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.
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.

Introduction: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin condition with a substantial impact on patients, particularly due to ocular involvement known as atopic keratoconjunctivitis (AKC). Current therapeutic approaches, such as dupilumab, often lead to conjunctivitis, prompting exploration of alternative treatments like upadacitinib. Methods: We collected dermatological and ophthalmological prospective clinical evaluations of six adults with moderate-to-severe AD, undergoing treatment with upadacitinib after discontinuation of dupilumab due to the onset of AKC during therapy and the worsening of dermatitis in particular in the head and neck region. Clinical evaluations, including EASI scores, itch and sleep NRS, DLQI, and ocular parameters, were performed at baseline (during screening assessment before switching to upadacitinib) and then at week 12 and week 24. Clinical evaluation of AKC was performed by a team of ophthalmologists. Results: Upadacitinib not only improved atopic dermatitis in terms of EASI, itching, and sleep NRS, but also demonstrated a notable reduction in ocular signs and symptoms, as indicated by the Visual Analogue Scale (VAS), the Efron scale, and the Ocular Surface Disease Index Symptom Severity (OSDISS) scores. Discussion: Our observation of common clinical practice underscores the substantial impact of biological and small-molecule therapies on AD, emphasizing the limitation posed by dupilumab-associated conjunctivitis. Switching to upadacitinib significantly improved both clinical and functional ocular outcomes, suggesting its potential as an alternative therapeutic option for AD patients with ocular involvement. Conclusion: The presented data provides insights into the complex interplay between systemic therapies and ocular manifestations in AD. Upadacitinib emerges as a promising option to address dupilumab-associated conjunctivitis, offering improved quality of life for patients.

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Upadacitinib, a selective JAK-1 inhibitor, was used as rescue therapy for ulcerative colitis in the setting of pregnancy following use of mesalamine, vedolizumab, infliximab, and corticosteroids. This resulted in an uncomplicated live full birth without need for surgical intervention.

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Vernal keratoconjunctivitis is a persistent allergic ocular disease predominantly mediated by the T-helper 2 lymphocyte-associated immune response. The standard therapeutic approaches for vernal keratoconjunctivitis include topical corticosteroids and immunosuppressive eye drops. However, managing vernal keratoconjunctivitis with only topical treatments becomes challenging during seasonally exacerbated periods. Systemic treatments such as oral corticosteroids or cyclosporine may be alternative options. Recently, dupilumab\'s efficacy in refractory vernal keratoconjunctivitis treatment has been documented. Here, we report a case of refractory vernal keratoconjunctivitis coexisting with atopic dermatitis that rapidly improved after upadacitinib administration. An 18-year-old Japanese woman presented with atopic dermatitis, vernal keratoconjunctivitis, and hay fever. In winter, the patient experienced widespread erythema and escalated itching, leading to significant discomfort and insomnia. Owing to the difficulty in maintaining her current regimen, upadacitinib (15 mg), a Janus kinase inhibitor was initiated. After upadacitinib administration, the treatment-resistant vernal keratoconjunctivitis and erythema improved. Upadacitinib is beneficial in severe cases of atopic dermatitis. Consequently, in our case, upadacitinib may offer therapeutic benefits for refractory vernal conjunctivitis by improving the T-helper 1/2 type immune response, autoimmunity, and oxidative stress. To our knowledge, this is the first report suggesting the potential utility of upadacitinib in managing severe vernal conjunctivitis.

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UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Atopic dermatitis is a chronic inflammatory skin disease that may progress to erythroderma in severe cases. Biologic agents such as dupilumab have recently become the mainstay of systemic treatment for moderate-to-severe cases, yet many patients remain refractory to therapy. Here, we present a case of erythrodermic atopic dermatitis, resistant to prednisone and dupilumab, with remarkably rapid achievement of remission following treatment with upadacitinib, an oral selective Janus kinase 1 inhibitor.

To explore the effectiveness and safety of upadacitinib for managing axial spondyloarthritis. Four databases (PubMed, EMBASE, Cochrane, and Web of Science) were applied to search randomized controlled trials (RCTs) for assessing upadacitinib treatment for axial spondyloarthritis published until January 2024. Five RCTs involving 1,246 participants were included. The upadacitinib group had significantly higher percentages of participants achieving Assessment of spondyloarthritis international society (ASAS) 20, ASAS40, ASAS partial remission, Bath ankylosing spondylitis disease activity index (BASDAI) 50, Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity, ASDAS inactive disease, ASDAS clinically important improvement, and ASDAS major improvement, except for Work Productivity and Activity Impairment (WPAI) absenteeism. Obvious improvements were observed in the upadacitinib group for ASDAS (CRP), BASDAI, Modified BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), Canadian Spondyloarthritis Research Consortium (SPARCC) MRI spine, SPARCC MRI sacroiliac joint, Ankylosing Spondylitis Quality of Life (ASQoLS), ASAS Health Index, Bath Ankylosing Spondylitis Metrology Index (BASMI), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), Total Back Pain, Nocturnal Back Pain, WPAI overall work impairment, WPAI presenteeism, and WPAI activity impairment. Adverse events (AEs) and serious adverse events (SAEs) incidence rates showed no significant difference differ between upadacitinib and placebo groups. Subgroup analysis revealed that disease subtype and age did not significantly affect efficacy, and upadacitinib demonstrated comparable efficacy to adalimumab for axial spondyloarthritis. Upadacitinib exhibited satisfactory efficacy in treating axial spondyloarthritis, reducing disease activity and significantly enhancing patients\' physical function, emotional well-being, and social engagement. This meta-analysis offers robust evidence supporting upadacitinib as a new treatment for axial spondyloarthritis patients.