Dataset Information

Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials.

ABSTRACT:

Objectives

Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are double-blind, phase 3 trials designed to evaluate efficacy and safety of bimekizumab, a novel dual interleukin (IL)-17A and IL-17F inhibitor, across the axSpA spectrum.

Methods

In parallel 52-week trials, patients with active disease were randomised 1:1 (nr-axSpA) or 2:1 (r-axSpA) to bimekizumab 160 mg every 4 weeks:placebo. From week 16, all patients received bimekizumab 160 mg every 4 weeks. Primary (Assessment of SpondyloArthritis international Society ≥40% improvement (ASAS40)) and secondary endpoints were assessed at week 16. Here, efficacy and treatment-emergent adverse events (TEAEs) are reported up to week 24.

Results

254 patients with nr-axSpA and 332 with r-axSpA were randomised. At week 16, primary (ASAS40, nr-axSpA: 47.7% bimekizumab vs 21.4% placebo; r-axSpA: 44.8% vs 22.5%; p<0.001) and all ranked secondary endpoints were met in both trials. ASAS40 responses were similar across TNFi-naïve and TNFi-inadequate responder patients. Improvements were observed in Ankylosing Spondylitis Disease Activity Score (ASDAS) states and objective measures of inflammation, including high-sensitivity C-reactive protein (hs-CRP) and MRI of the sacroiliac joints and spine. Most frequent TEAEs with bimekizumab (>3%) included nasopharyngitis, upper respiratory tract infection, pharyngitis, diarrhoea, headache and oral candidiasis. More fungal infections (all localised) were observed with bimekizumab vs placebo; no major adverse cardiovascular events (MACE) or active tuberculosis were reported. Incidence of uveitis and adjudicated inflammatory bowel disease was low.

Conclusions

Dual inhibition of IL-17A and IL-17F with bimekizumab resulted in significant and rapid improvements in efficacy outcomes vs placebo and was well tolerated in patients with nr-axSpA and r-axSpA.

SUBMITTER: van der Heijde D

PROVIDER: S-EPMC10086273 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials.

van der Heijde Désirée D Deodhar Atul A Baraliakos Xenofon X Brown Matthew A MA Dobashi Hiroaki H Dougados Maxime M Elewaut Dirk D Ellis Alicia M AM Fleurinck Carmen C Gaffney Karl K Gensler Lianne S LS Haroon Nigil N Magrey Marina M Maksymowych Walter P WP Marten Alexander A Massow Ute U Oortgiesen Marga M Poddubnyy Denis D Rudwaleit Martin M Shepherd-Smith Julie J Tomita Tetsuya T Van den Bosch Filip F Vaux Thomas T Xu Huji H

Annals of the rheumatic diseases 20230117 4

<h4>Objectives</h4>Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are double-blind, phase 3 trials designed to evaluate efficacy and safety of bimekizumab, a novel dual interleukin (IL)-17A and IL-17F inhibitor, across the axSpA spectrum.<h4>Methods</h4>In parallel 52-week trials, patients with active disease were randomised 1: ...[more]

PMID: 36649967

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Project description:BackgroundThe efficacy and safety of bimekizumab (BKZ), an inhibitor of interleukin (IL)-17F in addition to IL-17A, has been established in axial spondyloarthritis (axSpA). Early assessment of new bone formation is possible using 18F-fluoride positron emission tomography-computerised tomography (PET-CT) imaging to quantitatively monitor osteoblastic activity.ObjectivesThis exploratory study, initiated before phase IIb/III studies, assessed the efficacy and safety of BKZ in patients with radiographic (r-)axSpA and its effect on new bone formation.DesignPatients were randomised 2:1 to BKZ 160 mg every 2 weeks (Q2W; Weeks 0-10) then 320 mg Q4W (Weeks 12-44), or the reference drug: certolizumab pegol (CZP) 400 mg Q2W (Weeks 0-4), then 200 mg Q2W (Weeks 6-10), 400 mg Q4W (Weeks 12-44).MethodsPrimary (Axial Spondyloarthritis Disease Activity Score (ASDAS) change from baseline (CfB)) and secondary endpoints (ASDAS-ID, ASDAS-MI) were assessed at Week 12. PET-positive axSpA lesion counts and osteoblastic activity quantification (mean SUVauc) were performed at baseline and Weeks 12 and 48 in the sacroiliac joints and spine (PET-CT substudy; not powered to evaluate differences).ResultsIn total, 76 patients were randomised; 26/76 entered the PET-CT substudy. At Week 12, the mean ASDAS CfB with BKZ was -2.1 (CZP: -1.8); ASDAS-ID and ASDAS-MI were achieved by 23.9% (11/46) (CZP: 20.8% (5/24)) and 60.9% (28/46) (CZP: 45.8% (11/24)) patients. Across treatments, clinical efficacy was maintained or increased further at Week 48. In the PET-CT substudy, the total number of PET-positive axSpA lesions and mean SUVauc were substantially reduced from baseline at Week 12 with BKZ and CZP, with reductions maintained or further reduced at Week 48. Treatments were well tolerated with no new safety signals.ConclusionDual inhibition of IL-17A and IL-17F with BKZ resulted in improved clinical outcomes and reduced osteoblastic activity in patients with r-axSpA, suggesting the potential of BKZ to reduce disease activity and new bone formation within 12 weeks of treatment. CZP findings were consistent with previous data. No new safety signals were identified.Trial registrationClinicalTrials.gov, NCT03215277 (https://clinicaltrials.gov/study/NCT03215277).

Project description:PurposeTo evaluate the efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis (nr-axSpA).MethodsPatients fulfilled Assessment of Spondyloarthritis international Society (ASAS) criteria for axial spondyloarthritis, had a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥ 4, total back pain score of ≥ 4 (10 cm visual analogue scale) and inadequate response, intolerance or contraindication to non-steroidal anti-inflammatory drugs (NSAIDs); patients fulfilling modified New York criteria for ankylosing spondylitis were excluded. Patients were randomised to adalimumab (N=91) or placebo (N=94). The primary endpoint was the percentage of patients achieving ASAS40 at week 12. Efficacy assessments included BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS). MRI was performed at baseline and week 12 and scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) index.ResultsSignificantly more patients in the adalimumab group achieved ASAS40 at week 12 compared with patients in the placebo group (36% vs 15%, p<0.001). Significant clinical improvements based on other ASAS responses, ASDAS and BASDAI were also detected at week 12 with adalimumab treatment, as were improvements in quality of life measures. Inflammation in the spine and sacroiliac joints on MRI significantly decreased after 12 weeks of adalimumab treatment. Shorter disease duration, younger age, elevated baseline C-reactive protein or higher SPARCC MRI sacroiliac joint scores were associated with better week 12 responses to adalimumab. The safety profile was consistent with what is known for adalimumab in ankylosing spondylitis and other diseases.ConclusionsIn patients with nr-axSpA, adalimumab treatment resulted in effective control of disease activity, decreased inflammation and improved quality of life compared with placebo. Results from ABILITY-1 suggest that adalimumab has a positive benefit-risk profile in active nr-axSpA patients with inadequate response to NSAIDs.

Project description:ImportancePsoriasis is a chronic disease requiring long-term management; understanding the long-term safety profiles of psoriasis treatments, such as bimekizumab, is important.ObjectiveTo evaluate the 2-year safety profile of bimekizumab in patients with moderate to severe plaque psoriasis.Design, setting, and participantsSafety data were pooled from a cohort of patients from 4 phase 2 randomized clinical trials (BE ABLE 1, BE ABLE 2, PS0016, and PS0018) and 4 phase 3 randomized clinical trials (BE VIVID, BE READY, BE SURE, and BE BRIGHT) to include 2 years of study treatment. Data were obtained on adults with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index level ≥12, ≥10% body surface area affected by psoriasis, and an Investigator's Global Assessment score ≥3 on a 5-point scale) who were eligible for systemic psoriasis therapy and/or phototherapy.InterventionsIncluded patients received 1 or more doses of bimekizumab during the phase 2 or phase 3 trials.Main outcomes and measuresTreatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to treatment discontinuation are reported using exposure-adjusted incidence rates (EAIRs) per 100 person-years.ResultsA total of 1789 patients (1252 [70.0%] men; mean [SD] age, 45.2 [13.5] years) were treated with 1 or more doses of bimekizumab across the phase 2/3 trials and were included in these analyses; total bimekizumab exposure was 3109.7 person-years. TEAEs occurred at an EAIR of 202.4 per 100 person-years and did not increase with longer duration of bimekizumab exposure. The 3 most frequently reported TEAEs were nasopharyngitis (19.1 per 100 person-years; 95% CI, 17.4-20.9 per 100 person-years), oral candidiasis (12.6 per 100 person-years; 95% CI, 11.3-14.0 per 100 person-years), and upper respiratory tract infection (8.9 per 100 person-years; 95% CI, 7.8-10.1 per 100 person-years). Most oral candidiasis events were mild or moderate; 3 events led to discontinuation. The EAIRs of inflammatory bowel disease (0.1 per 100 person-years; 95% CI, 0.0-0.3 per 100 person-years), adjudicated suicidal ideation and behavior (0.0 per 100 person-years; 95% CI, 0.0-0.2 per 100 person-years), and adjudicated major adverse cardiac events (0.5 per 100 person-years; 95% CI, 0.3-0.8 per 100 person-years) were low.Conclusions and relevanceIn these pooled analyses of data from a cohort of patients from 8 randomized clinical trials, bimekizumab was well tolerated aside from an increased incidence of mild to moderate oral candidiasis. No safety signals were observed compared with previous reports, and there was no increased risk of AEs with longer duration of bimekizumab exposure.

Project description:IntroductionPsoriatic arthritis (PsA) is a chronic inflammatory disease requiring long-term treatment. Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated tolerability and sustained clinical efficacy for up to 1 year for patients with PsA. Here, we report the longer-‍term safety and efficacy of bimekizumab up to 2 years.MethodsBE OPTIMAL (biologic disease-modifying antirheumatic drug [bDMARD]-naïve) and BE COMPLETE (prior inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi-IR]) assessed subcutaneous bimekizumab 160 mg every 4 weeks in patients with PsA. BE OPTIMAL included a reference arm (adalimumab 40 mg every 2 weeks); patients switched to bimekizumab at week 52 with no washout between treatments. BE OPTIMAL week 52 and BE COMPLETE week 16 completers were eligible for the BE VITAL open-label extension. Efficacy outcomes are reported to week 104/100 (BE OPTIMAL/BE COMPLETE).ResultsA total of 710/852 (83.3%) bDMARD-naïve and 322/400 (80.5%) TNFi-IR patients completed week 104/100. Up to 104 weeks, patients treated with bimekizumab in BE OPTIMAL and BE COMPLETE had treatment-emergent adverse event incidence rates (exposure-adjusted incidence rate/100 patient-years) of 179.9 (95% CI 166.9, 193.7) and 100.3 (89.2, ‍112.4), respectively. The proportion of patients achieving efficacy outcomes (≥ 50% improvement from baseline in American College of Rheumatology [ACR] response criteria, 100% improvement from baseline in Psorisis Area and Severity Index [PASI], minimal disease activity [MDA]) was sustained in all patients from week 52 to week 104/100.ConclusionsBimekizumab was well tolerated for up to 2 years of treatment and no new safety signals were observed. Sustained clinical efficacy was observed up to 2 years in bDMARD-naïve and TNFi-IR patients with active PsA. Patients switching from adalimumab to bimekizumab demonstrated further improvement in skin and nail symptoms, and sustained efficacy in joint symptoms.Trial registrationBE OPTIMAL (NCT03895203), BE COMPLETE (NCT03896581), BE VITAL (NCT04009499).

Project description:IntroductionA previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other treatments for patients with radiographic axial spondyloarthritis (r-axSpA; i.e., ankylosing spondylitis), including the IL-17A inhibitors secukinumab and ixekizumab. This matching-adjusted indirect comparison (MAIC) assessed 52-week relative efficacy of bimekizumab versus secukinumab and ixekizumab.MethodsIndividual patient data from BE MOBILE 2 (bimekizumab 160 mg; N = 220) were matched to pooled summary data from MEASURE 1/2/3/4 (secukinumab 150 mg), MEASURE 3 (secukinumab 300 mg; escalated dose for inadequate responders), COAST-V (ixekizumab) and COAST-V/-W (ixekizumab). BE MOBILE 2 patients were reweighted using propensity score weights based on age, sex, ethnicity, tumor necrosis factor inhibitor (TNFi) exposure, weight, baseline ASDAS and BASFI (secukinumab) and baseline BASDAI (ixekizumab), and 52-week efficacy outcomes from the trial recalculated. Odds ratios (OR) or mean difference for unanchored comparisons are reported with 95% confidence intervals (CI).ResultsAt week 52, MAIC demonstrated that patients may have higher likelihood of improvement in key efficacy outcomes with bimekizumab versus secukinumab 150 mg (e.g., ASAS40: [OR (95% CI): 1.48 (1.05, 2.10); p = 0.026]; effective sample size [ESS] = 177). Differences in 52-week efficacy outcomes between bimekizumab and secukinumab 300 mg dose escalation were non-significant (ESS = 120). Bimekizumab versus ixekizumab 80 mg comparisons (COAST-V only; ESS = 84) also suggested that differences were non-significant for most key efficacy outcomes. Other ixekizumab comparisons (COAST-V/-W; ESS = 45) suggested bimekizumab may have higher comparative efficacy for many of the same efficacy outcomes, however ixekizumab analyses were limited by poor population overlap, likely due to the greater proportion of patients with previous TNFi exposure.ConclusionsPatients treated with bimekizumab may have a higher likelihood of achieving improved longer-term efficacy versus secukinumab 150 mg, suggesting bimekizumab may be a favorable therapeutic option for r-axSpA. Differences in efficacy outcomes with bimekizumab versus ixekizumab 80 mg were mostly non-significant, depending on the populations considered.

Dataset Information

Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials.

Objectives

Methods

Results

Conclusions

Publications

Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials.

Similar Datasets

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