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We present a patient with isolated autoimmune anterior scleritis and a patient with nonspecific orbital inflammation (NSOI). Both patients were treated with systemic corticosteroids during multiple recurrences, with the addition of various disease-modifying antirheumatic drugs (DMARDs), including biologics, in the case of scleritis, resulting in complications and local adverse events. Both patients were subsequently effectively managed using Janus kinase inhibitors (JAK-i), specifically baricitinib and tofacitinib without relapses of inflammation during the follow-up of more than one year. Only a slight transient increase in liver enzymes was reported in a patient with scleritis and no serious side effects. [ABSTRACT FROM AUTHOR]

Acute Severe Ulcerative Colitis (ASUC) is a well-known and potentially fatal disease state, characterized by symptoms of systemic toxicity including fever, severe anemia, elevated inflammatory markers, and autonomic instability. The life-threatening nature of this condition requires clinicians to make prompt diagnoses and take rapid action, either directing patients towards surgical interventions or medical management. Failure to treat ASUC may lead to toxic dilation of the colon, hemorrhage, or sepsis. Current algorithms suggest the use of intravenous (IV) corticosteroids upon diagnosis, with transition to oral corticosteroids, calcineurin inhibitors or tumor necrosis factor (TNF) inhibitors upon reduction of severe symptoms for candidates deemed to be amenable to medical management. Within these classes, TNF inhibitors such as Infliximab (IFX) have proven to be the most safe, efficacious, and tolerable for patients. While IFX has much data supporting its benefits in achieving short term remission, there are still high rates of long-term need for colectomy and failure to maintain remission. This is due to interactions between the inflamed gastrointestinal tract, the increased metabolic activity seen in ASUC, and intrinsic pharmacodynamic properties of IFX. Certain novel studies suggest that Janus Kinase (JAK-STAT) inhibitors such as Tofacitinib and Upadacitinib are potent agents to salvage clinical remission achieved by IFX, upon its failure. Here we discuss methods to optimize the dosing of IFX to maximize its efficacy, while exploring recent work done on the safety and efficacy of JAK-STAT inhibitors as a salvage therapy, therefore suggesting a novel treatment algorithm to improve clinical outcomes in medically managed ASUC patients. [ABSTRACT FROM AUTHOR]

Abstract: The introduction of biological therapies has revolutionized inflammatory bowel disease (IBD) management. A critical consideration in developing these therapies is ensuring adequate drug concentrations at the site of action. While blood-based biomarkers have shown limited utility in optimizing treatment (except for TNF-alpha inhibitors and thiopurines), tissue drug concentrations may offer valuable insights. In antimicrobial therapies, tissue concentration monitoring is standard practice and could provide a new avenue for understanding the pharmacokinetics of biological and small-molecule therapies in IBD. Various methods exist for measuring tissue concentrations, including whole tissue sampling, MALDI-MSI, microdialysis, and fluorescent labeling. These techniques offer unique advantages, such as spatial drug-distribution mapping, continuous sampling, or cellular-level analysis. However, challenges remain, including sampling invasiveness, heterogeneity in tissue compartments, and a lack of standardized bioanalytical guidelines. Drug pharmacokinetics are influenced by multiple factors, including molecular properties, disease-induced changes in the gastrointestinal tract, and the timing of sample collection. For example, drug permeability, solubility, and interaction with transporters may vary between Crohn's disease and ulcerative colitis. Research into the tissue concentrations of drugs like anti-TNF agents, ustekinumab, vedolizumab, and tofacitinib has shown variable correlations with clinical outcomes, suggesting potential roles for tissue concentration monitoring in therapeutic drug management. Although routine clinical application is not yet established, exploring tissue drug concentrations may enhance understanding of IBD pharmacotherapy. [ABSTRACT FROM AUTHOR]

Background: Granuloma formation is an uncommon and persistent skin inflammatory condition caused by the injection of dermal fillers. The exact cause of this reaction is not well understood, but it may be associated with irritating components or abnormal immune function. Treating granulomas can be difficult. However, recent research has shown that Janus kinase (JAK) inhibitors hold promise as a potential therapy for refractory granulomatous diseases. Objectives: The aim was to evaluate the efficacy and safety of tofacitinib as a treatment for granulomas secondary to filler injection and the possible mechanisms were discussed and summarized. Methods: This study focuses on three cases of patients who experienced granuloma formation after receiving filler injections and were subsequently treated with tofacitinib. The efficacy and safety of the treatment were evaluated using parameters such as photographs and monitoring for any adverse reactions. In addition, a literature review was conducted to explore the underlying mechanisms and potential effects of tofacitinib. Results: All three cases recovered from swelling and nodules without side effects through the off-label use of oral tofacitinib. Existing data review reveals some approaches for cutaneous granulomatous disorders like inhibiting macrophage activation and downregulation of the JAK–STAT pathway. Conclusion: This report emphasizes the effectiveness of JAK inhibitors in treating granulomas caused by filler injections. Recent advancements in understanding the underlying mechanisms of granulomatous reactions have paved the way for JAK inhibitors to be regarded as a promising treatment choice. However, further research is necessary to fully assess the safety and long-term effectiveness of using tofacitinib for granuloma treatment. [ABSTRACT FROM AUTHOR]

INTRODUCTION: There are limited real-world data comparing the effectiveness of upadacitinib and tofacitinib in patients with ulcerative colitis (UC). METHODS: We conducted a retrospective cohort study using TriNetX, a multi-institutional database, to compare the effectiveness of upadacitinib and tofacitinib in patients with UC. The primary aim was to assess the risk of a composite outcome of hospitalization requiring intravenous steroids and/or colectomy within 6 and 12 months. One-to-one propensity score matching was performed for demographics, comorbid conditions, mean hemoglobin, C-reactive protein, albumin, and calprotectin, and prior UC medications including recent oral or intravenous steroid use between the cohorts. Risk was expressed as adjusted odds ratio (aOR) with 95% confidence intervals (CI). RESULTS: There were 526 patients in the upadacitinib cohort (mean age 40.4 6 16.3, 44.8% female sex, 76.6% White race) and 1,149 patients in the tofacitinib cohort (mean age 42 6 17.1, 41.9% female sex, 76% White race). After propensity score matching, there was no significant difference in the risk of the composite outcome of need for intravenous steroids and/or colectomy within 6 months (aOR 0.75, 95% CI 0.49–1.09). However, there was a lower risk of the composite outcome (aOR 0.63, 95% CI 0.44–0.89) in the upadacitinib cohort compared with the tofacitinib cohort within 12 months. There was no difference in the risk of intravenous steroid use (aOR 0.70, 95% CI 0.48–1.02) but lower risk of colectomy (aOR 0.46, 95% CI 0.27–0.79). In sensitivity analysis, there was also a lower risk of the composite outcome (aOR 0.64, 95% CI 0.44–0.94), including lower risk of intravenous steroid use (aOR 0.67, 95% CI 0.45–0.99) and colectomy (aOR 0.49, 95% CI 0.26–0.92) in the upadacitinib cohort compared with the tofacitinib cohort within 12 months. DISCUSSION: This study utilizing real-world data showed that upadacitinib was associated with improved disease- specific outcomes at 12 months compared with tofacitinib in patients with UC. [ABSTRACT FROM AUTHOR]

Background: Janus kinase-inhibitors (JAK-i) have recently been approved for treating patients with Ulcerative Colitis (UC); therefore, further information is needed, particularly regarding efficacy and safety. Objectives: To provide a comprehensive review regarding the efficacy and safety of currently available JAK-i in UC. Methods: The PubMed and Scopus databases were considered, searching for 'JAK', 'JAK-inhibitor', 'Janus Kinases', 'Tofacitinib', 'Filgotinib', 'Upadacitinib', individually or in combination with 'IBD', 'Ulcerative Colitis', 'safety', 'efficacy', 'study' and 'trial'. The search was focused on full-text papers published in English, with no publication date restrictions. Results: The efficacy and safety of JAK-i approved for treating patients with UC have been summarized. These included Tofacitinib, Filgotinib and Upadacitinib. Findings from both clinical trials and real-life studies in UC were reported, with particular regard to their efficacy in inducing clinical response and remission, steroid-free remission and endoscopic and histological healing. Overall, JAK-i proved to be effective and safe in selected subgroups of patients with UC. The rapid onset of action and the oral route of administration represent the most relevant characteristics of these drugs. Safety concerns using Tofacitinib in subgroups of patients (infections, hypercholesterolemia, venous thromboembolism and cardiovascular events) were initially raised. More recently, all JAK-i for UC showed an overall satisfactory safety profile. However, indication should be carefully given. Conclusions: The use of JAK-i UC is promising, although no predictive markers of response are currently available. Optimizing their use, as monotherapy or combined with other immunomodulators, may increase their efficacy in appropriately selected subgroups of patients with UC. [ABSTRACT FROM AUTHOR]

To evaluate experience in a tertiary rheumatology service with melanoma differentiation‐association‐protein‐5 (MDA5) disease and testing, patients with positive autoantibody results were reviewed for the presence of clinical disease. Anti‐MDA5 positivity was detected in 2% of myositis‐specific antibody tests. Of these, 29% did not have features consistent with anti‐MDA5 disease. However, when present, MDA5 disease is severe with a high mortality. [ABSTRACT FROM AUTHOR]

To investigate the incidence of the discontinuation among tofacitinib and biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). This retrospective population-based cohort study included 5,008 RA patients who initiated treatment with either tofacitinib or bDMARDs (etanercept, adalimumab, golimumab, tocilizumab, or abatacept) between January 1, 2014, and December 31, 2020. We conducted Cox proportional hazards regression and subsequent time-dependent regression to assess the risk of drug discontinuation, with adjustments for potential variables. The highest drug discontinuation rate was observed with etanercept (43.27%), while the lowest was with tofacitinib (21.8%). Tofacitinib was associated with a significantly lower risk of discontinuation compared to etanercept (HR: 0.67, 95% CI: 0.57–0.80) and other bDMARDs. Higher steroid dosage and the presence of concomitant connective tissue diseases were significant risk factors for drug discontinuation. Conversely, the use of methotrexate was associated with a reduced risk of discontinuation. Tofacitinib demonstrated a lower risk of drug discontinuation compared to TNFi, with the risk factors for discontinuation including higher steroid dosage and concomitant connective tissue diseases. The study highlights the importance of considering several potential risk factors in drug discontinuation. Key Points • Non-TNFi biologic agents demonstrated better drug retention than TNFi among patients diagnosed with rheumatoid arthritis, with tofacitinib showing the lowest discontinuation rate (21.8%), underscoring its potential for superior drug retention in rheumatoid arthritis management. • Several factors were associated with drug discontinuation: higher steroid dosage and concomitant connective tissue diseases were linked to a higher discontinuation rate, whereas the concomitant use of methotrexate was associated with a lower risk of discontinuation. [ABSTRACT FROM AUTHOR]

Introduction: ORAL Surveillance, a post-authorisation safety study of patients with rheumatoid arthritis (RA) enriched for cardiovascular (CV) risk, demonstrated increased risk of major adverse CV events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) for tofacitinib versus tumour necrosis factor inhibitors (TNFi). This analysis of a real-world Canadian observational study evaluated tofacitinib safety/effectiveness in patients meeting or not meeting CV risk criteria. Methods: CANTORAL included patients with moderate-to-severe RA initiating tofacitinib (10/2017–07/2020; N = 504). Interim data (data-cut: 07/2021) were stratified as CV risk-enriched (CV+ ; patients ≥ 50 years with ≥ 1 additional CV risk factor) or not CV risk-enriched (CV−; ≥ 50 years without additional CV risk factors and 18–49 years with/without CV risk factors). Safety and persistence were evaluated to month (M) 36. Effectiveness outcomes to M18 included Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA)/remission (CANTORAL co-primary endpoints) and Disease Activity Score in 28 joints, C-reactive protein (DAS28-4[CRP]) < 3.2/ < 2.6. Results: Overall, 272/232 patients were included in CV+ /CV− cohorts (full analysis set) (435/356 patient-years [safety analysis set]). Incidence rates (events/100 patient-years) in CV+ /CV− cohorts were 138.5/112.5 for treatment-emergent adverse events (AEs); 17.0/5.6 for serious AEs; 1.2/0.3 for deaths; 5.5/1.7 for serious infections; 1.4/1.1 for herpes zoster; 1.6/0.0 for MACE; 2.1/0.3 for malignancies (excluding NMSC); 0.7/0.6 for NMSC; 0.5/0.0 for venous thromboembolic events. Persistence was generally comparable between cohorts. In CV+ /CV− cohorts, at M6, CDAI LDA and remission rates were 51.5%/54.6% and 12.0%/19.6%; DAS28-4(CRP) < 3.2/ < 2.6 rates were 44.0%/39.3% and 31.5%/28.8%, respectively; effectiveness was generally maintained to M18. Conclusions: In concordance with studies of background risk, AEs were more common in patients with CV risk enrichment, particularly those aged ≥ 65 years. Tofacitinib effectiveness/persistence were generally similar regardless of CV risk enrichment. These findings support individualised treatment benefit–risk assessment, including CV assessment/management, to optimise RA outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Routine care studies of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) demonstrated attenuated responses to tumor necrosis factor inhibitors in current/past versus never smokers. This post hoc analysis assessed tofacitinib efficacy and safety in patients with PsA or AS by cigarette smoking status at trial screening. Methods: Pooled data from phase 3 and long-term extension (safety only) PsA trials and phase 2 and 3 AS trials were assessed by current/past versus never smoker status. Analysis included efficacy and safety data for tofacitinib 5 (PsA/AS) and 10 (PsA only) mg twice daily (BID) or placebo, and safety data in AS for tofacitinib 2 and 10 mg BID. Efficacy outcomes included American College of Rheumatology ≥ 50% responses (ACR50) and minimal disease activity (MDA) responses to month (M)6/M3 (tofacitinib/placebo) in PsA; and ≥ 40% improvement in Assessment of SpondyloArthritis international Society responses (ASAS40) and AS Disease Activity Score (ASDAS) < 2.1 responses to week (W)16 in AS. Safety was assessed to M48/W48 (PsA/AS), adjusted for treatment/smoking status/median body mass index (BMI) status/sex/trial/treatment-smoking status interaction. Results: PsA/AS cohorts included 342/178 current/past and 572/194 never smokers. Tofacitinib efficacy was generally greater versus placebo to M3/W6 (PsA/AS), and comparable in current/past and never smokers to M6/W16 (PsA/AS). In patients receiving ≥ 1 tofacitinib dose, adjusted treatment-emergent adverse event (TEAE)/serious AE (SAE)/discontinuation due to AE incidence rates (IRs) to M48 in PsA were higher in current/past versus never smokers; adjusted IRs to W48 in AS were higher in current/past versus never smokers for TEAEs, but similar for SAEs/discontinuation due to AEs. Conclusions: In both patients with PsA and AS, tofacitinib efficacy was greater versus placebo, and comparable across smoking categories. Adjusted IRs were higher in current/past versus never smokers for TEAEs, SAEs, discontinuation due to AEs in PsA, and for TEAEs in AS, complementing reports of associations between smoking and comorbidities in spondyloarthritis. Findings support increased surveillance/caution for patients with PsA or AS with smoking history. Trial Registration: ClinicalTrials.gov: NCT01877668/NCT01882439/NCT03486457/NCT01976364/NCT01786668/NCT03502616. [ABSTRACT FROM AUTHOR]

Tissue cytokines in chronic hand eczema (CHE) can predict targeted therapy with novel drugs including JAK inhibitors. Our primary objective was to assess the tissue expression of cytokines of Th1 and Th2 cell lines in CHE patients and to study the efficacy of oral tofacitinib. We recruited patients presenting with recalcitrant CHE. Lesional and non-lesional tissue samples were assessed for Th1(IFN-γ, TNF-α) and Th2 related cytokines (IL-4, IL-13, IL-2,) using real time PCR. Tofacitinib 5 mg twice daily was initiated with 4 weekly assessment and we also noted relapses post therapy. Of 21 refractory hyperkeratotic CHE patients, cytokine analysis was performed in 11 patients which showed upregulation of IL-4 [n = 5/11, 1.87-fold increase], TNF-α (n = 5/11, 5.13-fold) and IFN-γ (n = 6/11, 1.98-fold) as compared to uninvolved skin. All patients (100%) had used topical corticosteroids (TCS) and 4/21 (19%) had failed methotrexate and 2/21 (9.5%) had failed acitretin. Tofacitinib 5 mg twice daily was given in 15/21 patients. The mean time to achieve hand eczema severity index 90 (HECSI 90) was 4 weeks (mean duration of treatment:5.8 months, n = 12). Side effects were observed in 4/12 (33.3%) patients and relapse was noted in 3/12 (25%) patients after a mean duration of 7 months after discontinuation of tofacitinib. Tofacitinib (pan-JAK inhibitor) showed an excellent response in refractory CHE patients with predominant tissue Th1/Th2 cells related cytokine expression. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Methods Results Conclusions Three Janus kinase (JAK) inhibitors are approved for ulcerative colitis (UC) in Japan.To compare the real‐world efficacy and safety of these three JAK inhibitors in UC.This was a multicentre, retrospective study of patients with UC started on JAK inhibitors. The primary outcome was clinical remission at 10, 26 and 58 weeks, and at the most recent follow‐up. To compare the efficacy and safety among the JAK inhibitors, we created three matched cohorts (upadacitinib vs. filgotinib, tofacitinib vs. filgotinib and upadacitinib vs. tofacitinib) using propensity score matching.We identified 228 upadacitinib‐treated patients (median follow‐up 49 weeks; IQR 25–72), 215 filgotinib‐treated patients (follow‐up 56 weeks; IQR 17–82) and 159 tofacitinib‐treated patients (follow‐up 112 weeks; IQR 10–258). Clinical remission rates for upadacitinib, filgotinib and tofacitinib at the most recent follow‐up were 72.8%, 50.6% and 45.8%, respectively. Over 70% of the patients previously treated with other biologics or JAK inhibitors achieved clinical remission with upadacitinib. On multivariate analysis, the number of previous advanced therapies was inversely associated with the efficacy of filgotinib and tofacitinib. Comparative analysis showed that upadacitinib‐treated patients had higher efficacy and lower risk of discontinuation than patients treated with other JAK inhibitors. However, upadacitinib had a significant risk of acne.Considering the particularly high efficacy of upadacitinib, even in patients with refractory UC, filgotinib or tofacitinib may be considered as an upfront JAK inhibitor before using upadacitinib. [ABSTRACT FROM AUTHOR]

β‐Branched chiral amines with contiguous stereocenters are valuable building blocks for preparing various biologically active molecules. However, their asymmetric synthesis remains challenging. Herein, we report a highly diastereo‐ and enantioselective biocatalytic approach for preparing a broad range of β‐branched chiral amines starting from their corresponding racemic ketones. This involves a dynamic kinetic resolution‐asymmetric reductive amination process catalyzed using only an imine reductase. Four rounds of protein engineering endowed wild‐type PocIRED with higher reactivity, better stereoselectivity, and a broader substrate scope. Using the engineered enzyme, various chiral amine products were synthesized with up to >99.9 % ee, >99 : 1 dr, and >99 % conversion. The practicability of the developed biocatalytic method was confirmed by producing a key intermediate of tofacitinib in 74 % yield, >99.9 % ee, and 98 : 2 dr at a challenging substrate loading of 110 g L−1. Our study provides a highly capable imine reductase and a protocol for developing an efficient biocatalytic dynamic kinetic resolution‐asymmetric reductive amination reaction system. [ABSTRACT FROM AUTHOR]

β‐Branched chiral amines with contiguous stereocenters are valuable building blocks for preparing various biologically active molecules. However, their asymmetric synthesis remains challenging. Herein, we report a highly diastereo‐ and enantioselective biocatalytic approach for preparing a broad range of β‐branched chiral amines starting from their corresponding racemic ketones. This involves a dynamic kinetic resolution‐asymmetric reductive amination process catalyzed using only an imine reductase. Four rounds of protein engineering endowed wild‐type PocIRED with higher reactivity, better stereoselectivity, and a broader substrate scope. Using the engineered enzyme, various chiral amine products were synthesized with up to >99.9 % ee, >99 : 1 dr, and >99 % conversion. The practicability of the developed biocatalytic method was confirmed by producing a key intermediate of tofacitinib in 74 % yield, >99.9 % ee, and 98 : 2 dr at a challenging substrate loading of 110 g L−1. Our study provides a highly capable imine reductase and a protocol for developing an efficient biocatalytic dynamic kinetic resolution‐asymmetric reductive amination reaction system. [ABSTRACT FROM AUTHOR]

Treatment-resistant asthma remains an unresolved clinical problem and a challenge for current medical science. Consequently, there is a growing and urgent need to develop novel or alternative therapeutic options for the treatment of asthma. The research problem raised in this study was to assess and compare mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase, and tofacitinib (TFB), a Janus kinase inhibitor, for anti-asthmatic properties, and consequently to determine whether these agents may have potential as alternative options for treatment of allergic asthma. For this purpose, we assessed the effect of administration of MMF and TFB on the development of a mouse model of allergic airway inflammation (AAI) and accompanying CD4+ (cluster of differentiation 4) T-cell immune response in the lung-draining mediastinal lymph nodes (MLNs) and lungs, i.e., in the inductive and effector sites, respectively, of the immune response underlying the development of allergic asthma. The results from a histopathological scoring system demonstrated that the administration of MMF and TFB did not prevent or abolish ovalbumin-induced AAI, but strongly attenuated its severity. The pulmonary function tests revealed that the treatment with MMF and TFB significantly reduced methacholine-induced bronchoconstriction. These results indicate that the treatment with TFB and MMF attenuated the development of ovalbumin-induced AAI. The magnitude of the anti-asthmatic effect was comparable between both agents. The study revealed that the impairment of the clonal expansion of effector CD4+ T cells in the MLNs is a critical event in the mechanism underlying the anti-asthmatic effect of MMF and TFB. Apart from this, the findings of the study strongly suggest that the suppression of the interleukin-33/suppression of tumorigenicity-2 signaling pathway may constitute an additional mechanism responsible for producing this effect. In turn, the results indicate that the anti-asthmatic action induced by the studied agents is not mediated by the generation of forkhead box protein 3-expressing CD4+ regulatory T cells. Clinical implication of the results: the results suggest that MMF and TFB may exert anti-asthmatic action, and thus they may be considered therapeutic options for the treatment of allergic asthma cases resistant to conventional/existing treatment. [ABSTRACT FROM AUTHOR]

Background: Many women of childbearing age with inflammatory bowel disease (IBD) require advanced therapies. While biologics are largely low risk during pregnancy, the novel small molecules tofacitinib, filgotinib, upadacitinib and ozanimod (TFUO) have shown concerning teratogenic effects, and decreased fertility in animal studies. Therefore, their use in women of childbearing age needs careful consideration. Design: RAND/University of California Los Angeles (UCLA) Appropriateness Method (RAM). Objective: To evaluate the appropriateness of TFUO in women of childbearing age. Methods: We convened a panel of six gastroenterologists, two IBD nurses, one IBD pharmacist and three expert patients. Following a literature review, 13 statements were drafted and voted upon in 2 rounds. Results: All 13 statements were deemed appropriate. The panel concluded that women with IBD of childbearing age who wish to commence therapy with TFUO, need to use effective contraception and be counselled regarding the risk in unplanned pregnancies. For women using contraception while on Janus kinase inhibitor (JAKi) therapy, we suggest the preferred use of progesterone-only or non-hormonal long-acting contraception. TFUO are contraindicated during pregnancy and breast feeding. We recommend that women receiving TFUO cease therapy in time to establish clinical remission for at least 3 months prior to conception. Therapies other than TFUO should be considered as first-line therapy in women with IBD of childbearing age, except in select individual circumstances. TFUO may be appropriate for women of childbearing age after failure of, intolerance or contraindications to one biological agent. Conclusion: TFUO should be avoided during pregnancy and breastfeeding, and alternative therapies should be considered as first-line treatments. Summary: We provide clinical practice recommendations regarding the use of TFUO for IBD in women of childbearing age. Plain language summary: Small Molecules for Patients with IBD of Childbearing Age The maintenance of remission is vital for good fetal and maternal outcomes in IBD pregnancies and biological therapies used in IBD have been associated with favourable pregnancy outcomes. The safety profile of novel small molecules in human pregnancy is however largely unknown. We conducted a RAND appropriateness panel to agree recommendation son the use of Tofacitinib, Filgotinib, Upadacitinib and Ozanimod in women of childbearing age. Tofacitinib, Filgotinib, Upadacitinib and Ozanimod should be avoided during pregnancy due to serious concerns regarding birth defects. Small molecule therapies Tofacitinib, Filgotinib, Upadacitinib and Ozanimod should be given due consideration in the management of IBD in women of childbearing age, provided there are no immediate plans for conception. Counselling about potential risk of adverse effects during pregnancy, risk of venous thromboembolism and effective contraception are needed. Clinicians need to consider time to establish alternative therapies when switching away from Tofacitinib, Filgotinib, Upadacitinib and Ozanimod in the pre-conception period. Future research should examine pregnancy outcomes in cases where Tofacitinib, Filgotinib, Upadacitinib and Ozanimod exposure occurred but data may be difficult to compare to biologics due to differences in exposure duration. Guidelines should be updated as further maternal and fetal safety data become available [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Tofacitinib and aminosalicylic acid (5‐ASA) are commonly used to treat ulcerative colitis (UC). However, evidence on the effect of concomitant 5‐ASA use in patients receiving tofacitinib is limited. This study investigated the effects of 5‐ASA combined with tofacitinib in UC patients.This retrospective cohort study used data from the Medical Data Vision database, including patients with UC treated with tofacitinib from May 2018 to April 2022. Patients were grouped according to tofacitinib dosage and assessed for the efficacy of concomitant 5‐ASA use. The primary endpoint was clinical relapse.A total of 1213 patients with UC were included in the analysis, with 416 in the 5 mg BID group and 797 in the 10 mg BID group. In the 5 mg BID group, the cumulative relapse‐free rate was significantly higher in patients receiving concomitant 5‐ASA (P < 0.0001). Multivariate Cox regression analysis confirmed that concomitant 5‐ASA use significantly reduced the risk of clinical relapse (adjusted hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.31–0.70). In the 10 mg BID group, no significant difference was noted in the cumulative relapse‐free rate between patients treated with and without 5‐ASA (P = 0.445). Similarly, multivariate Cox regression analysis indicated that concomitant 5‐ASA use did not significantly affect relapse risk (adjusted HR, 0.97; 95% CI, 0.71–1.32).Concomitant 5‐ASA use reduced the risk of relapse in patients on 5 mg tofacitinib BID, suggesting benefits at lower doses. However, no significant benefit was observed with 5‐ASA use in those 10 mg tofacitinib BID. [ABSTRACT FROM AUTHOR]

This retrospective cohort study assessed the efficacy and safety of Janus kinase (JAK) inhibitors, tofacitinib and baricitinib, in 14 patients with refractory dermatomyositis (DM), a multisystemic autoimmune disorder with limited therapeutic options. Results demonstrated a significant median decrease of 21 points and a 76% reduction in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores, along with a complete resolution of muscular symptoms in 64% of the patients. JAK inhibitors were effective in managing refractory DM across various subtypes with mild and manageable adverse events. [ABSTRACT FROM AUTHOR]

Objective This multicentre, retrospective study compared the efficacy and safety of tofacitinib, baricitinib, peficitinib and upadacitinib in real-world clinical settings after minimizing selection bias and adjusting the confounding patient characteristics. Method The 622 patients were selected from the ANSWER cohort database and treated with tofacitinib (TOF), baricitinib (BAR), peficitinib (PEF) or upadacitinib (UPA). The patient's background was matched using propensity score-based inverse probability of treatment weighting (IPTW) among four treatment groups. The values of Clinical Disease Activity Index (CDAI), C-reactive protein (CRP), and modified Health Assessment Questionnaire (mHAQ) after drug initiation and the remission or low disease activity (LDA) rates of CDAI at 6 months after drug initiation were compared among the four groups. Further, the predictive factor for TOF and BAR efficacy was analysed. Results The retention and discontinuation rates until 6 months after drug initiations were not significantly different among the four JAK inhibitors treatment groups. Mean CDAI value, CDAI remission rate, and CDAI-LDA rate at 6 months after drug initiation were not significantly different among treatment groups. Baseline CDAI (TOFA: OR 1.09, P   <  0.001; BARI: OR 1.07, P   <  0.001), baseline CRP (TOFA: OR 1.32, P   =  0.049), baseline glucocorticoid dose (BARI: OR 1.18, 95% CI 1.01–1.38, P   =  0.035), a number of previous biological or targeted synthetic disease-modifying antirheumatic drugs (biological/targeted synthetic DMARDs) (BARI: OR 1.36, P   =  0.004) were predictive factors for resistance to CDAI-LDA achievement to JAK inhibitor treatment. Conclusion The efficacy and safety of TOF, BAR, PEF and UPA were not significantly different for the treatment of patients with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Purpose: This study analyzes the efficacy and safety of tofacitinib in pediatric patients presenting with treatment-resistant uveitis and scleritis. Method: Retrospective Chart Review Result: Nine children diagnosed with uveitis and one with scleritis received oral tofacitinib treatment. The median age of these patients was 9 years, with bilateral involvement observed in nine of them. Juvenile idiopathic arthritis was the most identifiable cause of uveitis, with anterior uveitis (50%) being the most frequent subtype of inflammation among these children. The median duration of immunosuppressive treatment before switching to tofacitinib was 18 (16–49) months. Remission of uveitis was achieved in all but two children, who experienced recurrence – manifesting as anterior uveitis. The median duration of follow-up in these children after tofacitinib treatment was 277.5 (183–549) days. At the end of follow-up, topical steroids could be withdrawn in six children, and two children were on topical steroids once a day. None of the children developed any systemic side-effect during the follow-up period. The mean BCVA at presentation was 0.62 ± 0.55, which improved to a mean of 0.27 ± 0.325 at the final follow-up (p = 0.0014) Conclusion: Treatment of pediatric uveitis with tofacitinib can be a valuable second-line treatment option and useful alternative in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Objectives: We characterised changes in absolute lymphocyte counts (ALCs) and lymphocyte subset counts (LSCs), and their relationship to incidence of serious infection events (SIEs) and herpes zoster (HZ) events in Japanese patients with moderate to severe rheumatoid arthritis enrolled in the tofacitinib clinical programme. Methods: Data included 765 patients receiving tofacitinib in Phase 2, Phase 3, and long-term extension studies. ALCs/LSCs and incidence rates (patients with events/100 patient-years) of SIEs and HZ were analysed over 75 months. Results: Median ALCs were generally stable over 75 months of treatment. Transient numerical increases from baseline in median LSCs were observed at Month 3; LSCs were generally lower than baseline for Months 36–75. SIE/HZ incidence rates were higher in patients with ALC <0.5 × 103 cells/mm3 versus those with ALC ≥0.5 × 103 cells/mm3 during tofacitinib treatment. Baseline LSCs were similar in patients with/without SIEs or HZ events. Conclusions: SIE/HZ risk was highest in patients with ALC <0.5 × 103 cells/mm3, supporting this threshold as clinically relevant for defining increased SIE/HZ risk in Japanese patients with rheumatoid arthritis receiving tofacitinib. However, SIEs and HZ events did not necessarily occur simultaneously with confirmed lymphopenia, preventing conclusions on possible causal relationships being drawn. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a complex multi-organ autoimmune disease marked by the production of autoantibodies against nuclear structures, formation of immune complexes, and chronic inflammation triggered by their tissular deposition. SLE is characterized by alternating periods of relapse and remission and each flare has the potential to cause new organ damage related to either the disease process or the medication toxicity. Despite remarkable progress across its multiple domains, SLE is still an area with many unmet needs, calling for innovative and practical solutions. The efforts of the drug development programme in lupus have led to considerable growth in the last decade, owing to the approval of belimumab, anifrolumab, and voclosporin. The increasing understanding of the pathogenesis of the disease has enabled the exploration of novel therapeutic strategies. New discoveries in the intricate cytokine kaleidoscope of lupus have made the concept of targeted therapy an attractive and promising research focus. JAK inhibitors are oral targeted therapies approved for a wide variety of diseases across the Rheumatology, Gastroenterology, Dermatology, and Haematology fields. Multiple JAKis are currently being investigated in SLE. This paper aims to summarize existing data coming from both clinical trials and case reports regarding the use of JAK inhibitors in SLE. [ABSTRACT FROM AUTHOR]

Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). These post hoc exposure–response (E–R) analyses of pooled data from two Phase 3 studies (NCT01877668 and NCT01882439) characterized the relationships between tofacitinib exposure and efficacy (American College of Rheumatology [ACR] criteria), and changes in hemoglobin (Hgb) in patients with PsA. Efficacy data for the proportion of patients receiving tofacitinib 5 or 10 mg twice daily, or placebo, achieving ACR ≥20%, ≥50%, or ≥70% response criteria (ACR20, ACR50, and ACR70, respectively) at Month 3, were modeled jointly using a four‐category ordered categorical exposure–response model (ACR20 non‐responder, ACR20 responder but not ACR50 responder, ACR50 responder but not ACR70 responder, and ACR70 responder). A maximum drug effect (Emax) model (using average concentrations of tofacitinib at steady state [Cavg]) adequately described the exposure–ACR response rate relationship. Model‐predicted response rates for tofacitinib 5 and 10 mg twice daily were 51% and 58%, respectively, for ACR20; 29% and 36% for ACR50; and 15% and 20% for ACR70. The E–R relationship between tofacitinib exposure and changes in Hgb was assessed using an indirect response model, which generally predicted Hgb concentration–time profiles across treatments well. The proportions of patients experiencing a decrease in Hgb of >2 g/dL were similar with tofacitinib 5 mg twice daily or placebo. These results were generally consistent with previous analyses in rheumatoid arthritis and psoriasis, and support the use of tofacitinib 5 mg twice daily for active PsA. [ABSTRACT FROM AUTHOR]

Background and Aims: Upadacitinib is an oral selective Janus kinase (JAK) inhibitor approved in the United States for ulcerative colitis (UC) and Crohn's disease (CD). However, data regarding its use following prior treatment with the JAK inhibitor tofacitinib is sparse. As such, we aimed to evaluate the effectiveness of upadacitinib therapy following tofacitinib exposure. Methods: This is a multicenter retrospective study of patients with confirmed diagnosis of UC or CD who received upadacitinib after prior treatment with tofacitinib. The primary outcome of interest was patient-reported clinical improvement at first follow-up. Secondary outcome included discontinuation of corticosteroids, change in Mayo Endoscopic Score (MES) and change in inflammatory marker levels. Results: A total of 31 patients met the inclusion criteria. Following upadacitinib initiation, 80.6% (25/31) of patients had clinical improvement, including 92.3% (24/26) of those with UC and 20% (1/5) of those with CD. Of the patients initially requiring systemic corticosteroid therapy, 80% (12/15) were able to discontinue corticosteroids. Individual mean change of fecal calprotectin was a decrease of 501.5 mcg/g ± 608.6 (P value = 0.01) while C-reactive protein decreased on average by 14.8 mg/L ± 25.3 (P value = 0.02) compared to when patients were on tofacitinib, with significant changes observed in the UC cohort. In patients with UC, individual MES after initiating upadacitinib decreased compared to prior to tofacitinib discontinuation (P value = 0.04). Conclusion: Our study demonstrates that upadacitinib therapy in patients with prior tofacitinib exposure is associated with clinical improvement and a decrease in objective markers of inflammation in patients with UC. [ABSTRACT FROM AUTHOR]

Objective: To estimate the effectiveness and safety of tofacitinib in treating systemic lupus erythematosus (SLE) patients with arthritis. Methods: This research was a retrospective cohort study that focused on SLE patients who had arthritis and were treated with tofacitinib at the Department of Rheumatology and Immunology from January 2020 to January 2022. Clinical outcomes, disease activity, immunological parameters, and adverse events were systematically evaluated pre- and post-treatment at 4, 12, and 24 weeks. Results: Twenty-two patients were analyzed. At the 4-week mark, 5 (22.7%) patients were partially relieved, and 17 (77.3%) unalleviated. By the 12-week assessment, CR off corticosteroids was observed in four patients (18.2%), and CR on corticosteroids was seen in six patients (27.3%), with an additional six (27.3%) maintaining partial remission. At 24 weeks after treatment, three patients (13.6%) achieved CR off corticosteroids, ten patients (45.5%) achieved CR on corticosteroids, and all patients received remission. Compared to before treatment, The SLEDAI and PGA scores significantly improved. The level of C3 was increased significantly, and the absolute CD3+ T cell count, the 28-tender and the 28-swollen joint count, and the levels of serum IL-6 were significantly decreased at 24 weeks after treatment. Conclusion: Tofacitinib demonstrates significant therapeutic potential in SLE patients with arthritis, with a safety profile, and the therapeutic mechanism of tofacitinib may be related to reducing IL-6 expression and inhibiting T cell activation. Key Points • Tofacitinib demonstrates significant therapeutic potential in SLE patients with arthritis • The therapeutic mechanism of tofacitinib may be related to reducing IL-6 expression and inhibiting T cell activation [ABSTRACT FROM AUTHOR]

Janus Kinase (JAK) inhibitors have emerged as a novel category of medications to treat a variety of immune-mediated conditions. However, limited insight exists regarding the impact of safety concerns on their usage and prescribing practices. Therefore, the objective of this study was to describe the utilization of JAK-inhibitors in Canada, both nationally and within individual provinces. We used data from IQVIA's Compuscript database. We conducted a repeated cross-sectional study of all JAK-inhibitor units dispensed in retail pharmacies (tofacitinib, ruxolitinib, baricitinib, and upadacitinib) within the ten Canadian provinces from July 1, 2016, to June 30, 2022. Throughout Canada, outpatient pharmacies dispensed an estimated total of 26,126,409 JAK-inhibitor units between 2016 and 2022, averaging 9,431 units dispensed per 100,000 population. All provinces had increasing rates of JAK-inhibitor units dispensed over time, whereby between July 2021 to June 2022, New Brunswick exhibited the highest rates (27,696 units per 100,000), and Prince Edward Island demonstrated the lowest rates (10,065 units per 100,000). In this study, utilization of JAK-inhibitors increased in Canada over the study period, evident at both provincial and national levels. Variability in JAK-inhibitor utilization between provinces underscores the necessity for further investigations to ascertain appropriate usage practices. Key Points • From 2016 to 2022, an estimated total of 26,126,409 JAK-inhibitor units were dispensed in retail pharmacies across Canada, with an average rate of 9,431 units dispensed for every 100,000 people in the population. • Tofacitinib was the most dispensed JAK-inhibitor during the entire study period, making up 76% of all units dispensed. Ruxolitinib, upadacitinib, and baricitinib made up 16%, 7.9%, and 1.1% of the JAK-inhibitor units dispensed, respectively. • The variance in provincial adoption of JAK-inhibitors across Canada might be influenced by several factors, including drug coverage availability, disease prevalence, and physician prescribing patterns. [ABSTRACT FROM AUTHOR]

Introduction: The evolution of disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA) has improved patient prognosis. However, more real-world safety/effectiveness data comparing methotrexate (MTX), tofacitinib, tumor necrosis factor inhibitors (TNFi), and non-TNFi biologic DMARDs (bDMARDs) are warranted. Methods: The CorEvitas RA Japan registry was used to identify patients with rheumatologist-diagnosed RA who initiated MTX/tofacitinib/TNFi/non-TNFi bDMARDs. Safety outcomes included incidence of major adverse cardiovascular events (MACE), total cardiovascular disease, total serious infections, total herpes zoster, and total malignancies (excluding non-melanoma skin cancer). Effectiveness outcomes included change from baseline (Δ) in Clinical Disease Activity Index (CDAI) and proportion of patients achieving a minimum clinically important difference (MCID) in CDAI at month 6. Adjusted regression models were fit; marginal means were estimated. Results: Overall, 1972 patients were included in the safety cohort: MTX (N = 298); tofacitinib (N = 253); TNFi (N = 663); non-TNFi (N = 758). Mean follow-up time was 3.8, 2.9, 3.0, and 2.9 years for MTX, tofacitinib, TNFi, and non-TNFi, respectively. Adjusted incidence rates (IRs, patients with events/100 patient-years [95% confidence intervals]) for MACE and total cardiovascular disease, respectively, were numerically lower for MTX (0.34 [0, 0.83]; 0.42 [0, 0.92]) and TNFi (0.09 [0, 0.27]; 0.61 [0.15, 1.07]) versus tofacitinib (0.48 [0, 1.20]; 2.30 [0.38, 4.22]) and non-TNFi (0.77 [0.35, 1.19]; 1.28 [0.73, 1.82]). Serious infections were numerically higher for non-TNFi (4.47 [3.38, 5.56]); herpes zoster was higher for tofacitinib (7.41 [4.52, 10.29]), versus other groups. IRs for malignancies were comparable between groups. Mean ΔCDAI and rates of achieving MCID in CDAI at month 6 were generally greater with tofacitinib versus other groups. Conclusion: Some variations in incidence of safety outcomes were observed between treatments, while certain effectiveness outcomes favored tofacitinib. Sample size variation between groups and low number of safety events limited the analysis. Further studies are warranted to investigate observed differences. ClinicalTrials.gov: NCT05572567. [ABSTRACT FROM AUTHOR]

Introduction: In ORAL Surveillance, incidence rates (IRs) of major adverse cardiovascular events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) in cardiovascular (CV)-risk-enriched patients with rheumatoid arthritis (RA) were numerically greater with tofacitinib in North America versus the rest of the world, due to underlying risk factors. Here, we evaluated the safety and efficacy of tofacitinib versus tumor necrosis factor inhibitors (TNFi) among patients with RA across geographical regions. Methods: Patients with RA in ORAL Surveillance (NCT02092467), who were aged ≥ 50 years with ≥ 1 additional CV risk factor, received tofacitinib 5 or 10 mg twice daily or TNFi; 45.9% were from either Poland or North America. This post hoc analysis stratified patients by region (Poland, North America, Other countries). Efficacy endpoints included Clinical Disease Activity Index, Disease Activity Score in 28 joints, with C-reactive protein (DAS28-4[CRP]), and Health Assessment Questionnaire-Disability Index (HAQ-DI). IRs and hazard ratios for adverse events were reported. Results: Of 4362 patients (Poland, N = 759; North America, N = 1243; Other countries, N = 2360), more patients from North America versus Poland/Other countries had CV risk factors such as body mass index ≥ 30 kg/m2 and history of diabetes/hypertension; however, more patients from Poland versus other regions were ever smokers and more patients from Poland/North America versus Other countries had history of coronary artery disease. MACE IRs were similar in North America and Poland, and numerically higher versus Other countries. IRs for malignancies (excluding NMSC) were numerically higher in North America versus Poland/Other countries with tofacitinib. Serious infections IRs were numerically higher in North America versus Poland across treatments. Venous thromboembolism/all-cause mortality IRs were generally comparable across regions. DAS28-4(CRP)/HAQ-DI improvements were generally lowest in North America. Conclusions: Differences in safety outcomes were driven by the presence of baseline risk factors; North America and Poland demonstrated a higher proportion of patients with some baseline CV risk factors/comorbidities versus Other countries. Trial Registration: NCT02092467 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

In recent years Janus kinase inhibitors (JAKi) have joined tumor necrosis factor inhibitors (TNFi) and interleukin (IL)-17 inhibitors (IL-17i) as approved disease modifying anti-rheumatic drugs (DMARD) for moderate to severe forms of axial spondyloarthritis (axSpA). Drug survival in axSpA patients has not been well studied in a real-world outpatient scenario since the approval of JAKi. We aimed to analyze the three drug classes based on modes of actions (MoA) for their persistence rates among German axSpA outpatients. A retrospective analysis of the RHADAR database for axSpA patients with a new initiation of TNFi, IL-17i, or JAKi treatment between January 2015 and October 2023 was conducted. Analyses included Kaplan-Meier curves and adjusted Cox regressions for drug discontinuation. 1222 new biological DMARD (TNFi [n = 954], IL-17i [n = 190]) or JAKi (n = 78) treatments were reported. The median drug survival was 31 months for TNFi, 25 for IL-17i, and 18 for JAKi. The corresponding 2-year drug survival rate was 79.6%, 72.6%, and 62.8% for TNFi, IL-17i, and JAKi, respectively. The probability for discontinuation for JAKi was significantly higher compared with TNFi (HR 1.91 [95% CI 1.22–2.99]) as well as for IL-17i compared with TNFi (HR 1.43 [95% CI 1.02–2.01]), possibly related to more frequent use of TNFis as first-line therapy. IL-17i and JAKi discontinuation probabilities were similar. Primary non-response was the reason for drug discontinuation in most cases across all MoA. TNFi treatment might persist longer than JAKi and IL-17i in German axSpA outpatients, possibly related to more severe or refractory disease in patients with JAKi-treated or IL-17i-treated axSpA. [ABSTRACT FROM AUTHOR]

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that is associated with systemic inflammatory conditions. Currently, there is no universally accepted standard therapy for PG, but immunosuppressive (IS) treatment seems essential. We report a patient here who was successfully treated with tofacitinib despite being PG-refractory to multiple anti-tumor necrosis factor alpha (anti-TNF) therapies and conventional IS. In addition, we performed a comprehensive review of all cases of PG treated with JAK inhibitors. We identified 27 cases treated with JAK inhibitors. Approximately 80% of the patients achieved complete recovery within a median of 12 weeks, even though 17 patients (63%) had received biologics before JAKinib treatment. Notably, this recovery could appear as early as 2 weeks. JAK inhibitors may prove useful in the future, particularly for treating immunosuppressive and steroid-resistant pyoderma gangrenosum, according to recent case reports. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic inflammatory skin disease characterized by facial erythema and telangiectasia. Despite ongoing research, the pathogenesis of rosacea remains incompletely understood, and current therapies are not entirely satisfactory. The JAK/STAT signaling pathway plays an essential role in immunoregulation, inflammation, and neurovascular regulation. Inhibition of the JAK/STAT pathway appears to hold promise as a potential therapy for rosacea. This study aimed to investigate the effects of the JAK inhibitor tofacitinib on rosacea and to preliminarily explore its therapeutic mechanism. To this end, a rosacea-like mouse model was induced using LL37 and treated with a 2% tofacitinib emulsion. The results demonstrated that topical application of tofacitinib significantly ameliorated rosacea-like phenotype, reduced the infiltration of CD4+ T cells and mast cells, and suppressed dermal angiogenesis. RT-qPCR analysis revealed a reduction in mRNA expression levels of STAT1, STAT4, and STAT5a in skin lesions following topical tofacitinib treatment. Additionally, three patients diagnosed with erythematotelangiectatic rosacea (ETR) were included in the study and treated with oral tofacitinib, leading to a significant improvement in erythema and flushing symptoms. These findings collectively suggest that tofacitinib alleviates LL37-induced rosacea-like skin inflammation in mice and rosacea skin lesions by inhibiting the JAK/STAT signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Clinical amyopathic dermatomyositis is characterized by cutaneous symptoms but lacks muscle symptoms. Anti-melanoma differentiation-associated gene 5 antibodies are frequently found in Japanese patients with clinical amyopathic dermatomyositis. Patients with rapidly progressive interstitial lung disease with positive anti-melanoma differentiation-associated gene 5 antibodies have poor prognoses, and majority of them are treated with combination immunosuppressive therapy; however, the best treatment is yet to be determined. Case presentation: A 52-year-old Asian male patient presented with a chief complaint of dyspnea on exertion. He had a typical skin rash and rapidly progressive interstitial pneumonia. Additionally, anti-melanoma differentiation-associated gene 5 antibodies were detected; therefore, he was diagnosed with dermatomyositis-associated interstitial pneumonia. Respiratory failure worsened despite administering steroid pulse therapy, tacrolimus, and cyclophosphamide. Consequently, plasma exchange was performed on day 13 of admission. After a slight improvement, the patient's respiratory failure worsened. Thus, cyclophosphamide was replaced by tofacitinib on day 28. Although respiratory failure improved and the progression of interstitial pneumonia seemed under control, βD-glucan level increased and Aspergillus antigen was detected on day 49. Micafungin and voriconazole were administered, but the patient succumbed to worsening respiratory failure on day 61. The pathological autopsy revealed multiple nodular lesions with cavity formation in both lungs and the presence of Aspergillus with severe neutrophilic infiltration and necrosis, which supported the diagnosis of invasive pulmonary aspergillosis. Conclusion: The patient with anti-melanoma differentiation-associated gene 5 antibody-related rapidly progressive interstitial lung disease, whose disease was difficult to control after the administration of triple immunosuppressive therapy (steroids, tacrolimus, and cyclophosphamide), showed good response with tofacitinib. Unfortunately, the patient died of invasive pulmonary aspergillosis owing to severe immunosuppression; thus, the signs of complications should be promptly detected. [ABSTRACT FROM AUTHOR]

Background: Juvenile Dermatomyositis (JDM) is a rare disorder with subtypes associated with different myositis-specific antibodies (MSAs) including anti-MDA5. Hepatic involvement in JDM is rare and has not previously been documented in anti-MDA5 JDM. There is a lack of formal research on treatment protocols for anti-MDA5 JDM, though tofacitinib is a highly regarded emerging therapy. Case presentation: A previously healthy 14-month-old Hispanic female presented to a pediatric rheumatology clinic with eight months of worsening rash, weakness, periorbital edema, intermittent fevers, and weight loss. Her physical exam was notable for fever, thinning of hair, heliotrope rash, periorbital edema, violaceous macules on her bilateral elbows, forearms, arms, and knees, arthritis, Gottron's sign, and hepatomegaly. The patient was admitted, and symptoms progressed to include hypoxemia. Subsequent workup was notable for ground glass opacities of bilateral lung fields on chest CT, myositis visualized on MRI and confirmed with muscle biopsy, and liver biopsy showing nonspecific signs of liver injury. After a thorough infectious disease workup to rule out concomitant infection, the patient was started on high-dose steroids and induction with cyclophosphamide. She responded well with disease remission maintained with tofacitinib in the outpatient setting. Discussion and conclusions: Our patient is notable due to her young age at presentation, histopathologically confirmed liver injury, and response to treatment. The case adds to the growing body of literature supporting tofacitinib for anti-MDA5 JDM in the pediatric population. Future research can better standardize effective treatment protocols and define the mechanism of liver involvement. For patients with nonspecific liver injury, muscular, and cutaneous disease, anti-MDA5 JDM should be considered in the differential diagnosis with treatment options including tofacitinib for confirmed cases. [ABSTRACT FROM AUTHOR]

This article discusses a case report of a successful treatment of lichen planus pemphigoides (LPP) with tofacitinib, a JAK inhibitor. LPP is a rare condition characterized by pruritic papules, plaques, and bullae on the skin. Previous treatments have shown limited efficacy, so alternative strategies such as JAK inhibitors have been explored. The patient in this case experienced significant improvement with tofacitinib, allowing for a gradual tapering of prednisolone. The article suggests that JAK inhibitors could be a promising treatment option for LPP by targeting the inflammatory processes and suppressing aberrant cytokine production. [Extracted from the article]

Anti-melanoma differentiation-associated gene-5 antibody (anti-MDA-5 Ab) associated with clinically amyopathic dermatomyositis (CADM) is characterized by vasculopathic ulcers, mechanic's hands, and progressive interstitial lung disease (ILD). We present a case of 38-year-old female who presented with all these classical clinical features. Her investigations revealed normal serum muscle enzyme levels and the presence of anti-Mi2 and anti-MDA-5 antibodies by immunoblot. Imaging study revealed changes suggestive of ILD. She was treated with rituximab along with oral glucocorticoid and other supportive treatment to which she didn't respond adequately. Recently, it has been postulated that plasmacytoid dendritic cells produce interferon which is responsible for tissue injury in dermatomyositis (DM). Tofacitinib, by inhibiting JAK-STAT pathway, inhibits downstream cytokines, mainly type 1 interferon. So, we added tofacitinib as adjuvant therapy in our patient. Post-six months of commencement of adjuvant tofacitinib, patient experienced remarkable improvement in cutaneous features as well as in pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Background: Alopecia areata (AA) is an autoimmune hair loss disorder characterised by collapse of hair follicle immune privilege and mediated by autoreactive CD8+ T lymphocytes and natural killer cells. Treatment is often unsatisfactory. The Janus kinase‐signal transducer and activator of transcription (JAK–STAT) pathway is implicated in the pathogenesis of AA and Janus Kinase inhibitor (JAKi) medications are promising emerging treatments for AA. Objectives: We evaluated the safety and effectiveness of tofacitinib in a real‐world setting over 18 months of treatment. Methods: A retrospective cohort study of all patients with scalp AA commenced on tofacitinib between 1 November 2016 and 31 May 2019. The primary endpoint was the percent change in Severity of Alopecia Tool (SALT) score at 18 months. Results: Two hundred and two patients were included. After 18 months of treatment, 55.9%, 42.6% and 29.2% achieved 50%, 75% and 90% reductions in their SALT scores respectively. Increased duration of AA was a negative predictor of hair regrowth. Males and patients with baseline SALT ≥90 were slower to respond to treatment in the first 12 months. One hundred and twenty‐four patients and 168 patients received concomitant systemic corticosteroids or low‐dose oral minoxidil during tofacitinib therapy respectively. There were no serious adverse events. Conclusion: Tofacitinib was a safe and effective treatment for patients with moderate‐to‐severe AA. Further randomised controlled studies are needed to establish the optimal treatment regimen. [ABSTRACT FROM AUTHOR]

Alopecia areata totalis and universalis are disabling conditions and therapeutically challenging as they are refractory to conventional options. Tofacitinib is a Janus-kinase (JAK) inhibitor utilized to treat alopecia areata (AA) as an off-label drug. In India, FDA-approved JAK inhibitors such as baricitinib and ritlecitinib are not available. There are only a few case reports on tofacitinib in AA in the Indian population. We present the data of 9 pediatric cases of clinically and histologically proven alopecia areata totalis (AT) and alopecia universalis (AU), for whom oral tofacitinib was given after baseline investigations. The following parameters were analysed: Photographic image and severity of alopecia tool (SALT) score at baseline, 3 months and 6 months, and Children Dermatology Life Quality Index (cDLQI) at baseline and 6 months. The mean ± standard deviation (M ± SD) of the SALT score and cDLQI(M ± SD) at baseline were 95 ± 5 and 17 ± 2. At weeks 4 and weeks 12, the SALT (M ± SD) score was 92.7 ± 6.1 and 34.35 ± 11.16, respectively. At weeks 24, the SALT (M ± SD) score and cDLQI (M ± SD) were 3.33 ± 5 and 6 ± 2. The final reduction in SALT score from the baseline was 100% in 6/9 cases (66.67%), 75% to 99% in 3/9 (22.23%), and 50 to 75% in 1/9 (11.12%). We also observed minimal adverse effects (one child developed herpes zoster) with tofacitinib. Our study demonstrates that oral tofacitinib represents a viable modality in managing difficult-to-treat pediatric AA, such as AT and AU, with a good safety profile. [ABSTRACT FROM AUTHOR]

Objective: Thalidomide is an effective medication for refractory mucocutaneous lesions of systemic lupus erythematosus (SLE) and can treat arthritis in some autoimmune diseases, but it has some adverse reactions. Recently, the effectiveness of tofacitinib in treating mucocutaneous lesions of SLE has been reported. We aimed to compare the efficacy and safety of tofacitinib with thalidomide in treating mucocutaneous and musculoskeletal lesions in patients with SLE. Methods: This study was a real-world cohort study based on the Chinese SLE Treatment and Research group (CSTAR) registry. SLE patients who manifested mucocutaneous and/or musculoskeletal symptoms and were prescribed tofacitinib or thalidomide were included. We retrospectively conducted comparisons between the tofacitinib and thalidomide groups regarding clinical improvements, SLE disease activity, serological indicators, glucocorticoid doses, and adverse events at the 1, 3, and 6-months time points. Results: At 3 and 6 months, the tofacitinib group exhibited a higher proportion of patients with improvement in mucocutaneous and musculoskeletal issues. Additionally, a greater percentage of patients in the tofacitinib group achieved remission or a low disease activity state (LLDAS) at these time points. No significant serological improvements were observed in either the tofacitinib or thalidomide groups. Fewer adverse events were observed in the tofacitinib group than in the thalidomide group. Conclusions: Tofacitinib might be superior to thalidomide in the improvement of mucocutaneous and musculoskeletal lesions in SLE, and had a good safety profile. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation, joint swelling, and pain involving multiple joints. While biologic disease‐modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are popular treatments for RA, there is limited research on their combined use. This study examined a cohort of RA patients who demonstrated inadequate response to bDMARDs and subsequently initiated combination therapy with tofacitinib and bDMARDs, assessing both the efficacy and safety profile of this therapeutic approach. Methods: In this study, we retrospectively collected the electronic medical records (EMR) of 62 adult patients with RA who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine between August 2018 and December 2022. All patients had received at least one bDMARD treatment for more than 3 months and still exhibited moderate‐to‐high disease activity. Tofacitinib 5 mg bid was added to their original biological treatment in 28 cases, and other 34 cases switched to another bDMARD or tsDMARD as control group. Treatment was continued for 24 weeks following the initiation of combination therapy. Changes in DAS28‐ESR and ACR20, 50, 70 response rates at week 24 were collected and analyzed from baseline, while changes in C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at weeks 4, 8, 12, 24 were also collected and analyzed. Results: After 24 weeks of treatment, the DAS28‐ESR score in combined treatment group decreased significantly from a baseline of 5.26 ± 0.90 (3.87–8.31) to 2.67 ± 0.86 (1.41–5.11), with remission achieved by 19 patients (67.9%) and low disease activity achieved by five patients (17.9%). The DAS28‐ESR in the control group exhibited a decrease from 5.20 ± 0.77 (3.87–7.23) at baseline to 3.25 ± 1.29 (1.54–5.69). In all, 13 patients (38.2%) achieved remission, while another 11 patients (32.4%) achieved low disease activity. The ACR20, 50, 70 response rates were 85.71%, 75%, and 39.29% in the combined treatment group, whereas it were 75.0%, 53.57%, 21.43% in the control group. Additionally, both ESR and CRP levels decreased significantly during the course of treatment without any reported adverse events leading to discontinuation. Conclusion: Our findings offer some evidence, supporting the effectiveness and safety of combining bDMARD with JAKi tofacitinib in RA patients who have an inadequate response to bDMARD monotherapy. This combination effectively manages disease activity while maintaining a relatively low and manageable incidence of adverse events. Further prospective randomized controlled trials with large sample sizes are anticipated to provide evidence‐based medical support. [ABSTRACT FROM AUTHOR]

This study aims to test the hypothesis that disease duration may affect the response to generic tofacitinib (TOF) and investigate the influence of concomitant medications with TOF on elderly rheumatoid arthritis (RA). This study retrospectively collected 76 elderly patients (age > 60) treated with TOF from 2019 to 2023 and grouped them according to age of disease onset. Data were collected from baseline to the last follow-up visit within 24 months. The demographic characteristics and follow-up results were compared. TOF retention and the effect of concomitant drugs (methotrexate, MTX, prednisone) were analyzed using Kaplan–Meier plots and COX regression analysis. Canonical correlation analysis (CCA) was used to explore the correlation among demographic characteristics, medication regimen, and improved clinical outcomes. There was no significant difference in the proportion of patients achieving low disease activity (LDA) between different disease duration groups. Patients in the group of MTX had a shorter time of using TOF in follow-up (log-rank p = 0.041). Prednisone dosage at baseline had a predictive value for functionally disabled situation. We found significant associations between discontinuation of TOF in the last follow-up and getting LDA. A total result of CCA yielded a significant positive correlation with set 1 (demographic characteristics and medication regimen) and set 2 (improved clinical outcomes) (canonical coefficient = 0.887, p < 0.001). Disease duration may not affect response to generic TOF and medication regimen was the factor related to efficacy of generic TOF in elderly RA in the real world. Demographic characteristics and medication regimen were correlated positively with improved clinical outcomes. Key Points • There is scarce data from the western area of China regarding the use of tofacitinib in elderly rheumatoid arthritis patients, despite widespread use. • In this retrospective analysis of 76 elderly patients at a single center, we found disease duration may not affect response to generic TOF. • Concomitant MTX might contribute to better control of the disease activity. • Concomitant prednisone dosage at baseline was the independent risk factor for functionally disabled situation. [ABSTRACT FROM AUTHOR]

Background: Alopecia areata (AA) is an autoimmune pathology manifested by loss of hair. Objective: To evaluate and compare the efficacy and safety of tofacitinib and azathioprine in patients with AA and variants. Methods: In this double-blind randomized controlled trail (RCT) carried out at the Department of Dermatology, Medical Teaching Institute-Lady Reading Hospital (MTI-LRH), Peshawar, Pakistan, patients aged ≥ 12 years diagnosed with AA, alopecia totalis (AT) or alopecia universalis (AU) with minimum 50% scalp hair loss for a period ≥ 06 years were included. Patients were randomly assigned to receive oral tofacitinib 5 mg twice daily (Group I) or oral azathioprine 2 mg/kg body weight once daily (Group II). The primary endpoint was Severity of Alopecia Tool (SALT) score, evaluated at baseline and 06 months follow-up. Safety was consistently assessed during the study. Results: A total of 104 patients underwent random allocation into either the tofacitinib group (n = 52) or the azathioprine group (n = 52). The mean (SD) age of patients was 20.23 (7.14) years and 22.26 (8.07) years, while the mean (SD) disease duration was 6.59 (4.01) years and 7.98 (4.40) years in in Group I and II, respectively. Overall, 40 (38.5%) patients were adolescents while 70 (67.3%) were male. 52 (50%) had AA, 37 (35.5%) had AT and 15 (14.5%) had AU. Mean baseline SALT score in tofacitinib group was 91.02 ± 10.21 and azathioprine group was 91.02 ± 10.63, which at 06 months follow-up improved to 14.1 ± 24.6 and 63.9 ± 33.9, respectively (difference, 11.5 points; 95% confidence interval, 38.3–61.3, p < 0.0001). Overall, no major adverse effects and no difference among the minor adverse effects in the two groups (04 adverse events for tofacitinib group and 08 for azathioprine group: p = 0.23) was observed. Conclusions: Efficacy of tofacitinib was significantly higher than azathioprine, whilst both drugs were well-tolerated in patients with AA and variants. [ABSTRACT FROM AUTHOR]

Background: Alopecia areata (AA) is a recurrent immune‐mediated disorder causing hair loss without any scarring being present. It affects hairs on the head or other parts of the body and can occur at any age and in both genders. It seems that AA is associated with a higher rate of psychological disorders resulting from hair loss and the esthetic and social repercussions of it. Common treatments like corticosteroids do not work for every patient and recent treatment options focusing on the immunologic mechanisms like tofacitinib have shown some promising results. Methods: It's a retrospective study on patients with AA, AT, AU taking oral tofacitinib as a treatment for at least 6 months. Scalp hair loss was assessed before treatment and at each visit using the Severity of Alopecia Tool (SALT) score. Results: Of 97 cases, 69.1% demonstrated over 50% SALT score improvement, with 44.3% having 90% or more decrease in SALT score. Patients who suffered from patchy AA were more responsive compared to patients with AT and AU subtypes and had a greater percent change in SALT score. Tofacitinib was tolerated quite well and no significant adverse events were reported. Conclusions: Tofacitinib should be taken into consideration as an efficacious treatment option for patients with AA, AT and AU. [ABSTRACT FROM AUTHOR]

Background: Treatment strategy against immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) frequently requires other immunosuppressive agents. Tofacitinib is a rapidly acting JAK-STAT inhibitor with proven efficacy in multiple autoimmune diseases. We aimed to evaluate the efficacy and safety of tofacitinib in the management of irAEs in cancer patients. Methods: Cancer patients who received ICIs and were treated with tofacitinib for the management of irAEs at 6 institutions were retrospectively included in this study. Demographic and clinical characteristics were obtained from electronic medical records. Longitudinal assessment of cardiac troponin T (cTnT) with clinical assessment was utilized to evaluate the benefit of tofacitinib treatment in patients with ICI myocarditis. Overall survival (OS) was also assessed. Results: Fifty-three patients were included in this study. The median time from irAE onset to tofacitinib therapy was 17 (range, 2–186) days and the median duration of tofacitinib treatment was 52.5 (range, 3–277) days. Enrolled patients were subdivided into 3 groups based on clinical severity and steroid responsiveness including 11 life-threatening cases, 30 steroid-resistant cases, and 12 cases with steroid taper failure. Clinical remission rate in each group was 54.5%, 96.7%, and 100%, respectively (P < 0.01). Tofacitinib was well-tolerated with 4 patients (7.5%) developing infectious events. From the ICI initiation, the overall median OS was 16.1 (95% CI 7.8–26.9) months. Conclusion: Tofacitinib showed promising clinical efficacy in patients experiencing irAEs, particularly in patients who failed to respond to steroids or experienced relapse during steroid tapering. Moreover, and most importantly, tofacitinib exhibited a favorable safety profile in cancer patients developing irAEs in terms of both toxicity and anti-tumor activity. Future prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We aimed to identify the safety and effectiveness of tofacitinib in patients with UC in routine clinical settings in Korea. Methods: This open-label, observational, prospective, post-marketing surveillance study was conducted at 22 hospitals in the Republic of Korea. Patients with moderate to severe active UC who received tofacitinib were included and followed up for up to 52 weeks. Tofacitinib was administered at a dosage of 10 mg twice daily for at least 8 weeks, followed by 5 or 10 mg twice daily at the investigator's discretion based on clinical evaluation according to the approved Korean label. Safety including adverse events (AEs) and effectiveness including clinical remission, clinical response, and endoscopic mucosal healing were evaluated. Safety analysis set was defined as all patients registered for this study who received at least one dose of tofacitinib according to the approved Korean label and followed up for safety data. Effectiveness analysis set included patients in the safety analysis set who were evaluated for overall effectiveness assessment and excluded patients who had received tofacitinib less than 8 weeks. Results: A total of 110 patients were enrolled, of whom 106 patients were included in the safety population. The median duration of treatment was 370 days and the treatment duration ranged from 16 to 684 days for the safety population. AEs occurred in 42 patients (39.6%). Serious AEs (SAEs) occurred in 7 patients (6.6%) and of them, there were 2 cases of serious infections. These serious infections were reported as Adverse Event of Special Interest (AESI) in this study and no other AESI were reported. There were no cases of death during the study period. Clinical remission rates were 40.0%, 46.7%, 57.6%, and 55.1% at 8, 16, 24, and 52 weeks, and clinical response rates were 77.8%, 87.9%, 56.6%, and 81.4% at each visit, respectively. Endoscopic mucosal healing rates were 58.7% at 16 weeks and 46.2% at 52 weeks. Conclusion: Tofacitinib was effective in Korean patients with moderate to severe active UC and the safety findings were consistent with the known safety profile of tofacitinib. Summary: This study confirmed the safety and effectiveness of tofacitinib in Korean patients with moderate to severe active UC in routine clinical settings. Trial registration: This study is registered in the ClinicalTrials.gov under the identifier NCT04071405, registered on 28 August 2019. [ABSTRACT FROM AUTHOR]

Background/Objectives: Janus kinase inhibitors (JAKis) belong to a new class of targeted oral drugs that have been added to the therapeutic arsenal for rheumatoid arthritis (RA). The aim of this study was to evaluate the efficacy and safety profiles of these four available molecules (tofacitinib, baricitinib, filgotinib, and upadacitinib) in real life. Methods: A retrospective, single-center observational study including all patients treated with JAKis for RA from 1 October 2017 to 1 December 2023. We assessed the maintenance rate at 24 months, which is an indirect reflection of the clinical and biological safety and efficacy profiles. Results: The 76 patients in our study were thus treated for the first time with anti-JAK, including 55 patients with baricitinib (BAR), 9 patients with tofacitinib (TOF), 4 patients with upadacitinib (UPA), and 8 patients with filgotinib (FIL). The majority of our patients had BAR introduced as the first intention. The therapeutic maintenance at 2 years for all our patients was 50%. The average maintenance duration was 8.6 months and was similar in all the groups. Of the 76 patients included in this study treated with Baricitinib (72.3%), 38 (50%) discontinued their treatment after two years of follow-up. Conclusions: Although this retrospective study is subject to various biases, it shows that the persistence rates of the four JAKi molecules in daily practice did not differ significantly, thus confirming the long-term efficacy of these drugs. [ABSTRACT FROM AUTHOR]

Tofacitinib is the first oral JAK inhibitor approved for treating rheumatoid arthritis (RA). To enhance our understanding of tofacitinib drug response, we used hierarchical clustering to analyse the profiles of patient who responded to the treatment in a real-world setting. Patients who commenced on tofacitinib treatment were selected from 12 major rheumatology centres in Malaysia. The aim was to assess their response to tofacitinib defined as achieving DAS28-CRP/ESR ≤ 3.2 and DAS28 improvement > 1.2 at 12 weeks. A hierarchical clustering analysis was performed using sociodemographic and clinical parameters at baseline. All 163 RA patients were divided into three clusters (Clusters 1, 2 and 3) based on specific clinical factors at baseline including bone erosion, antibody positivity, disease activity and anaemia status. Cluster 1 consisted of RA patients without bone erosion, antibody negative, low baseline disease activity measure and absence of anaemia. Cluster 2 comprised of patients without bone erosion, RF positivity, anti-CCP negativity, moderate to high baseline disease activity score and absence of anaemia. Cluster 3 patients had bone erosion, antibody positivity, high baseline disease activity and anaemia. The response rates to tofacitinib varied among the clusters: Cluster 1 had a 79% response rate, Cluster 2 had a 66% response rate, and Cluster 3 had a 36% response rate. The differences in response rates between the three clusters were found to be statistically significant. This cluster analysis study indicates that patients who are seronegative and have low disease activity, absence of bone erosion and no signs of anaemia may have a higher likelihood of benefiting from tofacitinib therapy. By identifying clinical profiles that respond to tofacitinib treatment, we can improve treatment stratification yielding significant benefits and better health outcomes for individuals with RA. [ABSTRACT FROM AUTHOR]

INTRODUCTION: There is paucity of data on the effectiveness and safety of tofacitinib among elderly patients with ulcerative colitis (UC). METHODS: Through a retrospective cohort study among the US National Veterans Affairs Healthcare System, we evaluated effectiveness among the elderly (≥65) and young (<65) patients with UC initiated on tofacitinib. RESULTS: Among 158 patients (53 elderly, 105 young), effectiveness at 12 months was 50.94% in the elderly and 33.33% in the young (P = 0.032). DISCUSSION: In a nationwide cohort of patients with UC initiating tofacitinib, effectiveness was seen in half of the elderly patients. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics. METHODS: A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints. RESULTS: Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents (P = 0.047) and of late VTE with vedolizumab (P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00). DISCUSSION: Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy. [ABSTRACT FROM AUTHOR]

This document summarizes a study on the cardiovascular risks of Janus kinase inhibitors (JAKi) in patients with rheumatic diseases. The study found that the impact of JAKi on cardiovascular risk is complex and may vary depending on factors such as baseline risk factors, disease activity, and type of rheumatic disease. Some studies suggest an increased cardiovascular risk with JAKi, especially in older patients with risk factors, while others found no significant difference compared to other treatments. More research is needed to fully understand the relationship between JAKi and cardiovascular risk. [Extracted from the article]

Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8+NKG2D+T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata. Reversal of alopecia areata with topical TFB NPs treatment by blocking the JAK-STAT signaling pathways, reduced the expression levels of IFN-γ and the frequencies of NKG2D+CD8+ T cells, restored immune environment and promoted hair regrowth. [Display omitted] • Ex vivo mouse hair follicles model was used to assess formulations. • Hair follicles blocked skin model was used to evaluate drug permeation. • Cationic nanostructured carriers minimize systemic circulation and maximize hair follicle targeting. • The formulation restored immune privilege and ensured safe topical delivery for the treatment of alopecia areata. [ABSTRACT FROM AUTHOR]