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Baseline characteristics and efficacy of Firsekibart /Compound betamethasone treated patients(FAS) Firsekibart (N = 156) Compound betamethasone (N = 155) Baseline Male (%) 100 97.4 Age (years) (mean (SD)) 45.7 (13.73) 44.1 (12.16) BMI (kg/m2) (mean (SD)) 27.45 (3.89) 27.55 (3.79) ≥ 3 flares reported during prior one year N(%) 143 (91.7) 135 (87.1) Percentage of patients with tophus N(%) 61 (39.1) 65 (41.9) Efficacy Change in pain intensity from baseline to 72 h (mm) (Least Squares mean (95%CI)) -57.09 (-60.08, -54.10) -53.77 (-56.77, -50.77) Median time to first new flare (24 weeks) Not estimable 45 days Time to First Achieving 50% Pain Reduction in the target joint (median (95CI%)) 24.5 h (24.10, 48.00) 24.3 h (24.03, 48.00) Percentage of patients with ≥ 1 new flare 12 weeks 10.9% 65.2% 24 weeks 14.7% 66.5% Mean number of new flares per patient (mean (SD)) 12 weeks 0.2 (0.52) 1.2 (1.27) 24 weeks 0.2 (0.79) 1.6 (1.79) The total adverse events and treatment-related adverse events were 365 and 146 in the Firsekibart-treated group, versus 471 and 188 in the CB-treated group, respectively. Data availability The datasets generated and/or analysed during the current study are not publicly available due [Firsekibart is currently under review at the Center for Drug Evaluation for NDA] but are available from the corresponding author on reasonable request. Declarations Ethics approval and consent to participate Ethical approval was obtained from the Ethics Review Committee of Huashan Hospital Affiliated to Fudan University, Number: 2022 (976).

Background To evaluate the efficacy and safety of HLX01, a rituximab biosimilar, as combination therapy with methotrexate in Chinese patients with active rheumatoid arthritis who had inadequate responses to methotrexate. Methods In this double-blind, placebo-controlled phase 3 trial, biologic-naïve patients with moderate-to-severe active rheumatoid arthritis and inadequate responses to methotrexate were randomized 2:1 to receive 1000 mg HLX01 or placebo intravenously on days 1 and 15. On the first day of weeks 24 and 26, patients in both groups received 1000 mg HLX01 via intravenous infusion. The primary endpoint was the American College of Rheumatology (ACR) 20 response rate at week 24. Secondary endpoints including efficacy, safety, immunogenicity, pharmacokinetics and pharmacodynamics were assessed up to week 48. Results Between 28 May 2018 and 11 September 2020, 275 patients were randomized to the HLX01 group ( n = 183) or the placebo group ( n = 92). At week 24, the proportion of patients achieving ACR20 response was significantly greater in the HLX01 group compared with the placebo group in the intention-to-treat population (60.7% vs 35.9%; P < 0.001) and per-protocol set (60.3% vs 37.1%; P < 0.001). Most secondary efficacy endpoints favoured HLX01 when assessed at weeks 12, 24, 36 and 48. Incidences of treatment-emergent adverse events were similar between groups. Infusion-related reactions occurred more frequently following the initial two doses of HLX01 than the subsequent doses. Conclusions HLX01 plus methotrexate improved clinical outcomes compared with placebo in Chinese patients with rheumatoid arthritis who had inadequate responses to methotrexate. This treatment regimen was well tolerated, showing comparable safety profiles to placebo. Trial registration ClinicalTrials.gov , NCT03522415 . Registered on 11 May 2018.

Objective To evaluate the efficacy and safety of firsekibart versus colchicine for prophylaxis against acute gout flares in participants initiating urate‐lowering therapy (ULT). Methods In this randomized, multicenter, open‐label, active‐controlled, phase 2 trial, participants were randomized (1:1:1) to receive a single subcutaneous injection of firsekibart 100 mg or 200 mg or oral colchicine 0.5 mg/day for 12 weeks. ULT was initiated at baseline or within 1 week before screening. The primary endpoint was the mean number of acute gout flares per participant over 12 weeks. Results A total of 162 participants received firsekibart 100 mg (n = 55), 200 mg (n = 52), or colchicine (n = 55). Baseline characteristics were comparable between groups. No flares were observed in the firsekibart 200 mg group within 12 weeks. The adjusted mean number of acute gout flares per participant was 0.02 with firsekibart 100 mg and 0.34 with colchicine, with a rate ratio of 0.05 (95% confidence interval 0.01–0.43; P = 0.0060). Both treatment groups receiving firsekibart (at either dose) had a lower proportion of patients with at least one acute gout flare than the colchicine group. Firsekibart had a favorable safety profile, with no treatment‐emergent adverse events (AEs) leading to treatment discontinuation/study withdrawal, no treatment‐related serious AEs, and no deaths. Conclusion Firsekibart provided superior prophylaxis against acute gout flares compared with colchicine in patients initiating ULT, with a favorable tolerability profile, supporting its potential as a treatment option for patients with gout initiating ULT.

ObjectivesEfficacy and safety of tofacitinib, an oral Janus kinase inhibitor, were evaluated in a 6-month, double-blind, phase 3 study in Chinese patients with active (polyarthritic) psoriatic arthritis (PsA) and inadequate response to ≥1 conventional synthetic disease-modifying antirheumatic drug.MethodsPatients were randomised (2:1) to tofacitinib 5 mg twice daily (N=136) or placebo (N=68); switched to tofacitinib 5 mg twice daily after month (M)3 (blinded). Primary endpoint: American College of Rheumatology (ACR50) response at M3. Secondary endpoints (through M6) included: ACR20/50/70 response; change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI); ≥75% improvement in Psoriasis Area and Severity Index (PASI75) response, and enthesitis and dactylitis resolution. Safety was assessed throughout.ResultsThe primary endpoint was met (tofacitinib 5 mg twice daily, 38.2%; placebo, 5.9%; p<0.0001). M3 ACR20/ACR70/PASI75 responses, and enthesitis and dactylitis resolution rates, were higher and HAQ-DI reduction was greater for tofacitinib 5 mg twice daily versus placebo. Incidence of adverse events (AEs)/serious AEs (M0–3): 68.4%/0%, tofacitinib 5 mg twice daily; 75.0%/4.4%, placebo. One death was reported with placebo→tofacitinib 5 mg twice daily (due to accident). One serious infection, non-serious herpes zoster, and lung cancer case each were reported with tofacitinib 5 mg twice daily; four serious infections and one non-serious herpes zoster case were reported with placebo→tofacitinib 5 mg twice daily (M0–6). No non-melanoma skin cancer, major adverse cardiovascular or thromboembolism events were reported.ConclusionIn Chinese patients with PsA, tofacitinib efficacy was greater than placebo (primary and secondary endpoints). Tofacitinib was well tolerated; safety outcomes were consistent with the established safety profile in PsA and other indications.Trial registration numberNCT03486457.

IntroductionIxekizumab, an interleukin 17A (IL-17A) inhibitor, has demonstrated rapid and sustained improvement in the signs and symptoms in patients with active radiographic axial spondyloarthritis (r-axSpA) in global and Chinese populations. We studied the effect of ixekizumab on patient-reported outcomes (PROs) (including patient global, spinal pain, stiffness, and fatigue) and overall health-related quality of life (HRQoL) of ixekizumab in the phase 3 study in China.MethodsIn this Chinese phase 3, randomized, double-blind, placebo-controlled study, patients with r-axSpA were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg) or placebo for 16 weeks. At week 16, patients receiving placebo were switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. Data for patient global, spinal pain, spinal pain at night, stiffness, and fatigue were collected through week 52. Minimally clinical important differences (MCIDs) were determined for spinal pain and spinal pain at night. The subgroup analyses by baseline disease duration since diagnosis and baseline C-reactive protein (CRP) level were conducted post hoc.ResultsCompared with placebo, patients treated with IXEQ4W reported significantly greater improvement with a rapid onset in changes from baseline of PROs (patient global, spinal pain, spinal pain at night, stiffness, and fatigue) through week 16. Improvements were maintained through week 52. A similar trend of improvement was also observed in MCID response in spinal pain and spinal pain at night. The improvement in overall HRQoL was supported by EQ-5D-5L assessment. Subgroup analyses demonstrated that IXEQ4W provided significantly greater efficacy at week 16 compared with placebo, irrespective of baseline disease duration or baseline CRP level.ConclusionIXEQ4W provided rapid and sustained improvement in clinically relevant PROs and overall HRQoL through 1-year treatment in Chinese patients with r-axSpA. Regardless of the baseline disease duration or baseline CRP level, consistent efficacy was observed.Trial RegistrationClinicalTrials.gov identifier NCT04285229.

Introduction: To assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX). Methods: This was a 52-week, randomized, double-blind, placebo controlled, phase III study in patients with RA who had an inadequate response to MTX. Patients (n = 290) receiving stable background MTX were randomly assigned (1:1) to receive placebo or baricitinib 4 mg once daily with a primary endpoint at week 12. PROs assessed included Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient’s Global Assessment of Disease Activity, patient’s assessment of pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), European Quality of Life-5 Dimensions-5 Level index scores and visual analogue scale, and measures collected in electronic patient daily diaries: duration of morning joint stiffness, Worst Tiredness, and Worst Joint Pain. Treatment comparisons were made with logistic regression and analysis of covariance models for categorical and continuous variables, respectively. Results: Statistically significant (p ⩽ 0.05) improvements in all PROs were observed in the baricitinib 4 mg group compared to placebo as early as week 1 to week 4; and were sustained to week 24. These improvements were maintained until week 52 for the baricitinib group. A significantly larger proportion of patients met or exceeded the minimum clinically important difference for HAQ-DI (⩾0.22) and FACIT-F (3.56) profiles in the baricitinib group. Conclusion: Baricitinib provided significant improvements in PROs compared to placebo to 52 weeks of treatment in patients with RA who had an inadequate response to MTX. Clinicaltrials.gov identifier: https://clinicaltrials.gov/ct2/show/NCT02265705; NCT02265705; RA-BALANCE. Registered 13 October 2014

Objectives The aim of this work is to verify the non-inferior efficacy and safety of CMAB008 compared with innovator infliximab in rheumatoid arthritis patients combined with methotrexate. Methods We conducted a randomized, double-blinded, parallel, positive control design, multicenter study, with a stable dose of methotrexate. Patients were enrolled randomly with a ratio of 1:1 to receive intravenously CMAB008 3 mg/kg or innovator infliximab 3 mg/kg at weeks 0, 2, 6, 14, 22 and 30. The primary efficacy endpoint was American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 30. The non-inferiority was established if the lower limit of the one-sided 97.5% confidence interval (CI) for the difference was more than − 15% and the equivalence was established if the two-sided 95% CI was within ± 15% in an exploratory equivalence analysis. The secondary endpoints included other efficacy assessment parameters, as well as immunogenicity, safety, and pharmacokinetics. Results In the full analysis population (FAS), 110 (57.6%) of 191 patients in the CMAB008 group and 120 (62.2%) of 193 patients in the innovator infliximab group reached the primary outcome of ACR20 at week 30. The differences of the rates were − 4.6% and the lower limit of one-sided 97.5% confidence interval was − 14.29%, not less than the lower limit of the non-inferiority margin (− 15%); so CMAB008 was non-inferior to innovator infliximab. Further, CMAB008 was equivalent to innovator infliximab both in FAS (difference − 4.6%, 95% CI − 14.29% to 5.12%) and PPS (difference – 3.3%, 95% CI – 13.18% to 6.62%). The efficacy, safety, immunogenicity, and pharmacokinetics are highly similar between CMAB008 and innovator infliximab. Conclusions Non-inferior efficacy of CMAB008 to innovator infliximab is illustrated with similar early and lasting therapeutic effects, and the equivalence is further demonstrated. CMAB008 is well tolerated and has semblable safety compared with the innovator infliximab. Trial registration number NCT03478111.

Conductive hydrogels have potential applications in the field of wearable devices as carrier materials for flexible strain sensors. In this work, antifreeze filler glycerol (GL) and conductive filler graphene oxide (GO) were introduced into sodium polyacrylate (PAAS) chemical cross-linking network hydrogels, and the PAAS/GO/GL antifreeze conductive hydrogels were prepared by one-pot method. The structures and properties of the hydrogels were characterized and tested. The results showed that the addition of GO improved the mechanical properties and conductivity of the hydrogel. When the addition of GO was 0.6 wt%, the tensile strength of PAAS/GO/GL hydrogel reached the maximum of 0.215 MPa, the corresponding elongation at break reached 1180%, and the conductivity reached 1.056 S · m − 1 at room temperature. The addition of GL resulted in good freezing resistance and moisture retention of the hydrogel, with a conductivity of 0.846 S · m − 1 even after freezing at −20 °C. The PAAS/GO/GL hydrogel showed good sensing performance. When the tensile deformation reached 600%, the gauge factor (GF) reached 10.82. In addition, PAAS/GO/GL hydrogel also has good self-healing and adhesion, which has potential application value in flexible wearable sensors.

ObjectivesThis phase 2b, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of telitacicept, a novel fusion protein that neutralises signals of B lymphocyte stimulator and a proliferation-inducing ligand, in active systemic lupus erythematosus (SLE).MethodsAdult patients with active SLE (n=249) were recruited from 29 hospitals in China and randomised 1:1:1:1 to receive subcutaneous telitacicept at 80 mg (n=62), 160 mg (n=63), 240 mg (n=62) or placebo (n=62) once weekly in addition to standard therapy. The primary endpoint was the proportion of patients achieving an SLE Responder Index 4 (SRI-4) response at week 48. Missing data were imputed using the last observation carried forward method.ResultsAt week 48, the proportion of patients achieving an SRI-4 response was 75.8% in the 240 mg telitacicept group, 68.3% in the 160 mg group, 71.0% in the 80 mg group and 33.9% in the placebo group (all p<0.001). Significant treatment responses were observed in secondary endpoints, including a ≥4-point reduction on the Systemic Lupus Erythematosus Disease Activity Index, a lack of Physician’s Global Assessment score worsening and a glucocorticoid dose reduction in the 240 mg group. Telitacicept was well tolerated, and the incidence of adverse events and serious adverse events was similar between the telitacicept and placebo groups.ConclusionsThis phase 2b clinical trial met the primary endpoint. All telitacicept groups showed a significantly higher proportion of patients achieving an SRI-4 response than the placebo group at week 48, and all doses were well tolerated. These results support further investigations of telitacicept in clinical trials involving more diverse populations and larger sample sizes.Trial registration numberClinicalTrials.gov Registry (NCT02885610).

Introduction Ixekizumab, an interleukin-17A inhibitor, was efficacious and well tolerated for the treatment of active radiographic axial spondyloarthritis (r-axSpA) in international clinical studies. This phase III study aimed to determine the efficacy and safety of ixekizumab for treating Chinese patients with active r-axSpA. Methods Adults with active r-axSpA naïve to biologic disease-modifying antirheumatic drugs (bDMARDs), or with an inadequate response/intolerance to one tumor necrosis factor inhibitor, were randomized (1:1), double-blind, to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg), or placebo, for 16 weeks. Patients receiving placebo were then switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. The primary endpoint was the proportion of bDMARD-naïve patients achieving an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at week 16. Results In total, 147 patients were randomized to receive placebo ( n  = 73) or IXEQ4W ( n  = 74). At week 16, more bDMARD-naive patients achieved ASAS40 in the IXEQ4W group ( n  = 66; 40.9%) than the placebo group ( n  = 64, 7.8%; p  < 0.001). In the overall study population, ASAS40 was also achieved by more patients in the IXEQ4W group (37.8%) than the placebo group (8.2%; p  < 0.001) at week 16, with a significant difference observed as early as week 1. There were significant improvements in all key secondary endpoints at week 16 with IXEQ4W versus placebo. Efficacy was sustained at week 52 in patients who continued IXEQ4W and there were also clinical improvements from weeks 16 to 52 in patients switched to IXEQ4W. The safety profile of ixekizumab was consistent with that described previously. Infections and injection-site reactions were the most frequently reported events of special interest. Conclusions IXEQ4W was associated with rapid and significant improvements in the signs and symptoms of active r-axSpA in Chinese patients at week 16 that were sustained at week 52, with no new safety signals. Trial registration number ClinicalTrials.gov identifier: NCT04285229.