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تعداد آیتم قابل مشاهده باقیمانده : 3 مورد

Therapeutic options for macrophage activation syndrome in the setting of systemic juvenile idiopathic arthritis

Therapeutic options for macrophage activation syndrome in the setting of systemic juvenile idiopathic arthritis
Drug Dose Therapeutic considerations
First-line therapies
Glucocorticoids[1]

High (pulse) dosing: methylprednisolone = 30 mg/kg/day (maximum 1 g/day) IV for 1 to 3 days, followed by moderate dosing

Moderate dosing:
  • Oral prednisone or prednisolone, or IV methylprednisolone, dosed at 1 to 2 mg/kg/day (maximum 80 mg/day) divided every 12 hours
  • or
  • Oral or IV dexamethasone dosed at 10 mg/m2/day (maximum 40 mg/day) divided every 12 hours

Choice of glucocorticoid should be determined based on the patient, care setting, and provider experience.

Dexamethasone has better penetration into the central nervous system and a longer half-life.
Anakinra (IL-1 inhibitor)[1] 5 to 10 mg/kg/day in divided doses (every 6 or every 12 hours), IV (preferred) or SUBQ  
Second-line therapies
Cyclosporine, modified[1,2] Enteral administration (preferred):
  • Pediatric: 3 to 5 mg/kg/day orally, divided every 12 hours
  • Adult: 2 to 7 mg/kg/day orally, divided every 12 hours

Intravenous administration: 3 to 5 mg/kg/day IV, divided every 12 hours

Requires monitoring for drug levels and dose titration to target trough concentrations.

Notable adverse drug effects include kidney toxicity and hypertension.

When converting from oral to IV, FDA labeling suggests initiating IV at approximately one-third of the total daily oral dose
Emapalumab (IFNG neutralizer)[1] 6 mg/kg/dose once, then 3 mg/kg/dose every 3 days

Antifungal, HZV, and PJP prophylaxis and TB screening are required.*

Approved by the FDA for use in patients with refractory primary HLH.
Etoposide[1] 50 to 100 mg/m2/dose IV every week Antifungal and PJP prophylaxis are required.*
Intravenous immunoglobulin[1]

Pediatric dosing: 2 g/kg IV once or 1 g/kg/day for 2 days

Adult dosing: 0.4 to 1 g/kg IV once a day for 2 to 5 days		 May be helpful in situations where empiric immunomodulation is required during ongoing evaluation, and/or when there is a suspected concurrent infection. Must be used with other immunomodulating therapies (eg, anakinra).
Ruxolitinib (JAK inhibitor) (patients ≥12 years)[1] 0.5 mg/kg/dose orally or 25 mg/m2/dose orally, given twice daily

Antifungal and PJP prophylaxis are required.

Various dosing regimens under investigation for treatment of HLH.
Tacrolimus immediate-release[2]

Enteral administration (preferred): 0.1 mg/kg/day orally or sublingually, divided every 12 hours

Intravenous administration: 0.01 to 0.05 mg/kg/day as a continuous IV infusion over 24 hours

Requires monitoring for drug levels and dose titration to target trough concentrations.

Risk of anaphylaxis, kidney toxicity, and neurotoxicity with IV administration.
Tocilizumab (IL-6 inhibitor) Subcutaneous administration (dose based on patient weight):
  • <30 kg: 162 mg/dose SUBQ once every 2 weeks
  • ≥30 kg: 162 mg/dose SUBQ once every week

Intravenous administration (dose based on patient weight):

  • <30 kg: 12 mg/kg/dose IV once every 2 weeks
  • ≥30 kg: 8 mg/kg/dose IV once every 2 weeks (maximum 800 mg/dose)
 Dose regimen established in treatment of sJIA without MAS.
To be used with UpToDate content on the treatment of sJIA and MAS. NOTE: Treatment should be performed by clinicians who are experienced in the use, monitoring, adjustment, and drug interactions of these agents because of the potential toxicity of these drugs/combinations and the unpredictability of the disease. Dosing in this table is intended for children ≥2 years (except where noted) and adolescents with normal kidney and liver function.

FDA: US Food and Drug Administration; HLH: hemophagocytic lymphohistiocytosis; HZV: herpes zoster virus; IL: interleukin; IFNG: interferon gamma; IV: intravenous; JAK: janus kinase; MAS: macrophage activation syndrome; PJP: Pneumocystis jirovecii pneumonia; sJIA: systemic juvenile idiopathic arthritis; SUBQ: subcutaneous; TB: tuberculosis.

* Consider early consultation with infectious diseases specialist for infection screening and prophylaxis.
References:
  1. Shakoory B, Geerlinks A, Wilejto M, et al. The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS). Arthritis Rheumatol 2023; 75:1714.
  2. Halyabar O, Chang MH, Schoettler ML, et al. Calm in the midst of cytokine storm: a collaborative approach to the diagnosis and treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Pediatr Rheumatol Online J 2019; 17:7.
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