Autoinflammatory Pathogenesis and Targeted Therapy for Adult-Onset Still’s Disease

Li, Sheng; Zheng, Songbai; Tang, Sha; Pan, Yunlei; Zhang, Shan; Fang, Hong; Qiao, Jianjun

doi:10.1007/s12016-019-08747-8

Cited by 37 publications

(37 citation statements)

References 79 publications

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“…Of note, a very recent phase II randomized controlled trial has showed a not statistically significant difference in the frequency of patients reaching a DAS28 (ESR) reduction > 1.2 at week 12 between patients administered with CAN and those included in the placebo group. However, significantly higher American College of Rheumatology (ACR) 30%, ACR 50%, and ACR 70% response rates were observed among patients treated with CAN compared with those included in the placebo group [ 17 ]. This finding does not conflict with our own, since in our cohort of patients the improvement in articular manifestations proved to be persistent but progressive over time, with DAS28-CRP reduced in a statistically significant fashion starting from the 6-month assessment from the start of CAN.…”

Section: Discussionmentioning

confidence: 99%

Real-Life Data on the Efficacy of Canakinumab in Patients with Adult-Onset Still’s Disease

Vitale

Berlengiero

Sota

et al. 2020

Mediators of Inflammation

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Background. Interleukin-1 inhibition has revealed to be a successful treatment approach for patients with adult-onset Still’s disease (AOSD). However, real-life experience is focused on the use of anakinra, while data about canakinumab (CAN) are mainly based on case reports and small case series. Patients and Methods. Patients classified with AOSD according to Yamaguchi criteria and treated with CAN were consecutively enrolled. Their clinical and therapeutic data were retrospectively collected and statistically analysed to assess the role of CAN as a therapeutic opportunity in AOSD patients in terms of clinical and laboratory disease control along with corticosteroid-sparing effect. Results. Nine AOSD patients (8 females and 1 male) treated with CAN for 15.00 ± 12.3 months were enrolled. Resolution of clinical manifestations was reported in 8/9 cases at the 3-month assessment; a significant decrease in the number of tender joints ( p = 0.009 ), swollen joints ( p = 0.027 ), and disease activity score on 28 joints-C-reactive protein (DAS28-CRP) ( p = 0.044 ) was observed during the study period. The systemic score of disease activity significantly decreased at the 3-month and 6-month assessments and at the last visit compared to the start of treatment ( p = 0.028 , p = 0.028 , and p = 0.018 , respectively). The daily corticosteroid dosage was significantly reduced at the 3-month and at the last follow-up visits ( p = 0.017 and p = 0.018 , respectively). None of the patients experienced adverse events or severe adverse events during the follow-up. Conclusions. CAN has shown prompt and remarkable effectiveness in controlling AOSD activity in a real-life contest, with a significant glucocorticoid-sparing effect and an excellent safety profile.

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Section: Discussionmentioning

confidence: 99%

Real-Life Data on the Efficacy of Canakinumab in Patients with Adult-Onset Still’s Disease

Vitale

Berlengiero

Sota

et al. 2020

Mediators of Inflammation

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“…It is typically characterized by high spiking fever, arthralgia or arthritis, and transient maculopapular salmon-pink evanescent skin rash. Other manifestations are sore throat or pharyngitis, dynophagia, myalgia or myositis, generalized lymphadenopathy, hepatosplenomegaly, serositis, and cardiopulmonary or kidney involvement (5,6). Common laboratory abnormalities include neutrophilic leukocytosis, elevated acute-phase reactants, inflammatory anemia, and thrombocytosis accompanied by liver abnormalities.…”

Section: Aosdmentioning

confidence: 99%

“…Common laboratory abnormalities include neutrophilic leukocytosis, elevated acute-phase reactants, inflammatory anemia, and thrombocytosis accompanied by liver abnormalities. The diagnosis is primarily clinical, necessitates the exclusion of a wide range of mimicking disorders, and still lacks specific diagnostic testing (5,6). Different diagnostic criteria have been proposed for AOSD diagnosis ( Supplementary Table S1).…”

Section: Aosdmentioning

confidence: 99%

Case Report: Adult Still’s Disease in an Alemtuzumab-Treated Multiple Sclerosis Patient

et al. 2020

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Background: Autoimmune adverse events are the most relevant risks of alemtuzumab therapy. We present a patient with relapsing-remitting multiple sclerosis, who developed adult-onset Still's disease (AOSD) following alemtuzumab treatment. Case Presentation: The patient suffered from sore throat, swallowing difficulties, high spiking quotidian fever, generalized skin rash, arthritis, and myalgia 2 months after the second course of alemtuzumab. Laboratory tests revealed elevated acute-phase reactants, anemia, neutrophilic leukocytosis, and thrombocytosis. Serum calprotectin, interleukin-2, and interleukin-6 levels were strongly increased. Autoimmune, rheumatic, neoplastic, infectious, and granulomatous disorders were excluded. The NLRP1 and NLRP3 gene test, which was performed under the presumption of a cryopyrinassociated autoinflammatory syndrome, was negative. Based on the Yamaguchi and Fautrel criteria, and supported by the histological findings from a skin biopsy of the rash, the diagnosis of AOSD was established. Therapy with the anti-IL-1 agent (anakinra) led to a significant improvement of symptoms and blood parameters. However, anakinra had to be converted to rituximab due to generalized drug eruption. Following therapy with rituximab, the patient has fully recovered. Conclusion: The current case highlights AOSD as another rare and potentially life-threatening secondary autoinflammatory/autoimmune event following alemtuzumab treatment.

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“…Adult Still's disease (ASD) is a systemic in ammatory disorder characterized by spiking fever, skin rash, arthritis, and multisystem involvement [1]. ASD is considered to be an autoin ammatory disease because of the absence of autoantibodies, similar to other autoin ammatory diseases [2]. Although numerous studies have described potential biomarkers, none have been validated in clinical research, except the IL-1 family cytokine IL-18 [3,4].…”

Section: Introductionmentioning

confidence: 99%

Elevated serum levels of checkpoint molecules in patients with adult Still’s disease

Fujita¹,

Asano²,

Matsumoto³

et al. 2020

Preprint

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Background: The interaction between galectin-9 (Gal-9) and its ligand, T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3), one of the coinhibitory receptors, transduce the inhibitory signaling to regulate immune responses. The dysregulated expression of checkpoint molecules has been reported under various inflammatory or autoimmune conditions. The aim of this study is to investigate the levels of these checkpoint molecules and their associations between proinflammatory markers in patients with adult Still’s disease (ASD). Methods: Serum samples were collected from 47 patients with active ASD, 116 patients with rheumatoid arthritis (RA), and 37 healthy controls (HCs). Serum levels of Gal-9, soluble TIM-3 (sTIM-3), and IL-18 were determined using enzyme-linked immunosorbent assay (ELISA). Results were compared with clinical features of ASD. Results: Serum Gal-9 levels in patients with ASD (median: 21.57 ng/ml, interquartile range IQR [11.41–39.72]) were significantly higher compared to those in patients with RA (7.58 ng/ml, IQR [5.57–10.20] p < 0.001) as well as those in HCs (4.51 ng/ml, [IQR; 3.58–5.45], p < 0.001). Similarly, serum sTIM-3 levels in patients with ASD were significantly higher than those in patients with RA and HCs. Serum levels of Gal-9 or sTIM-3 showed positive correlations with IL-18 levels (Gal-9; r = 0.90, p< 0.001, sTIM-3; r = 0.78, p< 0.001) in patients with ASD. Serum levels of Gal-9 or sTIM-3 correlated with serum ferritin (Gal-9; r = 0.77, p< 0.001, sTIM-3; r = 0.71, p< 0.001) and ASD disease activity score (Pouchot’s score, Gal-9; r = 0.66, p< 0.001, sTIM-3; r = 0.59, p< 0.001). Whereas there was no significant correlation between serum Gal-9 or sTIM-3 and CRP. ASD patients with chronic arthritis phenotype had a significantly higher Gal-9/ferritin and sTIM-3/ferritin ratio than those without this phenotype. After immunosuppressive treatment, Gal-9 and sTIM-3 levels showed a significant decline in parallel to the disease activity scores. Conclusions: Serum levels of the coinhibitory checkpoint molecules were elevated and correlated with disease activity in patients with ASD. These coinhibitory checkpoint molecule may be implicated in the autoinflammatory process seen in ASD.

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Autoinflammatory Pathogenesis and Targeted Therapy for Adult-Onset Still’s Disease

Cited by 37 publications

References 79 publications

Real-Life Data on the Efficacy of Canakinumab in Patients with Adult-Onset Still’s Disease

Real-Life Data on the Efficacy of Canakinumab in Patients with Adult-Onset Still’s Disease

Case Report: Adult Still’s Disease in an Alemtuzumab-Treated Multiple Sclerosis Patient

Elevated serum levels of checkpoint molecules in patients with adult Still’s disease

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