Erdafitinib in Asian patients with advanced solid tumors: an open-label, single-arm, phase IIa trial.

BACKGROUND: FGFR genomic aberrations occur in approximately 5-10% of human cancers. Erdafitinib has previously demonstrated efficacy and safety in FGFR-altered advanced solid tumors, such as gliomas, thoracic, gastrointestinal, gynecological, and other rare cancers. However, its efficacy and safety in Asian patients remain largely unknown. We conducted a multicenter, open-label, single-arm phase IIa study of erdafitinib to evaluate its efficacy in Asian patients with FGFR-altered advanced cholangiocarcinoma, non-small cell lung cancer (NSCLC), and esophageal cancer. METHODS: Patients with pathologically/cytologically confirmed, advanced, or refractory tumors who met molecular and study eligibility criteria received oral erdafitinib 8 mg once daily with an option for pharmacodynamically guided up-titration to 9 mg on a 28-day cycle, except for four NSCLC patients who received erdafitinib 10 mg (7 days on/7 days off) as they were recruited before the protocol amendment. The primary endpoint was investigator-assessed objective response rate per RECIST v1.1. Secondary endpoints included progression-free survival, duration of response, disease control rate, overall survival, safety, and pharmacokinetics. RESULTS: Thirty-five patients (cholangiocarcinoma: 22; NSCLC: 12; esophageal cancer: 1) were enrolled. At data cutoff (November 19, 2021), the objective response rate for patients with cholangiocarcinoma was 40.9% (95% CI, 20.7-63.6); the median progression-free survival was 5.6 months (95% CI, 3.6-12.7) and median overall survival was 40.2 months (95% CI, 12.4-not estimable). No patient with RET/FGFR-altered NSCLC achieved objective response and the disease control rate was 25.0% (95% CI, 5.5-57.2%), with three patients with stable disease. The single patient with esophageal cancer achieved partial response. All patients experienced treatment-emergent adverse events, and grade ≥ 3 treatment-emergent adverse events were reported in 22 (62.9%) patients. Hyperphosphatemia was the most frequently reported treatment-emergent adverse event (all-grade, 85.7%). CONCLUSIONS: Erdafitinib demonstrated efficacy in a population of Asian patients in selected advanced solid tumors, particularly in those with advanced FGFR-altered cholangiocarcinoma. Treatment was tolerable with no new safety signals. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (NCT02699606); study registration (first posted): 04/03/2016.

A comprehensive insight from molecular docking and dynamics with clinical investigation on the impact of direct oral anticoagulants on atheroprotective protein in atrial fibrillation.

BACKGROUND: Direct oral anticoagulants (DOACs) have high potency against their therapeutic target and are widely used in the treatment of atrial fibrillation (AF). Most DOACs are often claimed to have adverse effects due to off-target inhibition of essential proteins. Human serum paraoxonase 1 (PON1), one of the essential proteins, known for its anti-inflammatory and antioxidant properties, could be affected by DOACs. Thus, a comparative evaluation of DOACs and their effect on PON1 protein will aid in recommending the most effective DOACs for AF treatment. This study aimed to assess the impact of DOACs on PON1 through a combination of computational and experimental analyses. METHODS: We focus on apixaban, dabigatran, and rivaroxaban, the most recommended DOACs in AF treatment, for their impact on PON1 through molecular docking and molecular dynamics (MD) simulation to elucidate the binding affinity and drug-protein structural stability. This investigation revealed the most influential DOACs on the PON1 protein. Then experimental validation was performed in DOAC-treated AF participants (n = 42; 19 treated with dabigatran and 23 treated with rivaroxaban) compared to a healthy control group (n = 22) through gene expression analysis in peripheral blood mononuclear cells (PBMC) and serum enzyme concentration. RESULTS: Our computational investigation showed rivaroxaban (-4.24 kcal/mol) exhibited a lower affinity against the PON1 protein compared to apixaban (-5.97 kcal/mol) and dabigatran (-9.03 kcal/mol) through molecular docking. Dabigatran holds complex interactions with PON1 at GLU53, TYR197, SER193, and ASP269 by forming hydrogen bonds. Additionally, MD simulation revealed that dabigatran disrupts PON1 stability, which may contribute functional changes. Further experimental validation revealed a significant down-regulation (p < 0.05) of PON1 gene expression in PBMC and decreased serum PON1 enzyme concentration on DOAC treatment. Rivaroxaban as about 48% has inhibitory percentage and dabigatran as about 75% of inhibitory percentage compared to healthy control. CONCLUSION: Overall, our computational and experimental results clearly show the higher inhibitory effect of dabigatran than rivaroxaban. Hence, rivaroxaban will be a better drug candidate for improving the outcome of AF.

Spatiotemporal distribution, risk levels, and transport variations in neonicotinoids and fipronil and its metabolites cross a river-to-sea continuum.

Neonicotinoids (NEOs) and fipronil are widely used in pest control, but their spatiotemporal distribution and risk levels in the "river-estuary-bay" system remain unclear. Between 2018 and 2021, 148 water samples from rivers to inshore and offshore seawater in Laizhou Bay, China were collected to investigate the presence of eight NEOs and fipronil and its metabolites (FIPs). Significant seasonal variations in NEOs were observed under the influence of different cultivation practices and climatic conditions, with higher levels in the summer than in the spring. The average concentrations of total neonicotinoids (ΣNEOs) and ∑FIPs decreased from rivers (63.64 ng/L, 2.41 ng/L) to inshore (22.62 ng/L, 0.14 ng/L) and offshore (4.48 ng/L, 0.10 ng/L) seawater of Laizhou Bay. The average concentrations of ΣNEOs decreased by 85.3 % from 2018 to 2021. The predominant insecticides in the study area were acetamiprid, thiamethoxam, imidacloprid, and fipronil sulfone, with a gradual shift toward low-toxicity and environmentally friendly species over time. Influenced by agricultural intensity, ∑NEOs were mostly distributed in the Yellow River, Xiaoqing River, and their estuaries, where they pose chronic ecological risks. However, FIP exhibited high risk in certain rivers and sewage treatment plants owing to the use of animal repellents or landscape gardening insecticides. This study provides evidence of the transfer of NEOs and FIPs from rivers to the ocean and also clarifies their transition dynamics and changes in risk levels from rivers to oceans. Additionally, the study offers data support for identifying critical pesticide control areas.

Biocatalytic Synthesis of Ruxolitinib Intermediate via Engineered Imine Reductase.

An enzyme catalyzed strategy for the synthesis of a chiral hydrazine from 3-cyclopentyl-3-oxopropanenitrile 5 and hydrazine hydrate 2 is presented. An imine reductase (IRED) from Streptosporangium roseum was identified to catalyze the reaction between 3-cyclopentyl-3-oxopropanenitrile 5 and hydrazine hydrate 2 to produce trace amounts of (R)-3-cyclopentyl-3-hydrazineylpropanenitrile 4. We employed a 2-fold approach to optimize the catalytic performance of this enzyme. First, a transition state analogue (TSA) model was constructed to illuminate the enzyme-substrate interactions. Subsequently, the Enzyme_design and Funclib methods were utilized to predict mutants for experimental evaluation. Through three rounds of site-directed mutagenesis, site saturation mutagenesis, and combinatorial mutagenesis, we obtained mutant M6 with a yield of 98% and an enantiomeric excess (ee) of 99%. This study presents an effective method for constructing a hydrazine derivative via IRED-catalyzed reductive amination of ketone and hydrazine. Furthermore, it provides a general approach for constructing suitable enzymes, starting from nonreactive enzymes and gradually enhancing their catalytic activity through active site modifications.

Management of apixaban anticoagulation in a patient requiring therapeutic plasma exchange: a case report and a literature review.

Therapeutic plasma exchange (TPE) is used as an effective treatment modality for a variety of autoimmune disorders. Apart from its desired effect of removing pathological blood components, it also can remove coagulation factors and drugs. Currently, there is an insufficient amount of information regarding the use of direct oral anticoagulants in this setting. In this article, we present a case report of a patient with myasthenia gravis and chronic anticoagulation with apixaban who underwent a series of TPE while continuing apixaban treatment. We observed that only 10% of daily dose was removed by the procedure and plasma levels of apixaban corresponded with expected range. TPE was not associated with shortened drug plasma half-life. We did not observe any significant alteration of apixaban pharmacokinetics during the period of TPE therapy, as well as no thrombotic or bleeding events. This case report supports the use of apixaban in patients treated by TPE, nevertheless, to firmly establish apixaban efficacy and safety profile in this clinical setting further research is needed.

Effect of different anticoagulants and antiplatelets on intraoral bleeding time during professional oral hygiene session.

OBJECTIVE: Patients with thromboembolic problems, prosthetic valves, or coagulation issues are commonly prescribed anticoagulants and antiplatelets. Anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The aim of the present study was to examine the bleeding durations associated with various anticoagulants and antiplatelets during professional dental hygiene sessions, utilizing a modified Ivy test adapted for the oral context. MATERIALS AND METHODS: Ninety-three consecutive patients undergoing professional oral hygiene were recruited. Debridement during oral hygiene was performed using ultrasonic mechanical instrumentation, and bleeding sites were assessed and treated with gentle pressure using sterile gauzes. The time for bleeding cessation was recorded. Patients were categorized into six groups based on their drug intake, Control: no anticoagulants or antiplatelets DTI: direct thrombin inhibitors (dabigatran) AntiXa: directa factor Xa inhibitors (endoxaban, apixaban, rivaroxaban) VKA: vitamin K antagonists (warfarin, acenocoumarol) SAPT: single anti-platelet therapy (acetylsalicylic acid or clopidogrel) DAPT: dual anti-platelet therapy (acetylsalicylic acid and clopidogrel). Bleeding time was measured in seconds and mean values were assessed among the different groups. Differences between groups were investigated with Kruskal-Wallis test followed by Dunn's post-hoc correction for multiple comparisons or two-way ANOVA followed by Dunnett post-hoc; RESULTS: Control patients presented the lowest bleeding time 50 s, followed by AntiXa (98), SAPT (105), DTI (120), DAPT (190) and VKA (203). A statistically significant difference was present among control and DTI (p = 0.004), VKA (p < 0.001), DAPT (p < 0.001). CONCLUSIONS: Based on the present outcomes, an increased risk of prolonged bleeding emerged in patients taking VKA and DAPT. CLINICAL SIGNIFICANCE: bleeding did not interfere with the oral hygiene session The optimal period for dental treatment of these patients should be 2-3 h before the next dose, without the need to temporarily suspend the medication.

Effectiveness and Safety of Extended Treatment Apixaban Versus Low-Molecular-Weight Heparin in Cancer-Associated Venous Thromboembolism.

BACKGROUND: Limited real-world evidence is available comparing the safety and effectiveness of apixaban and low-molecular-weight heparins (LMWHs) for preventing recurrent venous thromboembolism (VTE) in patients with active cancer receiving anticoagulation in an extended treatment setting. This study evaluated the risk of bleeding and recurrent VTE in patients with cancer-associated VTE who were prescribed apixaban or LMWH for ≥3 months. METHODS: A US commercial claims database was used to identify adult patients with VTE and active cancer who initiated apixaban or LMWH 30 days following the first VTE diagnosis and had ≥3 months of continuous enrollment and 3 months of primary anticoagulation treatment. Patients were followed from the day after the end of primary anticoagulation treatment until the earliest of: date of disenrollment, discontinuation of index anticoagulant, switch to another anticoagulant, or end of the study period. Inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Incidence rates (IRs) for the outcomes were calculated per 100 person-years (PY). Cox proportional hazard models were used to evaluate the adjusted risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB). RESULTS: A total of 13,564 apixaban- and 2,808 LMWH-treated patients were analyzed. Post-IPTW, the treatment cohorts were balanced. Patients receiving apixaban had lower adjusted IRs for recurrent VTE (4.1 vs 9.6 per 100 PY), MB (6.3 vs 12.6), and CRNMB (26.1 vs 36.0) versus LMWH (P<.0001 for all comparisons) during the follow-up period. Patients on apixaban had a lower adjusted risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.34-0.53), MB (HR, 0.50; 95% CI, 0.41-0.61), and CRNMB (HR, 0.76; 95% CI, 0.68-0.85) versus LMWH. CONCLUSIONS: Extended anticoagulation treatment of ≥3 months with apixaban was associated with lower rates of recurrent VTE, MB, and CRNMB compared with LMWH in adults with cancer-associated VTE.

Immunophenotyping and Therapeutic Insights from Chronic Mucocutaneous Candidiasis Cases with STAT1 Gain-of-Function Mutations.

PURPOSE: Heterozygous STAT1 Gain-of-Function (GOF) mutations are the most common cause of chronic mucocutaneous candidiasis (CMC) among Inborn Errors of Immunity. Clinically, these mutations manifest as a broad spectrum of immune dysregulation, including autoimmune diseases, vascular disorders, and malignancies. The pathogenic mechanisms of immune dysregulation and its impact on immune cells are not yet fully understood. In treatment, JAK inhibitors have shown therapeutic effectiveness in some patients. METHODS: We analyzed clinical presentations, cellular phenotypes, and functional impacts in five Taiwanese patients with STAT1 GOF. RESULTS: We identified two novel GOF mutations in 5 patients from 2 Taiwanese families, presenting with symptoms of CMC, late-onset rosacea, and autoimmunity. The enhanced phosphorylation and delayed dephosphorylation were displayed by the patients' cells. There are alterations in both innate and adaptive immune cells, including expansion of CD38+HLADR +CD8+ T cells, a skewed activated Tfh cells toward Th1, reduction of memory, marginal zone and anergic B cells, all main functional dendritic cell lineages, and a reduction in classical monocyte. Baricitinib showed therapeutic effectiveness without side effects. CONCLUSION: Our study provides the first comprehensive clinical and molecular characteristics in STAT1 GOF patient in Taiwan and highlights the dysregulated T and B cells subsets which may hinge the autoimmunity in STAT1 GOF patients. It also demonstrated the therapeutic safety and efficacy of baricitinib in pediatric patient. Further research is needed to delineate how the aberrant STAT1 signaling lead to the changes in cellular populations as well as to better link to the clinical manifestations of the disease.

Thermally-Induced Supersaturation Approach for Optimizing Drug Loading and Biopharmaceutical Properties of Supersaturated Lipid-Based Formulations: Case Studies with Ibrutinib and Enzalutamide.

Lipid-based formulations (LbFs) have demonstrated success in pharmaceutical applications; however, challenges persist in dissolving entire doses of the drug into defined liquid volumes. In this study, the temperature-induced supersaturation method was employed in LbF to address drug loading and pill burden issues. Supersaturated LbFs (super-LbF) were prepared using the temperature-induced supersaturation method, where the drug load is above its equilibrium solubility. Further, the influence of the drug's physicochemical and thermal characteristics on drug loading and their relevance with an apparent degree of supersaturation (aDS) was studied using two model drugs, ibrutinib and enzalutamide. All the prepared LbFs were evaluated in terms of physical stability, dispersion, and solubilization capacity, as well as pharmacokinetic assessments. Drug re-crystallization was observed in the lipid solution on long-term storage at higher aDS values of 2-2.5. Furthermore, high-throughput lipolysis studies demonstrated a significant decrease in drug concentration across all LbFs (regardless of drug loading) due to a decline in the formulation solvation capacity and subsequent generation of in-situ supersaturation. Further, the in vivo results demonstrated comparable pharmacokinetic parameters between conventional LbF and super-LbF. The short duration of the thermodynamic metastable state limits the potential absorption benefits. However, super-LbFs of Ibr and Enz showed superior profiles, with 1.7-fold and 5.2-fold increased drug exposure compared to their respective crystalline suspensions. In summary, this study emphasizes the potential of temperature-induced supersaturation in LbF for enhancing drug loading and highlights the intricate interplay between drug properties, formulation characteristics, and in vivo performance.

Design, synthesis and biological evaluation of novel pyrazole-based compounds as potential chemotherapeutic agents.

Aim: Design and synthesis of pyrazole-based chemotherapeutic agents. Materials & methods: A series of novel diphenyl pyrazole-chalcone derivatives were synthesized and assessed for their cytotoxic activities against 14 cancer cell lines and their antimicrobial activities against MRSA and Escherichia coli along with their safety using HSF normal cell line. Results & conclusion: Majority of the compounds showed moderate-to-significant anticancer activity with selective high percentage inhibition (>80%) against HNO-97 while being nontoxic toward normal cells. Compounds 6b and 6d were the most potent congeners with IC50 of 10 and 10.56 µM respectively. The synthesized compounds exhibited moderate to potent antimicrobial activities. Interestingly, compound 6d exhibited a minimum inhibitory concentration of 15.7 µg/ml against MRSA; and a minimum inhibitory concentration of 7.8 µg/ml versus E. coli.

[Box: see text].

Risk of Major Bleeding, Stroke/Systemic Embolism, and Death Associated With Different Oral Anticoagulants in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease.

BACKGROUND: Patients with atrial fibrillation and severe chronic kidney disease have higher risks of bleeding, thromboembolism, and mortality. However, optimal anticoagulant choice in these high-risk patients remains unclear. METHODS AND RESULTS: Using deidentified electronic health records from the Optum Labs Data Warehouse, adults with atrial fibrillation and severe chronic kidney disease (estimated glomerular filtration rate <30 mL/min per 1.73 m2) initiating warfarin, apixaban, or rivaroxaban between 2011 and 2021 were included. Using inverse probability of treatment weighting, adjusted risks of major bleeding, stroke/systemic embolism, and death were compared among agents. A total of 6794 patients were included (mean age, 78.5 years; mean estimated glomerular filtration rate, 24.7 mL/min per 1.73 m2; 51% women). Apixaban versus warfarin was associated with a lower risk of major bleeding (incidence rate, 1.5 versus 2.9 per 100 person-years; subdistribution hazard ratio [sub-HR], 0.53 [95% CI, 0.39-0.70]), and similar risks for stroke/systemic embolism (incidence rate, 1.9 versus 2.4 per 100 person-years; sub-HR, 0.80 [95% CI, 0.59-1.09]) and death (incidence rate, 4.6 versus 4.5 per 100 person-years; HR, 1.03 [95% CI, 0.82-1.29]). Rivaroxaban versus warfarin was associated with a higher risk of major bleeding (incidence rate, 4.9 versus 2.9 per 100 person-years; sub-HR, 1.65 [95% CI, 1.10-2.48]), with no difference in risks for stroke/systemic embolism and death. Apixaban versus rivaroxaban was associated with a lower risk of major bleeding (sub-HR, 0.53 [95% CI, 0.36-0.78]). CONCLUSIONS: These real-world findings are consistent with potential safety advantages of apixaban over warfarin and rivaroxaban for patients with atrial fibrillation and severe chronic kidney disease. Further randomized trials comparing individual oral anticoagulants are warranted.

TLE3 Is a Novel Fusion Partner of JAK2 in Myeloid/Lymphoid Neoplasm With Eosinophilia Responding to JAK2 Inhibition.

Chromosomal rearrangements involving Janus kinase 2 (JAK2) are rare but recurrent findings in lymphoid or myeloid neoplasia. Detection of JAK2 fusion genes is important as patients with aberrantly activated JAK2 may benefit from treatment with tyrosine kinase inhibitors such as ruxolitinib. Here, we report a novel fusion gene between the transcriptional co-repressor-encoding gene transducin-like enhancer of split 3 (TLE3) and JAK2 in a patient initially diagnosed with chronic eosinophilic leukemia with additional mutations in PTPN11 and NRAS. The patient was successfully treated with the JAK2 inhibitor ruxolitinib for 8 months before additional somatic mutations were acquired and the disease progressed into an acute lymphoblastic T-cell leukemia/lymphoma. The present case shows similarities to previously reported cases with PCM1::JAK2 and BCR::JAK2 with regard to disease phenotype and response to ruxolitinib, and importantly, provides an example that also patients harboring other JAK2 fusion genes may benefit from treatment with JAK2 inhibitors.

Comparison of canagliflozin and teneligliptin on energy intake and body weight in Japanese patients with Type 2 diabetes: a subanalysis of the CANTABILE study.

BACKGROUND: While the Sodium-glucose co-transporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) are widely used for the glycemic control in type 2 diabetes mellitus, the differences in the effects of SGLT2 inhibitors and DPP4 inhibitors on energy intake and diabetes-related indicators are unclear. METHODS: This was a subanalysis of the CANTABILE study which compared the effects of canagliflozin and teneligliptin on metabolic factors in Japanese patients with Type 2 diabetes. The changes at 24 weeks from the baseline of the diabetes-related indicators including Hemoglobin A1c (HbA1c), energy intake and body weight were compared between the canagliflozin and teneligliptin groups. RESULTS: Seventy-five patients in the canagliflozin group and 70 patients in the teneligliptin group were analyzed. A significant decrease in HbA1c was observed in both groups. In the teneligliptin group, although energy intake was significantly reduced, there was no significant change in body weight. Conversely, in the canagliflozin group, although energy intake tended to increase, body weight significantly decreased. CONCLUSION: Canagliflozin and teneligliptin have different effects on the dietary status of patients with Type 2 diabetes. Our result suggests that canagliflozin can manage blood glucose without weight gain, even with increased energy intake.

Method Development and Validation of Lorlatinib by RP-HPLC.

A simple, Accurate, precise method was developed for the estimation of the Lorlatinib in API form and Marketed pharmaceutical dosage form by RP-HPLC. Chromatogram was run through Hypersil C18 (4.6mm×150mm, 5µm) Particle size Column and Mobile phase containing Methanol and Water taken in the ratio of 25: 75% v/v was pumped through column at a flow rate of 1.0 ml/min. Temperature was maintained at 38ºC. Optimized wavelength selected was 310 nm. Retention times of Lorlatinib were found to be 3.513 minutes respectively. The %RSD for the Repeatability and Intermediate Precision of the Lorlatinib were found to be within limits. %Recovery was obtained 98.96% and it was found to be within the limits for Lorlatinib respectively. The LOD, LOQ values obtained from regression equations of Lorlatinib were 0.332µg/ml and 1.0078 µg/ml respectively. Regression equation of Lorlatinib was found to be y = 39948x + 16821 respectively. The Retention times was decreased and run time was decreased, so the method developed was simple and economical that can be adopted in regular Quality control test in Industries.

A Novel JAK2 Fusion in T-Cell Prolymphocytic Leukemia.

T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive mature T-cell malignancy characterized by marked lymphocytosis, B symptoms, lymphadenopathy, and hepatosplenomegaly. There is no standard treatment approach, and in the absence of an allogeneic transplant, the prognosis remains poor. The disease-defining cytogenetic abnormality in T-PLL is the juxtaposition of the TCL1-family oncogene to the TCR gene enhancer locus primarily due to an inversion of chromosome 14, that is, inv(14). The application of next-generation sequencing technologies led to the discovery of highly recurrent gain-of-function mutations in JAK1/3 and STAT5B in over 70% of T-PLL providing opportunities for therapeutic intervention using small molecule inhibitors. Additional genetic mechanisms that may contribute to the pathogenesis of T-PLL remain unknown. Herein we describe the identification of a novel gene fusion SMCHD1::JAK2 resulting from a translocation between chromosome 9 and 18 involving SMCHD1 exon 45 and JAK2 exon 14 (t(9;18)(p24.1;p11.32)(chr9:g.5080171::chr18:g.2793269)), a previously undescribed genetic event in a patient with T-PLL harboring the key disease defining inv(14) resulting in rearrangement of TCL1 and TRA/D. In this manuscript, we describe the clinical and genetic features of the patient's disease course over a 25-month post-treatment duration using ruxolitinib and duvelisib.

A meta-analysis of therapeutic trials of topical ruxolitinib cream for the treatment of vitiligo: therapeutic efficacy, safety, and implications for therapeutic practice.

Vitiligo, an autoimmune condition characterized by depigmented skin patches due to the loss of functional melanocytes, has been linked to dysregulation in the JAK-STAT signaling pathway, particularly in IFN-g signaling. The use of JAK inhibitors, such as ruxolitinib cream, a JAK1 and JAK2 inhibitor, presents a promising approach for vitiligo treatment. This study aims to systematically assess the effectiveness and safety of ruxolitinib cream in patients with vitiligo. We conducted a systematic review and meta-analysis following PRISMA guidelines to evaluate the efficacy and safety of ruxolitinib cream for the treatment of vitiligo. A comprehensive search of PubMed, Google Scholar, and Cochrane Library databases for randomized controlled trials (RCTs). Data selection, screening, extraction, and risk of bias assessment were meticulously performed. Statistical analysis was conducted using Review Manager Software, version 5.4, with significant heterogeneity addressed through appropriate methods. Our meta-analysis included 3 studies with 830 vitiligo patients. Significant improvements were observed in F-VASI, T-VASI, F-BSA, and T-BSA scores, with greater efficacy at 24 weeks compared to 12 weeks [MD -24.17, 95% CI (-31.78 to -16.56), P < 0.00001], [MD -14.12, 95% CI (-20.54 to -7.70); P < 0.0000], [MD -16.25, 95% CI (-22.20 to -10.31), P < 0.00001], [MD -9.19, 95% CI (-13.47 to -4.92); P < 0.00001]. Ruxolitinib showed increased risk ratios for F-VASI75, F-VASI90, and F-VASI50, indicating better outcomes with longer treatment durations [MD 2.9, 95% CI 1.88-4.49; P < 0.00001], [MD 4.66, 95% CI 2.09-10.39; P = 0.0002], [MD 2.53, 95% CI 1.84-3.46; P < 0.00001]. No significant differences were found in mild and moderate adverse events, while severe cases favored ruxolitinib. Placebo had a significant advantage in any adverse events, with no significant difference in drug-related adverse events. Serious adverse events did not significantly differ between groups. The findings strongly support the efficacy of ruxolitinib therapy in improving various parameters over time for treating vitiligo. However, thorough consideration of its safety profile, particularly concerning adverse events and potential side effects, is warranted. Further studies with larger sample sizes are needed to confirm these conclusions.