Therapeutic Research

目的：SGLT2 阻害剤等の血糖降下剤にシュアポスト®（レパグリニド）（以下，本剤）が新たに併用された2 型糖尿病患者を本剤投与開始後1 年間観察し，製造販売後の使用実態下における長期併用時の安全性および有効性を検討することを目的とした特定使用成績調査を実施した。　方法：中央登録方式により，患者背景，本剤の投与状況，SGLT2 阻害剤等の血糖降下剤の投与状況，有害事象，臨床検査値等について調査した。　結果：SGLT2 阻害剤併用例の安全性評価対象症例129 例に発現した副作用は悪心が2 例（1.55％）であった。悪心は2 例とも本剤投与3 ヵ月以内に発現しており，長期投与で副作用の発現割合の増加は認められなかった。SGLT2阻害剤併用例の有効性評価対象症例116 例のHbA1c 値は，本剤投与開始前の8.16±1.44％に対し，最終観察時には7.37±1.07％に低下し，最終観察時の変化量は－0.79±1.19％であった。変化量は，本剤投与開始3 ヵ月後は－0.79±1.10％，12 ヵ月後は－0.76±1.15％であり，長期にわたる改善が確認された。　結論：使用実態下での本剤とSGLT2阻害剤との長期併用において，新たな安全性の問題点は認められず，本剤の有効性に関しても特に懸念される点は認められなかった。

Background：A post‒marketing surveillance（PMS）of tiotropium/olodaterol（Spiolto® Respimat®；TIO/OLO）, a fixed‒dose combination of a long‒acting muscarinic antagonist and long‒acting β2‒agonist （LAMA/LABA）, approved for chronic obstructive pulmonary disease（COPD）, was conducted（NCT02850978）.　　Objective：To investigate baseline characteristics in patients with COPD who require LABA and LAMA for maintenance treatment other than TIO/OLO assessed in parallel with the PMS of TIO/OLO.　　Methods：The non‒interventional cross‒sectional survey（BCS；UMIN000023629） was conducted in parallel with the PMS to collect baseline characteristics for COPD patients newly prescribed LAMA/LABA other than TIO/OLO, in the same sites and physicians as the PMS. Baseline characteristics of the PMS and BCS were compared.　　Results：Mild COPD was slightly higher in the BCS（26.58％）than in the PMS （19.96％）. The mean post‒dose ％FEV1 and FEV1/FVC were numerically slightly higher in the BCS（62.14％ and 59.03％, respectively）than in the PMS （60.48％ and 55.84％, respectively）. The proportion of comorbidities, benign prostatic hyperplasia（BPH）and gastroesophageal reflux disease, was numerically higher and lower, respectively, in the BCS（6.53％ and 4.95％, respectively）than in the PMS（3.52％ and 7.83％, respectively）. The proportion of previously received respiratory medication（LAMA, LABA, or inhaled corticosteroids）was higher in the BCS（62.16％）than in the PMS（41.49％）. 　　Conclusions：Patient baseline characteristics of the PMS and BCS were different. BPH was numerically more prevalent in the BCS than in the PMS, indicating that the channeling bias regarding the contraindication（patients with micturition disorder due to prostatic hyperplasia etc.）of TIO/OLO probably affected the PMS.

Objective：To evaluate the general safety and effectiveness of hydroxychloroquine （HCQ）in Japanese patients with lupus erythematosus（LE）under Japanese good post‒marketing study practice（GPSP）regulation. 　Methods：This drug‒use results survey was designed to assess 1‒year general safety and effectiveness and at least 3 years of follow‒up for eye disorders. Patients with cutaneous（CLE）or systemic （SLE）LE and naïve to treatment with HCQ were eligible for enrollment. Basically, patients received HCQ as per the package insert. Safety was assessed, and effectiveness variables were determined from physician and patient impressions using the global improvement scale（GIS）for cutaneous symptoms. SLE patients evaluated fatigue and musculoskeletal pain on a visual analog scale（VAS）.　　Results：In interim 1‒year results from 1181 enrolled patients, safety and effectiveness were analyzed for 1007 and 863 patients, respectively. Mean（SD）treatment duration was 369.4（189.7）days, and HCQ dose was 259.1（60.3）mg/day. In the safety population, mean age（SD）was 41.7（14.9）years；CLE accounted for 7.15％ of patients and SLE for 92.45％；88.68％ were female. Incidence was 15.79％ for adverse drug reactions（ADRs）and 1.69％ for serious ADRs. Common ADRs were diarrhea（2.98％）, rash （2.88％）and drug eruption（2.09％）. All reported ADRs up to the 1‒year interim analysis were known. Improvement （improved or markedly improved）in cutaneous symptoms was rated at 50.3％ by physicians and 49.9％ by patients on the GIS after 52 weeks of HCQ treatment. From baseline to week 52, mean change（SD）was －1.24（2.06）for fatigue and －1.19（1.97）for musculoskeletal pain. 　　Conclusions：In this interim analysis, the use of HCQ in LE patients was associated with improved cutaneous symptoms, fatigue, and musculoskeletal pain. Safety results, monitored up to 1‒year after HCQ initiation, were consistent with the currently known safety profile. Nevertheless, long‒term safety, especially retinopathy, should be assessed in continuous surveillance.

Objective：To understand the patient journey and unmet medical needs of patients with systemic/cutaneous lupus erythematosus（SLE/CLE）in Japan. 　　Methods：Qualitative data were collected through semi‒structured, 45‒minute telephone interviews from Japanese patients with SLE/CLE（n＝10/n＝5）and medical specialists（dermatologists, nephrologists, rheumatologists）primarily responsible for SLE/CLE patient care. Interviewees were asked for their views and experience with regard to current care. 　　Findings：Only 3/15 patients suspected SLE/CLE and often delayed consultation of physicians. Three patients（1 SLE；2 CLE）presented directly to the diagnosing specialist, while 12 patients were referred from other departments, not being presented directly to specialists. Among the SLE/CLE patients, the time from the appearance of first symptoms to diagnosis ranged from 1 month to 18 years（mean 2.7 years）and from 2 months to 17 years（mean 3.7 years）, respectively. Oral and/or topical steroids were base medicines for both SLE and CLE patients. Immunosuppressants were used in 60％ and 0％ of SLE/CLE patients, and hydroxychloroquine in 30％ and 60％ of SLE/CLE patients, respectively. Key unmet needs highlighted by the specialists and patients were a lack of awareness about SLE/CLE, limited methods for early diagnosis, a lack of alternative to steroids and treatment effective for chronic symptoms, lack of tools/support aimed at improving education and patient quality of life. 　　Conclusions：In our sample, the mean time from the appearance of the first symptoms to diagnosis according to the SLE and CLE patients was 2.7 and 3.7 years, respectively. Improvements in awareness of SLE/CLE and the provision of accurate information and educational programs/materials for patients and non‒specialists are needed.

Background：Bile acids（BA）in the colon have a dual action as osmotic and stimulant agents. Inhibition of the ileal BA transporter reduces the ileal absorption of BA, increasing the content of BA in the colon, thereby stimulating colonic secretion and mobility. Newer agent such as elobixibat, an inhibitor of the ileal BA transporter, have proven beneficial in chronic constipation. In addition to their role as detergents facilitating dietary lipid absorption, BA modulate various metabolic events after binding to specific BA receptors such as the farnesoid X receptor （FXR）and the G‒protein‒coupled receptor 5（TGR5）. Thus, BA regulate lipid, carbohydrate and energy metabolism. The present study aimed to evaluate metabolic effects of elobixibat in patients with diabetes complicated with chronic constipation（CC）.　　Methods：Sixteen diabetic patients complicated with CC, mean age 75 years, were orally administered elobixibat 5‒15 mg for 3 months. In addition to FBS, HbA1c, LDL‒C, HDL‒C, TG, body weight were measured before and after elobixibat treatment.　　Results：During the study period of 3 months, FBS, HbA1c, LDL‒C, HDL‒C showed significant improvement. But there were not significant reduction of TG and body weight.　　Conclusion：The observation suggests that elobixibat proves beneficial in patients with diabetes complicated with CC.

This study, jointly conducted by the Gifu Pharmaceutical Association and Gifu Pharmaceutical University, used Pharmaceutical Intervention Records（PIR）project data to analyze the characteristics and economic impact of prescription audits resulting from drug discontinuation. Pharmacists entered audit data for 1546 prescriptions into the PIR database in 2018. For this analysis, we divided these 1546 prescriptions into a subject group（those that resulted in drug cancellation）and a control group（comprising all other prescriptions）. The reduction in drug cost per prescription was 1469 yen in the subject group, which was significantly greater than that in the control group（840 yen）. In the subject group, pharmacists tended to use prescription notes to identify drugs with the same indication, combined use contraindications, and residual drugs. In addition, the main indications of drugs that were subject to cancellation were digestive and central nervous system applications. This was considered a significant factor underlying reduced drug costs in the subject group, and is expected to improve regulation of polypharmacy practices. By confirming the prescription notes focusing on cancellation of digestive medicines, patient care for those taking multiple drugs can be improved. Also, these actions positively impact the medical economy because drug cancellation is required to prevent duplication and negative interactions between prescription drugs.

高齢者における抗コリン作用を有する薬剤の使用は認知機能障害のリスクを上昇させることが報告されている。第一世代抗ヒスタミン薬は抗コリン作用を有するため，認知症患者を含むすべての高齢者に対して慎重な投与を要する。本症例は抗コリン薬であるプロパンテリンを内服中のアルツハイマー型認知症と血管性認知症を合併した混合型認知症患者が，第一世代抗ヒスタミン薬であるクロルフェニラミンを含有するOTC 医薬品を内服し，服用2 日目に認知機能障害の悪化がみられ，服用9 日目に内服は中断された。内服中断2 日後に認知機能障害は改善した。認知症患者がOTC 医薬品を使用する場合，第一世代抗ヒスタミン薬を含有しないOTC 医薬品を選択する必要がある可能性が示唆された。

Rivastigmine is a cholinesterase inhibitor used in the treatment of Alzheimer‒type dementia. Since rivastigmine patch is a transdermal patch, the incidence of gastrointestinal disorders is lower than that associated with oral administration. Some case reports have reported cholinergic symptoms following the administration of rivastigmine patch, but the administration of rivastigmine patch was inappropriate in these reports. Nowadays, cholinergic symptoms following the appropriate administration of rivastigmine patch are rarely reported. We present a case with prodromal symptoms of cholinergic crisis following appropriate administration of rivastigmine patch. A 67‒year‒old woman with Alzheimer‒type dementia receiving 13.5 mg of rivastigmine patch presented with prodromal symptoms of cholinergic crisis such as nausea, vomiting, and diarrhea with low serum cholinesterase.　　Rivastigmine patch was removed immediately, and her gastrointestinal disorders were resolved in a day. This case suggests that careful attention to the appearance of prodromal symptoms of cholinergic crisis is important and serum cholinesterase should be checked even in case of appropriate administration of rivastigmine patch.