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Jessica J Madera,1 Pedro Such,2 Cathy Zhao,3 Ross A Baker11Global Medical Affairs, Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, NJ, USA; 2Medical Affairs Psychiatry, H. Lundbeck A/S, Valby, Denmark; 3Biostatistics, Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, NJ, USAObjective: To evaluate the effect of aripiprazole once-monthly 400 mg (AOM 400; Abilify Maintena®) on symptom stability in acute treatment and maintenance therapy settings in patients with schizophrenia.Methods: Results were analyzed from two pivotal maintenance studies (Studies 246 and 247), a long-term (52 weeks), open-label extension of these studies (Study 248), an open-label, mirror-image study in patients switching from oral to long-acting injectable antipsychotic therapy (Study 283), and a study of AOM 400 in the acute setting (Study 291). Symptom stability was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression (CGI) scale (CGI-Severity of Illness and CGI-Improvement). Results are reported for the total study population and in subgroups stratified by age.Results: In Study 246, AOM 400 resulted in significantly greater improvements from baseline vs placebo on all measures of symptom stability, with improvements maintained through 52 weeks. In Study 247, a non-inferiority study, AOM 400 resulted in improvements in PANSS and CGI scores comparable or significantly greater at all timepoints vs oral aripiprazole. In Study 248, AOM 400 resulted in the long-term stability of symptom improvements from the earlier studies. In Study 283, AOM 400 resulted in significant improvements from baseline in PANSS and CGI scores over 24 weeks. In Study 291, AOM 400 resulted in significantly greater improvements from baseline in PANSS and CGI scores vs placebo at all post-baseline timepoints. In post hoc analyses, AOM 400 showed similar efficacy in symptom improvement in adult patients aged ≤35 years and >35 years, with some evidence of a larger treatment effect on PANSS negative symptoms among younger patients in the acute treatment setting.Conclusion: In acute treatment and maintenance therapy settings, AOM 400 was effective in the rapid stabilization and long-term maintenance of symptoms in patients with schizophrenia.Keywords: aripiprazole, long-acting injectable, antipsychotics, schizophrenia

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (

Background: Despite the existence of multiple outcome measures for the clinical signs of atopic dermatitis (AD), there is a need to standardise and validate them, especially for skin of colour patients. Primary objectives: To compare the reliability of commonly used AD outcome measures and to validate them in skin of colour patients. Methods: First study: 12 AD patients were scored by 5 clinicians using Eczema Area Severity Index (EASI), objective SCORing AD score (oSCORAD), Six Area Six Signs AD (SASSAD) and Three Items Severity (TIS). Second study: photos of 18 AD patients of various skin colours were scored by 5 clinicians using EASI, oSCORAD, SASSAD and TIS. Third study: 25 AD patients of various skin colours were scored by 5 clinicians over 2 scoring sessions using EASI, oSCORAD, IGA and greyscale. Melanin index was measured using a mexameter. Reliability was assessed using the intra-class correlation coefficient (ICC). Results: First study - Inter-rater reliability: the EASI and SASSAD showed good ICCs of 0.730(95%CI: 0.500-0.900) and 0.680(0.440-0.880), but TIS and oSCORAD had poor ICCs; Intra-rater reliability: EASI and TIS showed excellent ICCs of 0.886(0.744-0.952) and 0.820(0.614-0.923), while SASSAD showed a good ICC and oSCORAD had a poor ICC. Second study had poor validity and was improved upon by the third study, where the inter-rater ICCs were: EASI 0.827(0.658-0.941) in lighter patients and 0.774(0.598-0.906) in skin of colour; oSCORAD 0.680(0.441-0.880) in lighter patients and 0.736(0.544-0.889) in skin of colour; IGA 0.803(0.618-0.932) in lighter patients and 0.696 (0.490-0.868) in skin of colour; grey-scale had an ICC of 0.638(0.400-0.838) alone and 0.776(0.601-0.907) when replacing EASI’s erythema scale. All scores had excellent intra-rater reliability. Erythema did not contribute to variability using coefficient of variance analysis. Conclusions: EASI demonstrated the excellent reliability in patients of all skin colours, supporting it as the optimal AD outcome measure.

Inflammation and fibrosis are essential elements of diabetic nephropathy (DN). We tested the hypothesis that these elements are dependent upon Toll-like receptor 2 (TLR2) signalling by examining WT and TLR2(-/-) mice in an experimental model of DN. Diabetes was induced in WT and TLR2(-/-) mice by i.p. injection of streptozotocin. Kidney injury was assessed at 6, 12 and 24 weeks after induction of diabetes. Gene expression of TLR2, its endogenous ligands and downstream cytokines, chemokines and fibrogenic molecules were upregulated in kidneys from WT mice with streptozotocin diabetes. TLR2(-/-) mice were protected against the development of DN, exhibiting less albuminuria, inflammation, glomerular hypertrophy and hypercellularity, podocyte and tubular injury as compared to diabetic WT controls. Marked reductions in interstitial collagen deposition, myofibroblast activation (α-SMA) and expression of fibrogenic genes (TGF-β and fibronectin) were also evident in TLR2 deficient mice. Consistent with our in vivo results, high glucose directly promoted TLR2 activation in podocytes and tubular epithelial cells (TECs) in vitro, resulting in NF-κB activation, inflammation and TGF-β production. We conclude that TLR2 was required for the full development of inflammation, kidney damage and fibrosis in this model of DN. As TLR2 is known to be expressed by intrinsic kidney cells and as high concentration glucose stimulated podocytes and TECs in vitro to express TLR2 and TLR2 ligands, pro-inflammatory and pro-fibrotic cytokines in a TLR2 dependent manner in the present study, it appears likely that TLR2 signalling in intrinsic kidney cells contributes to the pathogenesis of diabetic nephropathy.