Efficacy and safety of upadacitinib for active ankylosing spondylitis refractory to biological therapy: a double-blind, randomised, placebo-controlled phase 3 trial

Objectives: To evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to biological disease-modifying antirheumatic drugs (bDMARDs). Methods: Adults with active AS who met modified New York criteria and had an IR to one or two bDMARDs (tumour necrosis factor or interleukin-17 inhibitors) were randomised 1:1 to oral upadacitinib 15 mg once daily or placebo. The primary endpoint was Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Sequentially tested secondary endpoints included Ankylosing Spondylitis Disease Activity score, Spondyloarthritis Research Consortium of Canada MRI spine inflammation score, total back pain, nocturnal back pain, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and Maastricht Ankylosing Spondylitis Enthesitis Score. Results are reported from the 14-week double-blind treatment period. Results: A total of 420 patients with active AS were randomised (upadacitinib 15 mg, n=211; placebo, n=209). Significantly more patients achieved the primary endpoint of ASAS40 at week 14 with upadacitinib vs placebo (45% vs 18%; p<0.0001). Statistically significant improvements were observed with upadacitinib vs placebo for all multiplicity-controlled secondary endpoints (p<0.0001). Adverse events were reported for 41% of upadacitinib-treated and 37% of placebo-treated patients through week 14. No events of malignancy, major adverse cardiovascular events, venous thromboembolism or deaths were reported with upadacitinib. Conclusion: Upadacitinib 15 mg was significantly more effective than placebo over 14 weeks of treatment in bDMARD-IR patients with active AS. No new safety risks were identified with upadacitinib.</p

Safety and efficacy of upadacitinib in patients with active ankylosing spondylitis and an inadequate response to nonsteroidal antiinflammatory drug therapy: one-year results of a double-blind, placebo-controlled study and open-label extension

Objective To report the efficacy and safety of upadacitinib through 1 year in patients with ankylosing spondylitis (AS). Methods In the SELECT-AXIS 1 study, adults with active AS and an inadequate response to nonsteroidal antiinflammatory drugs were randomized to receive upadacitinib 15 mg once daily or placebo. At week 14, patients who had been randomized to receive placebo were switched to upadacitinib, and all patients continued in the open-label extension and received upadacitinib up to week 104; interim data up to week 64 are reported herein. Results Of 187 patients, 178 completed week 14 on study drug and entered the open-label extension. Similar proportions of patients in either group (continuous upadacitinib or placebo-to-upadacitinib) achieved Assessment of SpondyloArthritis international Society 40% response (ASAS40) or Ankylosing Spondylitis Disease Activity Score (ASDAS) showing low disease activity at week 64: >= 70% of patients achieved these end points based on nonresponder imputation (NRI) and >= 81% based on as-observed analyses. Furthermore, >= 34% (NRI) and >= 39% (as-observed analysis) achieved ASDAS showing inactive disease or ASAS showing partial remission at week 64. Mean changes from baseline (week 0) to week 64 in pain, function, and inflammation showed consistent improvement or sustained maintenance through the study. Among 182 patients receiving upadacitinib (237.6 patient-years), 618 adverse events (260.1 per 100 patient-years) were reported. No serious infections, major adverse cardiovascular events, venous thromboembolic events, gastrointestinal perforation, or deaths were reported. Conclusion Upadacitinib 15 mg once daily showed sustained and consistent efficacy over 1 year. Patients who switched from placebo to upadacitinib at week 14 showed similar efficacy versus those who received continuous upadacitinib.Pathophysiology and treatment of rheumatic disease

Ingestion of <i>Artemia</i> nauplii by Chinese mitten crab <i>Eriocheir sinensis</i> zoea larvae

A series of ingestion trials were conducted to determine the ingestion rate of Artemia nauplii by Eriocheir sinensis zoea larvae with increasing densities of Artemia and with or without rotifers as a co-feed. At each zoeal stage, 10 groups of 10 larvae were reared individually in glass beakers and fed with increasing densities of newly hatched Artemia nauplii (0.5, 2.5, 5, 10 and 20 individual (ind.) mL-1) with or without rotifers (15-25 ind. mL-1) as a co-feed. The average number of ingested Artemia was measured over 24 h. In addition, the average larval development rate (Larval Stage Index, LSI) over a longer period (time needed for the best treatment to reach 100% moult or metamorphosis to the next larval stage) was compared. The results showed that Artemia ingestion rate of E. sinensis larvae increased with increasing prey densities and larval development, and had a significantly negative correlation with rotifer consumption for all zoeal stages. Rotifers as an alternative prey significantly affected the intake of Artemia at early larval stages (Z1 and Z2) and promoted LSI at a lower Artemia density. Further experiments are needed to clarify the effect of prey density on survival and larval development when larvae are reared communally

Effect of feeding scheme and prey density on survival and development of Chinese mitten crab <i>Eriocheir sinensis</i> zoea larvae

The effect of feeding scheme and prey density on survival and development of Eriocheir sinensis zoea larvae was studied in three experiments. Different combinations and densities of rotifers (Brachionus rotundiformis) and newly hatched Artemia nauplii were fed to zoea larvae. Average survival at each stage, larval development (larval stage index, LSI), duration of zoeal stage and individual megalopa dry weight were compared among treatments. This study revealed that, under the experimental conditions, rotifers should be replaced with Artemia between the zoea 3 (Z3) and the zoea 4 (Z4) stage. The optimal rotifer feeding densities for zoea 1 (Z1) and zoea 2 (Z2) were 15 and 20 mL-1 respectively, while the optimal Artemia feeding density for Z3, Z4 and zoea 5 (Z5) was 3, 5 and 8 mL-1 respectively. Further trials in production scale are recommended

Effect of dietary soybean lecithin on reproductive performance of Chinese mitten crab <i>Eriocheir sinensis</i> (H. Milne-Edwards) broodstock

The effect of increasing levels of dietary phospholipids (PL) on the ovarian development and reproductive performance of Chinese mitten crab Eriocheir sinensis were investigated using four semipurified formulated diets supplemented with 0%, 1.2%, 2.4%, and 3.6% PL. Four groups of 40 females, with an average individual body weight of 95-120 g, were fed the experimental diets for a period of 7 months. Male crabs were introduced into the female rearing system in March, and mating, spawning, and egg hatching occurred in the following month. After 10 weeks of feeding, females fed the diet with 2.4% PL had a significantly higher gonadosomatic index (GSI) than females fed the diet with 0% PL, whereas females fed the diet with 1.2% PL had a significantly higher hepatic moisture content and lower hepatic lipid content than the other groups (P P E. sinensis broodstock. Further study should aim to investigate the optimal PL level in the broodstock diet of E. sinensis in respect to offspring quality

Larviculture techniques of Chinese mitten crab <i>Eriocheir sinensis</i>

Eriocheir sinensis is considered a luxury aquatic food for Chinese people due to its delicate flavor, and it therefore reaches a high market value. Its hatchery production and farming are being performed almost exclusively in China. Although breakthroughs in seed production and larval rearing techniques of E. sinensis have been achieved in the early 1980s. a fast expansion of hatchery production only took off in the 1990s, with the dramatic decline in natural recruitment. Many techniques have only been published as brief descriptions of local farmers' experience and most of these articles were written in Chinese. This paper provides general information on the hatchery techniques in aspects of broodstock maturation, spawning and larval rearing and points out the main bottlenecks of current mitten crab hatchery operations