Clinical comprehensive evaluation of three oral Janus kinase inhibitors for atopic dermatitis / 中国药房

OBJECTIVE To comprehensively evaluate the three oral Janus kinase inhibitors （JAKi） such as upadacitinib， abrocitinib and baricitinib in the treatment of atopic dermatitis. METHODS The six dimensions of safety， efficacy， economy， appropriateness， accessibility and innovativeness were used for evaluation. Meta-analysis was conducted to evaluate the safety and efficacy of three oral JAKi； pharmacoeconomic studies were searched， and the treatment costs were calculated to evaluate the economy of each JAKi. Appropriateness was described based on literature review and drug labels. Accessibility of three oral JAKi was assessed by using a questionnaire survey. The innovation of JAKi was elucidated from the perspective of its mechanism of action. RESULTS In terms of safety， the incidence of upper respiratory tract infection （OR＝1.47， 95%CI of 1.04-2.08， P＝0.03） and nasopharyngitis （OR＝1.44， 95%CI of 1.06-1.95， P＝0.02） in the upadacitinib 30 mg group was significantly higher than that in the placebo group； the incidence of nasopharyngitis in baricitinib 4 mg group was significantly higher than that in the placebo group （OR＝2.24， 95%CI of 1.39-3.61， P＝0.000 8） and baricitinib 2 mg group （OR＝0.48， 95%CI of 0.31-0.74，P＝0.001）. In terms of efficacy， regardless of the dosage， all three JAKi groups were superior to the placebo group， and the high-dose groups of upadacitinib and abrocitinib were superior to the low-dose groups （P＜0.000 1）. In terms of economy， the annual treatment cost of baricitinib was the lowest （13 870.0 yuan）， but it has not been approved for atopic dermatitis indication in China； next was upadacitinib （27 192.5 yuan）. In terms of appropriateness， the overall appropriateness of the three JAKis was good， but none of them was suitable for patients with severe liver injury. In terms of accessibility， baricitinib had the highest availability rate （59.4%）， but the affordability of upadacitinib was relatively good under China’s medical insurance system. In terms of innovation， among the three types of JAKi， upadacitinib and abrocitinib had better innovation. CONCLUSIONS Three oral JAKi treatments for atopic dermatitis have controllable safety and good efficacy. Considering the issue of medical insurance reimbursement， it is recommended that Chinese patients use upadacitinib.

Efficacy and safety of flurbiprofen cataplasms versus loxoprofen sodium cataplasms in knee osteoarthritis: a randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA.@*METHODS@#This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events.@*RESULTS@#Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain.@*CONCLUSIONS@#This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.

Data mining of adverse drug reaction signals for ado-trastuzumab emtansine and brentuximab vedotin based on FAERS database / 中国药房

OBJECTIVE To analyze the adverse drug reaction （ADR）signals of ado-trastuzumab emtansine and brentuximab vedotin，so as to provide reference for clinical medication safety. METHODS Using the FDA adverse drug event reporting system （FAERS）database and OpenVigil 2.1 data platform ，the ADR of the two drugs were collected from being approved by FDA to the Sep. 30th，2021. The ADR signals were detected by frequency method and sorted according to the occurrence frequency and signal strength respectively. RESULTS & CONCLUSIONS A total of 2 319 and 3 178 ADR reports related to ado-trastuzumab emtansine and brentuximab vedotin were collected ，215 and 329 ADR signals were detected respectively. According to the occurrence frequency，the most frequent ADR s of the two drugs were thrombocytopenia （109 cases）and febrile neutropenia （198 cases）， separately，which were consistent with the drug instructions. According to the signal strength ，the spider nevus of ado-trastuzumab emtansine（report odds ratio of 451.46）and the noninfectious endocarditis of brentuximab vedotin （report odds ratio of 304.35） ranked first ，both of which were not reported in the drug instructions. It is suggested that attention should be paid not only to the most common ADR s of blood and lymphatic system caused by both drugs ，but also to the ADRs not reported in the drug instructions such as spider nevus of ado-trastuzumab emtansine and noninfective endocarditis of brentuximab vedotin.