Ustekinumab for Crohn's disease: a nationwide real-life cohort study from Finland (FINUSTE)
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
Authors: Eberl, Anja; Hallinen, Taru; af Bjorkesten, Clas-Goran; Heikkinen, Markku; Hirsi, Eija; Kellokumpu, Mikko; Koskinen, Inka; Moilanen, Veikko; Nielsen, Christian; Nuutinen, Heikki; Suhonen, Ulla-Maija; Utriainen, Karri; Vihriala, Ilkka; Soini, Erkki; Wennerstrom, Christina; Nissinen, Riikka; Borsi, Andras; Koivunen, Minni; Tillonen, Jyrki; Sipponen, Taina
Abstract
Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn's Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD. Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48 CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey-Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn's disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up. Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p = .0001) and SES-CD from 12 to 3 (p = .009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up. Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed.
Altered expression of chondroitin sulfate structure modifying sulfotransferases in the articular cartilage from adult osteoarthritis and Kashin-Beck disease
OSTEOARTHRITIS AND CARTILAGE
Authors: Han, J.; Li, D.; Qu, C.; Wang, D.; Wang, L.; Guo, X.; Lammi, M. J.
Abstract
Objective: To investigate the expression of enzymes involved in chondroitin sulfate (CS) sulfation in the articular cartilage isolated from adult patients with osteoarthritis (OA) and Kashin-Beck disease (KBD), using normal adults as controls. Methods: Articular cartilage samples were collected from normal, OA and KBD adults aged 38-60 years old, and divided into three groups with six individual subjects in each group. The morphology and pathology grading of knee joint cartilage was examined by Safranin O staining. The localization and expression of enzymes involved in CS sulfation (CHST-3, CHST-11, CHST-12, CHST-13, carbohydrate (Nacetylgalactosamine 4-sulfate 6-O) sulfotransferase 15 e CHST-15, and uronyl 2-O-sulfotransferase e UST) were examined by immunohistochemical (IHC) staining and semi-quantitative analysis. Results: Positive staining rates for anabolic enzymes CHST-3, CHST-12, CHST-15, and UST were lower in the KBD and OA groups than those in the control group. Meanwhile, reduced levels of CHST-11, and CHST-13 in KBD group were observed, in contrast to those in OA and control groups. The expressions of all six CS sulfation enzymes were less detected in the superficial and deep zones of KBD cartilage compared with control and OA cartilage. Conclusion: The reduced expression of the CS structure modifying sulfotransferases in the chondrocytes of both KBD and OA adult patients may provide explanations for their cartilage damages, and therapeutic targets for their treatment. (C) 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.