Canakinumab treatment for patients with active recurrent or chronic TNF receptor-associated periodic syndrome (TRAPS): An open-label, phase II study

OBJECTIVE: To evaluate the efficacy of canakinumab, a high-affinity human monoclonal anti-interleukin-1β antibody, in inducing complete or almost complete responses in patients with active tumour necrosis factor receptor-associated periodic syndrome (TRAPS). METHODS: Twenty patients (aged 7-78 years) with active recurrent or chronic TRAPS were treated with canakinumab 150 mg every 4 weeks for 4 months (2 mg/kg for those ≤40 kg) in this open-label, proof-of-concept, phase II study. Canakinumab was then withdrawn for up to 5 months, with reintroduction on relapse, and 4 weekly administration (subsequently increased to every 8 weeks) for 24 months. The primary efficacy variable was the proportion of patients achieving complete or almost complete response at day 15, defined as clinical remission (Physician's Global Assessment score ≤1) and full or partial serological remission. RESULTS: Nineteen patients (19/20, 95%; 95% CI 75.1% to 99.9%) achieved the primary efficacy variable. Responses to canakinumab occurred rapidly; median time to clinical remission 4 days (95% CI 3 to 8 days). All patients relapsed after canakinumab was withdrawn; median time to relapse 91.5 days (95% CI 65 to 117 days). On reintroduction of canakinumab, clinical and serological responses were similar to those seen during the first phase, and were sustained throughout treatment. Canakinumab was well tolerated and clinical responses were accompanied by rapid and sustained improvement in health-related quality of life. Weight normalised pharmacokinetics of canakinumab, although limited, appeared to be consistent with historical canakinumab data. CONCLUSIONS: Canakinumab induces rapid disease control in patients with active TRAPS, and clinical benefits are sustained during long-term treatment

Self-Cleaning Surfaces Realized by Biologically Sized Magnetic Artificial Cilia

Magnetic artificial cilia (MAC) are small actuators inspired by biological cilia found in nature. In microfluidic chips, MAC can generate flow and remove microparticles, with applications in anti-fouling. However, the MAC used for anti-fouling in the current literature has dimensions of several hundred micrometers in length, which limits the application to relatively large length scales. Here, biologically-sized magnetic artificial cilia (b-MAC) which are only 45 micrometers long and that are randomly distributed on the surface, are used to remove microparticles. It is shown that microparticles with sizes ranging from 5 to 40 µm can be removed efficiently and the final cleanness ranges from 69% to 100%, with the highest cleanness for the highest actuation frequency applied (40 Hz). The lowest cleanness is obtained for microparticles with a size equal to the average pitch between the b-MAC. The randomness in cilia distribution appears to have a positive effect on cleanliness, compared with the authors’ earlier work using a regular cilia array. The demonstrated self-cleaning by the b-MAC constitutes an essential step toward efficient self-cleaning surfaces for real-life application in miniaturized microfluidic devices, such as lab-on-a-chip or organ-on-a-chip devices, as well as for preventing fouling of submerged surfaces such as marine sensors.</p

Canakinumab reverses overexpression of inflammatory response genes in tumour necrosis factor receptor-associated periodic syndrome

Objective To explore whether gene expression profiling can identify a molecular mechanism for the clinical benefit of canakinumab treatment in patents with tumour necrosis factor receptor-associated periodic syndrome (TRAPS). Methods Blood samples were collected from 20 patients with active TRAPS who received canakinumab 150 mg every 4 weeks for 4 months in an open-label proof-of-concept phase II study, and from 20 aged-matched healthy volunteers. Gene expression levels were evaluated in whole blood samples by microarray analysis for arrays passing quality control checks. Results Patients with TRAPS exhibited a gene expression signature in blood that differed from that in healthy volunteers. Upon treatment with canakinumab, many genes relevant to disease pathogenesis moved towards levels seen in the healthy volunteers. Canakinumab downregulated the TRAPS-causing gene (TNF super family receptor 1A (TNFRSF1A)), the drug-target gene (interleukin (IL)-1B) and other inflammation-related genes (eg, MAPK14). In addition, several inflammation-related pathways were evident among the differentially expressed genes. Canakinumab treatment reduced neutrophil counts, but the observed expression differences remained after correction for this. Conclusions These gene expression data support a model in which canakinumab produces clinical benefit in TRAPS by increasing neutrophil apoptosis and reducing pro-inflammatory signals resulting from the inhibition of IL-1 beta. Notably, treatment normalised the overexpression of TNFRSF1A, suggesting that canakinumab has a direct impact on the main pathogenic mechanism in TRAPS

Source data for the publication: Self-Cleaning Surfaces Realized by Biologically Sized Magnetic Artificial Cilia

This data set contains the source data of the publication: Cui, Z., Zhang, S., Wang, Y., Tormey, L., Kanies, O.S., Spero, R.C., Fisher, J.K. &amp; Toonder, J.M.J. den (2021). Self-cleaning surfaces realized by biologically sized magnetic artificial cilia. Adv. Mater. Interfaces 2021, 2102016. https://doi.org/10.1002/admi.202102016. In this study, biologically-sized magnetic artificial cilia (b-MAC) which are only 45 micrometers long and that are randomly distributed on the surface, are used to remove microparticles. The data are experimentally obtained with methods described in the publication

Canakinumab reverses overexpression of inflammatory response genes in tumour necrosis factor receptor-associated periodic syndrome

OBJECTIVE: To explore whether gene expression profiling can identify a molecular mechanism for the clinical benefit of canakinumab treatment in patents with tumour necrosis factor receptor-associated periodic syndrome (TRAPS)