Dual neutralisation of interleukin-17A and interleukin-17F with bimekizumab in patients with active ankylosing spondylitis: results from a 48-week phase IIb, randomised, double-blind, placebo-controlled, dose-ranging study

Objectives Bimekizumab selectively neutralises both interleukin (IL)-17A and IL-17F. We report efficacy and safety in a phase IIb dose-ranging study in patients with active ankylosing spondylitis (AS).Methods Adults with AS (fulfilling modified New York criteria) were randomised 1:1:1:1:1 to bimekizumab 16 mg, 64 mg, 160 mg, 320 mg or placebo every 4 weeks for 12 weeks (double-blind period). At week 12, patients receiving bimekizumab 16 mg, 64 mg or placebo were re-randomised 1:1 to bimekizumab 160 mg or 320 mg every 4 weeks to week 48; other patients continued on their initial dose (dose-blind period). The primary end point was Assessment of SpondyloArthritis international Society (ASAS) 40 response at week 12 (non-responder imputation (NRI) for missing data).Results 303 patients were randomised: bimekizumab 16 mg (n=61), 64 mg (n=61), 160 mg (n=60), 320 mg (n=61) or placebo (n=60). At week 12, significantly more bimekizumab-treated patients achieved ASAS40 vs placebo (NRI: 29.5%-46.7% vs 13.3%; p<0.05 all comparisons; OR vs placebo 2.6-5.5 (95% CI 1.0 to 12.9)). A significant dose-response was observed (p<0.001). The primary end point was supported by all secondary efficacy outcomes. At week 48, 58.6% and 62.3% of patients receiving bimekizumab 160 and 320 mg throughout the study achieved ASAS40, respectively (NRI); similar ASAS40 response rates were observed in re-randomised patients. During the double-blind period, treatment-emergent adverse events occurred in 26/60 (43.3%) patients receiving placebo and 92/243 (37.9%) receiving bimekizumab.Conclusions Bimekizumab provided rapid and sustained improvements in key outcome measures in patients with active AS, with no unexpected safety findings versus previous studies.Pathophysiology and treatment of rheumatic disease

BIMEKIZUMAB IN PATIENTS WITH ACTIVE NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: 24-WEEK EFFICACY & SAFETY FROM BE MOBILE 1, A PHASE 3, MULTICENTRE, RANDOMISED, PLACEBO-CONTROLLED STUDY

Deodhar A, Van der Heijde D, Gensler LS, et al. BIMEKIZUMAB IN PATIENTS WITH ACTIVE NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: 24-WEEK EFFICACY &amp; SAFETY FROM BE MOBILE 1, A PHASE 3, MULTICENTRE, RANDOMISED, PLACEBO-CONTROLLED STUDY. In: Annals of the Rheumatic Diseases. Vol 81. London: Bmj Publishing Group; 2022: 772-773

Safety and Efficacy of Bimekizumab in Patients With Active Ankylosing Spondylitis: Three-Year Results From a Phase IIb Randomized Controlled Trial and Its Open-Label Extension Study

Objective To assess the long-term safety, tolerability, and efficacy of bimekizumab in patients with active ankylosing spondylitis (AS). Methods Patients with active AS who completed the dose-ranging, 48-week BE AGILE randomized controlled trial were eligible to participate in an open-label extension (OLE) study, in which patients received 160 mg of bimekizumab every 4 weeks. We present the safety and efficacy results through 156 weeks. Missing efficacy data were imputed using nonresponder imputation analysis for binary outcomes and multiple imputation for continuous outcomes. Results From weeks 0-156, 280 of 303 patients (exposure-adjusted incidence rate 141.0 per 100 patient-years) experienced >= 1 treatment-emergent adverse event; the most frequent adverse events were nasopharyngitis (8.1 per 100 patient-years) and upper respiratory tract infection (5.0 per 100 patient-years). Additionally, 67 of 303 patients (9.8 per 100 patient-years) had mild to moderate localized fungal infections (28 of 303 patients had Candida infections [3.7 per 100 patient-years] and 23 of 303 patients had oral candidiasis [3.0 per 100 patient-years]), 10 patients had serious infections (1.3 per 100 patient-years), and no cases of active tuberculosis were reported. Active inflammatory bowel disease (1.1 per 100 patient-years), anterior uveitis (0.7 per 100 patient-years), and adjudicated major adverse cardiovascular events (0.3 per 100 patient-years) were infrequent. The efficacy of bimekizumab treatment demonstrated at week 48 was sustained in the OLE study. At week 156, nonresponder imputation analysis showed that 53.7% of patients (72.6% of observed cases) met the Assessment of SpondyloArthritis international Society criteria for 40% improvement and 28.0% of patients (37.9% of observed cases) achieved partial remission; Ankylosing Spondylitis Disease Activity Scores were reduced from baseline (mean +/- SEM 3.9 +/- 0.1) to week 48 (2.1 +/- 0.1) and week 156 (1.9 +/- 0.1) (multiple imputation). Patients showed sustained improvements in pain, fatigue, physical function, and health-related quality of life. Conclusion The safety profile of bimekizumab was found to be consistent with previously demonstrated findings, and no new safety signals were identified. The efficacy of bimekizumab in patients with AS was sustained through 3 years of treatment.Pathophysiology and treatment of rheumatic disease

Stimulus frequency dependence of the central and peripheral somatosensory evoked activity in rats treated with various pesticides

Rats were treated with a combination of insecticide agents in different timing schemes. In acute administration, 1/5 LD50 of the three insecticides: dimethoate, propoxur and cypermethrin, or their combination, was given once by gavage. In the developmental model, female rats received oral doses of 1/25 LD50 of the above insecticides in combination in three timing schemes including pregnancy and lactation. Responses in the somatosensory cortex and in the tail nerve, evoked by peripheral electric stimulation, were recorded in acute preparation under urethane anesthesia. It was tested whether the parameters of the cortical and peripheral evoked response are dependent on the frequency and whether this dependence is different in control and treated animals. The latency increase of the cortical responses with increasing stimulation frequency was significantly stronger in rats treated acutely with cypermethrin and the combination, and in rats receiving the combination during both intra- and extrauterine development. On the duration, the effects were less clear. Frequency dependent increase of the tail nerve action potential latency was significantly intensified by cypermethrin, and the amplitude decrease, by cypermethrin and dimethoate. Fatigue of this response during a stimulation series was also altered by the insecticides. Frequency dependence and fatigue possibly reflect the actual state of the nervous system and may have the potency to be developed to functional biomarkers