Tofacitinib in steroid-dependent relapsing polychondritis

Мешков, А. Д.; Novikov, Pavel; Ilevsky, Ilia David J; Moiseev, Sergey

doi:10.1136/annrheumdis-2018-213554

Cited by 16 publications

(6 citation statements)

References 4 publications

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“…Elevated serum levels of cytokines related to monocyte/macrophage activation have been reported in association with VEXAS and other forms of RP (1,27). Similarly, therapies that target macrophage‐related cytokines are at least partially efficacious in both VEXAS and other forms of RP (28–32). Activation of T lymphocytes was observed in patients with VEXAS‐RP relative to patients with RP and controls, possibly due to cell‐nonautonomous effects secondary to myeloid‐driven inflammation.…”

Section: Discussionmentioning

confidence: 99%

Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS

Ferrada

Sikora

Luo

et al. 2021

Arthritis & Rheumatology

168

138

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Objective Somatic mutations in UBA1 cause a newly defined syndrome known as VEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic syndrome). More than 50% of patients currently identified as having VEXAS met diagnostic criteria for relapsing polychondritis (RP), but clinical features that characterize VEXAS within a cohort of patients with RP have not been defined. We undertook this study to define the prevalence of somatic mutations in UBA1 in patients with RP and to create an algorithm to identify patients with genetically confirmed VEXAS among those with RP. Methods Exome and targeted sequencing of UBA1 was performed in a prospective observational cohort of patients with RP. Clinical and immunologic characteristics of patients with RP were compared based on the presence or absence of UBA1 mutations. The random forest method was used to derive a clinical algorithm to identify patients with UBA1 mutations. Results Seven of 92 patients with RP (7.6%) had UBA1 mutations (referred to here as VEXAS‐RP). Patients with VEXAS‐RP were all male, were on average ≥45 years of age at disease onset, and commonly had fever, ear chondritis, skin involvement, deep vein thrombosis, and pulmonary infiltrates. No patient with VEXAS‐RP had chondritis of the airways or costochondritis. Mortality was greater in VEXAS‐RP than in RP (23% versus 4%; P = 0.029). Elevated acute‐phase reactants and hematologic abnormalities (e.g., macrocytic anemia, thrombocytopenia, lymphopenia, multiple myeloma, myelodysplastic syndrome) were prevalent in VEXAS‐RP. A decision tree algorithm based on male sex, a mean corpuscular volume >100 fl, and a platelet count <200 ×103/μl differentiated VEXAS‐RP from RP with 100% sensitivity and 96% specificity. Conclusion Mutations in UBA1 were causal for disease in a subset of patients with RP. This subset of patients was defined by disease onset in the fifth decade of life or later, male sex, ear/nose chondritis, and hematologic abnormalities. Early identification is important in VEXAS given the associated high mortality rate.

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Section: Discussionmentioning

confidence: 99%

Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS

Ferrada

Sikora

Luo

et al. 2021

Arthritis & Rheumatology

168

138

View full text Add to dashboard Cite

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“…Tofacitinib is under investigation for use in various diseases, including RA, ulcerative colitis, Crohn's disease, relapsing polychondritis, atopic dermatitis, alopecia areata, cutaneous dermatomyositis, psoriasis, psoriatic arthritis, and ankylosing spondylitis. [352][353][354][355][356][357][358][359][360] In total, 5 or 10 mg of tofacitinib twice a day is the most commonly used dosage. 352 Recently, tofacitinib was regarded as a candidate in treating coronavirus disease 2019 (COVID-19), although no published study showed the benefits, several clinical trials are ongoing, clinical trial identifiers, including NCT04415151, NCT04469114, NCT04390061, and NCT04332042.…”

Section: Manipulation Of Activatorsmentioning

confidence: 99%

The JAK/STAT signaling pathway: from bench to clinic

et al. 2021

Sig Transduct Target Ther

1,171

623

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The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pathway. Moreover, we highlight the role of the JAK/STAT pathway and its inhibitors in various diseases.

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“…The patient, who declined treatment with any parenteral agents, provided informed consent for the off-label use of oral tofacitinib, a decision made by the authors. After a year, the patient achieved clinical remission and discontinued corticosteroid use, with concurrent improvement observed in laryngeal wall thickening as evidenced by computed tomography scanning [20].…”

Section: Jak Inhibitors For the Treatment Of Rpmentioning

confidence: 90%

Janus Kinase Inhibitors for Relapsing Polychondritis Treatment: A Hypothesis

Gokcen

2024

CAJMHE

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Relapsing polychondritis (RP) is a rare autoimmune disease marked by recurrent episodes of inflammation impacting cartilaginous structures. The underlying mechanism has not been fully elucidated; however, comprehensive genetic and histopathological evaluations have revealed the involvement of specific genes, cell-mediated immunity, and humoral immunity in the pathogenesis of RP. The spectrum of symptoms associated with this condition ranges from mild manifestations to severe, life-threatening presentations. Treatment options vary depending on the disease severity. Non-steroidal anti-inflammatory drugs, colchicine, dapsone, and systemic corticosteroids are commonly utilized as first-line therapeutic options. Furthermore, cyclophosphamide, methotrexate, azathioprine, cyclosporine, and biological disease-modifying anti-rheumatic drugs are employed as second-line treatment. Nevertheless, there is insufficient data regarding the use of Janus kinase inhibitors (JAKi) in RP patients as a treatment option. This hypothesis suggests that JAKi may be a viable treatment option for relieving symptoms in these patients.

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Tofacitinib in steroid-dependent relapsing polychondritis

Cited by 16 publications

References 4 publications

Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS

Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS

The JAK/STAT signaling pathway: from bench to clinic

Janus Kinase Inhibitors for Relapsing Polychondritis Treatment: A Hypothesis

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