Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, showed efficacy to 2 years in patients with axial spondyloarthritis (axSpA). In this post hoc analysis, we compare the impact of shorter versus longer symptom duration on the efficacy of bimekizumab to Week 104. Efficacy outcomes by symptom duration (≤ 2 [ASAS early axSpA definition] versus > 2 years; ≤ 5 versus > 5 years) were assessed across patients from BE MOBILE 1 and 2 (non-radiographic [NCT03928704]/radiographic axSpA [NCT03928743]) and the combined open-label extension (NCT04436640). (Relative) odds ratios and (relative) differences were calculated to compare 16-week bimekizumab versus placebo treatment effect and 104-week outcomes, and infer the significance of differences, between symptom duration subgroups. Analyses were neither powered for these comparisons nor multiplicity adjusted, and should be interpreted accordingly. Improved disease activity, physical function, fatigue, health-related quality of life and objective signs of inflammation were seen with bimekizumab versus placebo at Week 16 regardless of symptom duration. Outcomes were then sustained or improved with bimekizumab to Week 104 across all subgroups. 16-week bimekizumab versus placebo treatment effect was comparable between subgroups (e.g., ≤ 2-year versus > 2-year symptom duration relative odds ratio [95

BACKGROUND:There is a lack of direct comparative studies evaluating the long-term efficacy of the approved biologic therapies bimekizumab, secukinumab and adalimumab for moderate-to-severe hidradenitis suppurativa (HS) beyond Week 16. To address this evidence gap, this study uses matching-adjusted indirect comparisons (MAIC) to assess and compare their sustained efficacy. OBJECTIVE:To assess the long-term relative efficacy of bimekizumab 320 mg every 2 weeks/every 4 weeks (Q2W/Q4W) in moderate-to-severe HS compared with biologic therapies (secukinumab 300 mg Q2W and Q4W and adalimumab 40 mg every week [QW]) at Week 48-52. METHODS:Relevant trials were identified as part of a systematic literature review. Individual patient data for bimekizumab trials (BE HEARD I/II; Week 48) were combined and subsequently weighted to match aggregate baseline characteristics of trials for secukinumab (SUNRISE/SUNSHINE; Week 52) and adalimumab (PIONEER I/II; Week 48). Weights for patients receiving bimekizumab were determined using a propensity score model. Unanchored comparisons of reweighted bimekizumab and comparator data for key HS efficacy outcomes were analysed. RESULTS:Bimekizumab Q2W/Q4W demonstrated significantly higher odds of response for all HS Clinical Response (HiSCR) and HS Severity Score System (IHS4) outcomes compared with secukinumab Q4W, including HiSCR50 (odds ratio [OR]: 2.68; 95% confidence interval [CI]: 1.71, 4.19), HiSCR75 (OR: 2.20; 95% CI: 1.48, 3.26) and IHS4-55 (OR: 2.27; 95% CI: 1.48, 3.48); and for HiSCR50/75 compared with adalimumab QW (OR: 2.57; 95% CI: 1.48, 4.44/OR: 1.84; 95% CI: 1.08, 3.13, respectively). CONCLUSION:Compared with other approved biologics, bimekizumab showed favourable efficacy across the majority of outcomes assessed at Week 48-52, indicating its potential as a durable long-term therapeutic option for patients with moderate-to-severe HS.

OBJECTIVES:To assess sex-based differences in response to bimekizumab in patients with axial spondyloarthritis (axSpA) from two phase 3 trials. METHODS:Improvements to Week 52 in measures of disease activity (ASAS40, ASDAS <2.1, BASDAI) and function (BASFI), pain, fatigue, health-related quality of life (HRQoL) and objective signs of inflammation (MRI, hs-CRP) were assessed post hoc in patients with non-radiographic (nr-) and radiographic (r-)axSpA from BE MOBILE 1 (NCT03928704) and BE MOBILE 2 (NCT03928743), respectively. Comparisons were made between sexes at Week 16 (bimekizumab versus placebo treatment effect) and Week 52 (treatment response in bimekizumab-randomised patients only) using odds ratios for dichotomous outcomes and difference values for continuous outcomes. For hs-CRP, ratio to baseline was calculated due to skewed distribution. RESULTS:While sex distribution was balanced in nr-axSpA (54.3% male), 72.3% of patients with r-axSpA were male. At Week 16, bimekizumab-randomised male patients typically had better treatment responses versus placebo compared with female patients across ASAS40, ASDAS <2.1 and improvements in BASDAI, BASFI and measures of HRQoL. At Week 52, female patients had longer-term improvements across these outcomes, though male patients continued to have numerically higher treatment responses. In contrast, active inflammation (MRI, hs-CRP) was reduced to similarly low levels in both sexes at Week 16 and maintained to Week 52, despite baseline differences. CONCLUSIONS:Although male patients had earlier clinical responses to bimekizumab treatment, female patients demonstrated longer-term improvements in composite and patient-reported outcomes. Both sexes had substantial improvements in objective inflammation at Week 16 and 52, despite baseline differences. TRIAL REGISTRATION:Clinicaltrials.gov; NCT03928704 and NCT03928743.

Objectives To assess bimekizumab (BKZ) efficacy to Week (Wk)52 across the full axial spondyloarthritis (axSpA) disease spectrum, focusing on potential sex-based differences in treatment response. Methods BE MOBILE 1/2 ( NCT03928704 /NCT03928743) included a 16-wk double-blind and 36-wk maintenance period. Patients received BKZ 160mg every 4 wks (Q4W) or placebo (PBO) to Wk16; thereafter, all received BKZ. Sex-stratified outcomes reported to Wk52: ASAS40, ASDAS<2.1, BASDAI, Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL), and objective signs of inflammation (OSI; MRI SPARCC SIJ, MRI Berlin spine, hs-CRP). Wk16 BKZ vs PBO efficacy between males vs females were compared using adjusted relative odds ratios (rOR; logistic regression) and relative differences (RD; ANCOVA). Analyses were post-hoc (no p values). Results 220/254 BE MOBILE 1 (male: 124/138 [89.9%]; female: 96/116 [82.8%]) and 298/332 BE MOBILE 2 patients (male: 215/240 [89.6%]; female: 83/92 [90.2%]) completed Wk52. At baseline, females had longer mean symptom duration (years; non-radiographic [nr]-axSpA: 11.1 vs 7.2; radiographic [r]-axSpA: 15.0 vs 12.9) and lower HLA-B27 positivity (%) (nr-axSpA: 69.0 vs 84.8; r-axSpA: 78.3 vs 88.3) than males; males had lower mean ASQoL scores (nr-axSpA: BKZ: 8.5 vs 10.8, PBO: 8.6 vs 10.2; r-axSpA: BKZ: 8.3 vs 11.1, PBO: 8.4 vs 9.0), and generally higher OSI values than females. Across ASAS40, ASDAS<2.1, and BASDAI, rORs and RDs demonstrated greater Wk16 BKZ vs PBO treatment effect in males vs females (Figure 1). At Wk52, responses were higher in males with nr-axSpA than females, but comparable in r-axSpA. Overall, at Wk52, both sexes responded well in both trials, with >50% of BKZ-randomized patients achieving ASAS40, >40% achieving ASDAS <2.1, and BASDAI score improvements. For ASQoL, both males and females demonstrated substantial improvements with BKZ at Wk16 (nr-axSpA: −5.5 vs −4.8; r-axSpA: −4.8 vs −5.5) compared with PBO (nr-axSpA: −2.1 vs −2.9; r-axSpA: −3.1 vs −3.7). Improvements continued to Wk52 with BKZ (nr-axSpA: BKZ: −5.7 vs −6.2, PBO/BKZ: −5.5 vs −5.1; r-axSpA: BKZ: −5.4 vs −6.5, PBO/BKZ: −5.5 vs −5.8). For change from baseline in OSI outcomes, RDs indicated a higher Wk16 BKZ vs PBO treatment effect in males than females; absolute OSI values were comparable between males/females and maintained or improved to Wk52 with BKZ. Figure 1. ASAS40, ASDAS<2.1 and BASDAI to Wk52 and relative odds ratios and relative differences at Wk16, stratified by sex Conclusion Wk16 BKZ vs PBO treatment effect trended higher among males than females. By Wk52, females showed improvement in longer-term BKZ response, approaching levels comparable to males. Overall BKZ efficacy was demonstrated across clinical, patient-reported, and OSI outcomes in both sexes across the full axSpA disease spectrum.

The relative efficacy of bimekizumab and risankizumab in patients with PsA who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR) was assessed at 52 weeks (Wk52) using matching-adjusted indirect comparisons (MAIC). Relevant trials were systematically identified. For patients who were bDMARD naïve, individual patient data (IPD) from BE OPTIMAL (NCT03895203; N = 431) were matched with summary data from KEEPsAKE-1 (NCT03675308; N = 483). For patients who were TNFi-IR, IPD from BE COMPLETE (NCT03896581; N = 267) were matched with summary data from the TNFi-IR patient subgroup in KEEPsAKE-2 (NCT03671148; N = 106). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted to match the baseline characteristics of patients in the risankizumab trials. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Recalculated bimekizumab Wk52 outcomes for American College of Rheumatology (ACR) 20/50/70 response criteria and minimal disease activity (MDA) index (non-responder imputation) were compared with risankizumab outcomes via non-placebo-adjusted comparisons. In patients who were bDMARD naïve, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR50 (odds ratio [95

Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A and has shown rapid, clinically meaningful improvements in disease activity across the axial spondyloarthritis (axSpA) spectrum in two phase III studies (active non-radiographic axSpA [nr-axSpA; BE MOBILE 1, NCT03928704] and radiographic axSpA [r-axSpA; BE MOBILE 2, NCT03928743]). Here, we present outcomes up to week (Wk)104 for these two studies and their open-label extension study (BE MOVING, NCT04436640). BE MOBILE 1 and 2 both comprised a 16-Wk, double-blind period where patients were randomised 1:1 (BE MOBILE 1) or 2:1 (BE MOBILE 2) to BKZ 160 mg every 4Wks (Q4W) or placebo (PBO), followed by a 36-Wk maintenance period. From Wk16 onwards, all patients received BKZ 160 mg Q4W and could then enrol in an open-label extension study at Wk52. ASAS40 and BASDAI50 responses, and BASDAI and BASFI scores are reported up to Wk104. Missing data were imputed using non-responder imputation (NRI) for binary variables and multiple imputation for continuous variables. In total, 254 patients with nr-axSpA and 332 patients with r-axSpA were randomised (BKZ: 128, PBO: 126 and BKZ: 221, PBO: 111, respectively). At Wk104, 189 (74.4%) and 267 (80.4%) patients had completed the study, respectively. In both studies, ∼47% of patients on BKZ achieved BASDAI50 at Wk16, increasing to 50.8% and 56.3% in patients in BE MOBILE 1 and 2, respectively, at Wk104 (NRI, Table). Improvements in BASDAI, BASFI and ASAS seen in patients treated with BKZ at Wk16 were sustained or further improved up to Wk104 (Table). Of those randomised to BKZ and who were BASDAI50 responders at Wk16, 78.3% and 79.6% maintained BASDAI50 response at Wk104 in BE MOBILE 1 and BE MOBILE 2, respectively. Through Wk104, 514 (89.5%) patients reported at least one treatment-emergent adverse event (TEAEs), with 34 (5.9%) patients discontinuing due to TEAEs. No deaths were reported and no new safety signals observed. BKZ demonstrated sustained and clinically meaningful improvements in disease activity and function across the full axSpA spectrum through 104 weeks, with no new safety signals, supporting its potential as a long-term treatment option. K. Gaffney: Consultancies; Novartis, AbbVie, UCB, Lilly and Pfizer. Shareholder/stock ownership; Rheumatology events. Honoraria; Novartis, AbbVie, UCB, Lilly and Pfizer. Member of speakers’ bureau; Novartis, UCB, AbbVie and Lilly. Grants/research support; NASS, Versus Arthritis, AbbVie, Pfizer, UCB, Novartis, Lilly, Cellgene, Celltrion, Janssen, Gilead and Biogen. Other; Meeting expenses from AbbVie, Lilly, Roche, Novartis, Pfizer and UCB. N. D McKay: Member of speakers’ bureau; Gilead. Other; Travel fees from UCB and Gilead. R. Sengupta: Consultancies; AbbVie, Biogen, Novartis, Celgene, Lilly, Chugai, MSD and UCB. Honoraria; AbbVie, Biogen, Novartis, Celgene, Lilly, Chugai, MSD and UCB. Grants/research support; AbbVie, Celgene, Novartis and UCB. Other; Advisory boards for AbbVie, Biogen, Chugai, Lilly, Novartis and UCB. D. Voiniciuc: Other; Contractor for UCB Pharma and employee of Veramed. C. de la Loge: Other; Consultant to UCB, Brussels, Belgium. U. Massow: Other; Employee of UCB. V. Taieb: Other; Employee of UCB. S. Zhao: Honoraria; UCB. H. Marzo-Ortega: Consultancies; AbbVie, Biogen, Celgene, Janssen, Eli-Lilly, Moonlake, Novartis, Pfizer and UCB. Honoraria; AbbVie, Biogen, Celgene, Janssen, Eli-Lilly, Moonlake, Novartis, Pfizer and UCB. Grants/research support; Janssen, Novartis, Pfizer and UCB. Other; Speaker fees from AbbVie, Biogen, Celgene, Janssen, Eli-Lilly, Moonlake, Novartis, Pfizer and UCB.

OBJECTIVE:To assess the long-term effect of bimekizumab, a dual inhibitor of IL-17A and IL-17F, on patient-reported symptoms, function and health-related quality of life (HRQoL) in patients with axial spondyloarthritis (axSpA) from phase 3 studies and their open-label extension. METHODS:BE MOBILE 1 (non-radiographic-axSpA) and 2 (radiographic-axSpA) comprised 16-week double-blind placebo-controlled and 36-week maintenance periods. From week 16, all patients received subcutaneous bimekizumab 160 mg every 4 weeks. At week 52, eligible patients could enrol in the open-label extension BE MOVING and continue bimekizumab treatment. Spinal pain (rated on a numerical rating scale from 0 (no pain) to 10 (maximum pain)), morning stiffness (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) average of Q5/6), fatigue (BASDAI Q1; Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale), sleep quality (Medical Outcomes Study (MOS) Sleep Scale Index II), physical function (Bath Ankylosing Spondylitis Functional Index (BASFI)) and HRQoL (36-Item Short Form Survey (SF-36) physical component summary (PCS)/mental component summary (MCS); Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire) were reported to week 104. RESULTS:In total, 494/586 (84.3%) patients entered BE MOVING at week 52; 456 completed week 104. Patients reported substantial changes from baseline to week 104 in total spinal pain (-4.3), nocturnal spinal pain (-4.3), morning stiffness (-4.3) and fatigue (BASDAI Q1: -3.4; FACIT-Fatigue: +9.9). Over half reported total and nocturnal spinal pain scores ≤3 at week 104. Similar improvements to week 104 were shown in sleep (MOS-Sleep Scale: +10.2), physical function (BASFI: -2.9) and HRQoL (SF-36 PCS: +12.4; ASQoL: -5.6). CONCLUSIONS:Bimekizumab treatment resulted in sustained improvements in patient-reported symptoms and their impacts across the full disease spectrum of axSpA over 2 years, underscoring its long-term potential for improving patients' daily lives. TRIAL REGISTRATION NUMBERS:NCT03928704, NCT03928743, NCT04436640.

OBJECTIVE:To assess the effect of bimekizumab on pain, morning stiffness, and fatigue in patients with nonradiographic and radiographic axial spondyloarthritis (axSpA) in the phase III BE MOBILE studies (ClinicalTrials.gov: NCT03928704 and NCT03928743). METHODS:Patients were randomized to bimekizumab 160 mg or placebo every 4 weeks; and all patients received bimekizumab from week 16. Patients reported spinal pain, peripheral pain, morning stiffness, and fatigue to week 52. Total and nocturnal spinal pain were each assessed on a 0-10 numerical rating scale (NRS). Individual Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) items (0-10-point NRS) assessed peripheral arthritis pain (question [Q] 3), enthesitis pain/discomfort (Q4), morning stiffness (mean of Q5 and Q6), and fatigue (Q1). Functional Assessment of Chronic Illness Therapy Fatigue subscale score (FACIT-Fatigue) is also reported. RESULTS:At week 16, bimekizumab-treated patients reported lower mean nocturnal spinal pain, total spinal pain, and BASDAI scores (nominal except for nocturnal spinal pain; all P ≤ 0.001), as well as higher FACIT-Fatigue scores (nominal P < 0.05) vs placebo, indicating improved symptom levels. Improvements continued to week 52 in continuous bimekizumab-treated patients and in placebo-bimekizumab switchers. A higher proportion of bimekizumab- vs placebo-randomized patients achieved increasingly stringent thresholds for low spinal and peripheral pain at week 16; this was sustained or improved at week 52. Results were similar for morning stiffness and fatigue. At week 52, over half of patients were considered FACIT-Fatigue responders (≥ 8-point increase in score). CONCLUSION:Bimekizumab treatment led to rapid improvements in levels of pain and morning stiffness. Substantial improvements were seen in all domains across the full disease spectrum of axSpA and continued to week 52.

OBJECTIVE:The objective of this study was to evaluate 12-month persistence of biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) treatment in US patients with axial spondyloarthritis (axSpA) using real-world data, and patient baseline characteristics associated with increased or decreased persistence probability. METHODS:Anonymized US claims from Merative MarketScan provided patient data relative to an index date (initiation of a new b/tsDMARD of interest for axSpA), from which patients were followed for 12 months or until b/tsDMARD non-persistence (≥ 90-day gap or b/tsDMARD switch) or MarketScan disenrollment. Persistence probabilities were estimated using Kaplan-Meier survival curves. Association of variables with persistence was estimated using multivariable Cox regression analyses. RESULTS:Of the 5970 adults with axSpA, 76.7% were prescribed a TNFi as their index b/tsDMARD, and 55.1% were b/tsDMARD-unexposed while 44.9% were b/tsDMARD-exposed before index b/tsDMARD. b/tsDMARD persistence probability was 67.8%, 57.7%, and 54.4% at 6, 9, and 12 months, respectively. 12-month persistence probabilities stratified by index b/tsDMARD mode of action or history of b/tsDMARD treatment ranged from 51.8% to 55.7%. Female sex and history of dactylitis were associated with decreased b/tsDMARD persistence, while history of inflammatory bowel disease, uveitis, and obesity were associated with increased persistence probability. CONCLUSIONS:Around half of patients studied were non-persistent with any given b/tsDMARD within a year of initiating therapy. Persistence was not considerably affected by index b/tsDMARD mode of action or history of b/tsDMARD treatment. Patient characteristics associated with decreased persistence probability, including female sex and dactylitis, may help clinicians recognize patients who may benefit from additional support to improve long-term treatment outcomes.

BACKGROUND:Given the lack of head-to-head studies of approved biologic therapies in hidradenitis suppurativa (HS), a chronic, recurrent inflammatory skin disease, a systematic literature review (SLR) and network meta-analysis (NMA) were conducted to provide insight into their comparative short-term efficacy. OBJECTIVES:To assess the relative efficacy of approved biologic therapies (bimekizumab 320 mg every 2 weeks [Q2W], secukinumab 300 mg Q2W and every 4 weeks [Q4W] and adalimumab 40 mg every week [QW]) at Week 12-16 in moderate-to-severe HS. METHODS:A clinical SLR identified randomised controlled trials until 3rd July 2024 for inclusion in Bayesian NMAs. Two evidence networks (predominantly biologic-naïve and biologic-experienced) were constructed to represent populations with differing biologic treatment histories. Outcomes of interest were improved HS Clinical Response (HiSCR; ≥50%/≥75%/≥90%/100%), change from baseline (CFB) in International Hidradenitis Suppurativa Severity Score System (IHS4) and improvement from baseline of ≥55% (IHS4-55). Percentage CFB in abscess and inflammatory nodule (AN) count and CFB in absolute draining tunnels (DT) count were also assessed. RESULTS:The NMA included nine trials. Bimekizumab ranked as the most efficacious treatment across all predefined efficacy outcomes in both predominantly biologic-naïve and biologic-experienced networks, showing consistent response levels. In the predominantly biologic-naïve network, bimekizumab Q2W compared with secukinumab (Q4W) demonstrated significantly higher odds of response for all HiSCR outcomes (odds ratio [OR]: HiSCR50 = 1.69; HiSCR75 = 1.85; HiSCR90 = 1.62; HiSCR100 = 1.88) and IHS4-55 (OR = 1.91), and for HiSCR75 (OR = 1.60) and HiSCR90 (OR = 1.56) compared with adalimumab QW. Similar results were observed for secukinumab Q2W and both secukinumab dosing regimens in the biologic-experienced network. Note, adalimumab studies did not report the proportion of biologic-experienced patients. Systematic review of safety data is required for full benefit-risk assessment and decision-making. CONCLUSIONS:This NMA, the first to adjust for intercurrent events in moderate-to-severe HS across multiple efficacy outcomes, assessed up-to-date data, with estimates demonstrating bimekizumab's favourable efficacy among approved biologics.