Standard and increased canakinumab dosing to quiet macrophage activation syndrome in children with systemic juvenile idiopathic arthritis

Kostik, Mikhail M.; Исупова, Е. А.; Belozerov, Konstantin E.; Likhacheva, Tatyana; Suspitsin, Evgeny N.; Raupov, R.; Masalova, Vera; Чикова, И. А.; Dubko, Margarita; Kalashnikova, Olga V.; Chasnyk, Vyacheslav; Cron, Randy Q

doi:10.3389/fped.2022.894846

Cited by 12 publications

(8 citation statements)

References 27 publications

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“…Patient 1 received a dose of 8 mg/kg for the first time due to uncontrolled MAS, showing minimal response to the treatments in methylprednisolone pulse, etoposide, and doxorubicin liposome. Kostik MM et al described that 50% of patients received one scheduled injection of an increased dose (2–3 times standard doses) of canakinumab with rapid resolution of sJIA-associated MAS allowing for tapering back down to standard canakinumab dosing of 4 mg/kg every 4 weeks ( 15 ). In addition, 45.5% of patients in our study were given to JAKi at the initiation of canakinumab treatment.…”

Section: Discussionmentioning

confidence: 99%

Canakinumab in the treatment of systemic juvenile idiopathic arthritis: a retrospective single center study in China

Zhu,

Weng,

Huang

et al. 2024

Front. Pediatr.

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ObjectiveSystemic juvenile idiopathic arthritis (sJIA) is characterized by excessive production of proinflammatory cytokines. As an anti-IL-1 agent, canakinumab has been approved in the USA and Europe for the treatment of sJIA patients aged ≥2 years. However, the use of canakinumab has never been reported in China. In this study, we aimed to assess the efficacy and safety of canakinumab in Chinese patients with sJIA.MethodsA total of 11 patients with sJIA who were treated with canakinumab were included in this study. Clinical data were collected retrospectively from medical records. Efficacy was evaluated by the systemic juvenile arthritis disease activity score (sJADAS). The follow-up was performed at canakinumab initiation, at months 1, 3, 6, 9 and 12, or at the last follow-up.ResultsOf the 11 patients enrolled, 91.0% (10/11) had previously received treatment with tocilizumab. The mean duration of canakinumab was 9 (3–18) months. 45.5% (5/11) of patients showed complete response, 45.5% (5/11) showed partial response, and 9.0% (1/11) showed no response. 18.2% (2/11) experienced disease flare during the treatment with canakinumab. 81.8% (9/11) of patients successfully reduced the dose of corticosteroids, with six discontinuing corticosteroids. 45.6% (5/11) of patients experienced infection. No serious adverse events occurred during the treatment with canakinumab.ConclusionsCanakinumab may be effective and tolerable for Chinese sJIA patients, helping to reduce the dosage of corticosteroids. However, additional researches on large samples are required to evaluate its efficacy and safety.

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Section: Discussionmentioning

confidence: 99%

Canakinumab in the treatment of systemic juvenile idiopathic arthritis: a retrospective single center study in China

Zhu,

Weng,

Huang

et al. 2024

Front. Pediatr.

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“…Some researchers reasonably expect that the frequency of MAS in sJIA can be potentially reduced through treatment with IL-1 blockades [ 11 ]. Kostik et al [ 32 ] reported on eight patients with sJIA who developed MAS that was resolved by a short-term increase in canakinumab doses in all patients. In our study, three patients experienced four MAS events in the past, however, none developed MAS during canakinumab treatment.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of canakinumab in systemic juvenile idiopathic arthritis, the first Chinese experience

Qiu,

Ma,

Xie

et al. 2024

Pediatr Rheumatol

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Background Systemic juvenile idiopathic arthritis (sJIA) is a severe form of juvenile arthritis that is characterized by chronic joint inflammation and systemic symptoms such as fever, rash, and organ involvement. Anti-IL-6 receptor monoclonal antibody tocilizumab is an effective treatment. However, some patients still experience persisting or recurrent symptoms and the real-world effectiveness of canakinumab in Chinese patients with sJIA has never been reported. Therefore, this study aimed to assess the efficacy and safety of canakinumab in Chinese patients with sJIA using real-world data. Methods We conducted a retrospective study on children with active sJIA. Clinical features, laboratory data, corticosteroid dosage, and adverse events (AEs) were collected at baseline and at 4, 8, 12, and 24 weeks after initiating canakinumab treatment. Results Seven female and four male patients were included in the study. All patients had previously been treated with tocilizumab and were administered canakinumab for 12.4 ± 3.4 months. Notably, significant improvements were observed in both clinical signs and symptoms as well as laboratory indicators. Four children under corticosteroid treatment were able to successfully discontinue their corticosteroid therapy: one at week 4, two at week 12, and one at week 24. Notably, there was a significant reduction in the number of tender and swollen joints (P = 0.0059) as well as the systemic juvenile arthritis disease activity score (P < 0.0001). The most common AE was infection, but no patients experienced serious AEs. No cases of macrophage activation syndrome or death were reported during the follow-up period. Conclusions Canakinumab was found to be potentially efficacious and safe in Chinese patients with sJIA. No new AEs were observed with canakinumab treatment.

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“…Several patients had the dose of canakinumab increased and they experienced the resolution of MAS. And there were no notable short-term adverse events (160). In a case-based review of Deniz Gezgin Yıldırım et al, a case that did not respond to anakinra but well responded to canakinumab was reported (161).…”

Section: Il-1mentioning

confidence: 99%

Advances in attractive therapeutic approach for macrophage activation syndrome in COVID-19

et al. 2023

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Nowadays, people have relaxed their vigilance against COVID-19 due to its declining infection numbers and attenuated virulence. However, COVID-19 still needs to be concern due to its emerging variants, the relaxation of restrictions as well as breakthrough infections. During the period of the COVID-19 infection, the imbalanced and hyper-responsive immune system plays a critical role in its pathogenesis. Macrophage Activation Syndrome (MAS) is a fatal complication of immune system disease, which is caused by the excessive activation and proliferation of macrophages and cytotoxic T cells (CTL). COVID-19-related hyperinflammation shares common clinical features with the above MAS symptoms, such as hypercytokinemia, hyperferritinemia, and coagulopathy. In MAS, immune exhaustion or defective anti-viral responses leads to the inadequate cytolytic capacity of CTL which contributes to prolonged interaction between CTL, APCs and macrophages. It is possible that the same process also occurred in COVID-19 patients, and further led to a cytokine storm confined to the lungs. It is associated with the poor prognosis of severe patients such as multiple organ failure and even death. The main difference of cytokine storm is that in COVID-19 pneumonia is mainly the specific damage of the lung, while in MAS is easy to develop into a systemic. The attractive therapeutic approach to prevent MAS in COVID-19 mainly includes antiviral, antibiotics, convalescent plasma (CP) therapy and hemadsorption, extensive immunosuppressive agents, and cytokine-targeted therapies. Here, we discuss the role of the therapeutic approaches mentioned above in the two diseases. And we found that the treatment effect of the same therapeutic approach is different.

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Standard and increased canakinumab dosing to quiet macrophage activation syndrome in children with systemic juvenile idiopathic arthritis

Cited by 12 publications

References 27 publications

Canakinumab in the treatment of systemic juvenile idiopathic arthritis: a retrospective single center study in China

Canakinumab in the treatment of systemic juvenile idiopathic arthritis: a retrospective single center study in China

Efficacy and safety of canakinumab in systemic juvenile idiopathic arthritis, the first Chinese experience

Advances in attractive therapeutic approach for macrophage activation syndrome in COVID-19

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