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Background: Biologic disease modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis (r-axSpA), otherwise known as ankylosing spondylitis, when conventional therapies fail. We report efficacy and safety results of a Phase 3 study of ixekizumab, a high-affinity monoclonal antibody that selectively targets IL-17A, in bDMARDnaïve patients with r-axSpA. Methods: In this randomized, double-blind, Phase 3 study, adult patients with inadequate response/intolerance to NSAIDs, an established diagnosis of r-axSpA, and with radiographic sacroiliitis centrally defined by modified New York criteria and ≥1 spondyloarthritis feature according to Assessment of Spondyloarthritis International Society (ASAS) criteria were recruited from 84 sites (12 countries) in Europe, Asia, and North America. Patients were randomized 1:1:1:1 using a computer-generated random sequence to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference arm), or placebo. The primary endpoint was the proportion of patients achieving an ASAS40 response at Week 16. Findings: Between June 20, 2016 and August 22, 2017, 341 patients were randomized to placebo (N=87), adalimumab (N=90), ixekizumab Q2W (N=83), or ixekizumab Q4W (N=81). At Week 16, significantly more patients achieved ASAS40 with ixekizumab Q2W (n=43, 51•8%, p<0•0001), ixekizumab Q4W (n=39, 48•1%, p<0•0001), and adalimumab (n=32, 35•6%; p=0•0053) versus placebo (n=16, 18•4%). One serious infection occurred in each of the ixekizumab Q2W (1•2%), ixekizumab Q4W (1•2%), and adalimumab (1•1%) arms; none were reported with placebo. One (1•1%) Candida infection occurred in the adalimumab arm and one (1•2%) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease. No opportunistic infections, malignancies, or deaths occurred. Interpretation: Each dosing regimen of ixekizumab was superior to placebo for improving r-axSpA signs and symptoms in bDMARD-naïve patients; the safety profile was consistent with previous studies of ixekizumab. The adalimumab control arm performed as expected. Funding: Eli Lilly and Company Research in context Evidence before this study Pubmed was searched using the terms "ankylosing spondylitis", "axial spondyloarthritis", and "disease-modifying anti-rheumatic drugs", including articles through May 30, 2018. Axial spondyloarthritis (axSpA) is a chronic immune-mediated disease characterized by inflammation of the spine and sacroiliac joint (SIJ), peripheral joint involvement, extra articular manifestations, and a strong genetic association with human leukocyte antigen (HLA)-B27. Radiographic axSpA (r-axSpA) was previously classified as ankylosing spondylitis (AS) in 1984 and updated to r-axSpA as part of the ASAS criteria. Both criteria sets require the same radiographically confirmed structural damage to the sacroiliac joint as well as at least one accompanying clinical element. Recommendations for the management of r-axSpA generally include exercise and physiothera...

This paper introduces materials and architectures for ultrathin, stretchable wireless sensors that mount on functional elastomeric substrates for epidermal analysis of biofluids. Measurement of the volume and chemical properties of sweat via dielectric detection and colorimetry demonstrates some capabilities. Here, inductively coupled sensors consisting of LC resonators with capacitive electrodes show systematic responses to sweat collected in microporous substrates. Interrogation occurs through external coils placed in physical proximity to the devices. The substrates allow spontaneous sweat collection through capillary forces, without the need for complex microfluidic handling systems. Furthermore, colorimetric measurement modes are possible in the same system by introducing indicator compounds into the depths of the substrates, for sensing specific components (OH(-) , H(+) , Cu(+) , and Fe(2+) ) in the sweat. The complete devices offer Young's moduli that are similar to skin, thus allowing highly effective and reliable skin integration without external fixtures. Experimental results demonstrate volumetric measurement of sweat with an accuracy of 0.06 μL/mm(2) with good stability and low drift. Colorimetric responses to pH and concentrations of various ions provide capabilities relevant to analysis of sweat. Similar materials and device designs can be used in monitoring other body fluids.

This paper presents materials and designs for an ultrathin, stretchable class of device that is capable of lamination onto the surface of the skin, for wireless determination of dielectric and surface strain properties. The sensor exploits LC resonators with capacitive electrodes whose radio frequency characteristics change with variations in skin properties, and is capable of conformal and spontaneous integration with skin due to their skin‐like, “epidermal”, mechanical properties. Resonance frequencies of the LC resonators can be measured wirelessly through changes in the absorption of electromagnetic energy from a coil connected to an impedance measurement setup and placed in proximity to the epidermal device. Experimental results demonstrate that the device offers a precision of 1.1 (arbitrary unit of a reference commercial hydration meter) for hydration and 1.3% for strain detection, with good stability and low drift. Measurement of simulated lymphedema using an expandable balloon with an attached sensor further demonstrates the potential for using such a sensor in monitoring skin swelling. Finite element simulation of physical deformation and associated changes in electrical properties enable quantitative interpretation of the experimental results. The results may have relevance for wireless evaluation of the skin, for applications ranging from dermatology and cosmetology to health/wellness monitoring (lymphedema, transdermal water loss, edema, and psychological stress).

ACR20 response rates differed between secukinumab 75 mg, 150 mg and 300 mg doses and placebo; however, the primary efficacy endpoint was not achieved. Greater decreases in DAS28 were observed with secukinumab 75 mg, 150 mg and 300 mg than placebo. There were no unexpected safety signals and no specific organ-related toxicities. Further trials with secukinumab in the treatment of RA are warranted.