Search

Objective: The aim of this study is to investigate the effects of sarilumab on unacceptable pain [UP; visual analogue scale (VAS) >40 mm] and inflammation in patients with moderately-to-severely active rheumatoid arthritis., Methods: In this post hoc analysis of the KAKEHASI study, 243 patients received methotrexate with sarilumab 150 or 200 mg or placebo every other week, over 52 weeks. The proportion of patients with UP and correlations of changes in pain VAS from baseline with uncontrolled inflammation (C-reactive protein ≥1 mg/dl) and disease activity indices were assessed., Results: Almost 80% of patients (192/243) had UP at baseline, including ∼60% of patients with uncontrolled inflammation. Among patients receiving sarilumab, inflammation decreased rapidly, with 90% of patients achieving controlled inflammation by Week 2, while 63.1% continued to have UP. The proportion of patients with UP further decreased by Week 16 (28.5%, sarilumab vs. 64.0%, placebo). By Week 52, only ∼10% of patients had UP. Changes in pain VAS correlated with most disease activity indices and patient-reported outcomes. However, marked correlations between changes in pain VAS and C-reactive protein were observed only at Week 16., Conclusion: Sarilumab treatment reduced UP and inflammation in Japanese patients with rheumatoid arthritis., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Objectives: Anaemia is a frequent extra-articular manifestation in rheumatoid arthritis (RA); haemoglobin level changes are associated with changes in disease activity. This post-hoc analysis assessed potential relationships between haemoglobin and disease activity in Japanese patients with RA, enrolled in the KAKEHASI study (NCT02293902)., Methods: In this study, adult patients with moderate-to-severe active RA, who had an inadequate response to methotrexate, were randomised to subcutaneous sarilumab 150 mg every 2 weeks (q2w) or 200 mg q2w or placebo for 24 weeks. Post-hoc analyses were conducted on changes in haemoglobin and proportion of anaemic patients, using a mixed-effects model for repeated measures assuming an unstructured covariance. Relationships between haemoglobin and efficacy measures were explored., Results: At baseline, nearly half of patients had anaemia, defined by World Health Organization criteria (haemoglobin <12 g/dL, female; or <13 g/dL, male). At Week 24, the least squares mean change in haemoglobin levels was greater in sarilumab groups than for placebo (150 mg: 1.23 g/dL, 200 mg: 1.19 g/dL, placebo: 0.17 g/dL; p=0.0002 for both doses vs. placebo). By Week 24, the proportion of patients with anaemia was 17.8%, 22.9%, and 30.1% for sarilumab 150 mg, 200 mg, and placebo, respectively., Conclusions: In Japanese patients with RA, both doses of sarilumab were associated with greater improvement in haemoglobin levels and reduction in proportion of patients with anaemia, compared with placebo. Sarilumab may be a suitable treatment for patients with RA and anaemia.

Objectives: To assess the safety and pharmacokinetics (PK) of single-dose subcutaneous (SC) sarilumab or tocilizumab SC ± methotrexate (MTX) and to assess the pharmacodynamics (PD) of sarilumab SC or tocilizumab SC monotherapy in Japanese rheumatoid arthritis (RA) patients., Methods: TDU13402 was a randomized, double-blind, placebo-controlled, single-ascending dose Phase 1 study (NCT01850680). Twenty-four patients (6 per treatment group) received sarilumab 50, 100, or 200 mg plus MTX or placebo (2 per cohort) on Day (D) 1; PK and safety were assessed through D57. PDY14191 was a randomized, open-label, single-dose study (NCT02404558). Thirty patients (15 per arm) received sarilumab 150 mg or tocilizumab 162 mg on D1; PK, PD, and safety were assessed through D43., Results: TDU13402: mean serum sarilumab exposure increased in a greater than dose proportional manner from 50 to 200 mg dose with no clinically meaningful increase in treatment-emergent adverse events (TEAEs). PDY14191: PK profiles of single-dose sarilumab 150 mg or tocilizumab 162 mg were similar; some numerical differences in PD profiles and TEAEs were observed. Neutrophil count decrease/neutropenia was the most frequently reported TEAE with sarilumab treatment in both studies., Conclusions: PK, PD, and safety profiles of single-dose sarilumab SC with/without MTX were consistent with results anticipated in Japanese patients with RA., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Objectives: To describe the immunogenicity profile of sarilumab in Japanese patients with rheumatoid arthritis (RA)., Methods: Patients enrolled in the KAKEHASI and HARUKA studies were included in our analysis. In these studies, patients received sarilumab 150 mg or 200 mg every 2 weeks for 52 or 28 weeks in combination with methotrexate (MTX) (KAKEHASI), or for 52 weeks as monotherapy or in combination with non-MTX conventional synthetic disease-modifying anti-rheumatic drugs (HARUKA). Anti-drug antibodies (ADAs) and neutralising antibodies (NAbs) were assessed in the pooled population., Results: Positive ADA assay responses occurred in 10/149 (7.1%) patients treated with sarilumab 150 mg and 13/185 (7.0%) patients treated with sarilumab 200 mg, with persistent responses in 2 (1.4%) and 4 (2.2%) patients, respectively. Peak ADA titre was 30. No patients treated with the 150 mg dose and one patient (0.5%) treated with the 200 mg dose exhibited NAbs. There was no evidence of an association between ADA formation and hypersensitivity reactions or reduced efficacy., Conclusions: ADAs, which occurred at a low frequency and titre, did not affect the safety or efficacy of sarilumab 150 or 200 mg administered as monotherapy or combination therapy in Japanese patients with RA in the KAKEHASI or HARUKA studies., (© Japan College of Rheumatology 2021. Published by Oxford University Press.)

In adenocarcinoma of the small intestine, delays in diagnosis are frequent. The majority of patients present with advancedstage disease, and have either lymph node involvement or distant metastatic disease. Surgical resection is a mainstay in treatment of this disease, and the effectiveness of chemotherapy for advanced-stage or metastatic disease has been reported. We report a case of adenocarcinoma of the small intestine surviving for many years after surgical resection and chemotherapy. A 47-year-old woman underwent a small intestine resection, because she had a small intestinal tumor with obstruction. Histopathological examination revealed moderately-differentiated adenocarcinoma with lymph node metastasis. Adjuvant chemotherapy with S-1 was administered for a year, but in March 2006, a recurrent lesion at the right ovary was detected, and she underwent right adnexectomy. Because the ascites cytology revealed class V, chemotherapy was administered. In December 2008, CA19-9 elevated and magnetic resonance imaging showed a tumor behind the uterus, which was diagnosed as a recurrent disease. Because the tumor invaded the rectum, she received a low anterior resection, hysterectomy, and left adnexectomy. After surgical resection, UFT/UZEL was administered for half a year. In July 2010, computed tomography showed multiple lung metastases, and chemotherapy was performed again. However, the regimen was changed because her tumor marker elevated. She is being treated using a combination of cisplatin and irinotecan.

A 74-year old man was treated with first-cycle chemotherapy of paclitaxel (70 mg/m2=110 mg day 1, 8, 15) and carboplatin (AUC5=500 mg day 1) for lung cancer (c-T3N2M0, stage III A). On day 6 abdominal pain appeared, while on day 7 abdominal CT showed a perforation of the digestive tract. Thirty-three hours after the onset he underwent Hartmann operation during which we recognized a perforation 1.7 cm in size in the rectum. Although the cause of the perforation was unknown from the pathological findings, anticancer agents were suspected to be involved. Perforation should be taken into consideration in connection with acute abdominal disease after chemotherapy.

Background/aims: As endoscopic procedures become various and complicated, it becomes necessary to develop alternative techniques for tissue suture and ligation. We have developed a new suture technique intracorporeal knotting., Methodology: An 8-cm suture material having a knot on the other side of a needle, was used in laparoscopic surgery. Furthermore, a 5-mm2 Vicryl mesh was pierced as a buttress. The Lapra-ty was used to secure the tissue. Under laparotomy, the forestomach of a male Donryu rat at 6 weeks of age was incised and sutured with 3-0 Vicryl. 3-0 Vicryl was secured with the knot substitute (group A) or three-throw knot (group B) under Nembutal anesthesia. The animals were sacrificed 7 days after operation. Specimens were taken from the forestomach. Those were fixed with 10% formalin and stained with hematoxylin eosin and Elastica Wangieson methods. The histological findings were compared between group A and group B. A successful laparoscopic closure using Lapra-ty is reported in a patient with a perforation of the sigmoid colon., Results: Microscopically, in this method, neither erosion, ulcer nor microabscess is evidenced. This method may make an intracorporeal knot easy. Also we treated a patient who had a perforation of the sigmoid colon using Lapra-ty. The patient recovered without any trouble., Conclusions: This method could make ligation technique much easier and the operating time shorter.