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Objective To investigate the efficacy and safety of baricitinib in combination with iguratimod in the treatment of refractory rheumatoid arthritis (RRA). Methods Fifteen RRA patients admitted to Affiliated Southeast Hospital of Xiamen University from August 2021 to December 2022 were selected and treated with iguratimod (25 mg, bid) combined with baricitinib (4 mg, qd) for 24 weeks. The changes in swelling joint count (SJC), tenderness joint count (TJC), hypersensitive C-reactive protein (hs-CRP), Disease Activity Score using 28 joint counts (DAS28) CRP, and adverse reactions were observed after 12 and 24 weeks of treatment. Results All 15 patients with RRA had different degrees of remission. Compared with before treatment, TJC and SJC decreased, while hs-CRP levels and DAS28-CRP decreased after 12 weeks and 24 weeks of treatment (P＜0.05). After 24 weeks of treatment, 3 cases achieved clinical remission (DAS28-CRP≤2.6), and 6 cases achieved low disease activity (2.6＜DAS28-CRP≤3.2), with a compliance rate of 60.0% (9/15). All patients had good tolerance, without any adverse reactions such as herpes zoster, thrombotic events, liver and kidney damage. Conclusion Baricitinib combined with iguratimod is highly effective and safety in treating patients with RRA.

Abstract Objectives Several clinical trials have evaluated the efficacy and safety of baricitinib in COVID-19 patients. Recently, there have been reports on critical patients, which are different from previous research results. The meta-analysis was performed to investigate the effects of baricitinib in COVID-19, by pooling data from all clinically randomized controlled trials (RCTs) available to increase power to testify. Methods Studies were searched in PubMed, Embase, and Cochrane Library databases on January 31, 2023. We performed a meta-analysis to estimate the efficacy and safety of baricitinib for the treatment of hospitalized adults with COVID-19. This study is registered with INPLASY, number 202310086. Results A total of 3010 patients were included in our analyses. All included studies were randomized controlled trials or prospective study. There was no difference in 14-day mortality between the two groups [OR 0.23 (95% CI 0.03–1.84), I 2 = 72%, P = 0.17]. In subgroup analyses we found that baricitinib did not seem to improve significantly in 24-day mortality critically ill patients [OR 0.60 (95% CI 0.35–1.02), I 2 = 0%, P = 0.06]. Fortunately, baricitinib have led to faster recovery and shorter hospital stays for COVID-19 patients. There were no difference in infections and infestations, major adverse cardiovascular events, deep vein thrombosis and pulmonary embolism. Conclusions Baricitinib did not increase the incidence of adverse reactions. At the same time, we can find that it reduces the mortality of COVID-19 patients, not including the critically ill.

Abstract Background SLE is an autoimmune disease marked by broad immunological dysregulation and multi-system inflammation. Baricitinib is one of the novel treatments for SLE. We conducted this meta-analysis to evaluate its safety and effectiveness in treating SLE. Method We looked for all published randomized controlled trials in PubMed, Scopus, Web of Science, and Cochrane and included all RCTs comparing baricitinib and placebo in the treatment of SLE. Review Manager 5.4 program was used for data analysis. Results Three trials with a total of 1849 individuals were included. Participants in the baricitinib group were significantly more likely to attain SRI-4 response than those in the placebo group [RR = 1.11, 95% CI (1.02, 1.21), P = 0.01]. Additionally, baricitinib performed better than the placebo in terms of reduction of ≥ 4 points from baseline in SLEDAI-2 K score [RR = 1.13, 95% CI (1.04, 1.22), P = 0.004]. In terms of SLEDAI-2 K remission of arthritis or rash, baricitinib was also superior to placebo [RR = 1.08, 95% CI (1.00, 1.17), P = 0.04]. Treatment-emergent adverse events did not differ significantly [RR = 1.01, 95% CI (0.97, 1.05), P = 0.61]. Conclusion Baricitinib is potentially safe and effective in the treatment of SLE. It has successfully met the study’s primary endpoint and some secondary endpoints highlighting its potential to improve the outcomes of SLE. Despite achieving an SRI-4 response, glucocorticoids sparing and some other secondary outcomes weren’t reached by baricitinib.

Abstract Introduction The treatment of genital lichen sclerosus (GLS) remains challenging. Baricitinib has been introduced in the treatment of GLS, but there’s no imaging evaluation for GLS patients treated with it. No comparison of dermoscopy and reflectance confocal microscopy (RCM) assessments in GLS has been conducted. We performed this study to evaluate the efficacy and safety of baricitinib for GLS and to compare the value of dermoscopy and RCM assessments in GLS. Methods Participants were treated with baricitinib for 6 months and assessed at week 0, 2, 4, 6, 8, and every 4 weeks for the next 16 weeks. All patients were evaluated for clinical, dermoscopic, and RCM variables, with numeric scores assigned to each parameter. Results Twenty-six GLS patients were included in this study. All patients achieved Investigator’s Global Assessment score ≤ 1 (with ≥ 2-grade improvement) at week 20. The scores of pruritus and pain decreased since week 2 (both P

Abstract 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.

Abstract Objective To compare the efficacy and safety between baricitinib (BARI) and tofacitinib (TOFA) for the treatment of the rheumatoid arthritis (RA) patients receiving methotrexate (MTX) in clinical practice. Methods This retrospective study recruited 179 RA patients treated with BARI (2–4 mg/d) or TOFA (10 mg/d) at The First Affiliated Hospital of Guangxi Medical University from September 2019 to January 2022. The rate of low disease activity (LDA) was used as the primary end point. Secondary end points included the Disease Activity Scale-28 (DAS-28)-C-reactive protein (CRP); the rate of DAS28-CRP remission; visual analogue scale (VAS) for pain, swollen joint, and tender joint counts; and adverse events at the 6-month follow-up. Several factors affecting LDA achievement were also analyzed. Results Seventy-four patients were treated with BARI and 105 were treated with TOFA, including 83.24% females, with a median (IQR) age of 56.0 (53.0–56.0) years old and disease duration of 12.0 (6.0–12.0) months. There was no difference of the rate of LDA between the BARI and TOFA treatment groups. All disease indices in the two groups were significantly improved, including a significantly lower VAS in the BARI group (P

Abstract Background Baricitinib, an oral selective JAK1/JAK2 inhibitor, is approved for the treatment of adults with severe alopecia areata (AA). Objective To evaluate differences in response up to week 52 among subgroups based on the baseline severity of AA assessed with the Severity of Alopecia Tool (SALT) score. Methods Data were pooled from BRAVE-AA1 and BRAVE-AA2, two randomized, placebo-controlled, phase 3 trials, which enrolled adults with a SALT score ≥ 50. Patients were subdivided by the degree of AA severity at baseline. Results Among the 855 patients treated with baricitinib 2 mg and 4 mg, improvements in scalp hair growth continued through to week 52. A superior response was observed in patients with a SALT score of 50–94 versus a score of 95–100. Patients on baricitinib 4 mg had a faster and higher response rate compared to baricitinib 2 mg. Conclusion Across all degrees of severity for baricitinib 2 mg and 4 mg doses, the proportion of patients responding was yet to plateau up to week 52. Response to treatment was longer for patients with a baseline SALT score 95–100. Further studies are needed to analyze other parameters that may impact observed response rates.

Abstract Introduction Baricitinib, an orally available small-molecule inhibitor of Janus kinase (JAK)1 and JAK2, is indicated to treat active moderate-to-severe rheumatoid arthritis (RA). Objective This systematic review described the real-world clinical characteristics of baricitinib-treated patients with RA, prescription patterns, effectiveness, drug persistence, patient-reported outcomes (PROs; physical function, pain, health-related quality of life [HRQoL]), patient global assessment (PGA), and safety of baricitinib. Methods A PRISMA systematic review of real-world studies was conducted to identify relevant literature published between January 2016 and September 2022 using MEDLINE®, EMBASE®, and evidence-based medicine review databases. Websites or online repositories of the American College of Rheumatology and the European Alliance of Associations for Rheumatology were searched manually to include relevant abstracts from conferences held between January 2016 and November 2022. Results A total of 11,472 records were identified by searching online databases. Seventy studies were included in the study, of which 40 were abstracts. Most patients were older (51–71 years), female, and with mean RA duration of 4–19 years. Baricitinib was mostly used after the failure of one or more bDMARDs, and 4 mg dosing was prevalent in patients with RA (range 22–100%). Clinical effectiveness of baricitinib was reported in real-world settings regardless of prior biologic/targeted synthetic disease-modifying antirheumatic drug (DMARD) use and concomitant conventional synthetic DMARD use. Achievement of Clinical Disease Activity Index (CDAI) remission was reported in 8.7–60% of patients at week 12 and CDAI low disease activity (LDA) in 20.2–81.6% at week 24. The proportion of patients attaining Simple Disease Activity Index (SDAI) remission was reported in 12% at week 4 to 45.4% at 24 weeks. Drug persistence was high, similar, or equal to anti-tumor necrosis factor drugs. No new safety signals were identified. Conclusion Baricitinib demonstrated effectiveness in the real-world setting with a consistent safety profile observed in clinical studies. Better persistence rates for baricitinib compared to bDMARDs with improvement in PROs were reported, although baricitinib-treated patients had RA with poor prognostic characteristics.

Abstract Introduction 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. Methods 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]). Results Safety analyses included 667 patients (female, 82.3%; mean age, 53.3 years; mean RA duration, 86.9 months); 106/667 (15.9%) were 65–74 years old and 19/667 (2.8%) were ≥ 75 years old; 87.0% received baricitinib 2 mg 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 100 PY) 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. Conclusions 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. Trial Registration EU PAS Register: EUPAS34213.

Abstract Introduction RA-BE-REAL is a 3-year, multinational, prospective, observational study of adult patients with rheumatoid arthritis (RA) evaluating time to discontinuation of initial RA treatment along with patient baseline characteristics. This study’s primary objective was to assess the time to discontinuation of initial baricitinib, any other targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD), or any biologic disease-modifying anti-rheumatic drug (bDMARD) treatment for all causes (excluding sustained clinical response) over 24 months in a European population. Methods Patients initiated treatment with baricitinib (cohort A) or any bDMARD or tsDMARD (cohort B) for the first time. This study’s primary objective was to assess the time to discontinuation of initial baricitinib, any other targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD), or any biologic disease-modifying anti-rheumatic drug (bDMARD) treatment for all causes (excluding sustained clinical response) over 24 months in a European population. Comparative effectiveness analyses, over 24 months, included time to treatment discontinuation for all causes (excluding sustained clinical response), percentage of patients achieving Clinical Disease Activity Index (CDAI) remission or low disease activity (LDA), as well as mean changes from baseline for CDAI, pain visual analogue scale, and the Health Assessment Questionnaire-Disability Index (HAQ-DI). For this European subpopulation, comparative analyses were performed using a frequentist model averaging (FMA) framework based on a data-driven machine learning causal inference approach to compare time to discontinuation, effectiveness, rates of remission or LDA, and patient-reported outcomes over 24 months comparing baricitinib with TNFi, as well as non-TNFi and tsDMARD grouped as other mechanism of action (OMA) drugs. Results In the European sample of RA-BE-REAL, patients with RA treated with baricitinib experienced fewer discontinuations in comparison to those treated with tumour necrosis factor inhibitors or OMA. Overall, patients naïve to b/tsDMARDs achieved a higher rate of LDA and remission compared with experienced patients. A significantly greater proportion of patients treated with baricitinib achieved LDA compared with b/tsDMARDs. Conclusion This real-world data can better inform clinicians about baricitinib effectiveness and drug survival when prescribing treatment for patients with RA across different subpopulations.

Abstract Introduction The efficacy of conventional treatments for alopecia areata (AA) has been extremely variable and disappointing, with a high rate of relapse. Recent clinical trials and real-life studies have demonstrated efficacy and safety of baricitinib (an oral Janus kinase 1 and 2 inhibitor) in alopecia areata. Methods We retrospectively evaluated the effectiveness and tolerance of baricitinib in alopecia areata in a real-life Belgian monocentric adult cohort. The primary outcome was evaluated by the percentage of patients who achieved a Severity of Alopecia Tool (SALT) score of ≤ 20 at the end of the follow-up. All treatment-emergent adverse events were collected. Results In this 19-patient series, with a median ± interquartile range (IQR) follow-up duration of 13 ± 16.2 months, we demonstrated that: (i) hair regrowth was observed in nearly 90% of patients between 4 and 16 weeks after initiation of baricitinib; (ii) at the end of the follow-up, more than 70% and, in particular, 100% of patients with patchy AA, reached the primary outcome (SALT score ≤ 20); (iii) almost half of the patients, mostly with patchy AA, showed a complete hair regrowth (SALT score = 0), within a median ± IQR treatment time of 8.5 ± 10 months; (iv) baricitinib was discontinued in three patients with total hair regrowth, two of whom relapsed; and (v) no serious adverse events were reported. Conclusion Baricitinib is effective in treating patients with alopecia areata, particularly for the patchy phenotype, but with a risk of relapse after discontinuation. Safety data are reassuring, with lipid changes being the most frequent adverse event.

Alopecia areata (AA) is a chronic, tissue-specific autoimmune disorder, characterized by non-scaring hair loss, with a global prevalence of approximately 2%. Typically, it affects a young population, with initial onset frequently occurring before the age of 30 years. Even though the exact pathogenesis of AA remains unclear, the predominant hypothesis is the breakdown of immune privilege of the hair follicle, resulting in increased self-antigen and major histocompatibility complex expression in the follicular epithelium. The relapsing nature of the disease negatively impacts patients’ quality of life and makes them more susceptible to developing psychiatric comorbidities. Although many treatment modalities have been proposed, there are no currently available treatments able to induce and sustain disease remission. Traditional treatment modalities, despite being widely used, present limited results and a high risk of adverse effects. Hence, there exists an unfulfilled requirement for treatments that are both more efficient and safer. The latest understanding of the pathophysiology of AA and its connection to the JAK–STAT pathway has prompted the advancement of JAK inhibitors. These small-molecule agents function by obstructing the JAK–STAT intracellular signalling pathway. Baricitinib an orally administered, selective JAK1 and JAK2 inhibitor is a promising alternative to the available treatments, and is already approved for the treatment of AA.

Anna Felis-Giemza,1 Magdalena Massalska,2 Leszek Roszkowski,3 Katarzyna Romanowska-Próchnicka,4 Marzena Ciechomska2 1Biologic Therapy Center, National Institute of Geriatrics, Rheumatology, and Rehabilitation (NIGRiR), Warsaw, Poland; 2Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation (NIGRiR), Warsaw, Poland; 3Department of Outpatient Clinics, National Institute of Geriatrics, Rheumatology, and Rehabilitation (NIGRiR), Warsaw, Poland; 4Department of Biophysics, Physiology and Pathophysiology, Faculty of Health Sciences, Warsaw Medical University, Warsaw, PolandCorrespondence: Magdalena Massalska, Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, Spartanska 1, Warsaw, 02-637, Poland, Tel +48226709564, Email magdalena.massalska@spartanska.plAbstract: It is well known that fatigue is a highly disabling symptom commonly observed in inflammatory rheumatic diseases (IRDs). Fatigue is strongly associated with a poor quality of life and seems to be an independent predictor of job loss and disability in patients with different rheumatic diseases. Although the pathogenesis of fatigue remains unclear, indirect data suggest the cooperation of the immune system, the central and autonomic nervous system, and the neuroendocrine system in the induction and sustainment of fatigue in chronic diseases. Fatigue does not correspond with disease activity and its mechanism in IRDs. It is suggested that it may change over time and vary between individuals. Abnormal production of pro-inflammatory cytokines such as interleukin-6 (IL-6), interferons (IFNs), granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF, IL-15, IL-17 play a role in both IRDs and subsequent fatigue development. Some of these cytokines such as IL-6, IFNs, GM-CSF, and common gamma-chain cytokines (IL-15, IL-2, and IL-7) activate the Janus Kinases (JAKs) family of intracellular tyrosine kinases. Therapy blocking JAKs (JAK inhibitors – JAKi) has been recently proven to be an effective approach for IRDs treatment, more efficient in pain reduction than anti-TNF. Therefore, the administration of JAKi to IRDs patients experiencing fatigue may find rational implications as a therapeutic modulator not only of disease inflammatory symptoms but also fatigue with its components like pain and neuropsychiatric features as well. In this review, we demonstrate the latest information on the mechanisms of fatigue in rheumatic diseases and the potential effect of JAKi on fatigue reduction.Plain Language Summary: JAKi block pro-inflammatory cytokines, decrease activation of IDO, diminish the effects of genetic polymorphism (particularly mediated by IL-6 and IL-1β) as well as sickness behavior also connected with IL-1β expression, which result in fatigue and pain inhibition.In patients treated with JAKi, it was observed that there was significantly greater improvement compared to placebo and MTX in fatigue and pain reduction measured using PROs.Administration of JAKi (BARI+UPA) benefits over TNFi treatment in pain and fatigue reduction assessed by PtGA in RA patients.The effectiveness of fatigue reduction in PROs under recently approved JAKi still needs to be proven in clinical practice, especially in selective and nonselective groups of JAKi.Keywords: fatigue, JAK inhibitors, patient-reported outcomes, tofacitinib, baricitinib, upadacitinib

Abstract Background The Janus kinase (JAK)1/JAK2 inhibitor baricitinib in combination with topical corticosteroids (TCS) improved moderate‐to‐severe atopic dermatitis (AD) in the phase 3 BREEZE‐AD7 trial. Patients with previous systemic therapy may have more severe, treatment‐resistant disease. Objectives To assess the efficacy of baricitinib 4 mg in adults with moderate‐to‐severe AD with and without previous use of systemic therapy. Methods Patients were randomized 1:1:1 to TCS plus once‐daily oral placebo, 2 mg baricitinib or 4 mg baricitinib for 16 weeks. Outcomes were assessed in patients treated with baricitinib 4 mg with and without previous use of systemic therapy (N = 68, N = 43) versus placebo (N = 75, N = 34). Prior use of systemic therapy was defined as treatment of AD with oral corticosteroids, immunosuppressants or biologics. Endpoints included the proportions of patients achieving a vIGA‐AD® score 0 or 1 with >2‐point improvement from baseline, 75% improvement in the Eczema area and severity index score (EASI75), ≥4‐point improvement on the Itch numeric rating scale (NRS) and ≥4‐point improvement in the dermatology life quality index (DLQI). Logistic regression was used to evaluate consistent treatment effects across subgroups. Results At Week 16, among patients with and without previous use of systemics treated with baricitinib 4 mg versus placebo, respectively, vIGA‐AD score (0, 1) was achieved in 27.9% and 34.9% versus 13.3% and 17.6%, EASI75 was met in 47.1% and 48.8% versus 22.7% and 23.5%, Itch NRS ≥ 4‐point improvement was observed in 44.4% and 43.2% versus 14.1% and 33.3% and DLQI ≥ 4‐point improvement was seen in 75.8% and 69.2% versus 52.1% and 54.8%. Consistent treatment effects were observed between patients with or without prior use of systemics (treatment‐by‐subgroup interactions p = 0.085 for Itch NRS, p > 0.1 for all others). Conclusions Baricitinib 4 mg significantly reduced disease severity in AD compared to placebo regardless of prior systemic therapy.

This article discusses a case of rapid progression of cutaneous T-cell lymphoma in a patient with erythroderma during treatment with dupilumab, following prior sequential treatments with azathioprine, baricitinib, and cyclosporine. The patient initially presented with general itching, eczematous plaques, and ichthyosis vulgaris. Despite various treatments, including dupilumab, the patient's condition worsened, and a diagnosis of mycosis fungoides with CD30+ large cell transformation was made. The patient ultimately achieved remission with chemotherapy and brentuximab vedotin. The article highlights the challenges in diagnosing and treating mycosis fungoides in patients with erythroderma and emphasizes the need for caution when using systemic immunomodulators in these cases. Further research is needed to investigate the potential association between dupilumab and the development of cutaneous T-cell lymphoma. [Extracted from the article]

Actinic prurigo is a rare photodermatosis characterized by pruritic papulonodular lesions. Treatment is challenging, especially in children, as sun protection strategies need to be rigorously implemented and symptoms often persist throughout the year. Herein, we present a case of actinic prurigo in an 8‐year‐old patient with rapid and successful relief with baricitinib. [ABSTRACT FROM AUTHOR]

Background: Baricitinib is an oral selective inhibitor of Janus kinase 1 and 2 approved for the treatment of rheumatoid arthritis, atopic dermatitis, and alopecia areata. In a 24-week phase 2 study in patients with systemic lupus erythematosus (SLE), baricitinib 4 mg significantly improved SLE disease activity compared with placebo. The objective of this trial was to evaluate the efficacy and safety of baricitinib in patients with active SLE in a 52-week phase 3 study. Methods: In a multicentre, double-blind, randomised, placebo-controlled, parallel-group, phase 3 study, SLE-BRAVE-I, patients (aged ≥18 years) with active SLE receiving stable background therapy were randomly assigned 1:1:1 to baricitinib 4 mg, 2 mg, or placebo once daily for 52 weeks with standard of care. Glucocorticoid tapering was encouraged but not required per protocol. The primary endpoint was the proportion of patients reaching an SLE Responder Index (SRI)-4 response at week 52 in the baricitinib 4 mg treatment group compared with placebo. The primary endpoint was assessed by logistic regression analysis with baseline disease activity, baseline corticosteroid dose, region, and treatment group in the model. Efficacy analyses were done on a modified intention-to-treat population, comprising all participants who were randomly assigned and received at least one dose of investigational product. Safety analyses were done on all randomly assigned participants who received at least one dose of investigational product and who did not discontinue from the study for the reason of lost to follow-up at the first post-baseline visit. This study is registered with ClinicalTrials.gov, NCT03616912. Findings: 760 participants were randomly assigned and received at least one dose of baricitinib 4 mg (n=252), baricitinib 2 mg (n=255), or placebo (n=253). A significantly greater proportion of participants who received baricitinib 4 mg (142 [57%]; odds ratio 1·57 [95% CI 1·09 to 2·27]; difference with placebo 10·8 [2·0 to 19·6]; p=0·016), but not baricitinib 2 mg (126 [50%]; 1·14 [0·79 to 1·65]; 3·9 [-4·9 to 12·6]; p=0·47), reached SRI-4 response compared with placebo (116 [46%]). There were no significant differences between the proportions of participants in either baricitinib group reaching any of the major secondary endpoints compared with placebo, including glucocorticoid tapering and time to first severe flare. 26 (10%) participants receiving baricitinib 4 mg had serious adverse events, 24 (9%) participants receiving baricitinib 2 mg, and 18 (7%) participants receiving placebo. The safety profile of baricitinib in participants with SLE was consistent with the known baricitinib safety profile. Interpretation: The primary endpoint in this study was met for the 4 mg baricitinib group. However, key secondary endpoints were not. No new safety signals were observed. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a patient with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) who experienced an acute exacerbation of their condition. The patient was treated with high-dose corticosteroids and immunosuppressive therapy, but their symptoms worsened. However, when the patient was given baricitinib, a Janus kinase (JAK) inhibitor, in combination with intensive immunosuppressive therapy, their respiratory symptoms improved and their lung infiltrates decreased. The article suggests that JAK inhibitors may be effective in treating acute exacerbations of RA-ILD and reducing the risk of fatal outcomes. [Extracted from the article]

Recently, alopecia areata (AA) treatment via the Janus kinase (JAK)‐signal transducer and activator of transcription pathway has been reported. However, as baricitinib, a JAK1/2 inhibitor is only approved for adult patients, children, and adolescent patients still lack treatment options. We present a case that showed improvement of severe AA in an adolescent patient on upadacitinib, which has been approved by the Food and Drug Administration (FDA) for use in patients with rheumatoid disease or atopic dermatitis (AD) in children aged 12 years or older and weighing 40 kg or more. Herein, we suggest that upadacitinib can be a good alternative for adolescent patients with AA, particularly those who may also have AD. [ABSTRACT FROM AUTHOR]

Topical ocular drug delivery faces several challenges due to the eye’s unique anatomy and physiology. Physiological barriers, tear turnover, and blinking hinder the penetration of drugs through the ocular mucosa. In this context, nanoparticles offer several advantages over traditional eye drops. Notably, they can improve drug solubility and bioavailability, allow for controlled and sustained drug release, and can be designed to specifically target ocular tissues, thus minimizing systemic exposure. This study successfully designed and optimized PLGA and PCL nanoparticles for delivering baricitinib (BTB) to the eye using a factorial design, specifically a three-factor at five-levels central rotatable composite 23+ star design. The nanoparticles were small in size so that they would not cause discomfort when applied to the eye. They exhibited low polydispersity, had a negative surface charge, and showed high entrapment efficiency in most of the optimized formulations. The Challenge Test assessed the microbiological safety of the nanoparticle formulations. An ex vivo permeation study through porcine cornea demonstrated that the nanoparticles enhanced the permeability coefficient of the drug more than 15-fold compared to a plain solution, resulting in drug retention in the tissue and providing a depot effect. Finally, the in vitro ocular tolerance studies showed no signs of irritancy, which was further confirmed by HET-CAM testing.

Hyperinflammatory Coronavirus disease 2019 (COVID-19) and rapidly-progressive interstitial lung diseases (RP-ILD) secondary to inflammatory myopathies (IIM) present important similarities. These data support the use of anti-rheumatic drugs for the treatment of COVID-19. The aim of this study was to compare the efficacy of combining baricitinib and pulse steroids with the Standard of Care (SoC) for the treatment of critically ill COVID-19 patients. We retrospectively enrolled consecutive patients admitted to the Intensive Care Unit (ICU) with COVID-19-pneumonia. Patients treated with SoC (dexamethasone plus remdesivir) were compared to patients treated with baricitinib plus 6-methylprednisolone pulses (Rheuma-group). We enrolled 246 patients: 104/246 in the SoC and 142/246 in the Rheuma-group. All patients presented laboratory findings suggestive of hyperinflammatory response. Sixty-four patients (26.1%) died during ICU hospitalization. The mortality rate in the Rheuma-group was significantly lower than in the SoC-group (15.5 vs. 40.4%, p < 0.001). Compared to the SoC-group, patients in the Rheuma-group presented significantly lower inflammatory biomarker levels after one week of treatment. Higher ferritin levels after one week of treatment were strongly associated with mortality (p < 0.001). In this large real-life COVID-19 cohort, baricitinib and pulse steroids led to a significant reduction in mortality, paralleled by a prompt reduction in inflammatory biomarkers. Our experience supports the similarities between hyperinflammatory COVID-19 and the IIM-associated RP-ILD.

Abstract Objective The study explored improvements in pulmonary inflammation and fibrosis in a bovine type II collagen-induced rheumatoid arthritis-associated interstitial lung disease mouse model after treatment with baricitinib and the possible mechanism of action. Methods A rheumatoid arthritis-associated interstitial lung disease mouse model was established, siRNA Jak2 and lentiviral vectors were transfected with human embryonic lung fibroblast cells. And the levels of relevant proteins in mouse lung tissue and human embryonic lung fibroblasts were detected by Western blotting. Results The levels of JAK2, p-JAK2, p-STAT3, p-SMAD3, SMA, TGFβR2, FN and COL4 were increased in the lung tissues of model mice (P

Qianqian Zhou,1 Shengru Zhou,1 Huizi Xiong,1 Jianqiu Yang,1 Ziliang Yang,2 Naihui Zhou,2 Jinzhu Mao,2 Min Li1,2 1Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), Suzhou, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Min Li, Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), No. 9, Chongwen Road, Suzhou, 215123, People’s Republic of China, Tel +86-18936140383, Email lm@suda.edu.cnIntroduction: Psoriasis is an immune-mediated chronic inflammatory skin disease. As our understanding of the pathogenesis of psoriasis has improved, biologic agents have become increasingly important in the treatment of psoriasis. However, the use of biologic agents is associated with cutaneous side effects. A new type of side effect called paradoxical reactions is an emerging threat arising from the increasing use of biologic agents.Case: Here, we present a case of paradoxical skin reactions – pyoderma gangrenosum (PG) and eczema – induced by biologic therapy. The case was successfully and eventually treated with baricitinib.Discussion: PG is a rare inflammatory disease characterised by painful and necrotic ulcerations containing neutrophils. It has been associated with autoimmune diseases such as inflammatory bowel disease (IBD). TNF (tumor necrosis factor) -α inhibitors can effectively treat refractory PG, while IL (interleukin) − 17A inhibitors may worsen IBD symptoms. The cause of PG in this case was believed to be secukinumab, not adalimumab. The patient was diagnosed with eczematous dermatitis due to TNF-α inhibitors, and baricitinib was added to treat eczematous dermatitis.Conclusion: Paradoxical reactions are unpredictable events that may occur during treatment with biologics at anytime. They need further research in order to formulate personalised treatment.Keywords: biology drugs, pyoderma gangrenosum, eczema, adalimumab, secukinumab, baricitinib

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.

Background: Janus kinase inhibitors (jakinibs) are immunomodulators used for treating malignancies, autoimmune diseases, and immunodeficiencies. However, they induce adverse effects such as thrombosis, lymphocytosis, and neutropenia that could be mediated by extracellular vesicles (EVs). These particles are cell membrane-derived structures that transport cellular and environmental molecules and participate in intercellular communication. Jakinibs can modify the content of EVs and enable them to modulate the activity of different components of the immune response. Objective: to evaluate the interactions between immune system components of healthy individuals and EVs derived from monocytic and lymphoid lineage cells generated in the presence of baricitinib (BARI) and itacitinib (ITA) and their possible effects. Methods: EVs were isolated from monocytes (M) and lymphocytes (L) of healthy individuals, as well as from U937 (U) and Jurkat (J) cells exposed to non-cytotoxic concentrations of BARI, ITA, and dimethyl sulfoxide (DMSO; vehicle control). The binding to and engulfment of EVs by peripheral blood leukocytes of healthy individuals were analyzed by flow cytometry using CFSE-stained EVs and anti-CD45-PeCy7 mAb-labeled whole blood. The effect of EVs on respiratory burst, T-cell activation and proliferation, cytokine synthesis, and platelet aggregation was evaluated. Respiratory burst was assessed in PMA-stimulated neutrophils by the dihydrorhodamine (DHR) test and flow cytometry. T-cell activation and proliferation and cytokine production were assessed in CFSE-stained PBMC cultures stimulated with PHA; expression of the T-cell activation markers CD25 and CD69 and T-cell proliferation were analyzed by flow cytometry, and the cytokine levels were quantified in culture supernatants by Luminex assays. Platelet aggregation was analyzed in platelet-rich plasma (PRP) samples by light transmission aggregometry. The EVs’ fatty acid (FA) profile was analyzed using methyl ester derivatization followed by gas chromatography. Results: ITA exposure during the generation of EVs modified the size of the EVs released; however, treatment with DMSO and BARI did not alter the size of EVs generated from U937 and Jurkat cells. Circulating neutrophils, lymphocytes, and monocytes showed a 2-fold greater tendency to internalize ITA-U-EVs than their respective DMSO control. The neutrophil respiratory burst was attenuated in greater extent by M-EVs than by L-EVs. Autologous ITA-M-EVs reduced T-cell proliferation by decreasing IL-2 levels and CD25 expression independently of CD69. A higher accumulation of pro-inflammatory cytokines was observed in PHA-stimulated PBMC cultures exposed to M-EVs than to L-EVs; this difference may be related to the higher myristate content of M-EVs. Platelet aggregation increased in the presence of ITA-L/M-EVs by a mechanism presumably dependent on the high arachidonic acid content of the vesicles. Conclusions: Cellular origin and jakinib exposure modify the FA profile of EVs, enabling them, in turn, to modulate neutrophil respiratory burst, T-cell proliferation, and platelet aggregation. The increased T-cell proliferation induced by BARI-L/M-EVs could explain the lymphocytosis observed in patients treated with BARI. The higher proportion of arachidonic acid in the FA content of ITA-L/M-EVs could be related to the thrombosis described in patients treated with ITA. EVs also induced a decrease in the respiratory burst of neutrophils.

Objectives: The persistence in therapy of rheumatoid arthritis drugs and particularly bDMARD is a limiting factor for their long-term use. The randomized controlled trials (RCTs) may not reflect real-world contexts due to strict inclusion and exclusion criteria. Baricitinib, which targets both JAK1 and JAK2, has been used in Italy for several years. The aim of this multi-center study is to assess the real world persistence on therapy of baricitinib in RA patients and to identify predictive factors of baricitinib's survival rate. Methods: This is a retrospective, multicentric, Italian, longitudinal study. All patients were enrolled according to the following criteria: a) age ≥ 18 years old; b) diagnosed with RA according 2010 ACR/EULAR classification criteria; c) treated with baricitinib. In order to describe baricitinib clinical efficacy, the survival rate was evaluated by The Kaplan–Meier curve. Then, predictive factors of drug retention rate were assessed by performing the Cox analysis, identifying which risk factors influenced treatment persistence. Results: Overall, we included 478 patients treated with baricitinib. Among them, 380 (79.5%) were females. Baricitinib's survival rate was 94.6% at 6 months, 87.9% at 12 months, 81.7% at 24 months and 53.4% at 48 months. The Cox analysis regression showed that a higher bDMARDs/tsDMARD line of therapy seems to be a negative prognostic factor for the drug retention rate (HR 1.26 CI 95% 1.07–1.49, p = 0.006. Conclusion: Real-life study confirms baricitinib effectiveness up to 4 years, but previous treatment with bDMARDs was a negative prognostic factor for its survival rate.

AbstractBackground Atopic dermatitis (AD) is a chronic eczematous disease with severe pruritus. Janus kinase (JAK) inhibitors, upadacitinib, baricitinib, and abrocitinib, are systemic treatments for AD. The outcomes of switching from one JAK inhibitor to another have not been examined.Objectives We assessed the outcomes of switching from baricitinib 4 mg to upadacitinib 30 mg in Japanese patients with moderate-to-severe AD.Methods Twenty patients treated with baricitinib 4 mg, showing insufficient response or adverse events, were switched to treatment with upadacitinib 30 mg. We evaluated total eczema area and severity index (EASI), EASI at head and neck, trunk, upper, or lower limbs, EASI of erythema, edema/papulation, excoriation, or lichenification, and peak pruritus numerical-rating scale (PP-NRS) at baseline (start of baricitinib), weeks 0 (time of switching), and 4 and 12 after switching.Results Total EASI, EASI at each anatomical site, EASI of each clinical sign, and PP-NRS were markedly reduced at weeks 4 or 12 compared to week 0. Achievement rates of more than 75% or 90% reduction of EASI from baseline significantly improved after switching.Conclusions Switching from baricitinib 4 mg to upadacitinib 30 mg effectively improved rash and pruritus.

Juvenile systemic lupus erythematosus (jSLE) is a complex inflammatory autoimmune disorder. In the last decades, genetic factors and activation pathways have been increasingly studied to understand their potential pathogenetic role better. Genetic and transcriptional abnormalities directly involved in the type I interferon (IFN) signaling cascade have been identified through family-based and genome-wide association studies. IFNs trigger signaling pathways that initiate gene transcription of IFN-stimulated genes through the activation of JAK1, TYK2, STAT1, and STAT2. Thus, the use of therapies that target the IFN pathway would represent a formidable advance in SLE. It is well known that JAK inhibitors have real potential for the treatment of rheumatic diseases, but their efficacy in the treatment of SLE remains to be elucidated. We report the case of a 13-year-old girl affected by jSLE, carrying a novel heterozygous missense variant on Three prime Repair EXonuclease 1 (TREX1), successfully treated with baricitinib on top of mofetil mycophenolate. The TREX1 gene plays an important role in DNA damage repair, and its mutations have been associated with an overproduction of type 1 interferon. This report underlines the role of translational research in identifying potential pathogenetic pathways in rare diseases to optimize treatment.

ISG15 deficiency is a rare disease caused by autosomal recessive variants in the ISG15 gene, which encodes the ISG15 protein. The ISG15 protein plays a dual role in both the type I and II interferon (IFN) immune pathways. Extracellularly, the ISG15 protein is essential for IFN-γ-dependent anti-mycobacterial immunity, while intracellularly, ISG15 is necessary for USP18-mediated downregulation of IFN-α/β signalling. Due to this dual role, ISG15 deficiency can present with various clinical phenotypes, ranging from susceptibility to mycobacterial infection to autoinflammation characterised by necrotising skin lesions, intracerebral calcification, and pulmonary involvement. In this report, we describe novel variants found in two different families that result in complete ISG15 deficiency and severe skin ulceration. Whole exome sequencing identified a heterozygous missense p.Q16X ISG15 variant and a heterozygous multigene 1p36.33 deletion in the proband from the first family. In the second family, a homozygous total ISG15 gene deletion was detected in two siblings. We also conducted further analysis, including characterisation of cytokine dysregulation, interferon-stimulated gene expression, and p-STAT1 activation in lymphocytes and lesional tissue. Finally, we demonstrate the complete and rapid resolution of clinical symptoms associated with ISG15 deficiency in one sibling from the second family following treatment with the Janus kinase (JAK) inhibitor baricitinib.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. It affects multiple organ systems and is associated with significant morbidity and mortality. The treatment for SLE primarily aims at controlling and remitting the disease. Baricitinib is a kinase inhibitor that selectively inhibits JAK1 and JAK2 enzymes. Recently this drug is being investigated as a potential therapeutic option for SLE. Objective: To analyze the efficacy of baricitinib in treating SLE. Methods: Search of databases identified relevant studies that reported the efficacy of baricitinib. Data of patient characteristics, intervention details, and outcomes was extracted. The data from the studies were pooled using a random-effects model. The odds ratio with their respective 95 % confidence intervals (CI) were calculated to analyze the results. A p value of

Background Baricitinib is an oral selective Janus kinase 1/2 inhibitor approved for moderate-to-severe atopic dermatitis (AD) in adults. Objectives To evaluate absolute Eczema Area and Severity Index (EASI) and SCORing of Atopic Dermatitis (SCORAD) outcomes over 16 weeks and to link disease severity categories to quality of life (QoL) improvements. Methods This post-hoc analysis included patients enrolled in Phase3 monotherapy (BREEZE-AD1/AD2) and topical corticosteroid (TCS) combination therapy (BREEZE-AD7) trials and analyzed baricitinib 2 and 4 mg vs. placebo. Categorical outcomes were analyzed using Fisher’s exact test. Results Significantly more baricitinib-treated patients reached EASI ≤ 7 and SCORAD < 25 as early as week 1 in monotherapy and week 2 in TCS combination therapy, compared to placebo. Significant response vs. placebo was sustained until week 16 for EASI ≤ 7 (AD1/2 [p-value vs. placebo]: 2 mg = 19.9%, 4 mg = 25.4% [p = 0.001] and AD7: 2 mg = 40.4% [p = 0.087], 4 mg = 48.6% [p = 0.003]) and SCORAD < 25 (AD1/2: 2 mg = 12.2%, 4 mg = 19.4% [p = 0.001] and AD7: 2 mg = 30.3% [p = 0.025], 4 mg = 34.2% [p = 0.004]) severity categories. These effects were accompanied by rapid improvements in QoL. Conclusion Baricitinib-treated patients rapidly achieved recommended absolute EASI and SCORAD treatment outcomes which were sustained until week 16. Improvements in QoL were greater than EASI severity categories reflected, indicating that physician-assessed scores do not necessarily correlate with patients’ impression of AD severity.

Background Patients who completed the originating studies, BREEZE-AD1 (NCT03334396), BREEZE-AD2(NCT03334422), and BREEZE-AD7 (NCT03733301), were eligible for enrollment in the multicenter,phase-3, long-term extension study BREEZE-AD3 (NCT03334435). Methods At week 52, responders and partial responders to baricitinib 4 mg were re-randomized (1:1) into the sub-study to dose continuation (4 mg, N = 84), or dose down-titration (2 mg, N = 84). Maintenance of response was assessed from week 52 to 104 of BREEZE-AD3. Physician-rated outcomes included vIGA-AD (0,1), EASI75, and mean change from baseline in EASI. Patient-reported outcomes included DLQI, P OEM total score, HADS, and from baseline: WPAI (presenteeism, absenteeism, overall work impairment, daily activity impairment) and change from baseline in SCORAD itch and sleep loss. Results With continuous treatment with baricitinib 4 mg, efficacy was maintained up to week 104 in vIGA-AD (0,1), EASI75, EASI mean change from baseline, SCORAD itch, SCORAD sleep loss, DLQI, P OEM, HADS, and WPAI (all scores). Patients down-titrated to 2 mg maintained most of their improvements in each of these measures. Conclusion The sub-study of BREEZE AD3 supports flexibility in baricitinib dosing regimens. Patients who continued treatment with baricitinib 4 mg and down-titrated to 2 mg maintained improvements in skin, itch, sleep, and quality of life for up to 104 weeks.

Background Baricitinib, a selective Janus kinase (JAK)1/JAK2 inhibitor, is approved for treatment of moderate-to-severe atopic dermatitis (AD) in adults. Objectives We report integrated baricitinib safety data in patients with up to 3.9-years exposure. Methods Three datasets from the integrated AD clinical trial program were analyzed: placebo-controlled, 2-mg–4-mg extended, and All-bari. Data cutoffs were up to 21-December-2021 for long-term extension studies. Proportions of patients with events and incidence rates (IR)/100 patient years (PY) at risk were calculated. Results 2636 patients received baricitinib for 4628.4 PY. Discontinuation due to adverse events was low (IR = 3.4). IRs in All-bari were: serious adverse events, 5.2; infection, 67.2 (any infection), 6.7 (herpes simplex), 2.8 (herpes zoster), and 0.3 (opportunistic infections). Adverse events of special interest in All-bari included seven patients with positively adjudicated major adverse cardiovascular events (MACE) (IR = 0.15), three pulmonary emboli (PE) (IR = 0.06), 14 malignancies excluding nonmelanoma skin cancer (IR = 0.3), one gastrointestinal perforation (IR = 0.02), and four deaths (IR = 0.1). No deep vein thromboses (DVT) or tuberculosis were reported. Conclusion In this analysis, baricitinib maintained a similar safety profile to earlier analyses with no new safety signals. Rates of MACE, DVT/PE, malignancies, and serious infections were within ranges of background rates in patients with AD. Clinicaltrials.gov NCT02576938 (JAHG), NCT03334396 (JAHL; BREEZE-AD1), NCT03334422 (JAHM; BREEZE-AD2), NCT03334435 (JAHN; BREEZE-AD3), NCT03428100 (JAIN; BREEZE-AD4), NCT03435081 (JAIW; BREEZE-AD5), NCT03559270 (JAIX; BREEZE-AD6), NCT03733301 (JAIY; BREEZE-AD7)

Introduction This post hoc analysis assessed association between scalp hair regrowth and improvements in health-related quality of life (HRQoL) and psychological burden in patients with severe alopecia areata (AA). Methods Data were pooled from two phase-3 trials (N = 1200). Patients randomized to once-daily placebo, baricitinib 2-mg, or 4-mg were analyzed independently of treatment allocation, and categorized according to scalp hair regrowth (at Week 36): meaningful regrowth (Severity of Alopecia Tool (SALT) score ≤20); intermediate regrowth (≥30% SALT improvement [SALT30] at any post-baseline visit to Week 36, but SALT score > 20 at Week 36); no/minimal regrowth (never achieved SALT30). Skindex-16 for AA score change-from-baseline and proportion of patients with baseline Hospital Anxiety and Depression Scale (HADS) scores ≥8 that shifted to

Background: Tocilizumab and baricitinib are considered standard treatments for hospitalized COVID-19 patients with an inflammatory status. However, the effects of co-administering these medications aiming for more rapid patient recovery are controversial among practitioners. The potential benefits include the rapid improvement of patients and regulation of the immune system, and the potential risks include the increased chance of serious adverse events, including infections. This study aimed to investigate the effects of co-administering these two medications on the 28-day mortality rate, other efficacy parameters, and safety issues. Methods: In this randomized open-label trial, 68 patients were recruited. The study was conducted at Dr. Masih Daneshvari Hospital during 6 months (from 21 March 2022 to 23 August 2022). Severely ill patients aged between 18 and 100 years old with confirmed COVID-19 were enrolled. The primary outcomes included the need for invasive mechanical ventilation and a 28-day mortality rate. Secondary outcomes included the need for non-invasive mechanical ventilation, the need for admission to the intensive care unit (ICU), the length of hospital stay, and the need for a second dose of tocilizumab. Safety assessments were also performed for 28 days. The data were collected from the patients' medical records, which included age, gender, and comorbidities. Results: The 28-day mortality rate or the need for mechanical ventilation was not statistically different among the two groups (p-value = 0.49 for both outcomes). The need for non-invasive mechanical ventilation, the need for admission to the ICU, or the need for a second dose of tocilizumab and the length of hospital stay was not affected either (p-value = 1; 0.1; 0.49 and 0.9, respectively). One patient developed thrombosis in the combination group. No adverse events related to infectious complications were recorded in any groups. Conclusion: This study showed no beneficial effects of combining tocilizumab and baricitinib in managing severe COVID-19 cases. However, the need for ICU admission was meaningfully lower in the combination group. Studies with larger sample sizes are needed to confirm these results. [ABSTRACT FROM AUTHOR]

The Janus kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathway has been identified as a key player in the pathophysiology of alopecia areata and a potential target for therapy. Here, we give a narrative review of what is known about Janus kinase inhibitors in alopecia areata. Several clinical trials as well as smaller studies have demonstrated hair regrowth and remission with oral Janus kinase inhibitors therapy, even in patients who failed conventional treatment. Baricitinib is the only US FDA-approved treatment for alopecia areata but data for other oral Janus kinase inhibitors such as tofacitinib, ruxolitinib and ritlecitinib are also promising. Fewer clinical trials have investigated topical Janus kinase inhibitors for alopecia areata, with many of them terminated early due to unfavourable results. Overall, Janus kinase inhibitors are an efficacious addition to the therapeutic arsenal for treatment-refractory alopecia areata. Further work is needed to examine the effects of long-term usage of Janus kinase inhibitors, the efficacy of topical Janus kinase inhibitors, as well as to identify biomarkers that could predict differential therapeutic responses to the various Janus kinase inhibitors. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of four different drug classes on soluble urokinase plasminogen activator receptor (suPAR), a biomarker active in multiple inflammatory processes and a risk factor for complications, in people with type 1 and type 2 diabetes. Methods: We conducted post hoc analyses of a randomized, open‐label, crossover trial including 26 adults with type 1 and 40 with type 2 diabetes with urinary albumin‐creatinine ratio ≥30 and ≤500 mg/g assigned to 4‐week treatments with telmisartan 80 mg, empagliflozin 10 mg, linagliptin 5 mg and baricitinib 2 mg, separated by 4‐week washouts. Plasma suPAR was measured before and after each treatment. SuPAR change after each treatment was calculated and, for each individual, the best suPAR‐reducing drug was identified. Subsequently, the effect of the best individual drug was compared against the mean of the other three drugs. Repeated‐measures linear mixed‐effects models were employed. Results: The baseline median (interquartile range) plasma suPAR was 3.5 (2.9, 4.3) ng/mL. No overall effect on suPAR levels was observed for any one drug. The individual best‐performing drug varied, with baricitinib being selected for 20 participants (30%), followed by empagliflozin for 19 (29%), linagliptin for 16 (24%) and telmisartan for 11 (17%). The individual best‐performing drug reduced suPAR by 13.3% (95% confidence interval [CI] 3.7, 22.8; P = 0.007). The difference in suPAR response between the individual best‐performing drug and the other three was −19.7% (95% CI −23.1, −16.3; P < 0.001). Conclusions: We demonstrated no overall effect of 4‐week treatment with telmisartan, empagliflozin, linagliptin or baricitinib on suPAR. However, individualization of treatment might significantly reduce suPAR levels. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the safety and effectiveness of baricitinib in patients with systemic lupus erythematosus (SLE). Methods: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register to find relevant publications. Using data from randomized controlled trials (RCTs), we performed a meta-analysis to investigate the safety and efficacy of baricitinib in patients with active SLE who did not respond well to standard treatments. Results: A total of 1849 individuals (1235 experimental participants and 614 controls) from three RCTs on baricitinib were included. A reduction of ≥ 4 points from baseline in SLEDAI-2K score in the baricitinib 4 mg group was greater than the placebo group's reduction (odds ratio [OR] = 1.407, 95% confidence interval [CI] 1.123–1.763, p =.003). The baricitinib 4 mg group significantly outperformed the placebo group in terms of SLEDAI-2K remission of arthritis or rash (OR = 1.327, 95% CI = 1.059–1.663, p =.014). Other effectiveness outcomes such as the SRI4 response did not substantially improve in the baricitinib 4 mg group when compared with the placebo group. And there were no significant increase in the efficacy outcomes in the baricitinib 2 mg group than in the placebo group. However, there was a substantially higher incidence of severe adverse events (SAE) and serious infections in the baricitinib 4 mg group (OR = 1.493, 95% CI = 1.002–2.225, p =.049; OR = 2.303, 95% CI = 1.147–4.622, p =.019) compared to the placebo group. There were no differences between the baricitinib 2 mg and placebo groups in any of the safety outcome data. Conclusion: Meta-analysis reveals that baricitinib 4 mg is beneficial for treating active SLE in terms of a reduction of ≥ 4 points from baseline in SLEDAI-2K score and SLEDAI-2K remission of arthritis or rash. However, the higher frequency of SAEs and serious infections was observed in the group receiving baricitinib 4 mg. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy of conventional treatments for alopecia areata (AA) has been extremely variable and disappointing, with a high rate of relapse. Recent clinical trials and real-life studies have demonstrated efficacy and safety of baricitinib (an oral Janus kinase 1 and 2 inhibitor) in alopecia areata. Methods: We retrospectively evaluated the effectiveness and tolerance of baricitinib in alopecia areata in a real-life Belgian monocentric adult cohort. The primary outcome was evaluated by the percentage of patients who achieved a Severity of Alopecia Tool (SALT) score of ≤ 20 at the end of the follow-up. All treatment-emergent adverse events were collected. Results: In this 19-patient series, with a median ± interquartile range (IQR) follow-up duration of 13 ± 16.2 months, we demonstrated that: (i) hair regrowth was observed in nearly 90% of patients between 4 and 16 weeks after initiation of baricitinib; (ii) at the end of the follow-up, more than 70% and, in particular, 100% of patients with patchy AA, reached the primary outcome (SALT score ≤ 20); (iii) almost half of the patients, mostly with patchy AA, showed a complete hair regrowth (SALT score = 0), within a median ± IQR treatment time of 8.5 ± 10 months; (iv) baricitinib was discontinued in three patients with total hair regrowth, two of whom relapsed; and (v) no serious adverse events were reported. Conclusion: Baricitinib is effective in treating patients with alopecia areata, particularly for the patchy phenotype, but with a risk of relapse after discontinuation. Safety data are reassuring, with lipid changes being the most frequent adverse event. [ABSTRACT FROM AUTHOR]

This article discusses a case report of a patient with Common Variable Immunodeficiency (CVID) enteropathy, a condition characterized by immune dysregulation in the gastrointestinal tract. The patient experienced severe symptoms and complications, including chronic diarrhea and weight loss, despite various treatments. The authors found that treatment with the JAK1/2 inhibitor baricitinib resulted in disease control and improvement in symptoms. The article highlights the challenges of managing CVID enteropathy and suggests that JAK inhibitors may be a potential treatment option. Further research is needed to confirm the clinical use of JAK inhibitors in CVID-related enteropathy. [Extracted from the article]

This point of view explores the safety concerns of Janus kinase inhibitors (JAK-Is), used in treating rheumatoid arthritis (RA) and other rheumatologic conditions. Increasing evidence shows that JAK-Is may elevate the risk of venous thromboembolism (VTE), especially pulmonary embolism. This fact has prompted the European Medicines Agency to advise cautious use of these drugs in patients over 65, smokers, and those at risk of cardiovascular issues or cancer. The paper analyses the evidence on the association between VTE risk and RA and whether different JAK-Is pose different risks. It also probes the link between VTE, lipids, and JAK inhibition, noting that JAK-Is can alter HDL and LDL levels. On the other hand, some evidence indicates that tighter LDL-cholesterol control could mitigate VTE risk, particularly pulmonary embolism. Moreover, data from trials show little attention to treating this main cardiovascular and VTE risk factor in rheumatological patients. Although the lipid paradox theory emphasizes the U-shaped relationship between LDL cholesterol and cardiovascular risk in patients with RA, uncontrolled levels of clinically relevant LDL cholesterol remain closely linked to cardiovascular and VTE risk. In conclusion, high-potency statins could help to manage the increased cardiovascular and VTE risk concomitant to JAK-Is treatment in rheumatologic patients without depriving them of the best therapeutic choice and, in addition, reducing the inherent risk associated with the disease. [ABSTRACT FROM AUTHOR]

Background: Gain-of-function mutations in STING1 (also known as TMEM173) which result in constitutive activation of STING, have been reported to cause STING-associated vasculopathy with onset in infancy (SAVI). Although a wider spectrum of associated manifestations and perturbations in disease onset have been observed since its description, the genotype-phenotype correlations are not definite, and there is no established treatment protocol for SAVI. Case presentation: Herein, we report a kindred, heterozygous STING mutation (p.V155M) in which the 2-year-old proband suffered from severe interstitial lung disease (ILD) while her father was initially misdiagnosed with connective tissue disease associated with ILD at an adult age. Baricitinib was initiated after the diagnosis of SAVI in the proband combined with steroids, and during the 14-month follow-up, the respiratory symptoms were improved. However, as the improvement of laboratory indicators was limited, especially in autoimmune indices, and the lung CT images remained unaltered, it seems that JAK1/2 inhibition was unsatisfactory in completely controlling the inflammation of the disease in our study. Conclusions: Baricitinib was shown to elicit some effect on the ILD but failed to control the inflammation of the disease completely. Further exploration of JAK inhibitors or other therapeutic strategies are needed to more optimally treat this inflammatory disease. [ABSTRACT FROM AUTHOR]