Janus Kinase Inhibitor Research Articles

Pacritinib Response Is Associated With Overall Survival in Myelofibrosis: PERSIST-2 Landmark Analysis of Survival.

Spleen volume reduction (SVR) is a key endpoint in inhibitors of Janus kinase (JAK) inhibitor studies. Retrospective analyses have demonstrated an association between SVR and improved overall survival (OS) among patients treated with ruxolitinib with a platelet count > 100 × 109/L. Whether this association occurs in patients with thrombocytopenia is unclear. Pacritinib, a JAK2/IRAK1/ACVR1 inhibitor, demonstrated improved SVR versus best available therapy (BAT [best available therapy]; including ruxolitinib) in patients with myelofibrosis and platelet counts ≤ 100 × 109/L in the PERSIST-2 study. Patients on study at the start of the 12-week SVR window on pacritinib 200 mg twice daily or BAT were included. OS was evaluated among SVR responders versus non-responders using different SVR thresholds (≥ 35%, ≥ 20%, ≥ 10%, and > 0%). Among patients on pacritinib (n = 89), SVR ≥ 10% demonstrated the greatest separation in OS curves between responders and non-responders (HR, 0.00; 95% CI, 0.00-0.14; p < 0.01), though SVR ≥ 0% and SVR ≥ 20% were also associated with improved OS. No SVR threshold conferred OS benefit on BAT (n = 84), including ruxolitinib (n = 39). In patients with myelofibrosis and platelets ≤ 100 × 109/L, achieving SVR on pacritinib, but not BAT (including ruxolitinib), was associated with significant OS benefit, suggesting that pacritinib may offer a unique survival advantage in patients with myelofibrosis and thrombocytopenia who achieve any SVR. Trial Registration: ClinicalTrials.gov number: NCT02055781.

Urticarial vasculitis

Purpose of review Urticarial vasculitis is a rare condition manifesting with a variety of clinical presentations ranging from skin limited lesions to life-threatening systemic illnesses. This review aims to highlight the recent findings on the etiology, diagnostic modalities, and therapeutic strategies and course of urticarial vasculitis. Recent findings In addition to well established triggers, urticarial vasculitis (UV) cases associated with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) disease and COVID-19 vaccines, vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, and adenosine deaminase (ADA) deficiency have been reported. A clinical-dermoscopic model for differentiating urticarial vasculitis has been developed with purpuric patches and globules favoring UV diagnosis and thus diminishing the need for histopathology. The efficacy of treatment modalities has been reviewed, and antihistamines, systemic corticosteroids, omalizumab, cyclophosphamide, tocilizumab, anti-interleukin (IL)-1 agents, and rituximab were shown to have the highest success rates. Regarding the durability of remission, rituximab, dapsone, and MMF were related to long-lasting treatment free responses. The course of hypocomplementemic urticarial vasculitis was investigated in an epidemiological study, revealing 5- and 10-year survival rates of 92% and 83%, respectively. Chronic obstructive pulmonary disease, septicemia, and end-stage renal disease were identified as causes of mortality. Summary With the aid of dermoscopy, a noninvasive tool, differentiation from chronic spontaneous urticaria can be made, and the need for histopathological examination can be diminished. Although clear definitions and consensus criteria for performing disease severity are lacking, careful screening is needed to tailor the treatment on an individual basis. Emerging infections like SARS-CoV 2, vaccines, and autoinflammatory disorders like VEXAS syndrome and ADA deficiency are new associations. The optimal use of well established agents like systemic corticosteroids and immunomodulators are mainstay treatment modalities, whereas IL-1 inhibitors, omalizumab, rituximab and Janus Kinase inhibitors may represent viable alternatives in selected cases.

Methotrexate promotes the release of granulocyte–macrophage colony-stimulating factor from rheumatoid arthritis fibroblast-like synoviocytes via autocrine interleukin-1 signaling

BackgroundActivated fibroblast-like synoviocytes (FLS) are drivers of synovitis and structural joint damage in rheumatoid arthritis (RA). Despite the use of disease-modifying drugs, only about 50% of RA patients reach remission in real-world settings. We used an unbiased approach to investigate the effects of standard-of-care methotrexate (MTX) and a Janus kinase inhibitor, tofacitinib (TOFA), on gene expression in RA-FLS, in order to identify untargeted disease mediators.MethodsPrimary RA-FLS were activated by stimulation with interleukin-1β (IL-1β) or platelet-derived growth factor + IL-1β in the presence or absence of MTX or TOFA, with or without additional inhibitors. Co-cultures of synovial cells were performed in direct and indirect systems. Cells were collected for RNA sequencing or qPCR, and supernatants were analyzed for protein concentrations.ResultsSix thousand three hundred fifty genes were differentially expressed, the majority being upregulated, in MTX-treated activated RA-FLS and 970 genes, the majority being downregulated, in TOFA-treated samples. Pathway analysis showed that MTX had largest effects on ‘Molecular mechanisms of cancer’ and TOFA on ‘Interferon signaling’. Targeted analysis of disease-associated genes revealed that MTX increased the expression of cell cycle-regulating genes but also of pro-inflammatory mediators like IL-1α (IL1A) and granulocyte–macrophage colony-stimulating factor, GM-CSF (CSF2). The MTX-promoted expression of CSF2 in activated RA-FLS peaked at 48 h, could be mediated via either NF-κB or AP-1 transcription factors, and was abrogated by IL-1 inhibitors (IRAK4 inhibitor and anakinra). In a co-culture setting, MTX-treatment of activated RA-FLS induced IL1B expression in macrophages.ConclusionsMTX treatment induces secretion of IL-1 from activated RA-FLS which by autocrine signaling augments their release of GM-CSF. This unexpected effect of MTX might contribute to the persistence of synovitis.

Consensus Statements on Assessments and Vaccinations Prior to Commencement of Advanced Therapies for the Treatment of Inflammatory Bowel Diseases.

Given the introduction of new advanced therapies for inflammatory bowel diseases (IBDs), expanded risk mitigation strategies are essential. To create a comprehensive set of statements on assessment procedures and vaccinations before starting monoclonal antibodies, Janus kinase (JAK) inhibitors or sphingosine-1-phosphate (S1P) modulators for IBD. We examined literature, guidelines and drug product information regarding vaccination and assessment recommendations for initiating advanced IBD therapies. Using a modified Delphi approach, delegates voted anonymously on the acceptability of these statements prior to and following consensus discussion. We developed eight statements on the domains of infectious diseases screening, vaccinations and assessments prior to commencing JAK inhibitors and S1P modulators. Six statements received agreement. Pre-advanced therapy screening for infectious diseases was established, and the vaccination protocol was revised. Malignancy, cardiovascular and thromboembolic risk assessments are necessary before initiating JAK inhibitors. Those starting S1P modulators need cardiac and ophthalmic assessments. These consensus statements combine vaccination and assessments on the currently available advanced therapies for IBD as a single comprehensive document that may reduce IBD complications associated with use of advanced therapies. Knowledge gaps identified during the consensus process will provide further research opportunities.

Maintenance of hematopoietic stem cells by non-tyrosine-phosphorylated STAT5 and JAK inhibition

AbstractAdult hematopoietic stem cells (HSCs) are responsible for the lifelong production of blood and immune cells, a process regulated by extracellular cues, including cytokines. Many cytokines signal through the conserved Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in which tyrosine-phosphorylated STATs (pSTATs) function as transcription factors. STAT5 is a pivotal downstream mediator of several cytokines known to regulate hematopoiesis, but its function in the HSC compartment remains poorly understood. In this study, we show that STAT5-deficient HSCs exhibit an unusual phenotype, including reduced multilineage repopulation and self-renewal, combined with reduced exit from quiescence and increased differentiation. This was driven not only by the loss of canonical pSTAT5 signaling, but also by the loss of distinct transcriptional functions mediated by STAT5 that lack canonical tyrosine phosphorylation (uSTAT5). Consistent with this concept, expression of an unphosphorylatable STAT5 mutant constrained wild-type HSC differentiation, promoted their maintenance, and upregulated transcriptional programs associated with quiescence and stemness. The JAK1/2 inhibitor, ruxolitinib, which increased the uSTAT5:pSTAT5 ratio, had similar effects on murine HSC function; it constrained HSC differentiation and proliferation, promoted HSC maintenance, and upregulated transcriptional programs associated with stemness. Ruxolitinib also enhanced serial replating of normal human hematopoietic stem and progenitor cells (HSPCs), CALR-mutant murine HSCs, and HSPCs obtained from patients with myelofibrosis. Our results therefore reveal a previously unrecognized interplay between pSTAT5 and uSTAT5 in the control of HSC function and highlight JAK inhibition as a potential strategy for enhancing HSC function during ex vivo culture. Increased levels of uSTAT5 may also contribute to the failure of JAK inhibitors to eradicate myeloproliferative neoplasms.

Successful treatment of Crohn's disease-related peripheral spondyloarthritis with upadacitinib: two case reports and case-based review.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease (CD), not only causes significant intestinal inflammation but also leads to extra-intestinal manifestations such as spondyloarthritis (SpA). Although the efficacy of tumor necrosis factor (TNF) inhibitors has been reported for IBD-related SpA, some cases still encounter treatment failure, highlighting the need for novel therapeutic alternatives. Recently, Janus kinase inhibitors have demonstrated their efficacy in IBD and SpA, yet their impact on CD-related SpA remains unexplored. Here we present the first two cases of CD-related peripheral SpA successfully treated with upadacitinib. Additionally, our literature review identified a reported case of CD-related peripheral SpA treated with tofacitinib. All cases achieved clinical remission of both CD and peripheral SpA with Janus kinase inhibitors, and no adverse events or disease relapses were reported during the observation period. Our cases and literature review highlight the promising potential of Janus kinase inhibitors as a novel treatment not only for intestinal inflammation of CD, but also for CD-related peripheral SpA.

Treatment of Pemphigoid Vegetans with Abrocitinib.

We report the first case of 43-year-old female patient with recalcitrant pemphigoid vegetans succefully treated with combination of the selective Janus kinase 1 inhibitor (JAK1i) abrocitinib and oral corticosteroids. After abrocitinib therapy at a dose of 100mg/day, the itching relieved significantly within 24 hours. Three months later BPDAI decreased to 9, both the anti-BP230 and anti-BP180 antibody levels also decreased. Then the dose of prednisone tapered to 20mg daily and abrocitinib discontinued without a relapse in the following up.

Drug-Induced Acne in Inflammatory Bowel Disease: A Practical Guide for the Gastroenterologist.

Drug-induced acne is a common side effect to a wide array of pharmacological therapies and is characterized by a monomorphic, papulopustular eruption typically affecting the face, scalp, and the upper thorax. Corticosteroids and Janus kinase inhibitors (JAKi) are commonly used for the treatment of inflammatory bowel disease (IBD) and are known to aggravate a prior tendency to acne or trigger the development of new acneiform eruptions. Recent attention on managing drug-induced acne has been driven by the increasing use of JAKi, an expanding therapeutic class in IBD and several other immune-mediated inflammatory diseases. Both randomized controlled trials and real-world studies have identified acne as one of the most common treatment-emergent adverse events in JAKi. Left untreated, this common skin reaction can significantly impact patient self-esteem and quality of life leading to poor treatment adherence and suboptimal IBD control. This review examines the characteristics of drug-induced acne in IBD treatments, provides a practical guide for gastroenterologists to manage mild to moderate occurrences, and highlights when to seek specialist dermatology advice. Such approaches enable early treatment of a common and often distressing adverse event and optimizes the management of IBD by preventing the premature discontinuation or dose reduction of efficacious IBD drugs.

Tofacitinib for child-onset systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause diverse clinical manifestations in multiple organ systems. Child-onset SLE (cSLE) is associated with significantly higher morbidity and mortality than adult-onset SLE. The traditional treatments for SLE (glucocorticoids, antimalarials, conventional and biological disease-modifying antirheumatic drugs) often have significant adverse effects and may not fully control disease activity. Tofacitinib is an oral Janus kinase (JAK) inhibitor that inhibits the JAK-STAT pathway and has the potential to reduce SLE severity. cSLE patients who received tofacitinib and had at least one follow-up visit were retrospectively examined. Case histories, laboratory test results, and treatment regimens were analyzed at disease onset, initiation of tofacitinib treatment, and 1, 3, 6, 9, 12, 18, and 24 months after starting tofacitinib. We examined 9 patients with refractory cSLE. All patients were female and the average age at diagnosis was 10.67 years. At initiation of tofacitinib, the average age was 13.28 years and the average disease duration was 2.62 years. Four patients experienced alleviation of symptoms and reduced their daily prednisone dosages; one of them also discontinued cyclosporine A and two of them also discontinued belimumab. The other 5 patients experienced no apparent benefit. Tofacitinib may provide clinical benefits for some patients with refractory cSLE, and can also allow reduction in the glucocorticoid dosage. Tofacitinib has the potential as an adjunctive treatment for some patients with cSLE.

Interpreting modern randomized controlled trials of medical therapy in inflammatory bowel disease.

Treatment options for the medical management of inflammatory bowel disease (IBD) have expanded substantially over the past decade. Multiple classes of advanced therapies, including both monoclonal antibodies and novel oral small molecules, are now available for the treatment of moderately-to-severely active Crohn's disease and ulcerative colitis, highlighted by the approvals of the first IL23p19 antagonists, selective Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators. These advances have been accompanied by the identification of novel targets and the rapid growth in both the number and size of IBD clinical trials. Over a dozen landmark randomized controlled trials (RCTs) have been completed in the past 5 years, including the first head-to-head biologic trials, the first combination biologic studies, and multiple phase III registrational trials of novel compounds with new co-primary and composite end points that will change the treatment landscape for years to come. Importantly, the methodology of RCTs in IBD has evolved substantially, with new trial designs, evaluation of unique patient populations, and different types of efficacy and safety end points being key innovations. In this Review, we provide a comprehensive evaluation of how modern RCTs of IBD medical therapies have evolved and the implications for their appraisal that will help guide the application of these data to clinical practice.

Infection risk with JAK inhibitors in dermatoses: a meta-analysis.

Evolving evidence suggests that Janus Kinase Inhibitors (JAKi) may predispose to certain infections, including tuberculosis and human herpes viruses. This review aimed to compare the infection risk in patients on a systemic JAKi for a dermatologic indication to a placebo. A systematic review was carried out from inception to June 2023, using the EMBASE, Medline, SCOPUS, and Cochrane Library of Registered Trials databases. Eligible studies included placebo-controlled randomized trials that investigated the incidence of infection in patients with a dermatologic indication. Primary outcomes included the most commonly reported infections pertaining to serious and opportunistic infections, upper respiratory tract infections, nasopharyngitis, herpes simplex, varicella zoster, tuberculosis, neutropenia, and lymphopenia. A meta-analysis of incidence ratios was conducted to determine odds ratios (OR), with a 95% confidence interval (CI) analysis. The meta-analysis found no increased risk of serious (OR: 0.92, 95% CI: 0.61-1.43, P = 0.74) or opportunistic infections (OR: 0.65, 95% CI: 0.32-1.31, P = 0.23). The incidence of varicella-zoster infections was significantly higher in the JAKi cohort (OR: 1.72, 95% CI: 1.08-2.72, P = 0.022). From 25 studies, there was no overall increased risk of herpes simplex infections (OR: 1.43, 95% CI: 0.93-2.23, P = 0.102) to placebo; however, a significantly higher risk in those with atopic dermatitis to alopecia areata was demonstrated (OR: 1.73, 95% CI: 1.13-2.69, P = 0.013). The results of this analysis do not suggest an increased risk of serious and opportunistic infections in those on JAKi compared to placebo. However, they support an increased risk of varicella-zoster infections and a higher risk of herpes simplex infections in those with atopic dermatitis to alopecia areata. The results of this report support these agents' short-term safety but signal that vigilance should be practiced in patients at risk for serious or recurrent herpes virus infections.

Ruxolitinib for steroid-refractory chronic graft-versus-host disease: Japanese subgroup analysis of REACH3 study.

Ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, has demonstrated safety and efficacy in patients with graft-versus-host disease (GvHD). This phase 3 randomized trial (REACH3) evaluated the efficacy and the safety of ruxolitinib 10mg twice daily compared with investigator-selected best available therapy (BAT) in a subgroup of Japanese patients (n = 37) with steroid-refractory or dependent (SR/D) chronic GvHD. At data cut-off, treatment was ongoing in 17 patients and discontinued in 20. The overall response rate (complete or partial) at week 24 was greater with ruxolitinib than BAT (50% vs. 20%; odds ratio, 4.13 [95% CI, 0.90-18.9]). The best overall response rate (complete or partial response at any time point up to week 24) was higher with ruxolitinib than BAT (68.2% vs. 46.7%; odds ratio, 2.69 [95% CI, 0.66-10.9]). Ruxolitinib led to longer median failure-free survival than BAT (18.6months vs. 3.7months; hazard ratio, 0.34; [95% CI, 0.14-0.85]). The most common grade ≥ 3 adverse events up to week 24 were anemia (ruxolitinib: 22.7%; BAT: 6.7%) and pneumonia (22.7% and 20.0%, respectively). Ruxolitinib showed a higher response rate and improvement in failure-free survival in Japanese patients with SR/D chronic GvHD, with a safety profile consistent with the overall study population.

Type 2 cytokine-JAK1 signaling is involved in the development of dry-skin induced mechanical alloknesis

BackgroundMechanical alloknesis (m-alloknesis) is itch hypersensitivity induced by normally innocuous stimuli. It is sometimes observed in dry skin based itch-related diseases such as atopic dermatitis (AD), and often triggers the vicious itch-scratch cycle. The acetone-ether and water (AEW) mouse model mimics dry skin induced m-alloknesis, yet its underlying mechanism remains unclear. Janus kinase (JAK) inhibitors are used to treat AD, but their effects on m-alloknesis are not fully known. ObjectiveTo reveal the effects of various oral JAK inhibitors on m-alloknesis and their action points, using AEW model. MethodsAEW model was prepared by treatment with a mixture of acetone-ether, and they were orally administrated a JAK1/2 inhibitor baricitinib, a selective JAK1 inhibitor abrocitinib, or a JAK2 selective inhibitor AZ960, and evaluated m-alloknesis score as the total number of scratching responses in 30 mechanical stimulations. To further elucidate the mechanism of action, IL-4, IL-13 or thymic stromal lymphopoietin (TSLP) or their neutralizing antibodies were also applied to mice. In addition, the levels of these cytokines in mouse skin were measured using multiple immunoassays. ResultsAll of JAK inhibitors effectively reduced m-alloknesis, with abrocitinib demonstrating the most significant inhibition. The neutralizing antibodies against IL-4, IL-13, and TSLP inhibited m-alloknesis in AEW mice. Intradermal administration of IL-4, IL-13, or TSLP induced m-alloknesis, and abrocitinib effectively mitigated each cytokine-induced response. Highly sensitive assays detected IL-4, IL-13, IL-31 and TSLP in AEW-treated skin, with TSLP levels significantly increased. ConclusionType 2 cytokine-JAK1 signaling is involved in the development of m-alloknesis in dry skin.

Inhibition of CEACAM1 expression in cytokine-activated neutrophils using JAK inhibitors

ObjectivesCarcinoembryonic-antigen-related cell-adhesion molecule 1 (CEACAM1) is an adhesion molecule that acts as a coinhibitory receptor in the immune system. We previously demonstrated that CEACAM1 is predominantly expressed on peripheral blood neutrophils in patients with RA. The aim of the present study was to investigate the effects of Janus kinase inhibitors (JAKi) on cytokine-activated human neutrophils and CEACAM1 expression.MethodsPeripheral blood neutrophils were obtained from healthy subjects. Isolated neutrophils were stimulated with tumor necrosis factor-alpha (TNF-α) or granulocyte–macrophage colony-stimulating factor (GM-CSF) in the presence or absence of JAKi. The expression of CEACAM1 in peripheral blood neutrophils was analyzed by flow cytometry. Protein phosphorylation of signal transducer and activator of transcription (STAT)1, STAT3, and STAT5 was assessed by western blot using phospho-specific antibodies.ResultsWe found that TNF-α-induced CEACAM1 expression was marginally suppressed after pretreatment with pan-JAK inhibitor, tofacitinib. Moreover, TNF-α induced STAT1 and STAT3 phosphorylation at the late stimulation phase (4 to 16 h). The expressions of CEACAM1 on neutrophils were markedly up-regulated by GM-CSF not by interleukin (IL)-6 stimulation. All JAKi inhibited GM-CSF-induced CEACAM1 expressions on neutrophils, however, the inhibitory effects of baricitinib were larger compared to those of tofacitinib or filgotinib. Moreover, CEACAM1 was marginally upregulated in interferon (IFN)-γ stimulated neutrophils. Similarly, JAKi inhibited IFN-γ-induced CEACAM1 expressions on neutrophils.ConclusionsWe demonstrated that JAKi prevent GM-CSF-induced CEACAM1 expression in neutrophils, and JAKi-induced inhibition depends on their selectivity against JAK isoforms. These findings suggest that JAKi can modulate the expression of CEACAM1 in cytokine-activated neutrophils, thereby limiting their activation.

JAK 1-3 inhibitors and TYK-2 inhibitors in dermatology: Practical pearls for the primary care physician

ABSTRACT Guidelines for primary care clinicians on monitoring and safety guidelines regarding Janus kinase and tyrosine kinase 2 inhibitors in the treatment of inflammatory skin conditions are often unclear. This review aims to provide the primary care physician with a review of clinically relevant and updated information regarding the monitoring and overall profile of these medications. To do so, a systematic review was conducted using the PubMed database and relevant Food and Drug Administration (FDA) approved drug inserts from manufacturers. Janus kinase and tyrosine kinase 2 inhibitors have recently gained FDA approval for the treatment of several inflammatory skin conditions including atopic dermatitis, plaque psoriasis, alopecia areata, and vitiligo. There is a known box warning associated with the Janus kinase inhibitors that create the need for monitoring and close follow-up while patients are undergoing these treatments. Although these medications are often prescribed by specialists, as their use becomes more prevalent and therapies continue to gain approval for the treatment of these commonly encountered conditions, it is important for the primary physician to be updated and aware of the current monitoring guidelines and safety profile for this class of medication. Both Janus kinase inhibitors and tyrosine kinase 2 inhibitors display significant efficacy in the treatment of their approved conditions and research continues to move forward with the approval of more medications from these classes.

Real-world treatment outcomes of systemic treatments for moderate-to-severe atopic dermatitis in children aged less than 12 years: 2-year results from PEDISTAD

The arrival of biologics and small-molecule therapies (e.g. Janus kinase inhibitors) changed atopic dermatitis (AD) treatment, but older systemic treatments continue to be prescribed. To provide real-world effectiveness, safety, and adherence data for dupilumab, cyclosporine, and methotrexate. PEDISTAD (NCT03687359) is a real-world, prospective, observational, 10-year study of children (<12 years) with inadequately controlled moderate-to-severe AD. We report 2-year interim results. Median treatment durations were 8.1, 13.0, and 10.7 months for dupilumab (n = 144), methotrexate (n = 114), and cyclosporine (n = 121), respectively. Dupilumab had numerically greater within-group improvements than methotrexate and cyclosporine in Eczema Area and Severity Index (-12.4* vs -5.7* and -3.3); body surface area affected (-19.9%* vs -11.8%* and -8.8%*); itching (nighttime: -2.1* vs -0.4 and +0.1; daytime: -1.5* vs +0.1 and +0.2; ≥6 years); itching/scratching (-3.6* vs -1.4* and -0.2; <6 years); and Patient-Oriented Eczema Measure (-7.0* vs -4.7* and -1.5) (*P < .05 within-group improvements from baseline). Dupilumab had less discontinuations (8.3% vs 28.9% and 43.0%) and adverse event(s) (18.1% vs 29.8% and 31.4%). No randomization, placebo, or specified dosages. Dupilumab was associated with numerically greater outcomes and higher adherence than cyclosporine or methotrexate.

Update on Behçet syndrome

Behçet syndrome (BS) is avasculitis of variable vessels with multiple organ manifestations. This article gives an overview of innovations in the last 2 years. A literature search was carried out using the keyword "Behcet" in 2022-2024 in PubMed. The selection of suitable articles was based on the relevance. With respect to the pathophysiology it is now clear that BS occupies an intermediate position between autoinflammatory and autoimmune clinical pictures. It is now classified as MHC-I-opathy, i.e., adisease that has astrong association with HLA classI antigens, which also play aprominent role in the pathogenesis. The diagnostic international criteria for Behcet's disease (ICBD) from 2014 with ascore of 4 points or more that makes the diagnosis of BS probable have become established; however, in countries with alow prevalence of BS, the differential diagnosis of BS from other diseases is difficult and ahigher point limit in the diagnostic score seems to make sense in order to avoid incorrect diagnoses. Clusters or phenotypes of the disease have now been described in various countries in which different symptom complexes frequently occur together; however, the clusters differ between the different countries of origin and depending on the age of the patients. Sonography of the common femoral vein with specific wall thickening in BS patients has been established as an additional tool for the differential diagnosis. Typical characteristics of oral aphthae in BS were also described and the frequency of positivity in the pathergy test could be significantly increased using pneumococcal antigens as the reagent. The treatment recommendations of the EULAR from 2018 still apply; in treatment-refractory cases, tocilizumab, secukinumab, Janus kinase inhibitors (JAKi) and ustekinumab have now also been successfully used. The new EULAR treatment recommendations are expected in 2025.

Google Search Trends About Systemic Psoriasis Treatment: What Do People Want to Know About Biologics and Janus Kinase Inhibitors?

This study investigates the most frequently asked questions regarding systemic treatments for psoriasis vulgaris using Google Trends and People Also Asked (PAA) tools, focusing on traditional DMARDs, biologics, and small-molecule inhibitors. Analyzing data from January 31, 2019, to January 31, 2024, Adalimumab was found to have the highest search volume, followed by Apremilast and Methotrexate in their respective categories. Based on Rothwell's Question Classification Criteria, questions about Adalimumab predominantly centered around their technical, factual details and cost of the medication. The study highlights significant public interest in these factors over their safety profile and it is likely influenced by Adalimumab's high direct-to-consumer marketing. Moreover, evaluation of 782 websites showed that potential patients were seeking commercial and government-based websites to learn more about systemic psoriasis treatment. According to the JAMA benchmark criteria, these source types also scored the highest in terms of information quality, while medical practice websites scored the lowest. The findings suggest the need for dermatologists to address factual details such as medication administration scheduling, dietary restrictions, and cost during patient consultations, and to guide patients towards high-quality online resources. Limitations include potential comprehensiveness of questions and evolving medication concerns.

The ABCs of JAKis: A Clinician's Guide to Safety and Monitoring of the Systemic JAK Inhibitors.

Janus kinase inhibitors (JAKis) have recently emerged in the arsenal of tools to treat dermatological conditions. However, there are some concerns regarding these treatments due to their boxed warning. Here we discuss the safe and effective use of JAKs for the treatment of a wide variety of dermatologic conditions. We will also discuss monitoring guidelines. J Drugs Dermatol. 2024;23(10):852-856. doi:10.36849/JDD.8073.

Multicenter observational study on the efficacy of selective Janus Kinase-1 inhibitor upatacitinib in rheumatoid arthritis.

Upadacitinib (UPA) is a selective, reversible Janus kinase inhibitor (JAKi) approved for the treatment of RA. However, there is still no solid evidence on the long-term efficacy of UPA in treated patients. The purpose of this study was to determine the efficacy of UPA to obtain remission or low disease activity (LDA) in a series of UPA patients in patients with RA after 6 and 12 months of treatment in a real-world setting. A series of 111 consecutive patients treated with UPA in 23 rheumatology centers were enrolled. Personal history, treatment history and disease activity at baseline, after 6 and 12 months were recorded. Intention-to-treat (ITT) and per-protocol (PP) analyses assessed achievement of remission or LDA or defined as DAS28 <2.6 and ≤3.2, respectively. Logistic regression analysis examined the role of several independent factors on the reduction of disease activity after 6 months of treatment. Of the initial group of 111 subjects at baseline, 86 and 29 participants completed clinical assessments at 6 and 12 months. According to ITT analysis, the rates of remission and LDA were 18% and 18% at 6 months and 31.5% and 12.5% at 12 months, respectively. PP analysis showed higher rates of remission and LDA at 6 (23.3% and 19.8%) and 12 months (55.2% and 20.7%). Results of multivariate logistic regression analysis indicated that a low DAS28 score (P=0.045) was the only predictor of achieving remission at 6 months. None of the baseline factors predicted remission/LDA at 6 months. RA patients treated with UPA achieved a significant rate of disease remission or LDA in a real-world setting. The 6-month response was found to depend only on the baseline value of DAS28, while it was not influenced by other factors such as disease duration, line of treatment or concomitant therapy with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or corticosteroids.