Use Of Baricitinib Research Articles

Experience with the use of janus kinase inhibitors in the treatment of COVID-19 in patients in Volgograd

The new coronavirus infection (COVID-19) is characterized by high morbidity and mortality. The main approach to COVID-19 therapy should be the proactive administration of treatment before the development of a complete symptom complex of life-threatening conditions, including acute respiratory distress syndrome. The use of a selective and reversible inhibitor of janus kinase 1 and 2 prevents viral endocytosis, reduces excessive inflammatory response. The purpose of the study - to evaluate the effectiveness of the use of the Janus kinase inhibitor of the drug Baricitinib (Olumiant, manufacturer Lilly del Caribe Inc., Spain) in the treatment of patients with moderate COVID-19 in a hospital setting. During the clinical use of Baricitinib, significant positive changes were obtained compared with the initial level of vital signs and laboratory data. Significant positive changes in the following indicators were obtained: oxygen saturation increased (from 95.3 ± 4.0 to 97.5 ± 3.2 %, p = 0.011), body temperature decreased (from 37.3 ± 0.7 to 36.7 ± 0.5 °C, p = 0.000), C-reactive protein decreased (from 47.1 ± 46.0 to 32.5 ± 41.7 g/l, p = 0.010), the number of platelets increased (from 178.0 ± 59.5 to 249.5 ± 84.5; p = 0.000), when assessing the condition of patients in points on the NEWS-2 scale positive dynamics (from 1.6 ± 1.2 to 1.1 ± 1.3, p = 0.001). The level of C-reactive protein increased simultaneously with an increase in interleukin-6, an increase to 200.0 ± 6.2 pg/ml was recorded. The positive dynamics is an increase in the number of lymphocytes to 2.0 • 109/l. By the end of inpatient treatment, ferritin levels had normalized to reference values of 27.7±2.1 mmol/l and D-dimer to the upper limit of normal. Positive dynamics of changes on the CT scan of the chest organs in the form of a decrease in infiltration. According to the combination of changes in clinical, laboratory signs and CT scan results, the therapy of patients was effective.

Baricitinib protects ICIs-related myocarditis by targeting JAK1/STAT3 to regulate Macrophage polarization

PurposeThe emergence of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, but these drugs can also cause severe immune-related adverse effects (irAEs), including myocarditis. Researchers have become interested in exploring ways to mitigate this side effect, and one promising avenue is the use of baricitinib, a Janus kinase inhibitor known to have anti-inflammatory properties. This study aimed to examine the potential mechanism by which baricitinib in ICIs-related myocarditis. MethodsTo establish an ICIs-related myocarditis model, BALB/c mice were administered murine cardiac troponin I (cTnI) peptide and anti-mouse programmed death 1 (PD-1) antibodies. Subsequently, baricitinib was administered to the mice via intragastric administration. Echocardiography, HE staining, and Masson staining were performed to evaluate myocardial functions, inflammation, and fibrosis. Immunofluorescence was used to detect macrophages in the cardiac tissue of the mice.In vitro experiments utilized raw264.7 cells to induce macrophage polarization using anti-PD-1 antibodies. Different concentrations of baricitinib were applied to assess cell viability, and the release of pro-inflammatory cytokines was measured. The activation of the JAK1/STAT3 signaling pathway was evaluated through western blot analysis. ResultsBaricitinib demonstrated its ability to improve cardiac function and reduce cardiac inflammation, as well as fibrosis induced by ICIs. Mechanistically, baricitinib treatment promoted the polarization of macrophages towards the M2 phenotype. In vitro and in vivo experiments showed that anti-PD-1 promoted the release of inflammatory factors. However, treatment with baricitinib significantly inhibited the phosphorylation of JAK1 and STAT3. Additionally, the use of RO8191 reversed the effects of baricitinib, further confirming our findings. ConclusionBaricitinib demonstrated its potential as a protective agent against ICIs-related myocarditis by modulating macrophage polarization. These findings provide a solid theoretical foundation for the development of future treatments for ICIs-related myocarditis.

E022 Audit on the baricitinib dose in elderly and patients with chronic kidney disease among a cohort of rheumatoid arthritis patients

Abstract Background/Aims Baricitinib use among elderly patients and in patients with chronic kidney disease needs modification of the dose. Baricitinib dose should be reduced to 2mg daily in patients who are 75 years or older given the associated increased risks in this age group. Additionally, baricitinib should be avoided in patients with creatinine clearance of less than 30 ml/min and dose needs to be reduced in patients with a creatinine clearance between 30-60 ml/min because it is primarily renally excreted drug. Methods All the blueteq requests for baricitinib at University Hospitals Coventry and Warwickshire, from 05/07/2021 to 05/07/2023 were evaluated. There were 128 patients who have been on baricitinib during this period. Twenty patients out of this, were 75 years or above. The baricitinib dose in patients above the age of 75 and in patients with chronic kidney disease was assessed by using NICE guidance on the use of baricitinib in patients with rheumatoid arthritis and the BNF as the audit standards respectively. Results Of the 20 patients who were 75 years and above, 13 patients were still on baricitinib. Ten patients were on a dose of 2mg daily which is in keeping with NICE guidance while 3 patients were still receiving a dose of 4mg daily. Seven patients were started on baricitinib after 75 years and 4 of them were started on 4mg daily which is not keeping with NICE guidance. Of the 128 patients, none of them had a creatinine clearance less than <30 ml/min while there were 16 patients who had received baricitinib (at some point) with a creatinine clearance of 30-60 ml/min. Of them, 14 patients were at some point on 4mg daily dose of Baricitinib which is not in keeping with guidance. Of those 14 patients, 6 patients were still receiving a dose of 4mg daily. Conclusion In conclusion, it appears that we have not completely adhered to standard criteria laid down by NICE guidelines and in the BNF. This presentation aims to raise awareness among rheumatologists regarding these guidelines. Also, changing the format of the prescription to include the age and renal functions would prompt the prescriber to amend the dose accordingly. The use of baricitinib may reduce in the future due to concerns of increased cardiovascular disease. However, there is a group of patients who are already on baricitinib and will want to continue, despite these concerns, given the significant improvements in disease control. Disclosure C. Rosa: None. J. Joseph: None. G. Kasavkar: None.

Off-label use of Baricitinib improves moderate and severe atopic dermatitis in China through inhibiting MAPK and PI3K/Akt/mTOR pathway via targeting JAK-STAT signaling of CD4+ cells.

As an inflammatory disease with a disrupted immune system, cytokine disorders in atopic dermatitis (AD) are closely related to the abnormal activation of JAK-STAT signal pathway. The critical relevance of the JAK-STAT signaling pathway to the pathogenesis of AD provides a strong rationale for JAK inhibitor research. Baricitinib, a small-molecule oral JAK inhibitor, has been proven to inhibit JAK-STAT signaling in a variety of diseases, including AD. It is currently available in China for off-label use. However, its efficacy in China and its mechanism are rarely reported. In our study, we found that the immune status of patients with moderate and severe AD was hyperactive. Among the 49 known immunotherapy targets, JAK1 and JAK2 genes on lymphocytes of AD patients were significantly upregulated, which was closely related to the symptom severity in moderate and severe AD patients. Baricitinib can improve immune hyperresponsiveness and clinical symptoms in moderate and severe AD by inhibiting the activation of Th2 cell subsets and the secretion of Th2-type cytokines through MAPK, mTOR and PI3K-Akt signaling pathways, providing an important theoretical basis for clinical off-label use of Baricitinib to treat moderate and severe AD.

JAK Inhibitor Baricitinib in the Treatment of Oral Lichen Planus: A Case Report

Baricitinib, a JAK1/2 inhibitor, has been expanding its role as a therapeutic agent with recent FDA approval for dermatologic use with alopecia areata. Clinical trials are underway for further use of baricitinib for severe atopic dermatitis and multiple off-label uses in inflammatory dermatologic conditions such as lichen planus have been suggested. Few reports exist of patients with concomitant alopecia areata and lichen planus treated with baricitinib. We present a case of refractory oral lichen planus with marked improvement within one month following treatment with once daily baricitinib. Our case adds to the growing body of literature regarding the therapeutic benefits of JAK inhibitors in the treatment of lichen planus.

Real-world comparative study of drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis.

Janus kinase (JAK) inhibitors (JAKis) are effective therapeutic agents against rheumatoid arthritis (RA). However, patients having RA with particular risk factors may have a higher incidence of adverse effects (AEs), including major cardiovascular events (MACE) and infections. In this multicenter cohort study, we aimed to clarify the risk factors affecting the drug retention of JAKis in patients with RA. We retrospectively evaluated patients with RA who received their first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) at our institute. The clinical outcomes, including AEs, were recorded, particularly MACE and serious infections. The drug retention rates were analyzed using the Kaplan-Meier method, and risk factors affecting drug retention rates were determined using a multivariable Cox regression hazards model. Overall 184 patients with RA receiving their first use of baricitinib (57.6%), tofacitinib (23.9%), upadacitinib (12.0%), or filgotinib (6.5%) were included in this study. Fifty-six (30.4%) patients discontinued JAKi treatment owing to ineffectiveness (9.2%) or AEs, including infections (21.2%). The overall drug retention rates were significantly lower in patients treated with pan-JAKi than in those treated with JAK1 inhibitors (p = 0.03). In the Cox regression model, the presence of baseline high RA disease activity, use of glucocorticoid and treatments with pan-JAKis were associated with reduced drug retention rates of JAKis (p < 0.001, p = 0.01 and 0.04, respectively). Pan-JAKi treated patients with high disease activity had significantly lower drug retention rates (p < 0.001). In a real-world setting, the drug retention rates of JAKis were reduced mainly by treatment discontinuation owing to AEs. Treatment with pan-JAKis and high baseline RA disease activity were identified as predictive factors for the discontinuation of JAKis. Lower drug retention rates were found in patients receiving pan-JAKis with high disease activity than in those without high disease activity.

Real-world experience of baricitinib in atopic dermatitis: including add-on therapy for patients using dupilumab.

Little real-world experience regarding the use of baricitinib, an oral selective JAK1/JAK2 inhibitor, for treating moderate to severe atopic dermatitis (AD) has been reported. This study aimed to assess the overall outcomes in Korean patients with AD treated with baricitinib. All patients with moderate to severe AD treated with baricitinib between June 2021 and June 2022 were included, and their cases were retrospectively analyzed using medical records. Patients with moderate to severe AD, aged ≥18 years who had failed previous therapies, including those who demonstrated unsatisfactory improvement with dupilumab, were prescribed baricitinib. Patients whose follow-up period was <8 weeks were excluded. The dermatologist evaluated the AD status, including eczema area and severity index (EASI), itch Numeric Rating Scale, and improvement of remaining lesions despite dupilumab therapy. We analyzed 34 AD patients who received baricitinib. Twelve patients treated with dupilumab were additionally prescribed baricitinib due to unsatisfactory treatment effects and demonstrated improvement in the remaining lesions despite dupilumab treatment. Their itching improved after 1.4 weeks. Among them, eight patients (66.7%) had head and neck dermatitis, and seven of them demonstrated improvement after the coadministration of baricitinib. Among the other 22 patients who were prescribed baricitinib only, 10 patients (45.5%) achieved EASI 75 at 8 weeks, with five (22.7%) revealing EASI 90. Overall, baricitinib was well tolerated and resulted in clinical improvement in AD patients in a real-world clinical setting. Additionally, baricitinib may be beneficial in treating lesions refractory to dupilumab therapy.

Treatments for Moderate-to-Severe Alopecia Areata: A Systematic Narrative Review.

Treatments for alopecia areata (AA) have traditionally been prescribed off-label, and there has been no universal agreement on how to best manage the condition. Baricitinib is the first oral selective Janus kinase (JAK) inhibitor approved for the treatment of adults with severe AA. As a better understanding of the evidence supporting the management of AA in clinical practice is needed, we conducted a systematic literature review and subsequent narrative review to describe available evidence pertaining to the efficacy and tolerability of treatments currently recommended for adults with moderate-to-severe forms of AA. From 2557 identified records, a total of 53 records were retained for data extraction: 9 reported data from 7 randomized controlled trials (RCTs) versus placebo, and 44 reported data from unique RCTs with no placebo arm, non-randomized trials, or observational studies. Across drug classes, data were reported heterogeneously, with little consistency of data collection or clinical endpoints used. The most robust evidence was for the JAK inhibitor class, in particular the JAK1/JAK2 inhibitor baricitinib. Five RCTs (three for baricitinib) demonstrated a consistent benefit of JAK inhibitor therapy over placebo across various clinical outcomes in adult patients with at least 50% scalp hair loss. Overall, hair regrowth varied widely for the other drug classes and was generally low for patients with moderate-to-severe AA. Relapses were commonly observed during treatment and upon discontinuation. Adverse effects were generally consistent with the known safety profile of each intervention. The heterogeneity observed prevented the conduct of a network meta-analysis or an indirect comparison of different treatments. We found that the current management of patients with moderate-to-severe AA often relies on the use of treatments that have not been well evaluated in clinical trials. The most robust evidence identified supported the use of baricitinib, and other oral JAK inhibitors, in patients with severe AA.

Safety and Effectiveness of Baricitinib in Chinese Patients with Moderate-to-Severe Rheumatoid Arthritis: 24-Week Results from a Post-Marketing Safety Study.

Baricitinib, a JAK1/JAK2 inhibitor, is approved for treatment of moderate-to-severe rheumatoid arthritis (RA) in China. This single-arm, prospective, multi-center, post-marketing safety study (PMSS) evaluated the safety and effectiveness of baricitinib in Chinese patients. This study included adult patients with moderate-to-severe active RA who received baricitinib over periods of approximately 12 and 24 weeks. The primary endpoint was safety, defined as week 12 adverse event (AE)/serious AE incidence. Secondary endpoints were week 24 safety and effectiveness (disease activity score with 28 joints/C-reactive protein [DAS28-CRP] and simplified/Clinical Disease Activity Index [SDAI/CDAI]). Safety analyses included 667 patients (female, 82.3%; mean age, 53.3years; mean RA duration, 86.9months); 106/667 (15.9%) were 65-74years old and 19/667 (2.8%) were ≥ 75years old; 87.0% received baricitinib 2mg QD. Total exposure was 262.1 patient-years (PY). At week 12, AEs had occurred in 214 (32.1%; exposure-adjusted incidence rate [EAIR], 172.5 per 100PY) patients (serious AEs: 22 [3.3%; EAIR, 15.0]). At week 24, AEs had occurred in 250 (37.5%; EAIR, 125.9) patients (serious AEs: 28 [4.2%; EAIR, 10.9]). Two patients (0.3%) died (of pneumonia and unknown cause); EAIR for death, 0.77. Serious infection occurred in 1.2% of patients (EAIR, 3.1). Hepatotoxicity occurred in 3.4% of patients (EAIR, 9.0). No patients met potential Hy's law laboratory criteria (alanine/aspartate aminotransferases ≥ 3 × upper limit of normal (ULN) and total bilirubin ≥ 2 × ULN). Malignancy occurred in one patient. No patients experienced venous thromboembolism (VTE) or major adverse cardiovascular events (MACE). At week 24, 52.4%, 27.5%, and 27.6% of patients achieved remission per DAS28-CRP, SDAI, and CDAI, respectively. This PMSS investigated the safety and effectiveness of baricitinib in clinical practice in China. No VTE/MACE or new safety signals were reported and there was promising effectiveness, supporting the use of baricitinib in Chinese patients with moderate-to-severe active RA. EU PAS Register: EUPAS34213.

Comment on 'Treatment of moderate-to-severe alopecia areata with baricitinib in preadolescent children'.

In this response to a recent article on the off-label use of baricitinib for paediatric alopecia areata (AA), we raise additional points regarding the relationship between viral infections and AA relapse on Janus kinase inhibitor (JAKi) therapy, and the potential benefits of concomitant oral minoxidil therapy in mitigating the risk of relapse during JAKi dose reduction or discontinuation.

Comment on ‘Treatment of moderate-to-severe alopecia areata in preadolescent children with baricitinib’: authors’ reply

In this response to a recent article on the off-label use of baricitinib for paediatric alopecia areata (AA), we raise additional points regarding the relationship between viral infections and AA relapse on Janus kinase inhibitor (JAKi) therapy, and the potential benefits of concomitant oral minoxidil therapy in mitigating the risk of relapse during JAKi dose reduction or discontinuation.

Is immunosuppressive therapy an effective treatment for COVID-19? – literature review

Introduction: The disease caused by SARS-CoV-2 is associated with a dysregulated immune response and a generalized inflammatory response. Therefore, during the search for effective therapy, attention was paid to drugs affecting and stabilizing such a response - tocilizumab, sarilumab, siltuximab, anakinra, baricitinib.Purpose of the work: Evaluation of the impact of immunosuppressant therapy on the course of the disease caused by the SARS-CoV-2 virus.Material and methods: The work was based on a review of available medical publications about immunosuppressive therapy for COVID-19 treatment. The literature in the PubMed and Google Scholar databases was searched based on the following keywords: tocilizumab, sarilumab, siltuximab, baricitinib, COVID-19, SARS-CoV-2, immunosuppressive therapy.Conclusion: Based on the analysis of the literature, the most effective therapeutic option seems to be tocilizumab. Promising alternatives may be sarilumab and siltuximab as they have the same target point of action. However, it is necessary to conduct further tests on their operation. The use of baricitinib may be useful, but probably only in certain circumstances. Anakinra proved to be much less effective. It should therefore be used with great caution.

Improving properties of baricitinib due to interaction with Pluronic micelles

Baricitinib is a new generation medicinal compound that has been recommended for the treatment of rheumatoid arthritis in 2017 as well as alopecia areata and COVID-19 in 2022. The use of baricitinib is complicated by its poor aqueous solubility and unwanted side effects. Therefore, the aim of this work is an improvement of the baricitinib solubility using Pluronic micelles. The effect of the micelles on the solubility and membrane permeability of baricitinib is revealed using the isothermal saturation method and the Franz diffusion cell, respectively. It was observed that degree of baricitinib solubilization depends on the Pluronics structure and pH. The regularities of the interaction of the drug with the micelles were established by means of light scattering and 1D and DOSY 1H NMR. It was demonstrated that the ionization state of baricitinib, depending on pH, affects the drug ability to be included in the micelles. The most effective solubilizer of baricitinib among the Pluronics under study was proposed. The data obtained may be useful for the development of water-soluble formulations of baricitinib.

Review of efficacy of baricitinib in the treatment of alopecia areata

Alopecia areata (AA) is a long-term autoimmune condition characterized by patchy, non-scarring hair loss. It involves an autoimmune inflammatory process that gives immunity privilege to some hair follicles, while subsequent inflammatory attacks target previously normal hair follicles. One of the most important discoveries in the pathogenesis of this disease is the Janus kinase (JAK)-signal transducer and activator of the transcription (STAT) pathway. Now that a greater understanding of the immunological processes contributing to the pathogenesis has been gained, current trials’ focus was on managing the immunological reaction involved in this disease. Baricitinib is a new first-generation JAK inhibitor that has been studied in multiple trials. This study's objectives were to review existing research and summarize information on the use of Baricitinib to treat AA. The Medline database was searched for relevant published research papers using variations of the following keywords: “AA,” “Baricitinib,” and “JAK inhibitors.” The search covered studies published from 2010–2022. Our findings showed that baricitinib’s use for severe AA in multiple studies generally led to improvement of patients’ conditions with minimal side effects.

Use of baricitinib in treatment of COVID-19: a systematic review.

To assess the role of baricitinib alone or in combination with other therapies as a treatment for patients with COVID-19. Systematic literature search was conducted in the WHO COVID-19 coronavirus disease database to find clinical studies on use of baricitinib for treatment of COVID-19 between December 1, 2019 and September 30, 2021. Two independent set of reviewers identified the eligible studies fulfilling the inclusion criteria, relevant data was extracted and a qualitative synthesis of evidence performed. The risk of bias was evaluated with validated tools. A total of 267 articles were found to be eligible after primary screening of titles and abstracts. Following assessment of full texts, 19 studies were finally included for this systematic review, out of which 16 are observational, and 3 are interventional studies. Collating the results from these observational and interventional studies, baricitinib used as add-on to standard therapy, either alone or in combination with other drugs, was found to have favorable outcomes in hospitalized patients with moderate to severe COVID-19. Furthermore, ongoing trials indicate that the drug is being extensively studied across the world for its safety and efficacy in COVID-19. Baricitinib significantly improves clinical outcomes in hospitalized patients with COVID-19 pneumonia, and further evidence will establish the drug as a standard treatment among such patients.

Baricitinib or Tocilizumab? Treatment of Patients Hospitalized With Severe COVID-19.

Baricitinib or Tocilizumab? Treatment of Patients Hospitalized With Severe COVID-19.

Emerging Role of Baricitinib in Dermatology Practice: All We Need to Know!

Baricitinib is a competitive inhibitor of the Janus Kinase family of non-receptor protein kinases, predominantly acting against JAK-1 and JAK-2 subtypes. By downregulating transcription of various pro-inflammatory cytokines, this drug has shown efficacy across various dermatoses. Approved for severe cases of alopecia areata and moderate-severe atopic dermatitis in adults, baricitinib is being increasingly tried across many other indications with promising results. It is prudent that dermatologists remain aware of boxed warnings and precautions with the use of this much-discussed molecule, including its infectious, thrombotic, cardiovascular, and malignant ramifications. Long-term data on the use of baricitinib in dermatological conditions are lacking and further research is warranted since most data on safety profile is extrapolated from its use in rheumatology. The present review aims to highlight the immunopathogenic mechanisms of JAK-1/2 blockade, approved and off-label uses in dermatology, along with a concise review of laboratory monitoring and the side-effect profile of baricitinib.

NICE alters guidance on COVID-19 treatments as manufacturer withdraws marketing authorisation application

Final draft guidance from the National Institute for Health and Care Excellence (NICE) has recommended nirmatrelvir plus ritonavir (Paxlovid; Pfizer), tocilizumab (RoActemra; Roche) and sotrovimab (Xevudy; GlaxoSmithKline) as options for treating COVID-19 in adults. This advice contrasts with previous draft guidance, published on 16 November 2022, in which NICE recommended the use of baricitinib […]

HTA160 A Systematic Review and Meta-Analysis of the Janus Kinase Inhibitors Safety Profile in Relation to the Risks of Secondary Bacterial Infections

Evaluation of the safety of drugs for preventive pathogenetic therapy of a newcoronavirus infection COVID-19 with the of Janus kinase inhibitors. A systematic review with a meta-analysis was conducted based on search queries in international databases. Search strategy included queries for controlled studies on the use of baricitinib and tofacitinib recommended for use as a preventive therapy for mild and moderate cases of a new coronavirus infection. Data were obtained from three randomized clinical trials. A meta-analysis of the results regarding the total number of serious adverse events (AEs) and adverse events belonging to the class "Infections and infestations" showed statistically significant evidence on the greater safety of baricitinib and tofacitinib in relation to the risks of these events compared with standard therapy: the risk ratio (RR) of serious adverse events in the comparison groups was 0.82 [95%, CI 0.69; 0.96] (p=0.02), the risk ratio of "Infections and invasions" was 0.78 [95% CI 0.63; 0.97] (p=0.03). In both cases RR was in favor of the use of Janus kinase inhibitors. The results of the meta-analysis demonstrated a favorable safety profile of baricitinib and tofacitinib when used in patients with COVID-19 in relation to the risks of developing serious AEs, as well as infections. Conducting studies of various designs in a wider patient population will allow more accurate assessment of the risks of developing secondary bacterial infections against the background of short-term use of Janus kinase inhibitors as part of their use as a preventive pathogenetic therapy during the COVID-19 pandemic.

Опыт применения препарата барицитиниб в лечении атопического дерматита у ВИЧ-инфицированных больных

Опыт применения препарата барицитиниб в лечении атопического дерматита у ВИЧ-инфицированных больных