Although several case reports and small clinical trials have reported promising outcomes with Janus kinase (JAK) inhibitors for vitiligo, high-quality evidence and guidelines are lacking. We evaluated the efficacy and safety of JAK inhibitors for the treatment of vitiligo using a meta-analysis of randomized controlled trials (RCTs). We searched the PubMed, Embase, and Cochrane Library databases up to August 2023, with additional studies from ClinicalTrials.gov and company websites. We assessed outcomes, including percentage improvement in total vitiligo area score index (TVASI) and facial vitiligo area score index (FVASI); the proportion of patients achieving 50% improvement in TVASI (TVASI50) and 50% and 75% improvement in FVASI (FVASI50 and FVASI75); the risk of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), infections, and skin-related adverse events (AEs). Five studies with 1,550 participants were included. JAK inhibitors were associated with a higher proportion of TVASI50 (relative risk [RR] 2.67, 95% confidence interval [CI] 1.24-5.78) and FVASI75 (RR 3.97, 95%CI 2.62-6.02) responders than placebo. JAK inhibitors significantly increased the risk of skin-related AEs (RR 1.96, 95% CI 1.29-2.98) compared with placebo. However, the risk of TEAEs, SAEs, and infections was not significantly different between the JAK inhibitor and placebo groups. Subgroup analysis showed that JAK1 and JAK1/2 inhibitors were more effective than JAK3 inhibitors. However, there was insufficient evidence to suggest that the route of administration affects the efficacy and safety of JAK inhibitors in vitiligo. These findings indicate that JAK inhibitors are effective in repigmentation and well tolerated in patients with vitiligo.

ObjectivesThis study aimed to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of Gerilimzumab (GB224), a recombinant humanized IgG1 lambda monoclonal antibody against interleukin-6, in healthy Chinese adults.MethodsFifty-eight subjects were randomly assigned to receive a single subcutaneous dose of 2, 5, 10, 15, 20, 30 mg GB224 or placebo. Safety assessments were performed, and blood samples were collected for PK, PD, and immunogenicity analyses during a follow-up of 112 days.ResultsThe most frequent adverse event was decreased fibrinogen (43.1%). GB224 was absorbed relatively fast with a median T-max of 48 h (24-168 h) but eliminated slowly with a long mean half-life (839.38-981.63 h). Dose proportionality was shown to be in the dose range of 10-30 mg. A dose-dependent increase in serum interleukin-6 concentration from baseline was observed in the subjects receiving GB224. Only two subjects tested positive for antidrug antibodies after administration of GB224.ConclusionGB224 had a well-tolerated safety profile, desirable PK, and a low immunogenicity following a single-dose subcutaneous administration in healthy Chinese subjects. These findings warrant further investigation.

Background: Chimeric antigen receptor T cells treatment targeting B cell maturation antigen (BCMA) is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) and has demonstrated outstanding outcomes in clinical studies. Objective: The aim of this comprehensive review and meta-analysis was to summarize the effectiveness and safety of anti-BCMA CAR-T treatment for patients with relapsed/refractory multiple myeloma (RRMM). Our research identifies variables influencing outcome measures to provide additional evidence for CAR-T product updates, clinical trial design, and clinical treatment guidance. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard was followed for conducting this comprehensive review and meta-analysis, which was submitted to PROSPERO (CRD42023390037). From the inception of the study until 10 September 2022, PubMed, Web of Science, EMBASE, the Cochrane Library, CNKI, and WanFang databases were searched for eligible studies. Stata software (version 16.0) was used to assess effectiveness and safety outcomes. Results: Out of 875 papers, we found 21 relevant trials with 761 patients diagnosed as RRMM and were given anti-BCMA CAR-T treatment. The overall response rate (ORR) for the entire sample was 87% (95% CI: 80–93%) complete response rate (CRR) was 44% (95% CI: 34–54%). The minimal residual disease (MRD) negativity rate within responders was 78% (95% CI: 65–89%). The combined incidence of cytokine release syndrome was 82% (95% CI: 72–91%) and neurotoxicity was 10% (95% CI: 5%–17%). The median progression-free survival (PFS) was 8.77 months (95% CI: 7.48–10.06), the median overall survival (OS) was 18.87 months (95% CI: 17.20–20.54) and the median duration of response (DOR) was 10.32 months (95% CI: 9.34–11.31). Conclusion: According to this meta-analysis, RRMM patients who received anti-BCMA CAR-T treatment have demonstrated both effectiveness and safety. Subgroup analysis confirmed the anticipated inter-study heterogeneity and pinpointed potential factors contributing to safety and efficacy, which may help with the development of CAR-T cell studies and lead to optimized BCMA CAR-T-cell products. Systematic Review Registration: Clinicaltrials.gov , PROSPERO, CRD42023390037.

Background: This study was conducted to explore the safety, tolerance, pharmacokinetics, pharmacodynamics, and immunogenicity of LY06006, a recombinant humanized monoclonal antibody to RANKL, when administrated subcutaneously in Chinese healthy adults.Research design and methods: This was a randomized, double-blinded, placebo-controlled, single ascending dose study performed in 32 healthy Chinese adults, who were randomly assigned to receive a single injection dose of 18, 60, 120 mg study drug or placebo with a follow-up of 140–252 days.Results: No deaths or drug-related serious adverse events occurred. LY06006 was rapidly absorbed in the 60 mg group with a Tmax range of 120–480 h and serum LY06006 concentrations decreased slowly 11–13 days after dosing with a long mean (SD) half-life of 389.58 (63.44) h. The most frequent AEs were elevated serum parathyroid hormone (PTH) level (83.3%), hypocalcemia (54.2%), and hypophosphatemia (45.8%). None of the 32 subjects tested positive for anti-drug antibody during the trial.Conclusion: Single-dose subcutaneous administration of LY06006 was safe and well-tolerated in healthy Chinese adults. Cmax showed linear pharmacokinetic characteristics in the dose range of 18–120 mg based on dose-exposure proportionality analysis.

Filgotinib是治疗对一种或多种改善病情抗风湿药(DMARDs)反应不佳或不耐受的中重度活动性类风湿关节炎(RA)成人患者的JAK1抑制剂,于2020年9月24日由欧洲药品管理局(EMA)和日本厚生劳动省(MHLW)批准上市.大量临床研究表明,Filgotinib对RA的疗效明确、安全性和耐受性良好.本文对Filgotinib的药理作用及作用机制、临床药代动力学、临床疗效、安全性、用法用量及药物相互作用等方面进行综述,同时介绍了临床研究最新进展,旨在为RA的创新临床治疗提供参考.

Background: Due to the lack of comprehensive evidence based on prospective studies, the efficacy and safety of Janus Kinase (JAK) inhibitors (including tofacitinib, ruxolitinib, baricitinib, ritlecitinib and brepocitinib) for alopecia areata (AA) are yet to be proved. Methods: The systematic review and meta-analysis was performed pursuant to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline and registered on PROSPERO (CRD42022303007). Results: Fourteen prospective studies (5 RCTs and 9 non-RCTs), enrolling a total of 1845 patients with AA, were included for quantitative analysis. In RCTs, oral JAK inhibitors resulted in higher good response rate compared with control (RR: 6.86, 95% CI: 2.91–16.16); topical JAK inhibitors did not show any difference compared with control (RR: 1.00, 95% CI: 0.31–3.18). In non-RCTs, the pooled rate of good response to oral, topical and sublingual JAK inhibitors were 63% (95% CI: 44%–80%), 28% (95% CI: 1%–72%) and 11% (95% CI: 1%–29%), respectively. The pooled recurrence rate in patients treated with JAK inhibitors was 54% (95% CI: 39%–69%), mainly due to the withdrawal of JAK inhibitors. In RCTs, no difference was found in the risk of experiencing most kind of adverse events; in non-RCTs, the reported adverse events with high incidence rate were mostly mild and manageable. Conclusion: JAK inhibitors are efficacious and generally well-tolerated in treating AA with oral administration, whereas topical or sublingual administration lacks efficacy. Subgroup analyses indicate that baricitinib, ritlecitinib and brepocitinib seem to have equal efficacy for AA in RCTs; ruxolitinib (vs. tofacitinib) and AA (vs. AT/AU) are associated with better efficacy outcomes in non-RCT. Due to the high recurrence rate after withdrawal of JAK inhibitors, continuous treatment should be considered to maintain efficacy. Systematic Review Registration: PROSPERO: CRD 42022303007