THE USE OF JANUS KINASE INHIBITORS ANTI-INTERLEUKIN THERAPY IN THE RUSSIAN FEDERATION WITH COVID-19: PHARMACOEPIDEMIOLOGICAL SRUDY

The objective of this study was to assess the volume of consumption of anti-interleukins and janus kinase inhibitors in the period 2018–2021, used as well as preventive pathogenetic therapy of COVID-19.Materials and methods. Based on actual sales data in the segments of public procurement (including regional and federal preferential drug provision) and retail sales segment in the period 2018–2021, obtained from the IQVIA database. All data was recalculated into the number of established daily doses (DDDs), with the calculation of pharmacoepidemiological indicators «Incidence of prescribing drugs», «Cumulative risk of prescribing drugs», as well as «Prescribing prevalence per year» for tocilizumab, olokizumab, levilimab, sarilumab, kanakinumab, anakinra, baricitinib, tofacitinib and upadacitinib. Results and discussion. The growth of total sales volumes was demonstrated in all market segments, but mostly in the segment of regional purchases, primarily related to the purchase of these groups of medicines for COVID-19 therapy in the period 2020–2021. It was demonstrated that the increase in the number of cases, accompanied by the expansion of prescribing preventive pathogenetic therapy, led to a twofold increase in the number of new cases of prescribing of janus kinase inhibitors and an increase in this indicator for anti-interleukins by 1.5 times, taking into account the estimated number of patients with moderate and severe COVID-19. The cumulative risk of prescribing these classes of drugs increased proportionally: for JAK inhibitors from 14 to 32%, and for anti-IL drugs from 38 to 69%. Calculations showed that the proportion of people over 18 years of age in the Russian Federation who received at least one dose of janus kinase inhibitors and anti-interleukins increased many times, in 1000 times and 500 times. Conclusions. Taking into account the expansion of the use of these groups of medicines, careful monitoring of information about their safety is required. © 2023, HIV Infection and Immunosuppressive Disorders.All Rights Reserved.

Effectiveness and Safety of Tofacitinib in the Management of Ulcerative Colitis: A Brazilian Observational Multicentric Study.

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease which affects the colorectal mucosa with a relapsing-remitting pattern. The therapeutic options currently available for the medical management of UC include many options. Tofacitinib is an oral small molecule, Janus kinase (JAK) inhibitor, more selective for JAK1 and JAK3, which reduces the inflammatory process involved in the pathogenesis of UC. Methods: Retrospective observational multicentric study of patients with UC who used tofacitinib in any phase of their treatment. Clinical remission and response (according to Mayo score), mucosal healing, primary and secondary loss of response, discontinuation of the drug with possible causes, and the need for dose optimization or switching to biologicals, need for surgery and adverse events were evaluated. Results: From a total of 56 included patients, clinical remission was observed in 43.6% at week 12, 54.5% at week 26, 57.9% at week 52, and 40% at the last follow-up visit. Clinical response was observed in 71.4%, 81.8%, 89.5%, and 61.8% at the same time periods, respectively. Mucosal healing rates were 50% and 17.8% needed colectomy. Conclusions: Tofacitinib was effective in induction and maintenance of clinical response and remission rates, compatible to other international real-word studies and meta-analyses.

Pleuropulmonary Manifestations of Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic Syndrome.

BACKGROUND: The vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a newly identified autoinflammatory disorder related to somatic UBA1 mutations. Up to 72% of patients may show lung involvement. RESEARCH QUESTION: What are the pleuropulmonary manifestations in VEXAS syndrome? STUDY DESIGN AND METHODS: One hundred fourteen patients were included in the French cohort of VEXAS syndrome between November 2020 and May 2021. Each patient included in the study who had an available chest CT scan was discussed in an adjudication multidisciplinary team and classified as showing potentially pleuropulmonary-specific involvement of VEXAS syndrome or others. RESULTS: Fifty-one patients had a CT scan available for review and 45 patients (39%) showed pleuropulmonary abnormalities on chest CT scan that were considered related to VEXAS syndrome after adjudication. Most patients were men (95%) with a median age 67.0 years at the onset of symptoms. Among these 45 patients, 44% reported dyspnea and 40% reported cough. All 45 patients showed lung opacities on chest CT scan (including ground-glass opacities [87%], consolidations [49%], reticulation [38%], and septal lines [51%]) and 53% of patients showed pleural effusion. Most patients showed improvement with prednisone, but usually required > 20 mg/d. The main clinical and biological features as well the median survival did not differ between the 45 patients with pleuropulmonary involvement and the rest of the cohort, suggesting that the prevalence of pleuropulmonary involvement might have been underdiagnosed in the rest of the cohort. INTERPRETATION: Pulmonary manifestations are frequent in VEXAS syndrome, but rarely are at the forefront. The initial outcome is favorable with prednisone and does not seem to lead to pulmonary fibrosis.

Late Worsening of COVID-19 Pneumonia: Successful Treatment with Ruxolitinib and Steroid.

We describe the case of a patient hospitalized for the second time in a month due to delayed worsening of lung lesions in COVID-19 infection without bacterial superinfection. He was treated with hydroxychloroquine, IV dexamethasone and ruxolitinib with rapid improvement of respiratory failure; 1 month after the second discharge, maintaining low-dose oral prednisone, lung consolidations were significantly reduced on control CT. LEARNING POINTS: Modulation of immune over-response in late phases of COVID-19 can influence global outcome.Ruxolitinib and IV steroids can reverse the inflammatory process and lung lesions.

The development of COVID-19 treatment.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic named coronavirus disease 2019 (COVID-19) that has become the greatest worldwide public health threat of this century. Recent studies have unraveled numerous mysteries of SARS-CoV-2 pathogenesis and thus largely improved the studies of COVID-19 vaccines and therapeutic strategies. However, important questions remain regarding its therapy. In this review, the recent research advances on COVID-19 mechanism are quickly summarized. We mainly discuss current therapy strategies for COVID-19, with an emphasis on antiviral agents, neutralizing antibody therapies, Janus kinase inhibitors, and steroids. When necessary, specific mechanisms and the history of therapy are present, and representative strategies are described in detail. Finally, we discuss key outstanding questions regarding future directions of the development of COVID-19 treatment.

JAK-STAT inhibition reduces endothelial prothrombotic activation and leukocyte-endothelial proadhesive interactions.

BACKGROUND: Vascular activation is characterized by increased proinflammatory, pro thrombotic, and proadhesive signaling. Several chronic and acute conditions, including Bcr-abl-negative myeloproliferative neoplasms (MPNs), graft-vs-host disease, and COVID-19 have been noted to have increased activation of the janus kinase (JAK)-signal transducer and downstream activator of transcription (STAT) pathways. Two notable inhibitors of the JAK-STAT pathway are ruxolitinib (JAK1/2 inhibitor) and fedratinib (JAK2 inhibitor), which are currently used to treat MPN patients. However, in some conditions, it has been noted that JAK inhibitors can increase the risk of thromboembolic complications. OBJECTIVES: We sought to define the anti-inflammatory and antithrombotic effects of JAK-STAT inhibitors in vascular endothelial cells. METHODS: We assessed endothelial activation in the presence or absence of ruxolitinib or fedratinib by using immunoblots, immunofluorescence, qRT-PCR, and function coagulation assays. Finally, we used endothelialized microfluidics perfused with blood from normal and JAK2V617F+ individuals to evaluate whether ruxolitinib and fedratinib changed cell adhesion. RESULTS: We found that both ruxolitinib and fedratinib reduced endothelial cell phospho-STAT1 and STAT3 signaling and attenuated nuclear phospho-NK-κB and phospho-c-Jun localization. JAK-STAT inhibition also limited secretion of proadhesive and procoagulant P-selectin and von Willebrand factor and proinflammatory IL-6. Likewise, we found that JAK-STAT inhibition reduced endothelial tissue factor and urokinase plasminogen activator expression and activity. CONCLUSIONS: By using endothelialized microfluidics perfused with whole blood samples, we demonstrated that endothelial treatment with JAK-STAT inhibitors prevented rolling of both healthy control and JAK2V617F MPN leukocytes. Together, these findings demonstrate that JAK-STAT inhibitors reduce the upregulation of critical prothrombotic pathways and prevent increased leukocyte-endothelial adhesion.

Olumiant® (Baricitinib)-A Newly Approved Janus Kinase Inhibitor for the Treatment of Alopecia Areata

Olumiant® (Baricitinib) is a newly approved treatment for alopecia areata. Baricitinib is a selective and reversible inhibitor of Janus kinase that has shown promising results in two randomized, placebo-controlled phase-3 trials. A significantly higher number of patients achieved at least 80% scalp coverage following 36 weeks of treatment, compared to the placebo group. Adverse effects reported include acne and urinary tract infections, in addition to the warnings and precautions as highlighted in the product monograph. The current recommended regimen is 2 mg or 4 mg taken once daily, depending on the extent of hair loss. Other approved indications for baricitinib treatment include management of rheumatoid arthritis and the COVID-19 infections. (SKINmed. 2022;20:452-455).

[Janus kinase inhibitors in immunoinflammatory rheumatic diseases].

Despite great advances in the diagnosis and treatment of immunoinflammatory rheumatic diseases, which have led to a significant improvement in the prognosis in many patients, the fundamental medical problems of this pathology the restoration of the quality of life and the reduction of mortality to the population level are far from being resolved. This served as a stimulus for the study of new approaches to the pharmacotherapy of IVRD, one of which is associated with the use of low molecular weight chemically synthesized drugs that inhibit intracellular "signaling" molecules Janus kinase. Modern advances regarding the use of Janus kinase inhibitors in the treatment of immunoinflammatory rheumatic diseases and COVID -19 are considered.

Current Use of Baricitinib in COVID-19 Treatment and Its Future: An Updated Literature Review.

The levels of infectivity and mortality that ensued due to the coronavirus disease 2019 (COVID-19) pandemic caused an apparent global outcry. The health system, burdened by increasing deaths and hospitalizations, sought more effective treatment. This necessitated scientists and researchers to utilize existing drugs such as baricitinib, which has proved itself as anti-inflammatory and immunomodulatory. A qualitative systematic review was conducted using databases such as Google Scholar, Science Direct, PubMed, and BioMed Central to locate relevant articles published from 2019 onward on the effectiveness of baricitinib. After evaluation of the full-text articles, 16 were selected for review. Overall, baricitinib was seen as beneficial in decreasing respiratory failure and the use of mechanical ventilation, also preventing deterioration of COVID-19 symptoms. When used as a single agent or combined with other drugs, baricitinib improves the peripheral capillary oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio. The drug does not introduce any major side effects, but a mild increase in liver enzymes has been observed. Baricitinib proves to be a safe and effective treatment for COVID-19. Administered as monotherapy or in conjunction with other drugs, baricitinib provides tremendous clinical benefit to infected patients and shows good potential in terms of efficacy for future COVID-19 regimens.

Oral Janus kinase inhibitors for treating hospitalized patients with COVID-19: An updated systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study investigated the clinical efficacy and safety of oral Janus kinase inhibitors (JAKis) in the treatment of hospitalized patients with COVID-19. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for relevant articles written before January 29, 2022. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of oral JAKis in patients with COVID-19 were included. RESULTS: In the pooled analysis of the 7 RCTs, the all-cause 28-day mortality rate in the study group receiving JAKis was significantly lower than that in the control group (9.4% [183/1941] vs. 10.9% [184/1687], risk ratio [RR] = 0.69, 95% confidence interval [CI], 0.58-0.81, I2 = 0%). In addition, the risk of 14-day mortality was in the study group was lower than that in the control group (RR = 0.65, 95% CI, 0.46-0.92, I2 = 0%). Finally, the study group and the control group exhibited similar risks of any adverse events (RR = 0.96, 95% CI, 0.89-1.04, I2 = 0%). CONCLUSIONS: Oral JAKis can significantly reduce the risk of death among patients with COVID-19. In addition, JAKis are tolerable for hospitalized patients with COVID-19.

Baricitinib in hospitalised patients with COVID-19: A meta-analysis of randomised controlled trials.

Background: To date, only dexamethasone and tocilizumab have been shown to reduce mortality in patients with COVID-19. Baricitinib is a Janus kinase 1/2 inhibitor with known anti-inflammatory and anti-viral properties. We performed a meta-analysis of RCTs assessing the role of baricitinib in hospitalised patients with COVID-19. Methods: Electronic databases such as MEDLINE, EMBASE, and Cochrane Central were searched up until March 31, 2022, for RCTs evaluating the efficacy of baricitinib in hospitalised patients with COVID-19. The outcomes assessed were 28-day mortality, progression to invasive mechanical ventilation (IMV) or ECMO, progression to respiratory failure needing positive pressure ventilation, IMV or death, duration of hospitalisation and time to discharge. The meta-analysis was registered in the PROSPERO database (CRD42022314579). Findings: Four studies (with 10,815 patients) were included in the analysis. Pooled analysis using random-effects model showed a statistically significant reduction in 28-day mortality (OR 0.69, 95% CI 0.50-0.94; p=0.04, I2=65%) and composite outcome of progression to severe disease needing positive pressure ventilation, IMV or death (OR 0.89, 95% CI 0.80-0.99, p= 0.03, I2=0%). There was a favorable trend towards reduced progression to IMV or ECMO (OR 0.76, 95% CI 0.58-1.01; p=0.06, I2=49%) in the baricitinib arm compared to standard therapy, even though it was not statistically significant. Statistical significance was achieved for all outcomes with fixed-effects model analysis. Interpretation: In hospitalised patients with COVID-19, baricitinib was associated with reduced 28-day mortality although there was not a statistically significant reduction in progression to IMV or ECMO. Baricitinib used in conjunction with standard of care treatments is associated with improved mortality in hospitalised patients with COVID-19 disease. Funding: None.

Tofacitinib and newer JAK inhibitors in inflammatory bowel disease-where we are and where we are going.

Inflammatory bowel diseases, comprising ulcerative colitis (UC) and Crohn's disease, are chronic, immune-mediated and progressive inflammatory disorders affecting the gastrointestinal tract. Tofacitinib is the first oral small-molecule Janus kinase (JAK) inhibitor licensed and approved by the National Institute for Health and Care Excellence (NICE) for use in moderately-to-severely active UC after intolerance, inadequate response, or loss of response to conventional treatment or biologic therapy. The pivotal OCTAVE studies demonstrated the efficacy and safety of tofacitinib for the induction and maintenance of remission in UC. A growing body of evidence from real-world data supports the positive clinical and endoscopic benefits observed with tofacitinib treatment in the OCTAVE trials. This narrative review summarizes the current literature regarding the mechanism of action of tofacitinib, data from registrational trials, emerging real-world evidence, and an overview of the most recent safety evidence. We explore evolving treatment paradigms, including the use of tofacitinib in the COVID-19 era, pregnancy and extraintestinal manifestations, as well as the emerging concept of combining tofacitinib with biological therapy. We will also present a brief overview of the next generation of JAK inhibitors in the pipeline.

The Efficacy and Safety of Janus Kinase Inhibitors for Patients With COVID-19: A Living Systematic Review and Meta-Analysis.

BACKGROUND: Cytokine storm observed in patients with severe Coronavirus Disease 2019 (COVID-19) contributes to poor clinical outcomes and increased mortality. Janus kinases (JAKs) are important mediators in the cytokine storm. Therefore, we conduct a living systematic review and meta-analysis of the literature investigating efficacy and safety of JAK inhibitors for patients with COVID-19. METHODS: Databases were searched up to December 1, 2021 for interventional and observational studies comparing JAK inhibitor treatment with concurrent control in patients with COVID-19. Efficacy and safety outcomes were evaluated by pooled risk ratio (RR). RESULTS: Of 3,170 records retrieved, 15 studies were eligible and 13 were evaluated in the meta-analysis (n = 3,977). Based on data from three randomized controlled trials (RCTs), baricitinib treatment significantly decreased mortality by day 28 in hospitalized patients with COVID-19 (RR = 0.64, 95% CI 0.51-0.80) without increasing the incidence of adverse outcomes. In subgroup analysis, patients who required supplemental oxygen (RR = 0.62, 95% CI 0.41-0.95) or high-flow oxygen/non-invasive ventilation (RR = 0.59, 95% CI 0.42-0.85) at baseline benefited most. Pooled analysis of all eligible studies for JAK inhibitors (baricitinib, ruxolitinib, tofacitinib, and nezulcitinib) demonstrated a significant decrease in mortality (RR = 0.62, 95% CI 0.49-0.78) with no increase in the risk of adverse events. CONCLUSION: Baricitinib probably decreases mortality in hospitalized adult patients with COVID-19, especially for patients who required supplemental oxygen or high-flow oxygen/non-invasive ventilation at baseline. The efficacy and safety of other JAK inhibitors, such as ruxolitinib, tofacitinib, and nezulcitinib, await more evidence. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021261414, identifier: CRD42021261414.

COVID-19 and renin angiotensin aldosterone system: Pathogenesis and therapy.

AIMS: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the ACE2 component of the renin-angiotensin aldosterone system (RAAS) and infects the human cells. The aims of the present review were to look at the role and alteration of the RAAS components in SARS-CoV-2 infection, therapeutic approaches, and clinical trials in this field. METHODS: We surveyed the literature (PubMed, Web of Science, and Scopus) till August 18, 2021, and 59 published papers regarding the components of the RAAS and their role and alterations in SARS-CoV-2 infection along with various COVID-19 therapies based on the RASS components were included in the study. RESULTS: ACE inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor inhibitors are agents that significantly enhance the ACE2 and Ang-(1-7) levels, which can be suggestive for their role as therapeutics against SARS-CoV-2 infection. Beta-adrenergic blockers, which negatively regulate renin release from juxtaglomerular cells, and vitamin D, as a regulator of the RAAS and renin expression, are proposed therapeutics in the treatment of COVID-19. Some antihyperglycemic agents could be potentially protective against COVID-19-induced lung injury. Also, the inhibition of the Janus kinase/signal transducer and activator of the transcription pathway as a potential treatment for COVID-19 has been suggested. Finally, resveratrol, an antioxidant that can suppress Ang II, has been suggested as an adjunct to other therapies. CONCLUSION: Regarding the suggested potential therapies for COVID-19, there are many clinical trials whose results might change the treatment strategies of SARS-CoV-2 infection. So, the results of well-organized clinical trials on the efficacy and safety of the mentioned agents in the treatment of COVID-19 will be useful in the management and therapy of the disease.

Rheumatoid arthritis patients treated with Janus kinase inhibitors show reduced humoral immune responses following BNT162b2 vaccination.

OBJECTIVES: The mRNA-based COVID-19 vaccines are now employed globally and have shown high efficacy in preventing SARS-CoV-2 infection. However, less is known about the vaccine efficacy in immune-suppressed individuals. This study sought to explore whether humoral immunity to the COVID-19 vaccine BNT162b2 is altered in RA patients treated with Janus kinase inhibitors by analysing their antibodies titre, neutralization activity and B cell responses. METHODS: We collected plasma samples from 12 RA patients who were treated with Janus kinase inhibitors and received two doses of the BNT162b2 vaccine, as well as 26 healthy individuals who were vaccinated with the same vaccine. We analysed the quantity of the anti-spike IgG and IgA antibodies that were elicited following the BNT162b2 vaccination, the plasma neutralization capacity and the responsiveness of the B-lymphocytes. We used ELISA to quantify the antibody titres, and a plasma neutralization assay was used to determine the virus neutralization capacity. Alteration in expression of the genes that are associated with B cell activation and the germinal centre response were analysed by quantitative PCR. RESULTS: Reduced levels of anti-spike IgG antibodies and neutralization capacity were seen in the RA patients who were treated with JAK inhibitors in comparison with healthy individuals. Furthermore, B cell responsiveness to the SARS-CoV-2 spike protein was reduced in the RA patients. CONCLUSION: RA patients who are treated with JAK inhibitors show a suppressed humoral response following BNT162b2 vaccination, as revealed by the quantity and quality of the anti-spike antibodies.

Ruxolitinib in severe COVID-19: Results of a multicenter, prospective, single arm, open-label clinical study to investigate the efficacy and safety of ruxolitinib in patients with COVID-19 and severe acute respiratory syndrome

Introduction: COVID-19 morbimortality is mainly associated with development of severe acute respiratory syndrome (SARS), which has been related to an augmented immune response of the host with elevated circulating cytokines. Methods: In this prospective, multicenter, single arm (compared with a historical control), add-on, experimental phase 2 study, ruxolitinib 5 mg BID was added to standard of care in COVID-19 patients. Main objective was to determine efficacy and safety of ruxolitinib in patients with COVID-19-related SARS. Results: Even though we could not show a significant reduction of COVID-19 pneumonia patients requiring intensive care unit admission and mechanical ventilation (primary endpoint), a trend to a lower mortality rate in critical ill patients receiving ruxolitinib was reported. Administered ruxolitinib dose had to be increased according to protocol in 32% of patients, without additional toxicity. Conclusion: Side effects profile was manageable, and no direct organ injury was caused by the study drug. Ruxolitinib had a fast anti-inflammatory effect, and one-third of patients felt well immediately after starting treatment.

Introducción: La morbimortalidad por COVID-19 se asocia principalmente con el síndrome respiratorio agudo severo (SARS), relacionado con una respuesta inmunitaria aumentada del huésped con aumento de los niveles circulantes de citoquinas. Métodos: En este estudio prospectivo, multicéntrico, de un solo brazo (en comparación con un control histórico), en fase 2, se agregó ruxolitinib 5 mg dos veces al día al estándar de tratamiento en pacientes con COVID-19. El objetivo principal fue determinar la eficacia y seguridad de ruxolitinib en pacientes con SARS relacionado con COVID-19. Resultados: aunque no fue posible demostrar una reducción significativa de la proporción de pacientes con neumonía por COVID-19 que requerían ingreso en la unidad de cuidados intensivos y ventilación mecánica (criterio de valoración principal), se observó una tendencia a una menor tasa de mortalidad en los pacientes críticos que recibieron ruxolitinib. La dosis de ruxolitinib administrada tuvo que aumentarse de acuerdo con el protocolo en el 32% de los pacientes, sin toxicidad adicional. Conclusión: El perfil de efectos secundarios fue manejable y el fármaco en estudio no causó lesiones orgánicas directas. El ruxolitinib tuvo un efecto antiinflamatorio rápido y un tercio de los pacientes manifestó bienestar inmediatamente después de comenzar el tratamiento.

Upadacitinib plus topical corticosteroids in atopic dermatitis: Week 52 AD Up study results.

BACKGROUND: Primary (week 16) results from the ongoing phase 3, double-blind AD Up study (NCT03568318) demonstrate a positive benefit-risk profile for upadacitinib + topical corticosteroid (TCS) in patients with moderate-to-severe atopic dermatitis. OBJECTIVE: We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks. METHODS: Patients aged 12 to 75 years with chronic moderate-to-severe atopic dermatitis (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] ≥16, Validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] ≥3, and Worst Pruritus Numerical Rating Scale [WP-NRS] score ≥4) were randomized 1:1:1 to once-daily upadacitinib 15 mg + TCS, upadacitinib 30 mg + TCS, or placebo (PBO) + TCS (rerandomized at week 16 to upadacitinib + TCS). Safety and efficacy, including proportion of patients experiencing ≥75% improvement in EASI (EASI-75), vIGA-AD of clear/almost clear with improvement ≥2 grades (vIGA-AD 0/1), and WP-NRS improvement ≥4, were assessed through week 52. Missing data were primarily handled by nonresponse imputation incorporating multiple imputation for missing values due to coronavirus disease 2019 (COVID-19). RESULTS: Of 901 patients, 300 were randomized to upadacitinib 15 mg + TCS, 297 to upadacitinib 30 mg + TCS, and 304 to PBO + TCS. For all end points, efficacy for upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS at week 16 was maintained through week 52. At week 52, the proportions of patients treated with upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS who experienced EASI-75 were 50.8% and 69.0%, respectively; 33.5% and 45.2%, respectively, experienced vIGA-AD 0/1; and 45.3% and 57.5%, respectively, experienced WP-NRS improvement ≥4. Upadacitinib + TCS was well tolerated through 52 weeks; no new important safety risks beyond the current label were observed. No deaths were reported; major adverse cardiovascular events and venous thromboembolic events were infrequent (≤0.2/100 patient-years). CONCLUSIONS: Results through 52 weeks demonstrate long-term maintenance of efficacy and a favorable safety profile of upadacitinib + TCS in patients with moderate-to-severe AD.

The use of Janus Kinase inhibitors in hospitalized patients with COVID-19: Systematic review and meta-analysis.

BACKGROUND: The evidence of using JAK inhibitors among hospitalized patients with COVID-19 is conflicting. The systematic review and meta-analysis aimed to address the efficacy of Janus Kinase (JAK) Inhibitors in reducing risk of mortality among hospitalized patients with COVID-19. METHODS: Several electronic databases, including PubMed, EuropePMC, and the Cochrane Central Register of Controlled Trials, with relevant keywords "COVID-19″ AND ("JAK inhibitor" OR "Ruxolitinib" OR "Tofacitinib" OR "Fedratinib" OR "Baricitinib") AND ("Severe" OR "Mortality"), were used to perform a systematic literature search up to December 11, 2020. All studies pertinent to the predetermined eligibility criteria were included in the analysis. Our outcome of interest was all types of mortality, clinical improvement, and clinical deterioration. Dichotomous variables of our outcomes of interest were analyzed using Maentel-Haenszel formula to obtain odds ratios (ORs) and 95% confidence intervals (CI) with random-effects modeling regardless of heterogeneity. RESULTS: Five studies with a total of 1190 patients and were included in this systematic review and meta-analysis. The use of JAK inhibitors was associated with a reduced risk of mortality (OR 0.51, 95% CI 0.28-0.93, P = 0.02; I2: 7.8%, P = 0.354) and clinical improvement (OR 1.76, 95% CI 1.05-2.95, P = 0.032; I2: 26.4%, P = 0.253). The use of JAK inhibitors was not associated with a reduced risk of clinical deterioration (OR 0.58, 95% CI 0.28-1.19, P = 0.136; I2: 24.1%, P = 0.267). CONCLUSION: The use of JAK inhibitors was significantly associated with a reduced risk of mortality, and clinical improvement in hospitalized patients with COVID-19.

Baricitinib: From Rheumatoid Arthritis to COVID-19.

Baricitinib is a JAK1/2 inhibitor that was first approved for treating moderate to severe rheumatoid arthritis (RA) but that later showed considerable efficacy in the control of exaggerated inflammatory responses that occur in a wide range of diseases. There is a growing body of evidence, obtained from clinical trials and case reports, demonstrating clinical and paraclinical improvement in patients following administration of baricitinib including RA, systemic lupus erythematosus, psoriasis, atopic dermatitis, alopecia areata, interferon-mediated autoinflammatory diseases, graft-versus-host disease, diabetic kidney disease, and, recently, coronavirus disease-19. However, despite overall encouraging results, many adverse effects have been observed in baricitinib-treated patients, ranging from simple infections to increased risk of malignancies, particularly in long-term use. The significant efficacy of baricitinib, versus the probable adverse effects, urge further investigation before establishing it as a part of standard therapeutic protocols. Here, we have provided a review of the studies that have used baricitinib for treating various inflammatory disorders and summarized the advantages and disadvantages of its administration.