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Background Achieving ≥90% improvement in Psoriasis Area and Severity Index (PASI90) is achievable with newer biologic therapies, such as ixekizumab. Standard of care payment systems such as the Merit-based Incentive Payment System (MIPS) responder criteria could lead to under treatment and lower quality of life (QoL) outcomes compared with PASI90.Objective Show PASI90 is a higher standard than MIPS and is associated with greater improvements in QoL and other PRO outcomes.Methods Patients with moderate-to-severe psoriasis meeting PASI90 and MIPS criteria were compared in 3 phase 3 clinical trials of the interleukin-17A inhibitor ixekizumab (pooled UNCOVER-2/3 and IXORA-S). Patients satisfying MIPS criteria met either static Physician Global Assessment score ≤2, body surface area <3%, PASI <3, or Dermatology Life Quality Index ≤5. Improvements in QoL were compared between patients meeting PASI90 and MIPS criteria.Results All PASI90 responders were also MIPS responders (PASI90 responders). Not all MIPS responders met PASI90 (MIPS-only responders). Significantly larger change from baseline improvements for all health (skin pain, Itch NRS, DLQI, PtGA, WPAI-PsO work productivity loss, and WPAI-PsO activity impairment) and quality of life (EQ-5D 5L VAS and acute SF-36 PCS/MCS) outcome measures were observed in the PASI90 responders vs the MIPS-only responders.Conclusion PASI90 is a higher standard of response than MIPS and is associated with greater improvements in health and quality of life outcome measures.

Introduction: The Work Productivity and Activity Impairment Specific Health Problem Questionnaire (WPAI:SHP) is used to assess the impact of an intervention on work productivity in patients with psoriatic arthritis (PsA). Unfortunately, studies reporting changes or improvements in domains of WPAI:SHP by patients with PsA have a limited threshold of meaning due to the absence of published minimal clinically important differences (MCIDs). Our objective was to determine the MCIDs for improvement in WPAI:SHP in patients with active PsA. Methods: MCIDs for WPAI:SHP domains (presenteeism, work productivity loss, and activity impairment) were derived for patients with active PsA who were biologic naïve or TNF inhibitor (TNFi) experienced using 24-week results from two phase 3 trials (SPIRIT-P1 and SPIRIT-P2). MCIDs were derived using the anchor-based method supplemented by the distribution-based method. Anchors included achievement of the American College of Rheumatology 20 responder index (ACR20), the minimal disease activity (MDA), and the Health Assessment Questionnaire and Disability Index (HAQ-DI) MCID (improvement ≥ 0.35). Anchor validity was assessed by biserial correlation and analysis of covariance modeling against the domains. MCIDs were triangulated using the receiver operating characteristic (ROC) method supplemented by the distribution-based method. Results: The analyses included 417 biologic-naïve and 363 TNFi-experienced patients. ACR20, MDA, and HAQ-DI were valid anchors. Significant differences in WPAI:SHP domain scores were observed between patients achieving ACR20, MDA, or HAQ-DI compared to patients not achieving these clinical thresholds (all P&lt; 0.001). ROC analyses suggested that a ≥ 20% improvement in presenteeism, a 15% improvement in work productivity loss, and a 20% improvement in activity impairment represented clinically meaningful improvements in both populations. The distribution-based method supported the results. Conclusion: MCIDs for the presenteeism, work productivity loss, and activity impairment domains were estimated to be 20%, 15%, and 20%, respectively, in biologic-naïve or TNFi-experienced PsA populations. These results will help improve the meaningfulness of WPAI:SHP improvements reported by PsA patients. Trial Registration: SPIRIT-P1: NCT01695239, SPIRIT-P2: NCT02349295. Funding: Eli Lilly and Company.

Optical sectioning microscopy in wide-field fashion has been widely used to obtain three-dimensional images of biological samples; however, it requires scanning in depth and considerable time to acquire multiple depth information of a volumetric sample. In this paper, in vivo optical sectioning microscopy with volumetric hybrid illumination, with no mechanical moving parts, is presented. The proposed system is configured such that the optical sectioning is provided by hybrid illumination using a digital micro-mirror device (DMD) for uniform and non-uniform pattern projection, while the depth of imaging planes is varied by using an electrically tunable-focus lens with invariant magnification and resolution. We present and characterize the design, implementation, and experimentally demonstrate the proposed system’s ability through 3D imaging of in vivo Canenorhabditis elegans’ growth cones.

A wide-field multi-plane endoscopic system incorporating multiplexed volume holographic gratings and Talbot illumination to simultaneously acquire optically sectioned fluorescence images of tissue structures from different depths is presented. The proposed endoscopic system is configured such that multiple Talbot-illumination planes occur inside a volumetric sample and serve as the input focal planes for the subsequent multiplexed volume holographic imaging gratings. We describe the design, implementation, and experimental data demonstrating this endoscopic system’s ability to obtain optically sectioned multi-plane fluorescent images of tissue samples in wide-field fashion without scanning in lateral and axial directions.

Background: The efficacy and safety of ixekizumab (IXE) with and without continuous concomitant methotrexate (MTX), for up to 52 weeks of treatment, were evaluated in patients with active psoriatic arthritis (PsA). Methods: Patients with active PsA who were biologic-naive (SPIRIT-P1) or had prior inadequate response to tumor necrosis factor inhibitors (SPIRIT-P2) were randomized to 80 mg IXE every 4 (IXE Q4W) or 2 weeks (IXE Q2W), after a 160-mg initial dose. In this post hoc analysis, efficacy and safety were assessed up to week 52 in the subgroups of patients who received (i) IXE as monotherapy and (ii) IXE along with a stable dose of MTX (no dose tapering or increase). Efficacy outcomes included, but were not limited to, the percentage of patients achieving the American College of Rheumatology (ACR) responses. Results: Out of 455 patients initially randomized to IXE, 177 (38.9%) received monotherapy, 230 (50.5%) had concomitant MTX use, and 48 (10.5%) had other concomitant medication. Overall, 183 (40.2%) received IXE with a stable dose of concomitant MTX for 1 year. At week 52, the percentage of patients achieving ACR20/50/70 responses in IXE Q4W monotherapy versus concomitant MTX groups were 66.3% versus 55.3%, 48.4% versus 38.8%, and 35.8% versus 27.1%, respectively; these responses were generally similar with IXE Q2W. The safety profiles were similar between patients receiving IXE with or without concomitant MTX. Conclusions: In this post hoc analysis, treatment with IXE demonstrated sustained efficacy in patients with PsA up to 1 year of treatment, with or without concomitant MTX therapy. Trial registration: ClinicalTrials.gov NCT01695239and NCT02349295.