ObjectiveTo evaluate the efficacy, safety and dose response of a novel oral Janus kinase inhibitor, peficitinib (ASP015K), as monotherapy in Japanese patients with moderate to severe rheumatoid arthritis (RA).MethodsIn a 12-week, double-blind study, 281 adult patients with RA with active disease not on concomitant disease-modifying antirheumatic drug therapy were randomised equally to once-daily placebo or peficitinib 25, 50, 100 and 150 mg. The primary endpoint was American College of Rheumatology (ACR) 20 response in the peficitinib treatment groups versus placebo at week 12.ResultsMean age was 53.0 years, 81.1% were female and 25.3% had previously used antitumour necrosis factor therapy. Peficitinib 50, 100 and 150 mg each showed statistically significantly higher ACR20 response rates compared with placebo, and response rates increased up to 150 mg with a statistically significant dose response. The total incidence of treatment-emergent adverse events (TEAEs) was similar between the placebo (64.3%) and peficitinib 25, 50, 100 and 150 mg groups (70.9%, 64.9%, 52.7% and 67.2%, respectively). TEAEs occurring more frequently in the peficitinib group compared with the placebo group included nasopharyngitis, increased blood creatine phosphokinase and diarrhoea. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in peficitinib 25 and 100 mg).ConclusionsTreatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed acceptable safety profile. These findings support further developments of peficitinib for RA treatment.Trial registration numberNCT01649999; Results.

Background Elevated parathyroid hormone (PTH) levels in secondary hyperparathyroidism (SHPT) lead to vascular calcification, which is associated with cardiovascular events and mortality. Increased PTH production is caused by the excessive proliferation of parathyroid gland cells, which is accelerated by abnormal mineral homeostasis. Evocalcet, an oral calcimimetic agent, inhibits the secretion of PTH from parathyroid gland cells and has been used for the management of SHPT in dialysis patients. We observed the effects of evocalcet on ectopic calcification and parathyroid hyperplasia using chronic kidney disease (CKD) rats with SHPT. Methods CKD rats with SHPT induced by adenine received evocalcet orally for 5 weeks. The calcium and inorganic phosphorus content in the aorta, heart and kidney was measured. Ectopic calcified tissues were also assessed histologically. To observe the effects on the proliferation of parathyroid gland cells, parathyroid glands were histologically assessed in CKD rats with SHPT induced by 5/6 nephrectomy (Nx) after receiving evocalcet orally for 4 weeks. Results Evocalcet prevented the increase in calcium and inorganic phosphorus content in the ectopic tissues and suppressed calcification of the aorta, heart and kidney in CKD rats with SHPT by reducing the serum PTH and calcium levels. Evocalcet suppressed the parathyroid gland cell proliferation and reduced the sizes of parathyroid cells in CKD rats with SHPT. Conclusions These findings suggest that evocalcet would prevent ectopic calcification and suppress parathyroid hyperplasia in patients with SHPT.

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Background ASP015K is a novel oral Janus kinase (JAK) inhibitor in development for the treatment of rheumatoid arthritis (RA). ASP015K inhibits JAK1/3 with more selectivity over JAK2 and can be dosed once daily (QD). Objectives To evaluate the efficacy, safety and dose response of ASP015K monotherapy in Japanese patients with moderate to severe RA (Clinical Trials Registration: NCT01649999). Methods In a 12-week, double-blind study, patients 20 years or older with active RA (defined as either CRP >0.5 mg/dL or ESR ≥28 mm/hr and ≥6 tender joints (of 68) and ≥6 swollen joints (of 66)) not on concomitant DMARD therapy were randomized equally to once daily ASP015K 25 mg, 50 mg, 100 mg, 150 mg or placebo (PBO). The primary endpoint was ACR20-CRP response at week12 or early termination (week12/ET). Results 281 patients were randomized and dosed; 81.1% of patients were female, the mean age was 53.0 years, and 25.3% had previously used an anti-TNF therapy. At baseline, the mean tender joint count was 15.2, the mean swollen joint count 12.2, the mean CRP 2.41 mg/dL, and the mean ESR 48.0 mm/hr. ASP015K 50 mg, 100 mg and 150 mg each showed a statistically significantly higher ACR20-CRP response at week12/ET as compared to PBO and the response rates increased up to 150 mg. ACR50/70 response and DAS28-CRP remission were significantly higher in the 2 highest dose groups as compared to PBO. Dose-dependent improvement in DAS28-CRP was also seen. The incidence of adverse events (AEs) was similar between PBO and combined ASP015K groups (64.3% vs 64.0%). The most frequently reported AEs in the combined ASP015K groups as compared to PBO were nasopharyngitis (13.3% vs 5.4%), RA (12.4% vs 32.1%), blood creatine phosphokinase (CPK) increased (4.9% vs 0%), and diarrhoea (3.6% vs 1.8%). These CPK increases tended to be transient, and patients recovered without interruption of study drug treatment. The overall incidence of infections and serious adverse events were similar between placebo and ASP015K (21.4% vs 24.9% and 1.8% vs 2.7%, respectively). One study-drug unrelated death due to a cerebral haemorrhage occurred in the ASP015K 50 mg group. The safety profile was generally comparable among the ASP015K dose groups, with the highest dose having a higher rate of blood CPK increase AEs. Conclusions In Japanese patients, treatment with ASP015K as monotherapy for 12 weeks is well tolerated and efficacious. These data support further development of ASP015K for the treatment of RA. Disclosure of Interest T. Takeuchi Grant/research support: AbbVie, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Janssen, Mitsubishi-Tanabe, Nippon-Shinyaku, Otsuka, Pfizer, Sanofi, Santen, Takeda, Teijin, Consultant for: Astellas, AstraZeneca, Eli Lilly, Novartis, Mitsubishi-Tanabe, Asahi Kasei, Speakers bureau: AbbVie, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer, Takeda, Y. Tanaka Grant/research support: BMS, MSD, Chugai, Mitsubishi-Tanabe, Astellas, AbbVie, Eisai, Janssen, Speakers bureau: Mitsubishi-Tanabe, AbbVie, Eisai, Chugai, Janss...

127 Background: Although the usefulness of the postoperative management based on Enhanced Recovery After Surgery (ERAS) program of patents with colectomy is shown, there are a few papers concerning ERAS program for gastric cancer patients. The aim of the present study was to examined whether a new postoperative management based on ERAS was feasible for pts with gastrectomy. Methods: From September 2009 to April 2010, we have adopted the new clinical pathway (CP) based on ERAS and oral rehydration therapy (ORT) for 30 consecutive gastric cancer patients who underwent curative gastrectomy. These pts began a oral rehydration solution (ORS) on the first postoperative day, and after the volume of ORS got 1,000 ml, we stopped intravenous transfusion. The incidence of adverse events, postoperative pt's activity score, which pt's daily activity was evaluated with, and total infusion volume of these pts were compared with 30 pts with the previous CP that were enrolled as a control group. Results: There were no significant differences in the clinical and operative factors between the two groups. The post operative patient's activity score of ERAS group was significantly higher up to 7th postoperative day (POD). Total infusion volume was significantly little besides, in most cases, infusion therapy was substituted for ORT with OS-1 within 2 POD. There was no difference in the hospitalized days, and the incidence of adverse events were statistically no significance between two groups. Conclusions: Our CP based on ERAS and ORT is feasible for patients with gastrectomy. No significant financial relationships to disclose.