfB (MI), (B) HAQ-DI MCID (decrease ≥ 0.35, HAQ-DI ≥ 0.35 at baseline; NRI), and (C) HAQ-DI normative value responders (HAQ-DI ≤ 0.5; NRI). Randomized set. bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; CfB: change from baseline; HAQ-DI: Health Assessment Questionnaire–Disability Index; MCID: minimal clinically important difference; MI: multiple imputation; NRI: nonresponder imputation; PBO: placebo; Q4W: every 4 weeks; TNFi-IR: inadequate response or intolerance to tumor necrosis factor inhibitor.
An analogous trend was seen in the proportion of patients attaining HAQ-DI MCID (Figure 3B) and the proportion of patients reporting HAQ-DI normative value response (Figure 3C). Bimekizumab-randomized patients from both the bDMARD-naïve and TNFi-IR populations sustained improvements to week 52, and a similar proportion of placebo/bimekizumab switchers attained HAQ-DI MCID (Figure 3B) and normative value response (Figure 3C) by week 52.
• HRQOL. Improvements in mean SF-36 PCS scores reported at week 16 with bimekizumab treatment in both bDMARD-naïve and TNFi-IR patients were sustained or continued to improve to 1 year (Table 1). Similar SF-36 PCS scores were reported by 1 year in placebo/bimekizumab switchers. The high baseline SF-36 MCS scores, indicating a mental health level equivalent to or higher than the general US population, were maintained to week 16 for placebo- and bimekizumab-randomized patients in both bDMARD-naïve and TNFi-IR populations; these were further maintained or slightly improved to 1 year. A comparable trend was seen in the proportion of patients attaining SF-36 PCS and MCS MCID (Table 1).
Among SF-36 subscale scores, physical functioning, physical role, and bodily pain demonstrated the greatest improvements among bimekizumab-randomized patients in the bDMARD-naïve and TNFi-IR populations to 1 year (Figure 4; Supplementary Table S5, available with the online version of this article). Improvements were also seen across the other subscales, including general health, vitality, social functioning, emotional role, and mental health by week 52/40 across bimekizumab-randomized patients and placebo/bimekizumab switchers (Figure 4; Supplementary Table S5). In both the bDMARD-naïve and TNFi-IR populations, PsAID-12 total scores were similar at baseline, and scores from week 16 up to 1 year were sustained on bimekizumab treatment or improved following placebo/bimekizumab switch (Table 1).
SF-36 subscale scores at baseline, week 16, and week 52/40 (MI). Randomized set. Higher scores indicated better HRQOL. bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; HRQOL: health-related quality of life; MI: multiple imputation; PBO: placebo; Q4W: every 4 weeks; SF-36: 36-item Short Form Health Survey; TNFi-IR: inadequate response or intolerance to tumor necrosis factor inhibitor.
PsAQOL data collected to week 52 in the bDMARD-naïve population and week 16 in the TNFi-IR population demonstrated a continuous improvement over time across all items (Table 1; Supplementary Figure S2, available with the online version of this article).
BASDAI total and subdomain scores improved to week 52 on bimekizumab treatment, with similar improvements observed among bimekizumab-randomized patients and placebo/bimekizumab switchers in both the bDMARD-naïve and TNFi-IR populations (Table 1). Generally, similar trends were observed for the proportion of patients reporting ≥ 50% improvement in BASDAI by week 52.
Improvements in EQ-5D-3L scores attained by week 16 were sustained to 1 year in bimekizumab-randomized patients, and similar improvements were observed for placebo/bimekizumab switchers in both bDMARD-naïve and TNFi-IR populations (Table 1; Supplementary Figures S3-S4, available with the online version of this article).
• Work productivity. Overall mean reductions in work impairment were numerically greater in bimekizumab-randomized patients than placebo patients at week 16 in both the bDMARD-naïve and TNFi-IR populations (mean [95% CI] CFB: bDMARD-naïve: bimekizumab −16.7 [−20.1 to −13.2], placebo −3.0 [−7.3 to 1.2]; TNFi-IR: bimekizumab −15.6 [−20.3 to −10.8], placebo −3.6 [−10.0 to 2.8]; Figure 5A).
(A) Mean CfB in work productivityd (OC) and (B) proportion of patients unemployed at baseline gaining employmente (OC). Randomized set. a Ability to undertake regular, nonwork-related activities (eg, childcare). b Work time missed due to PsA. c Impairment while working due to PsA. d WPAI-SHP domain scores are expressed as percentages, where higher numbers indicate greater impairment and less productivity. A negative change from baseline score indicates a reduction in the score and therefore an improvement for the patient. e Proportion of patients gaining employment reported in patients without employment at baseline. bDMARD: biologic disease-modifying antirheumatic drug; BKZ: bimekizumab; CfB: change from baseline; OC: observed case; PBO: placebo; PsA: psoriatic arthritis; Q4W: every 4 weeks; TNFi-IR: inadequate response or intolerance to tumor necrosis factor inhibitor; WPAI-SHP: Work Productivity and Activity Impairment Questionnaire–Specific Health Problem (v2.0).
Overall work productivity further improved for bimekizumab-treated patients to week 52/40 (bDMARD-naïve: −21.1 [−25.1 to −17.0]; TNFi-IR: −21.5 [−26.3 to −16.8]). In placebo/bimekizumab switchers, similar improvements to bimekizumab-randomized patients were observed in overall work impairment at week 52/40 (bDMARD-naïve: −14.9 [−19.3 to −10.6]; TNFi-IR: −21.6 [−27.9 to −15.2]; Table 1 and Figure 5A).
Similar trends were observed across the WPAI-SHP domains, including absenteeism, presenteeism, and activity impairment outside of work. Improvements in workplace absenteeism in bimekizumab-randomized patients from baseline to week 16 were numerically greater than placebo patients, but the extent of improvement observed was smaller than the other domains. Further improvements in both populations were observed up to week 52/40 (Figure 5A).
An increase in the proportion of employed patients was observed with bimekizumab treatment in patients unemployed at baseline. Bimekizumab-randomized patients saw improvements to week 16 (bDMARD-naïve: 15/141 [10.6%]; TNFi-IR: 14/95 [14.7%]), which improved further to week 52/40 (bDMARD-naïve: 22/129 [17.1%]; TNFi-IR 14/82 [17.1%]; Figure 5B). Improvements were also seen after the placebo/bimekizumab switch from week 16 (bDMARD-naïve: 7/76 [9.2%]; TNFi-IR: 4/52 [7.7%]) to week 52/40 (bDMARD-naïve: 14/70 [20%]; TNFi-IR: 4/47 [8.5%]).
DISCUSSION
PsA profoundly alters patient QOL, with pain and fatigue identified among the disease impacts of greatest importance to patients.29 Evaluation of patient-reported symptom measures and HRQOL is therefore important when assessing PsA treatments.
Here, we demonstrated that treatment with bimekizumab during 2 phase III studies resulted in sustained improvements in all PROs evaluated to week 52/40, whether capturing symptoms, disease impact, physical functioning, HRQOL, or work productivity. These results complement published data showing clinical efficacy and tolerability of bimekizumab for PsA to 1 year.11,12
Overall, bimekizumab-randomized patients reported substantial improvements across most PRO measures reported up to 1 year, with consistent improvements observed across bDMARD-naïve and TNFi-IR patients.
Notable improvements were observed in pain and fatigue; these were consistent across multiple measures of pain (BASDAI question 2 [neck, back, or hip pain], pain VAS) and fatigue (BASDAI question 1 [fatigue/tiredness], FACIT-Fatigue MCID).
Improvements in physical function, assessed using HAQ-DI, were sustained to week 52 on bimekizumab. Over half of bimekizumab-randomized patients had normalized function at 1 year, suggesting bimekizumab treatment is associated with longer-term improvements such as better ability to undertake activities of daily living.
Improvements were demonstrated across all 8 SF-36 subscales, with the greatest improvements observed in physical functioning, physical role, and bodily pain, followed by general health and vitality. Mean SF-36 PCS scores in the bDMARD-naïve and TNFi-IR populations both showed substantial improvements among bimekizumab-randomized patients by 1 year. Mean baseline SF-36 MCS scores indicated normal psychological function at baseline; this was likely a result of the BE OPTIMAL and BE COMPLETE exclusion criteria.14,15 Notably, these scores remained stable to week 52/40, indicating mental well-being was not negatively affected with bimekizumab treatment.
In both the bDMARD-naïve and TNFi-IR populations, bimekizumab-randomized patients reported improvements across patient-reported symptoms and HRQOL outcomes. This was generally reflected in the placebo/bimekizumab switchers; however, among the TNFi-IR population, placebo/bimekizumab switchers improved but did not completely catch up to bimekizumab-randomized patients by week 52/40 for some measures (FACIT-Fatigue, HAQ-DI, and pain VAS ≥ 30/50/70% improvements). This may be due to the TNFi-IR population generally being more difficult to treat, with patients experiencing longer and more severe disease.30,31 Additionally, placebo-randomized TNFi-IR patients had a substantial period on nonactive treatment, which may have contributed to the lower responses observed: patients had a washout period following TNFi use mandated by the BE COMPLETE study design, and were then randomized to 16 weeks of placebo. Further, a 16-week delay in treatment is associated with radiographic progression,14 so patients may have experienced worsening of disease, in turn contributing to reduced response to treatment. Longer-term data may show continued improvements in this group.
PsA affects the physical health and functional ability of patients, which can contribute to reduced work productivity.5 Bimekizumab treatment resulted in sustained improvements up to 1 year across all domains of the WPAI-SHP questionnaire regardless of prior exposure to TNFi. The greatest improvements were seen in the activity impairment and presenteeism subdomains, with patients demonstrating > 20% improvement at week 52/40, previously identified as the MCID in patients with PsA.28 Smaller improvements were observed in absenteeism; however, baseline values for absenteeism were relatively low across both studies, leaving limited room for improvement. Future analyses should report the proportion of patients attaining MCID in work productivity domains.
Additionally, by 1 year, approximately 17% of bimekizumab-randomized patients across both trial populations gained employment. There was a slightly reduced response among the TNFi-IR placebo/bimekizumab patients compared with bDMARD-naïve patients, which may be a result of more severe disease characteristics and reduced overall employment at baseline vs bDMARD-naïve patients (Table 1). Longer-term data may allow improvements in the proportion of patients gaining employment to emerge, in line with improvements in other work productivity domains seen at week 40. It should be noted that change in employment may not be directly attributable to PsA treatment, and extraneous factors may contribute to this change.
The improvements in employment rates and work productivity across both absenteeism and presenteeism suggest that treatment with bimekizumab may allow patients living with PsA to reenter the employment market, indicating reduced burden of disease in individuals with a desire to return to work.5-7 This benefits not only the individual, but could also reduce the indirect costs of PsA.32,33
A strength of this analysis is that it included both bDMARD-naïve and TNFi-IR patients, showing the relevance to patients across the 2 PsA populations. It is noteworthy that the results show consistency in HRQOL improvements across both populations, given it is often more difficult to achieve efficacy outcomes among TNFi-IR patients.30,31 Additionally, reporting MCID thresholds in addition to CFB across measures allows patient-level responses to be considered alongside the average improvement in the study population, which is important given some patients may not respond to treatment.
Work productivity has been assessed in bimekizumab-randomized patients living with axSpA.34 The data presented here show similar improvements in work productivity in bimekizumab-treated patients with PsA, suggesting treatment with bimekizumab improves productivity across the spectrum of SpA.
Further, this study used a breadth of PROs and PsA-specific (PsAQOL, PsAID-12) and generic (SF-36, EQ-5D-3L) measures of HRQOL. This enables the comprehensive capture of symptoms that are important to patients and across the heterogeneous manifestations of PsA.
In terms of limitations, the data presented after week 16 in the TNFi-IR population were collected in an open-label extension, whereas data presented after week 16 in the bDMARD-naïve population were collected during active-blind treatment; this limits comparability of results between the populations. However, it should be noted that the trials were conducted in the same centers across the same time frame. Further, schedules of assessment after week 16 were misaligned across the bDMARD-naïve and TNFi-IR clinical studies, preventing direct comparison in some measures at week 52 and the pooling of data.
Longer-term data are needed to show how these PROs, HRQOL, and work productivity results are sustained in the context of a chronic disease requiring lifelong treatment. Additionally, some patients may not respond as well to treatment due to their baseline demographics and disease characteristics.35 Although beyond the scope of this manuscript, analyzing predictors of response to 1 year and beyond could be an avenue for future research and help inform clinical decision-making.
In conclusion, treatment with bimekizumab resulted in sustained improvements in PROs—including pain, fatigue, and physical function—HRQOL, and work productivity up to 1 year in patients with active PsA through dual inhibition of IL-17A and IL-17F. Consistent responses were observed across bDMARD-naïve and TNFi-IR populations. The improvements reported here add to the already published 1-year efficacy and safety data from these trials, demonstrating the efficacy of bimekizumab treatment across clinical and patient-reported symptoms in patients with PsA.11,12
ACKNOWLEDGMENT
The authors thank the patients and the investigators and their teams who took part in this study. The authors additionally thank Lars Erik Kristensen for his substantial contributions to the study conception and design, as well as analysis and interpretation of the data. The authors also acknowledge Heather Edens, PhD, from UCB, Smyrna, Georgia, USA, for publication coordination and Aditi Mehta, MSc, Barney Johnson, BA, and Sona Popat, BA, from Costello Medical, London, UK, for medical writing and editorial assistance based on the authors’ input and direction.
Footnotes
CONTRIBUTIONS
All authors made substantial contributions to study conception and design, analysis and interpretation of the data, and drafting the article or revising it critically for important intellectual content. All authors gave final approval of the version of the article to be published.
FUNDING
This study was sponsored by UCB. Support for third-party writing assistance for this article, provided by Aditi Mehta, MSc, Barney Johnson, BA, and Sona Popat, BA, from Costello Medical, London, UK, was funded by UCB in accordance with Good Publication Practice (GPP 2022) guidelines.
COMPETING INTERESTS
DDG has been a consultant and/or received grant support from AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. PJM has received research grants from AbbVie, Acelyrin, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, Sana, and UCB; consulting fees from AbbVie, Acelyrin, Amgen, BMS, Cullinan, Eli Lilly, GSK, Inmagene, Janssen, Moonlake, Novartis, Pfizer, Takeda, UCB, and Ventyx; and speakers bureau fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. LG has received grants or contracts from AbbVie, Biogen, Lilly, Novartis, and UCB; consulting fees from AbbVie, BMS, Celltrion, Janssen, Novartis, Pfizer, and UCB; honoraria for lectures from AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, MSD, Novartis, Pfizer, Stada, and UCB; support for attending meetings and/or travel from MSD, Novartis, and Pfizer; medical writing support from AbbVie, Amgen, Galapagos, Janssen, Pfizer, and UCB; and is a member of the Board of Directors for EULAR as EULAR Treasurer. MEH has been an advisory board member and consultant for AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. ABG has received research/educational grants from BMS, Janssen, Moonlake, and UCB (all paid to Mount Sinai School of Medicine); honoraria as an advisory board member and consultant for Amgen, Eli Lilly, Highlights Therapeutics, Janssen, Novartis, Sanofi, Sun Pharma, Takeda, Teva, UCB, and Xbiotech (with stock options for RA). BI is an employee of UCB and a shareholder of AbbVie, GSK, and UCB. RB, JC, NL, JL are employees and shareholders of UCB. WT has received research grants, consulting fees, speaking fees, and/or honoraria from AbbVie, Amgen, BMS, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ono Pharma, Pfizer, and UCB.
ETHICS AND PATIENT CONSENT
The BE OPTIMAL and BE COMPLETE studies 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. Separate ethics approval for the current study was not obtained, as it was a post hoc analysis. All the results presented in this article are in aggregate form, and no personally identifiable information was used for this study.
DATA SHARING POLICY
Data from this manuscript may be requested by qualified researchers 6 months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient data and redacted study documents, which may include raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. 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.
PLAIN LANGUAGE SUMMARY
The visual plain language summary of this article is also included as online supplementary material.
- Accepted for publication January 20, 2025.
- Copyright © 2025 by the Journal of Rheumatology
This is an Open Access article, which permits use, distribution, and reproduction, without modification, provided the original article is correctly cited and is not used for commercial purposes.
REFERENCES
SUPPLEMENTARY DATA
Supplementary material accompanies the online version of this article.
