Protocol for a systematic review and meta-analysis on Janus kinase inhibitors in the management of vitiligo.

BACKGROUND: Vitiligo is a disease that affects people of all skin shades and can impact their quality of life. Reliable evidence on the effectiveness and adverse events associated with the recent use of Janus kinase (JAK) inhibitors to treat vitiligo is needed. This protocol for a systematic review and meta-analysis seeks to collect evidence from both randomized controlled trials (RCTs) and observational studies to determine the effectiveness and patient-centered outcomes concerning treatment with JAK inhibitors. METHODS: We will conduct a systematic review of the literature for RCTs and observational studies that used upadacitinib, ritlecitinib, brepocitinib, ifidancitinib, cerdulatinib, deglocitinib, baricitinib, tofacitinib, and ruxolitinib JAK inhibitors as treatments for vitiligo compared to placebo, no treatment, or combination therapies. We will systematically search from inception in Epistemonikos, MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, EMBASE, ClinicalTrials.gov, PsycINFO, Allied and Complementary Medicine Database, Latin American and Caribbean Health Sciences Literature, Web of Science Core Collection, relevant preprint servers, and the gray literature. Ethics approval was not sought as the protocol and systematic review will not involve human participants, but rather summarized and anonymous data from studies. Primary outcomes include quality of life, percentage repigmentation, decreased vitiligo within 1 year or more, lasting repigmentation after a 2-year follow-up, cosmetic acceptability of repigmentation and tolerability or burden of treatment, and adverse events. Secondary outcomes are patient and study characteristics. We will include full-text articles, preprints, and clinical trial data in any language and all geographic regions. For data sources unavailable in English, we will obtain translations from global collaborators via the Cochrane Engage network. We will exclude articles for which sufficient information cannot be obtained from the authors of articles and systematic reviews. At least two investigators will independently assess articles for inclusion and extract data; reliability will be assessed before subsequent selection and data extraction of remaining studies. The risk of bias and certainty of evidence with Grading of Recommendations Assessment, Development, and Evaluation guidelines will be assessed independently by at least two investigators. We will estimate treatment effects by random-effects meta-analyses and assess heterogeneity using I2. Data that cannot be included in the meta-analysis will be reported narratively using themes. DISCUSSION: The proposed systematic review and meta-analysis describe the methods for summarizing and synthesizing the evidence on the effectiveness and patient-centered outcomes concerning the treatment of vitiligo with JAK inhibitors that were recently approved for this indication. To disseminate further the results of our systematic review, we plan to present them at international conferences and meetings. Our findings will provide robust evidence to facilitate decision-making at the policy or practitioner level. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023383920.

Oral Lichen Planus Successfully Treated With Upadacitinib.

With the rise of Janus kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) inhibitor use in dermatologic conditions, there has been increasing hope in treating extensive and difficult-to-treat inflammatory cutaneous conditions. Today we report a case of oral lichen planus successfully treated with an oral JAK1 inhibitor, upadacitinib. This case had been unresponsive by several standard methods but responded with 70% improvement within 1 month when treated with upadacitinib.  J Drugs Dermatol. 2024;23(4):7859.     doi:10.36849/JDD.7859e  .

Use of a topical Janus kinase inhibitor in immune checkpoint inhibitor-induced eczematous reaction: a case report.

In this report, we describe the case of a 28-year-old female with bilateral breast cancer in the setting of a BRCA1 mutation, who presented to dermatology with an eczematous reaction, ultimately diagnosed as a cutaneous immune-related adverse event (cirAE) secondary to an immune checkpoint inhibitor (ICI), pembrolizumab. Our case report highlights a novel therapeutic option for an eczematous cirAE: the topical JAK 1/2 inhibitor, ruxolitinib. CirAEs can occur in up to 55% of patients on ICIs, a class of medications seeing rapidly increasing use in cancer therapy, and prior research has demonstrated that ICI-induced dermatitis may involve different pathways than traditionally observed in their spontaneous counterparts. Specifically, marked Th1 skewing is noted in ICI-induced dermatitis, as opposed to a predominant Th2 response which typically characterizes spontaneous atopic dermatitis. To our knowledge, this is the first case report in the literature discussing use of a topical JAK inhibitor, ruxolitinib, in the treatment of topical steroid-refractory cirAEs. Furthermore, as topical JAK inhibitors are thought to not carry the risks of systemic JAK inhibitors, including malignancy, ruxolitinib cream is a promising therapeutic option for this challenging patient population.

Patients with STAT1 Gain-of-function Mutations Display Increased Apoptosis which is Reversed by the JAK Inhibitor Ruxolitinib.

INTRODUCTION: The signal transducer and activator of transcription (STAT1) gain-of-function (GOF) syndrome accounts for most cases of chronic mucocutaneous candidiasis but is characterized by a broader clinical phenotype that may include bacterial, viral, or invasive fungal infections, autoimmunity, autoinflammatory manifestations, vascular complications, or malignancies. The severity of lymphopenia may vary and influence the infectious morbidity. METHODS: In our cohort of seven STAT1-GOF patients, we investigated the mechanisms that may determine T lymphopenia, we characterized the interferon gene signature (IGS) and analyzed the effect of ruxolitinib in reverting the immune dysregulation. RESULTS: STAT1-GOF patients exhibited increased T lymphocyte apoptosis that was significantly augmented in both resting conditions and following stimulation with mitogens and IFNα, as evaluated by flow cytometry by Annexin V/ Propidium iodide assay. The JAK inhibitor ruxolitinib significantly reduced the IFNα-induced hyperphosphorylation of STAT1 and reverted the stimulation-induced T-cell apoptosis, in vitro. In two adult STAT1-GOF patients, the JAKinib treatment ameliorated chronic mucocutaneous candidiasis and lymphopenia. Most STAT1-GOF patients, particularly those who had autoimmunity, presented increased IGS that significantly decreased in the two patients during ruxolitinib treatment. CONCLUSION: In STAT1-GOF patients, T lymphocyte apoptosis is increased, and T lymphopenia may determine higher risk of severe infections. The JAKinib target therapy should be evaluated to treat severe chronic candidiasis and lymphopenia, and to downregulate the IFNs in patients with autoinflammatory or autoimmune manifestations.

Tofacitinib for managing granuloma formation after dermal filler injection: three case reports and literature review.

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.

TYK2 inhibition with deucravacitinib ameliorates erosive oral lichen planus.

Erosive oral lichen planus (OLP) is a challenging disease. This T cell driven disorder frequently shows a treatment unresponsive course and strongly limits patients' quality of life. The disease lacks FDA or EMA approved drugs for its treatment and the efficacy of the commonly administered treatments (i.e. topical and systemic steroids, steroid sparing agents) is often only partial. Although the etiopathogenesis of the disease still needs to be fully elucidated, recent advances helped to identify interferon-É£ (IFN-É£) as a pivotal cytokine in OLP pathogenesis, thus making the interference with its signalling a therapeutic target. Janus kinase (JAK) inhibitors therefore gained relevance for their inhibitory effect on IFN-É£ signalling. While some drugs such as abrocitinib, upadacitinib, tofacitinib directly interfere with IFN-É£ signalling through blockade of JAK1 and/or JAK2, deucravacitinib, a selective TYK-2 inhibitor indirectly interferes on IFN-É£ activation through interference with interleukin (IL)-12, a potent promotor for Th1/IFN-É£ responses. This mechanism of action makes deucravacitinib a candidate drug for the treatment of OLP. Here we provide initial evidence that deucravacitinib 6 mg daily has a beneficial effect in three patients with oral OLP.

The Role of JAK/STAT Signaling Pathway and Its Downstream Influencing Factors in the Treatment of Atherosclerosis.

Atherosclerosis is now widely considered to be a chronic inflammatory disease, with increasing evidence suggesting that lipid alone is not the main factor contributing to its development. Rather, atherosclerotic plaques contain a significant amount of inflammatory cells, characterized by the accumulation of monocytes and lymphocytes on the vessel wall. This suggests that inflammation may play a crucial role in the occurrence and progression of atherosclerosis. As research deepens, other pathological factors have also been found to influence the development of the disease. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is a recently discovered target of inflammation that has gained attention in recent years. Numerous studies have provided evidence for the causal role of this pathway in atherosclerosis, and its downstream signaling factors play a significant role in this process. This brief review aims to explore the crucial role of the JAK/STAT pathway and its representative downstream signaling factors in the development of atherosclerosis. It provides a new theoretical basis for clinically affecting the development of atherosclerosis by interfering with the JAK/STAT signaling pathway.

Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis.

BACKGROUND: Real-world data on tofacitinib (TOF) covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis (UC) are scarce. AIM: To investigate the long-term efficacy and safety of TOF treatment for UC, including clinical issues. METHODS: We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center. All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled. Patients were followed up until August 2020. The primary outcome was the clinical response rate at week 8. Secondary outcomes included clinical remission at week 8, cumulative persistence rate of TOF administration, colectomy-free survival, relapse after tapering of TOF and predictors of clinical response at week 8 and week 48. RESULTS: The clinical response and remission rates were 66.3% and 50.5% at week 8, and 47.1% and 43.5% at week 48, respectively. The overall cumulative clinical remission rate was 61.7% at week 48 and history of anti-tumor necrosis factor-alpha (TNF-α) agents use had no influence (P = 0.25). The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8 (30.9% vs 88.1%; P < 0.001). Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8 (odds ratio: 0.61, 95% confidence interval: 0.45-0.82, P = 0.001). Relapse occurred in 45.7% of patients after TOF tapering, and 85.7% of patients responded within 4 wk after re-increase. All 6 patients with herpes zoster (HZ) developed the infection after achieving remission by TOF. CONCLUSION: TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-α agents. Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF. Special attention is needed for tapering and HZ.

Long-term effectiveness and safety of upadacitinib for Japanese patients with moderate-to-severe atopic dermatitis: a real-world clinical study.

BACKGROUND: Previous clinical trials presented efficacy and safety of Janus kinase 1 inhibitor upadacitinib through 52 weeks for moderate-to-severe atopic dermatitis (AD). OBJECTIVES: To assess the effectiveness and safety of upadacitinib through 48 weeks in real-world clinical practice for Japanese AD patients (aged ≥12 years). METHODS: This retrospective study included 287 patients with moderate-to severe AD treated with 15 mg (n = 216) or 30 mg (n = 71) of upadacitinib daily. Effectiveness was assessed using eczema area severity index (EASI) scores, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and investigator's global assessment (IGA). Safety was evaluated through the incidence of treatment-emergent adverse events. RESULTS: From baseline, EASI, ADCT, PP-NRS, and IGA rapidly reduced at week 4, and the reduction was maintained until week 48 of treatment with upadacitinib at both doses. Achievement rates of EASI 75, EASI 90, and EASI 100 at week 48 were 63.5, 30.2, and 7.9 in 15 mg group, and 77.4, 54.8, and 3.2% in 30 mg group, respectively. Acne and herpes zoster were frequent, but no serious adverse events occurred. CONCLUSIONS: Upadacitinib was therapeutically effective and tolerable for moderate-to-severe AD through 48 weeks in real-world clinical practice.

Prospects of targeting JAK/STAT signal transduction pathways for vasculitis.

Vasculitis is the inflammation of blood vessels caused by autoimmunity and/or autoinflammation, and its etiology and pathogenesis remain largely unknown. The Janus kinase (JAK) and Signal transduction Transcription Activator (STAT) signal transduction pathways are a group of molecules involved in the major pathways by which many cytokines exert and integrate their functions, and their dysregulation has been implicated in the pathogenesis of a variety of autoimmune diseases. However, current data supporting the role of the JAK/STAT pathway in the development of vasculitis is limited. In terms of treatment, glucocorticoids and immunosuppressants have been the standard therapy. However, because of the huge burden of treatment side effects, people have long waited for new treatment options. JAK inhibitors reduce the production of multiple cytokines and inhibit inflammation by targeting the JAK/STAT pathway, and have the advantage of rapidly acting in oral formulations, reducing glucocorticoid dependence and associated adverse events, especially in refractory cases. Therefore, JAK inhibitors are expected to be a promising drug for the treatment of vasculitis.

Macrophage re-programming by JAK inhibitors relies on MAFB.

Monocyte-derived macrophages play a key pathogenic role in inflammatory diseases. In the case of rheumatoid arthritis (RA), the presence of specific synovial tissue-infiltrating macrophage subsets is associated with either active disease or inflammation resolution. JAK inhibitors (JAKi) are the first targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) approved for treatment of RA with comparable efficacy to biologics. However, the effects of JAKi on macrophage specification and differentiation are currently unknown. We have analyzed the transcriptional and functional effects of JAKi on human peripheral blood monocyte subsets from RA patients and on the differentiation of monocyte-derived macrophages promoted by granulocyte-macrophage colony-stimulating factor (GM-CSF), a factor that drives the development and pathogenesis of RA. We now report that JAKi Upadacitinib restores the balance of peripheral blood monocyte subsets in RA patients and skewed macrophages towards the acquisition of an anti-inflammatory transcriptional and functional profile in a dose-dependent manner. Upadacitinib-treated macrophages showed a strong positive enrichment of the genes that define synovial macrophages associated to homeostasis/inflammation resolution. Specifically, Upadacitinib-treated macrophages exhibited significantly elevated expression of MAFB and MAFB-regulated genes, elevated inhibitory phosphorylation of GSK3ß, and higher phagocytic activity and showed an anti-inflammatory cytokine profile upon activation by pathogenic stimuli. These outcomes were also shared by macrophages exposed to other JAKi (baricitinib, tofacitinib), but not in the presence of the TYK2 inhibitor deucravacitinib. As a whole, our results indicate that JAKi promote macrophage re-programming towards the acquisition of a more anti-inflammatory/pro-resolution profile, an effect that correlates with the ability of JAKi to enhance MAFB expression.

A case of generalized eosinophilic pustular folliculitis: treatment with JAK inhibitor.

AIM: This case study aims to report the efficacy and safety of a Janus kinase (JAK) inhibitor in the treatment of generalized eosinophilic pustular folliculitis (EPF). METHODS: We present a case of a 16-year-old Chinese patient who had been suffering from EPF for two years and had shown no response to both topical and systemic glucocorticoids. The patient was subsequently treated with oral tofacitinib at a dosage of 5mg daily. RESULTS: Significant remission of eruption and pruritus was observed in the patient upon treatment with tofacitinib. However, a relapse occurred upon dose reduction. Subsequent switch to the highly selective JAK1 inhibitor upadacitinib resulted in complete recovery, with the patient achieving a symptom-free status after six months. CONCLUSIONS: JAK inhibitors show promise as a potential treatment option for EPF patients who do not respond to traditional therapies.

TYK2: an emerging therapeutic target in rheumatic disease.

Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family of intracellular signalling molecules. By participating in signalling pathways downstream of type I interferons, IL-12, IL-23 and IL-10, TYK2 elicits a distinct set of immune events to JAK1, JAK2 and JAK3. TYK2 polymorphisms have been associated with susceptibility to various rheumatic diseases including systemic lupus erythematosus and dermatomyositis. In vitro and animal studies substantiate these findings, highlighting a role for TYK2 in diseases currently managed by antagonists of cytokines that signal through TYK2. Various inhibitors of TYK2 have now been studied in human disease, and one of these inhibitors, deucravacitinib, has now been approved for the treatment of psoriasis. Phase II trials of deucravacitinib have also reported positive results in the treatment of psoriatic arthritis and systemic lupus erythematosus, with a preliminary safety profile that seems to differ from that of the JAK1, JAK2 and JAK3 inhibitors. Two other inhibitors of TYK2, brepocitinib and ropsacitinib, are also in earlier stages of clinical trials. Overall, TYK2 inhibitors hold promise for the treatment of a distinct spectrum of autoimmune diseases and could potentially have a safety profile that differs from other JAK inhibitors.

Pain in axial spondyloarthritis: role of the JAK/STAT pathway.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that is characterized by new bone formation in the axial musculoskeletal system, with X-ray discriminating between radiographic and non-radiographic forms. Current therapeutic options include non-steroidal anti-inflammatory drugs in addition to biological disease-modifying anti-rheumatic drugs that specifically target tumor necrosis factor-alpha (TNFα) or interleukin (IL)-17. Pain is the most critical symptom for axSpA patients, significantly contributing to the burden of disease and impacting daily life. While the inflammatory process exerts a major role in determining pain in the early phases of the disease, the symptom may also result from mechanical and neuromuscular causes that require complex, multi-faceted pharmacologic and non-pharmacologic treatment, especially in the later phases. In clinical practice, pain often persists and does not respond further despite the absence of inflammatory disease activity. Cytokines involved in axSpA pathogenesis interact directly/indirectly with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling cascade, a fundamental component in the origin and development of spondyloarthropathies. The JAK/STAT pathway also plays an important role in nociception, and new-generation JAK inhibitors have demonstrated rapid pain relief. We provide a comprehensive review of the different pain types observed in axSpA and the potential role of JAK/STAT signaling in this context, with specific focus on data from preclinical studies and data from clinical trials with JAK inhibitors.

A panel of janus kinase inhibitors identified with anti-inflammatory effects protect mice from lethal influenza virus infection.

Influenza remains a significant threat to public health. In severe cases, excessive inflammation can lead to severe pneumonia or acute respiratory distress syndrome, contributing to patient morbidity and mortality. While antivirals can be effective if administered early, current anti-inflammatory drugs have limited success in treating severe cases. Therefore, discovering new anti-inflammatory agents to inhibit influenza-related inflammatory diseases is crucial. Herein, we screened a drug library with known targets using a human monocyte U937 infected with the influenza virus to identify novel anti-inflammatory agents. We also evaluated the anti-inflammatory effects of the hit compounds in an influenza mouse model. Our research revealed that JAK inhibitors exhibited a higher hit rate and more potent inhibition effect than inhibitors targeting other drug targets in vitro. Of the 22 JAK inhibitors tested, 15 exhibited robust anti-inflammatory activity against influenza virus infection in vitro. Subsequently, we evaluated the efficacy of 10 JAK inhibitors using an influenza mouse model and observed that seven provided protection ranging from 40% to 70% against lethal influenza virus infection. We selected oclacitinib as a representative compound for an extensive study to further investigate the in vivo therapeutic potential of JAK inhibitors for severe influenza-associated inflammation. Our results revealed that oclacitinib effectively suppressed neutrophil and macrophage infiltration, reduced pro-inflammatory cytokine production, and ultimately mitigated lung injury in mice infected with lethal influenza virus without impacting viral titer. These findings suggest that JAK inhibitors can modulate immune responses to influenza virus infection and may serve as potential treatments for influenza.IMPORTANCEAntivirals exhibit limited efficacy in treating severe influenza when not administered promptly during the infection. Current steroidal and nonsteroidal anti-inflammatory drugs demonstrate restricted effectiveness against severe influenza or are associated with significant side effects. Therefore, there is an urgent need for novel anti-inflammatory agents that possess high potency and minimal adverse reactions. In this study, 15 JAK inhibitors were identified through a screening process based on their anti-inflammatory activity against influenza virus infection in vitro. Remarkably, 7 of the 10 selected inhibitors exhibited protective effects against lethal influenza virus infection in mice, thereby highlighting the potential therapeutic value of JAK inhibitors for treating influenza.

Baricitinib for anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis-associated interstitial lung disease: a case series and literature review on Janus kinase inhibitors for the disease.

Anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis (anti-MDA5-DM) is frequently complicated by progressive interstitial lung disease (ILD), the prognosis of which is poor, and management is a major challenge. We treated three patients with anti-MDA5-DM-associated ILD (anti-MDA5-DM-ILD) using the Janus kinase (JAK) inhibitor, baricitinib, which improved lung opacities and saved two patients. We reviewed 6 patients with anti-MDA5-DM-ILD who had been treated with tofacitinib at our institution. Five of the patients survived, although discontinuation of tofacitinib due to complications was frequently observed. In addition, a literature search of patients with anti-MDA5-DM-ILD who were treated with JAK inhibitors yielded 21 articles involving 79 cases. All patients except one were treated with tofacitinib, and the survival rate was 75.9%. Although not statistically confirmed, the deceased patients tended to be older and had higher ferritin levels. A total of 92 complications were observed, 11 of which resulted in JAK inhibitor discontinuation. Cytomegalovirus reactivation comprised a substantial percentage of all complications and of those patients who required JAK inhibitor discontinuation. Five cases with fatal infective complications were also observed. While tofacitinib has been proposed to be a therapeutic option for anti-MDA5-DM-ILD, other JAK inhibitors, including baricitinib, are a treatment option. Further investigation is warranted to optimize treatment of anti-MDA5-DM-ILD.

Expert Recommendations on Use of Topical Therapeutics for Vitiligo in Pediatric, Adolescent, and Young Adult Patients.

Importance: Evidence-based recommendations for the treatment of vitiligo in pediatric, adolescent, and young adult patients in the US are needed. Objective: To develop evidence- and consensus-based expert recommendations on the diagnosis and treatment of vitiligo in young patients. Evidence Review: A process was developed to produce consensus recommendations addressing questions regarding pediatric vitiligo. A librarian-conducted literature review was performed using articles that met the inclusion criteria: published in English, containing primary data (including meta-analysis) and pediatric-specific data, and analysis of 6 or more patients. Included articles were graded by the Strength of Recommendation Taxonomy criteria and Oxford Centre for Evidence-based Medicine's Levels of Evidence and Grades of Recommendation. Research questions were reviewed on May 9, 2022, through a video conference. One month after the conference, participants participated in an online survey documenting their level of agreement with the generated statements, using a 5-point Likert scale. Findings: Articles on topical corticosteroids and/or topical calcineurin inhibitors (n = 50), topical Janus kinase inhibitors (n = 5), pseudocatalase (n = 2), and microdermabrasion (n = 2) met inclusion criteria. Forty-two recommendations were made on the diagnosis of vitiligo and optimal topical therapeutics, with 33 recommendations obtaining a 70% or greater composite agreement and strong agreement. Topical calcineurin inhibitors twice daily, topical corticosteroids with time limitation due to atrophy risk, and topical ruxolitinib, 1.5%, cream-used off-label for patients younger than 12 years and limited to nonsegmental vitiligo-were identified as evidence-based first-line therapies in the management of pediatric and adolescent patients, with specific guidance on age-based data, minimum therapeutic trial of 6 months or greater, prolonged therapy to prevent recurrence, and the positive benefit of coordinated use of UV therapeutic sources. Conclusions and Relevance: Evidence supports the use of topical calcineurin inhibitors, topical corticosteroids, and topical Janus kinase inhibitors as effective therapeutics for vitiligo in pediatric, adolescent, and young adult patients, with specific decisions on choice of agent based on factors such as site location, body surface area, and age.

New drugs in myelofibrosis: Critical assessment of additional value to monotherapy with JAK inhibitors.

Ruxolitinib in combination with navitoclax or pelabresib in myelofibrosis: activity in JAKi-naïve patients.

Upadacitinib for the treatment of moderate-to-severe Crohn's disease.

Despite an increasing number of therapies for Crohn's disease (CD), half of patients do not respond to initial treatment or lose response over time, highlighting the need for novel therapies. Inhibition of Janus kinases (JAKs) has emerged as an important therapeutic target for CD. Upadacitinib is an orally administered selective JAK1 inhibitor, which is effective for the induction and maintenance of remission in moderately-to-severely active CD, including in patients with prior failure of biological therapy. Nonselective JAK inhibition has been associated with thromboembolic disease, cardiovascular events and malignancy in patients older than 50 years with rheumatoid arthritis and pre-existing cardiovascular risk factors, which should be considered upon prescription. Upadacitinib is the first and currently only oral advanced therapy for CD.

Not all patients with Crohn's disease (CD) get better with treatment. Blocking Janus kinases (JAKs), enzymes that promote inflammation in the gut, could help these patients. The treatment upadacitinib blocks JAK1 (an enzyme transmitting inflammatory signals) and decreases inflammation in the gut. It eases symptoms. It also resolves gut inflammation in patients with CD. Regarding side effects, JAK inhibitors can cause blood clots in veins, and in the lungs, heart attacks, cancer and infections. Further studies are needed, but caution is advised. Upadacitinib is the first advanced therapy for CD given by mouth.

JAK inhibitors for the treatment of vitiligo.

Vitiligo is an autoimmune disease involving melanocyte-targeting T cells initiated by environmental and genetic factors. Steroids and tacrolimus have been used as topical treatments. Recently, novel topical agents targeting Janus kinase (JAK), a family of tyrosine kinases that regulates cytokine signaling, have emerged. Ruxolitinib is the first approved in vitiligo therapy. Furthermore, ritlecitinib is currently under clinical trials for oral treatment of active vitiligo. In this review, we discuss the possibility of topical JAK inhibitors as promising options for the treatment of vitiligo with regard to their mechanism of action, efficacy and safety.