Successful treatment of refractory hyperferritinemic syndromes with canakinumab: a report of two cases

Papa, Riccardo; Natoli, Valentina; Caorsi, Roberta; Minoia, Francesca; Gattorno, Marco; Ravelli, Angelo

doi:10.1186/s12969-020-00450-9

Cited by 9 publications

(6 citation statements)

References 26 publications

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“…There are also significant differences in pharmacokinetics, half-lives, and binding affinity. 5 The introduction of canakinumab provided a rapid reduction in nocturnal fevers within weeks. There was also a dramatic improvement in proteinuria from 3.4 g/day before canakinumab use to 0.2 g/ day observed within months of instituting this medication.…”

Section: Discussionmentioning

confidence: 99%

Case report on the use of canakinumab for treatment of recurrent fevers and proteinuria in refractory systemic lupus erythematosus

Yavari,

Grisanti

2023

Therapeutic Advances in Rare Disease

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Systemic lupus erythematosus (SLE) is a chronic multiorgan autoimmune disease with a wide range of clinical manifestations and a characteristic renal involvement leading to proteinuria. There remains an unmet need in SLE disease management as standard treatments including anti-inflammatory drugs, corticosteroids, antimalarial agents, and immunosuppressant therapies are not always effective in moderating disease activity. We report a 41-year-old Caucasian female patient with a 12-year history of SLE complicated by debilitating nocturnal fevers and WHO Class IV lupus nephritis who for years was refractory to standard therapies but improved dramatically with canakinumab, an interleukin-1β (IL-1β)antagonist. This is the first case of the use of canakinumab in SLE. The standard interventions demonstrated no significant impact on her proteinuria (>3 g/24 h), joint complaints, and nocturnal fevers. Additionally, her anti-dsDNA levels remained elevated, and her kidney function did not improve significantly. In contrast, the introduction of canakinumab provided a rapid reduction in nocturnal fevers within 6 weeks (i.e. decreased in frequency by 90%). Her proteinuria has also dropped from 3.5 g/24 h to 0.274 g/24 h, and her prednisone has been tapered and discontinued. In addition, her renal function has improved with an average glomerular filtration rate (GFR) level of 84.14 ± 7.56. There has also been a significant decrease in both erythrocyte sedimentation rate (ESR) and anti-dsDNA levels compared with the previous treatments. We report that canakinumab could potentially represent the next step in SLE patients’ treatment who have failed conventional therapies or who are intolerant to them. In this case, the addition of canakinumab facilitated the tapering and ultimately discontinuing of corticosteroids. This case represents the first successful use of canakinumab in the treatment of refractory fevers and diffuse proliferative glomerulonephritis in SLE.

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Section: Discussionmentioning

confidence: 99%

Case report on the use of canakinumab for treatment of recurrent fevers and proteinuria in refractory systemic lupus erythematosus

Yavari,

Grisanti

2023

Therapeutic Advances in Rare Disease

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“…Currently, there are limited data regarding the use of canakinumab and rilonacept for treating MAS in the setting of sJIA ( 23 – 25 ). Indeed, there are only a few cases of MAS reported to occur during or after canakinumab treatment of sJIA in randomized controlled trials ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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ObjectiveMacrophage activation syndrome (MAS) is a life-threatening, potentially fatal condition associated with systemic juvenile idiopathic arthritis (sJIA). Interleukin-1 (IL-1) is a key cytokine in the pathogenesis of sJIA MAS. Many cases of MAS are medically refractory to traditional doses of biologic cytokine inhibitors and may require increased dosing. When MAS occurs in the setting of sJIA treated with the IL-1 receptor antagonist (IL-1Ra), anakinra, increased anakinra dosing may be beneficial. Increased dosing of another IL-1 inhibitor, canakinumab, a monoclonal antibody to IL-1β, has not been reported to treat refractory MAS in the setting of sJIA.MethodsRetrospective data collection extracted from the electronic medical record focused on canakinumab usage and dosing in 8 children with sJIA who developed MAS at a single academic center from 2011 to 2020.ResultsEight sJIA children (five girls) with median age 8.5 years (range, 0.9–14.2 years) were included in the present study. Five children developed MAS at disease onset and three during ongoing canakinumab therapy. MAS resolved in all eight children with canakinumab treatment. When the canakinumab dosing was insufficient or MAS developed during canakinumab therapy, the dosing was temporally up-titrated (four patients, maximum 300 mg per dose) without observed side effects.ConclusionThis report provides evidence for the efficacy and safety of short-term increased doses (2–3-times normal) of canakinumab in treating sJIA associated MAS. Further study of the efficacy and safety of increased doses of canakinumab for treatment of MAS in children with sJIA is warranted.

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“… Target Drugs Combined drugs Condition Trigger Clinical and laboratory criteria Results Ref. IL-1 Anakinra Methylprednisolone, Ciclosporin, Prednisolone sJIA Methylprednisolone ↑Fever, ↑Splenomegaly, ↑Ferritin, ↓PLT, ↑AST, ↑Fibrinogen, ↑sCD25 Ferritin/PLT/AST/Fibrinogen normal range 95 IVIG, Aspirin, Infliximab, Methylprednisolone, Prednisolone KD, HLH Methylprednisolone, Prednisolone ↑Ferritin, ↑WBC, ↑PLT, ↑AST, ↑ALT, ↑TG Inflammatory marker recovery 96 Methylprednisolone, Ciclosporin, Prednisolone, Dexamethasone AOSD, HLH Methylprednisolone ↑Fever, ↑Hepatomegaly, Cervical lymphadenopathy, ↑Neutrophilic leukocytosis, ↑Ferritin, ↑AST, ↑TG, ↑Hematopoietic cells Ferritin/Inflammatory marker improvement 97 Methylprednisolone, Corticosteroids, Tocilizumab AOSD, HLH Anakinra (100 mg/day), Methylprednisolone, Tocilizumab ↑Fever, ↑Hepatomegaly, ↑Splenomegaly, ↑Ferritin, ↓PLT, ↑AST, ↑ALT, ↓Leucocyte count, lymphopenia, ↑Hematopoietic cells Ferritin/systemic inflammation and cytolysis improvement 98 Methylprednisolone, Infliximab, Prednisolone, MTX, Dexamethasone sJIA Infliximab, Prednisolone, MTX ↑Fever, ↑Splenomegaly, ↑Ferritin, ↓PLT Ferritin/WBC/PLT normal range 99 Prednisone, Adalimumab axSpA Adalimumab ↑Fever, ↑Splenomegaly, Lymphopenia, ↓PLT, ↑AST, ↑ALT, ↑Ferritin ESR/CRP/ferritin/fibrinogen/inflammatory marker improvement 100 Canakinumab Prednisone, Methylprednisolone, Anakinra, Cyclosporine A sJIA Prednisone, Methylprednisolone, Anakinra ↑Fever, ↑Ferritin, ↑PLT, ↑AST, ↑TG, ↑Fibrinogen Ferritin decrease, AST normal range 101 ...…”

Section: Immunopathology Of and Potential Therapeutics For Shlh/masmentioning

confidence: 99%

Immunopathology of and potential therapeutics for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a translational perspective

Nguyen,

Kim,

Jeong

et al. 2024

Exp Mol Med

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Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a life-threatening immune disorder triggered by rheumatic disease, infections, malignancies, or medications. Characterized by the presence of hemophagocytic macrophages and a fulminant cytokine storm, sHLH/MAS leads to hyperferritinemia and multiorgan failure and rapidly progresses to death. The high mortality rate and the lack of specific treatments necessitate the development of a new drug. However, the complex and largely unknown immunopathologic mechanisms of sHLH/MAS, which involve dysfunction of various immune cells, diverse etiologies, and different clinical contexts make this effort challenging. This review introduces the terminology, diagnosis, and clinical features of sHLH/MAS. From a translational perspective, this review focuses on the immunopathological mechanisms linked to various etiologies, emphasizing potential drug targets, including key molecules and signaling pathways. We also discuss immunomodulatory biologics, existing drugs under clinical evaluation, and novel therapies in clinical trials. This systematic review aims to provide insights and highlight opportunities for the development of novel sHLH/MAS therapeutics.

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Successful treatment of refractory hyperferritinemic syndromes with canakinumab: a report of two cases

Cited by 9 publications

References 26 publications

Case report on the use of canakinumab for treatment of recurrent fevers and proteinuria in refractory systemic lupus erythematosus

Case report on the use of canakinumab for treatment of recurrent fevers and proteinuria in refractory systemic lupus erythematosus

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

Immunopathology of and potential therapeutics for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a translational perspective

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