Adverse reactions to Janus kinase inhibitors: Study of their incidence and predictive factors in patients with rheumatoid arthritis. / Reacciones adversas a inhibidores de quinasa Janus: estudio de su incidencia y de factores predictivos en los pacientes con artritis reumatoide.

BACKGROUND AND OBJECTIVE: The safety profile of Janus Kinase (JAK) inhibitors has acquired attention due to post-marketing observed adverse drug reactions. The study focuses on the analysis of adverse reactions related to tofacitinib, baricitinib, upadacitinib, and filgotinib in rheumatoid arthritis patients, including identifying predictive factors linked to their occurrence. PATIENTS AND METHODS: Observational retrospective study. Adult patients with rheumatoid arthritis from a university hospital receiving JAK inhibitor treatment between September 2017 and January 2024 were included. The cumulative incidence of each adverse reaction was calculated using the Naranjo scale. Risk factors for developing adverse reactions were identified through logistic regression analyses. RESULTS: Two hundred twenty-three patients were included, with 28.7% presenting adverse reaction related to JAK inhibitor treatment. The adverse drug reactions with the highest cumulative incidence were infections and gastrointestinal disorders. Infections included: upper respiratory tract (4.5%), cellulitis (3.1%), urinary tract (2.7%), herpes zoster (1.8%). Gastrointestinal disorders comprised: abdominal pain (4.0%), diarrhea (3.6%), nausea and vomiting (3.6%), gastrointestinal perforation (1.3%), diverticulitis (0.9%). Classified at 0.5% were: headache, paresthesias, skin rash, severe neutropenia, insomnia, dyspnea, hypertensive crisis. As risk factors, were identified: the treatment with a non-selective JAK inhibitor (OR adjusted: 4.03; 95% CI: 1.15-14.10; P=.029) and older age (OR adjusted: 1.03; 95% CI: 1.00-1.05; P=.036). CONCLUSIONS: Infections and gastrointestinal disorders represented the adverse reactions related to JAK inhibitor treatment with the highest cumulative incidence, with risk factors for their occurrence being non-selective JAK inhibitor treatment and older age of the patient.

How international guidelines recommend treating children who have severe COVID-19 or risk disease progression.

AIM: This study reviewed the current knowledge and guidelines on managing COVID-19 in children and proposed a practical approach to drug treatment. METHODS: We analysed international guidelines from four prominent scientific bodies on treating COVID-19 in children. These were the UK National Institute for Health and Care Excellence, the American National Institutes of Health, the Infectious Diseases Society of America and the Australian National Clinical Evidence Taskforce COVID-19. RESULTS: Most paediatric patients with COVID-19 only require symptomatic treatment. There was limited evidence on treatment recommendations for children with severe COVID-19 or at risk of disease progression. However, several drugs are available for children and we have summarised the guidelines, in order to provide a concise, practical format for clinicians. All the guidelines agree that nirmatrelvir plus ritonavir or remdesivir can be used as prophylaxis for severe COVID-19 in high-risk patients. Remdesivir can also be used for severe COVID-19 cases. Glucocorticosteroids are recommended, particularly in patients requiring oxygen therapy. Tocilizumab or baricitinib should be reserved for patients with progressive disease and/or signs of systemic inflammation. CONCLUSION: The guidelines provide useful advice and a degree of consensus on specific drug treatment for children with severe COVID-19 or at risk of progression.

Baricitinib and Pulse Steroids Combination Treatment in Hyperinflammatory COVID-19: A Rheumatological Approach in the Intensive Care Unit.

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

Effect of JAK Inhibitors on the Risk of Death in Patients with Moderate to Severe COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The pathophysiology of COVID-19 involves a signalling pathway based on the Janus kinases (JAKs) and the signal transducer and activator of transcription (STAT) family of proteins. As such, there has been growing interest in exploring JAK inhibitors as potential therapeutic agents for this disease. Objective: To provide a comprehensive summary of the efficacy of JAK inhibitors in the treatment of COVID-19 through a systematic review and meta-analysis. Data Sources: A systematic literature search was conducted in multiple electronic databases (PubMed, Scopus, and the Cochrane Central Register of Controlled Trials) and preprint repositories, without language restrictions, to identify relevant studies published up to December 31, 2023. Study Selection and Data Extraction: The primary outcome of interest was all-cause mortality. Randomized controlled trials (RCTs) investigating the administration of JAK inhibitors in patients with COVID-19 were included. Data Synthesis: Through the systematic literature search, a total of 20 RCTs meeting the inclusion criteria were identified. A random-effects model was employed to estimate the pooled odds ratio for death with administration of a JAK inhibitor relative to non-administration of such an agent, with 95% confidence interval. Meta-analysis of these trials revealed a significant reduction in mortality among patients with COVID-19 who received JAK inhibitors relative to those who did not receive these agents (pooled odds ratio 0.70, 95% confidence interval 0.58-0.84). Conclusions: The results of this systematic review and meta-analysis suggest that JAK inhibitors, specifically baricitinib, may address the urgent need for effective treatments in the ongoing COVID-19 pandemic by reducing the risk of death among affected patients. However, further research, including larger-scale RCTs, is needed to establish the efficacy and safety of other JAK inhibitors in the treatment of COVID-19 and to generate more robust evidence regarding their use in this specific patient population.

Contexte: La physiopathologie de la COVID-19 implique une voie de signalisation basée sur les Janus kinases (JAK) et les protéines STAT (pour signal transducer and activator of transcription en anglais, soit, les protéines transductrices de signal et activatrices de transcription). C'est pourquoi l'étude des inhibiteurs de JAK en tant qu'agents thérapeutiques potentiels pour cette maladie suscite un intérêt croissant. Objectif: Fournir un résumé complet de l'efficacité des inhibiteurs de JAK dans le traitement de la COVID-19 grâce à une revue systématique et une méta-analyse. Sources des données: Une recherche systématique de la littérature a été menée dans plusieurs bases de données électroniques (PubMed, Scopus et le Cochrane Central Register of Controlled Trials) et dans les référentiels de prépublications, sans restrictions linguistiques, pour identifier les études pertinentes publiées jusqu'au 31 décembre 2023. Sélection des études et extraction des données: Le principal résultat d'intérêt était la mortalité, toutes causes confondues. Des essais contrôlés randomisés (ECR) portant sur l'administration d'inhibiteurs de JAK chez des patients atteints de COVID-19 ont été inclus. Synthèse des données: Grâce à la recherche documentaire systématique, un total de 20 ECR répondant aux critères d'inclusion ont été identifiés. Un modèle à effets aléatoires a été utilisé pour estimer le rapport de cotes groupé de décès avec l'administration d'un inhibiteur de JAK par rapport à la non-administration d'un tel agent, avec un intervalle de confiance de 95 %. La méta-analyse de ces essais a révélé une réduction significative de la mortalité chez les patients atteints de COVID-19 ayant reçu des inhibiteurs de JAK par rapport à ceux n'ayant pas reçu ces agents (rapport de cotes groupé 0,70, intervalle de confiance à 95 % 0,58­0,84). Conclusions: Les résultats de cette revue systématique et méta-analyse indiquent que les inhibiteurs de JAK, en particulier le baricitinib, pourraient répondre au besoin urgent de traitements efficaces dans le cadre de la pandémie de COVID-19 en cours en réduisant le risque de décès parmi les patients touchés. Cependant, des recherches supplémentaires, y compris des ECR à plus grande échelle, sont nécessaires pour établir l'efficacité et l'innocuité d'autres inhibiteurs de JAK dans le traitement de la COVID-19 et pour générer des éléments probants plus solides concernant leur utilisation dans cette population de patients en particulier.

A case of mother and child with CANDLE syndrome: Diagnosis and subsequent treatment with baricitinib.

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) or proteasome-associated autoinflammatory syndrome is a rare autoinflammatory disorder that typically presents in infancy with characteristic symptoms, including recurrent fever, panniculitis, and progressive lipodystrophy, among other findings. We present a case of mother and child with CANDLE syndrome. The child was eventually started on baricitinib with normalization of rash and systemic findings.

JAK inhibitors in refractory dermatomyositis: A case series.

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.

Pharmacokinetic review of janus kinase inhibitors and its clinical implications for the management of rheumatoid arthritis.

INTRODUCTION: In the realm of autoimmune rheumatic diseases, understanding JAK inhibitors (JAKi) nuances is vital. Baricitinib, tofacitinib, upaacitinib, filgotinib, and peficitinib exhibit subtle yet impactful pharmacokinetic (PK) and pharmacodynamic (PD) variations. AREAS COVERED: This narrative review critically assesses PK and PD distinctions among globally approved JAKi for rheumatoid arthritis, which primarily guide clinical decisions in autoimmune diseases, particularly rheumatoid arthritis. It explores the intricate JAK-STAT signaling pathway, offering insights into JAKs' roles in inflammation, hematopoiesis, and immune homeostasis. Emphasis on PK parameters, including absorption, distribution, metabolism, and excretion, along with CYP3A4 drug interactions, is highlighted. The review underscores integrating PK and PD properties, considering patient-specific factors like hepatic and renal clearance, for judicious JAKi selection in RA and related autoimmune conditions. The literature has been collected from all available databases based on the review question. EXPERT OPINION: Integrating PK and PD properties with patient-specific factors is pivotal for judicious JAKi selection. Recognizing disparities in PK and PD across diseases, ethnicities, and environmental factors is crucial for personalized JAKi choices. This expert opinion underscores the significance of a second compartment analysis, elucidating the interplay between PK and PD and its impact on JAKi efficacy.

Improvement in Measures of Quality of Life and Symptoms of Anxiety and Depression in Patients with Severe Alopecia Areata Achieving Sustained Scalp Hair Regrowth with Baricitinib.

INTRODUCTION: Alopecia areata (AA) is an autoimmune disease associated with high rates of emotional and psychosocial distress. The analysis reported here describes the evolution of measures assessing health-related quality of life (HRQoL) and symptoms of anxiety and depression up to week 104 in patients who achieved sustained scalp hair regrowth during treatment with baricitinib in the BRAVE-AA phase III trials. METHODS: This post-hoc analysis included data from the double-blind, parallel-group, randomized, placebo-controlled phase III trials BRAVE-AA1 (ClinicalTrials.gov number: NCT03570749) and BRAVE-AA2 (ClinicalTrials.gov number: NCT03899259). Adults with severe AA (defined as a Severity of Alopecia Tool [SALT] score ≥ 50) randomized to baricitinib 4 mg or baricitinib 2 mg at baseline who achieved SALT score ≤ 20 by week 36 and maintained SALT score ≤ 20 through week 104 on the same dose of baricitinib were included in this analysis of integrated data. Scalp hair regrowth (SALT score) and improvements in Skindex-16 AA Scale and Hospital Anxiety and Depression Scale (HADS) domain scores were analyzed over the 104-week period using descriptive statistics. RESULTS: In total, 131 patients (88 on baricitinib 4 mg and 43 on baricitinib 2 mg) were included in this analysis. Across the two groups, the mean age (standard deviation) was 37.2 years (12.7), and 84 (64.1%) patients were female. The interquartile range) for time to achieve a SALT score ≤ 20 for patients treated with baricitinib 4 mg and baricitinib 2 mg was 13.1 and 19.6 weeks, respectively. By week 104, 91% (baricitinib 2 mg) and 96% (baricitinib 4 mg) of patients had achieved a SALT score ≤ 10 on baricitinib treatment. In both groups, progressive improvements in the Skindex-16 AA and HADS domain scores were observed up to week 104. CONCLUSION: This analysis of adults with severe AA treated with baricitinib revealed that achievement of sustained clinically meaningful scalp hair regrowth (SALT score ≤ 20) was associated with improvements in both measures of HRQoL and symptoms of anxiety and depression up to week 104.

Case report: Sequential therapy with dupilumab and baricitinib for severe alopecia areata with atopic dermatitis in children.

An 8-year-old female child presented with patchy hair loss for 1 year, accompanied by eyebrow loss for 6 months. Microscopic examination of the hair confirmed the features of active stage alopecia areata, with a Severity of Alopecia Tool (SALT) score of 70%. The diagnosis was severe alopecia areata. The patient had a history of atopic dermatitis since infancy, with recurrent episodes of scattered papules and pruritus for 8 years. Initial treatment involved subcutaneous injections of dupilumab 300mg every 2 weeks for 6 months, resulting in a reduction of SALT score to 20% and improvement of atopic dermatitis symptoms. Discontinuation of Dupilumab and initiation of daily oral Baricitinib at a dose of 2mg for a duration of 5 months. According to the SALT score evaluation, the severity of hair loss was less than 10% and there was significant regrowth of hair. No significant adverse reactions were observed during the treatment period.

Repositioning of baricitinib for management of memory impairment in ovariectomized/D-galactose treated rats: A potential role of JAK2/STAT3-PI3K/AKT/mTOR signaling pathway.

AIMS: Neuroinflammation plays a pivotal role in amyloid ß (Aß) plaques formation which is among the hallmarks of Alzheimer's disease (AD). The present study investigated the potential therapeutic effects of baricitinib (BAR), a selective JAK2/ STAT3 inhibitor, in ovariectomized/ D-galactose (OVX/D-gal) treated rats as a model for AD. MAIN METHODS: To induce AD, adult female rats (130-180 g) underwent bilateral ovariectomy and were injected daily with 150 mg/kg, i.p. D-gal for 8 consecutive weeks. BAR (10 and 50 mg/kg/day) was then given orally for 14 days. KEY FINDINGS: BAR in a dose-dependent effect mitigated OVX/D-gal-induced aberrant activation of JAK2/STAT3 signaling pathway resulting in significant decreases in the expression of p-JAK 2, and p-STAT3 levels, along with deactivating AKT/PI3K/mTOR signaling as evidenced by deceased protein expression of p-AKT, p-PI3K, and p-mTOR. As a result, neuroinflammation was diminished as evidenced by decreased NF-κß, TNF-α, and IL-6 levels. Moreover, oxidative stress biomarkers levels as iNOS, and MDA were reduced, whereas GSH was increased by BAR. BAR administration also succeeded in reverting histopathological alterations caused by OVX/D-gal, increased the number of intact neurons (detected by Nissl stain), and diminished astrocyte hyperactivity assessed as GFAP immunoreactivity. Finally, treatment with BAR diminished the levels of Aß. These changes culminated in enhancing spatial learning and memory in Morris water maze, and novel object recognition test. SIGNIFICANCE: BAR could be an effective therapy against neuroinflammation, astrogliosis and cognitive impairment induced by OVX/ D-gal where inhibiting JAK2/STAT3- AKT/PI3K/mTOR seems to play a crucial role in its beneficial effect.

Baricitinib ameliorates inflammatory and neuropathic pain in collagen antibody-induced arthritis mice by modulating the IL-6/JAK/STAT3 pathway and CSF-1 expression in dorsal root ganglion neurons.

BACKGROUND: Janus kinase (JAK) inhibitors, such as baricitinib, are widely used to treat rheumatoid arthritis (RA). Clinical studies show that baricitinib is more effective at reducing pain than other similar drugs. Here, we aimed to elucidate the molecular mechanisms underlying the pain relief conferred by baricitinib, using a mouse model of arthritis. METHODS: We treated collagen antibody-induced arthritis (CAIA) model mice with baricitinib, celecoxib, or vehicle, and evaluated the severity of arthritis, histological findings of the spinal cord, and pain-related behaviours. We also conducted RNA sequencing (RNA-seq) to identify alterations in gene expression in the dorsal root ganglion (DRG) following baricitinib treatment. Finally, we conducted in vitro experiments to investigate the direct effects of baricitinib on neuronal cells. RESULTS: Both baricitinib and celecoxib significantly decreased CAIA and improved arthritis-dependent grip-strength deficit, while only baricitinib notably suppressed residual tactile allodynia as determined by the von Frey test. CAIA induction of inflammatory cytokines in ankle synovium, including interleukin (IL)-1ß and IL-6, was suppressed by treatment with either baricitinib or celecoxib. In contrast, RNA-seq analysis of the DRG revealed that baricitinib, but not celecoxib, restored gene expression alterations induced by CAIA to the control condition. Among many pathways changed by CAIA and baricitinib treatment, the interferon-alpha/gamma, JAK-signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) pathways were considerably decreased in the baricitinib group compared with the celecoxib group. Notably, only baricitinib decreased the expression of colony-stimulating factor 1 (CSF-1), a potent cytokine that causes neuropathic pain through activation of the microglia-astrocyte axis in the spinal cord. Accordingly, baricitinib prevented increases in microglia and astrocytes caused by CAIA. Baricitinib also suppressed JAK/STAT3 pathway activity and Csf1 expression in cultured neuronal cells. CONCLUSIONS: Our findings demonstrate the effects baricitinib has on the DRG in relation to ameliorating both inflammatory and neuropathic pain.

Effectiveness of janus kinase inhibitors in relapsing giant cell arteritis in real-world clinical practice and review of the literature.

BACKGROUND: A substantial proportion of patients with giant cell arteritis (GCA) relapse despite standard therapy with glucocorticoids, methotrexate and tocilizumab. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is involved in the pathogenesis of GCA and JAK inhibitors (JAKi) could be a therapeutic alternative. We evaluated the effectiveness of JAKi in relapsing GCA patients in a real-world setting and reviewed available literature. METHODS: Retrospective analysis of GCA patients treated with JAKi for relapsing disease at thirteen centers in Spain and one center in United States (01/2017-12/2022). Outcomes assessed included clinical remission, complete remission and safety. Clinical remission was defined as the absence of GCA signs and symptoms regardless of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values. Complete remission was defined as the absence of GCA signs and symptoms along with normal ESR and CRP values. A systematic literature search for other JAKi-treated GCA cases was conducted. RESULTS: Thirty-five patients (86% females, mean age 72.3) with relapsing GCA received JAKi therapy (baricitinib, n = 15; tofacitinib, n = 10; upadacitinib, n = 10). Before JAKi therapy, 22 (63%) patients had received conventional synthetic immunosuppressants (e.g., methotrexate), and 30 (86%) biologics (e.g., tocilizumab). After a median (IQR) follow-up of 11 (6-15.5) months, 20 (57%) patients achieved and maintained clinical remission, 16 (46%) patients achieved and maintained complete remission, and 15 (43%) patients discontinued the initial JAKi due to relapse (n = 11 [31%]) or serious adverse events (n = 4 [11%]). A literature search identified another 36 JAKi-treated GCA cases with clinical improvement reported for the majority of them. CONCLUSIONS: This real-world analysis and literature review suggest that JAKi could be effective in GCA, including in patients failing established glucocorticoid-sparing therapies such as tocilizumab and methotrexate. A phase III randomized controlled trial of upadacitinib is currently ongoing (ClinicalTrials.gov ID NCT03725202).

Interferon-γ induces combined pyroptotic angiopathy and APOL1 expression in human kidney disease.

Elevated interferon (IFN) signaling is associated with kidney diseases including COVID-19, HIV, and apolipoprotein-L1 (APOL1) nephropathy, but whether IFNs directly contribute to nephrotoxicity remains unclear. Using human kidney organoids, primary endothelial cells, and patient samples, we demonstrate that IFN-γ induces pyroptotic angiopathy in combination with APOL1 expression. Single-cell RNA sequencing, immunoblotting, and quantitative fluorescence-based assays reveal that IFN-γ-mediated expression of APOL1 is accompanied by pyroptotic endothelial network degradation in organoids. Pharmacological blockade of IFN-γ signaling inhibits APOL1 expression, prevents upregulation of pyroptosis-associated genes, and rescues vascular networks. Multiomic analyses in patients with COVID-19, proteinuric kidney disease, and collapsing glomerulopathy similarly demonstrate increased IFN signaling and pyroptosis-associated gene expression correlating with accelerated renal disease progression. Our results reveal that IFN-γ signaling simultaneously induces endothelial injury and primes renal cells for pyroptosis, suggesting a combinatorial mechanism for APOL1-mediated collapsing glomerulopathy, which can be targeted therapeutically.

Infectious events in patients with alopecia areata treated with JAK inhibitors: low burden and minimal impact on persistence in treatment.

BACKGROUND: Alopecia areata (AA) is a non-scarring disorder characterized by hair loss that greatly affects patients' quality of life and has a chronic, recurring course. This disease is marked by an inflammatory process, mainly on an autoimmune basis primarily regulated by Janus kinase (JAK). RESEARCH DESIGN AND METHODS: We conducted a retrospective study evaluating the safety of JAKi in a real-world setting in 91 AA patients, with a specific focus on the assessment of infectious events. RESULTS: Overall, 34 infectious events were observed in 28 patients (30.8%), among them 17 patients (60.7%) suspended treatment with JAKi until the infection was clinically resolved. Only in one case the infectious event led to a permanent discontinuation of the treatment. The data we observed in the study are consistent with results reported in clinical trials. CONCLUSION: It can be stated that, during treatment with JAKi in AA patients, infectious events may occur, but in most cases these events are easily manageable and do not result in permanent discontinuation of the drug.

Toward an Improved Electrocatalytic Determination of Immunomodulator COVID Medication Baricitinib Using Multiwalled Carbon Nanotube Nickel Hybrid.

The study presents a first electrochemical method for the determination of the immunomodulator drug Baricitinib (BARI), crucial in managing COVID-19 patients requiring oxygen support. A unique electrode was developed by modifying graphite carbon nickel nanoparticles (NiNPs) with functionalized multiwalled carbon nanotubes (f.MWCNTs), resulting in nanohybrids tailored for highly sensitive BARI detection. Comparative analysis revealed the superior electrocatalytic performance of the nanohybrid-modified electrode over unmodified counterparts and other modifications, attributed to synergistic interactions between f.MWCNTs and nickel nanoparticles. Under optimized conditions, the sensors exhibited linear detection within a concentration range from 4.00 × 10-8 to 5.56 × 10-5 M, with a remarkably low detection limit of 9.65 × 10-9 M. Notably, the modified electrode displayed minimal interference from common substances and demonstrated high precision in detecting BARI in plasma and medicinal formulations, underscoring its clinical relevance and potential impact on COVID-19 treatment strategies.

Biologics Versus JAK Inhibitors. Part I: Cancer Risk. A Narrative Review.

INTRODUCTION: Biological drugs (BD) and Janus kinase inhibitors (JAKi) have revolutionized the treatment of diverse dermatoses. However, there are concerns regarding their safety, especially the risk of cancer and opportunistic infections. Here, we discuss the risk of cancer associated with the BD and JAKi used in dermatology. METHODS: A narrative review was carried out. All relevant articles evaluating the risk of cancer associated with BD or JAKi and published between January 2010 and February 2024 were selected. RESULTS: Multiple large studies have evaluated the association between BD, JAKi and cancer risk. However, there is a lack of prospective, comparative studies. Overall, patients undergoing BD and JAKi present a cutaneous cancer incidence similar to that in the general population. The drugs more strongly associated with non-skin cancer risk were anti-tumor necrosis factor (anti-TNFs) agents and JAKi (especially tofacitinib and oral ruxolitinib). This risk appears to increase with age, the presence of other factors (such as chronic immunosuppression from previous drugs or other comorbidities), and specific diseases such as rheumatoid arthritis (RA) and myelodysplastic syndrome. Conversely, BD such as interleukin (IL)-17 and IL-23 inhibitors may even reduce the risk of some visceral and hematological malignancies. In patients with dermatological conditions such as psoriasis and atopic dermatitis, the risk of malignancies may be lower than in other subgroups, and probably comparable to the general population. CONCLUSIONS: The incidence of cancer in patients undergoing BD or JAKi is generally low. This incidence can be higher in elderly patients with RA or myelodysplastic syndrome, and in those undergoing prolonged therapy with tofacitinib or ruxolitinib (oral), or anti-TNF agents.

Baricitinib Improvement Across Regions in Atopic Dermatitis Patients with Baseline Body Surface Area up to 40% and Severe Itch.

INTRODUCTION: Patients with moderate-to-severe atopic dermatitis (AD) who are most likely to respond to the Janus kinase (JAK) 1/2 inhibitor baricitinib (BARI) are known to have an impacted body surface area (BSA) ≤ 40% and severe itch (numerical rating scale [NRS] ≥ 7], collectively termed 'BARI itch-dominant' patients. Our objective is to build on our previous work by providing a body region-specific, clinical characterization of the BARI itch-dominant patient at baseline and their response to BARI 4 mg. METHODS: BREEZE-AD7 was a phase 3 trial in adults with moderate-to-severe AD receiving placebo or 2 mg or 4 mg BARI in combination with topical corticosteroids. Assessing only data from BARI itch-dominant patients, we summarized the baseline characteristics and conducted body region-specific analyses on Eczema Area and Severity Index (EASI) data in order to report the response to placebo versus BARI 4 mg within this patient subtype. RESULTS: BARI 4 mg was highly effective across all body regions; at week 16, 75% improvement was seen in EASI scores (EASI75), and response rates with BARI 4 mg (head/neck, 58.3%; trunk, 69.2%; upper extremities, 61.5%; lower extremities, 87.5%) all exceeded those with placebo (head/neck: 37.5%; trunk, 40.6%; upper extremities, 18.8%; lower extremities, 40.6%) as well as the overall EASI75 rates of the intent-to-treat (ITT) population (BARI, 48.0%; placebo, 23.0%). At baseline, most BARI itch-dominant patients presented with involvement of all regions (mean regional BSA 22.7%-40.3%), highest in the head and neck, mean EASI region scores of 15.7-24.0, and considerably severe sign ratings (mean EASI sub-scores: 1.4-2.3, out of 3), especially for erythema. CONCLUSION: BARI itch-dominant patients exhibit AD involvement across all body regions and considerable sign severity, especially erythema. In response to BARI 4 mg, EASI quickly improved across regions, substantially more so in this subtype than in the ITT population.