Table 2.

sHLH/MAS therapeutics reported in the literature.

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
		Methylprednisolone, Glucocorticoid, Cyclosporine A, Anakinra	sJIA	Prednisone, Thrombophlebitis	↑Fever, ↑Ferritin, ↓PLT, ↑AST, ↑ALT, ↑TG, ↓Fibrinogen	Improvements in all MAS biomarkers	101
IL-2	Daclizumab	Corticosteroids	HLH	-	↑Fever, ↑Ferritin, ↓WBC, ↓PLT, ↑AST, ↑ALT	Fever/Ferritin normal range	102
IL-6	Tocilizumab	Methotrexate, Prednisolone, Cyclosporine, Omalizumab, Anakinra	AOSD, HLH	EBV, Dexamethasone	↑Fever, ↑Ferritin, ↑Leukocytosis, ↓PLT, ↑AST, ↑TG, ↓ Fibrinogen	AOSD and idiopathic urticaria nonrecurrence	103
		Prednisolone, Ganciclovir, Sulfamethoxazole, Trimethoprim	AOSD	Prednisolone, Sulfamethoxazole, Trimethoprim, CMV	↑Fever, ↑Hepatomegaly, ↑Ferritin, ↓PLT, ↑AST, ↑ALT, ↑TG, ↓ Fibrinogen	Fever/skin rash improvement	104
IFN-γ	Emapalumab	Tocilizumab, Anakinra, Prednisolone, Corticosteroids, Alemtuzumab	sJIA	Parainfluenza 3 virus, Anakinra,	↑Fever, ↑Hepatomegaly, ↑Splenomegaly, ↑Ferritin, ↓WBC, ↓PLT, ↑AST, ↑ALT, ↑TG, ↑sCD25	Inflammatory marker/Ferritin/CXCL9 improvement	105
		Prednisolone, Methylprednisolone, Anakinra, Corticosteroids, Dexamethasone, Acyclovir, Fluconazole	AOSD	Prednisolone, Methylprednisolone, Anakinra	↑Fever, ↑Splenomegaly, ↑Ferritin, ↓PLT, ↑AST, ↑ALT, ↑TG, ↑Fibrinogen, ↑sCD25	Ferritin/PLT/Fibrinogen/TG improvement	106
		Etoposide, Dexamethasone, Rituximab, IVIG	HLH	EBV	↑Fever, ↑Hepatomegaly, ↑Splenomegaly, ↓WBC, ↓PLT, ↑Ferritin, ↓Fibrinogen, ↑sCD25,	Clinical symptom/ Ferritin/sCD25 level improvement	17
		Canakinumab, Sulfamethoxazole Methylprednisolone, Trimethoprim	sJIA	EBV	↑Fever, ↓PLT, Neutropenia, Lymphopenia, ↑Ferritin, ↑AST, ↓Fibrinogen,	Cytopenia/hypofibrinogenemia improvement	61
TNF-α	Etanercept	Ibuprofen, Solumedrol, Steroid, Prednisolone	sJIA	Ibuprofen	↑Fever, ↑Hepatomegaly, ↑Splenomegaly, ↑WBC, ↓PLT, ↑Ferritin, ↓PLT, ↑TG, ↓ Fibrinogen	Fever/Chest pain/Rash improvement	107
		Etoposide, Methylprednisolone, Prednisolone, Tacrolimus, MTX, Infliximab	AOSD	Prednisolone	↑Fever, ↑Ferritin, ↑WBC, ↓PLT, ↑AST, ↑TG, ↑Fibrinogen, ↑sCD25	Fever and polyarthralgia improvement	108
	Infliximab	IVIG, Acetylsalicylic acid, Methylprednisolone, Cyclosporine A	KD	IVIG, Acetylsalicylic acid	↑Fever, ↑Hepatomegaly, ↑Splenomegaly, ↑Ferritin, ↓PLT, ↑AST, ↑TG, ↓ Fibrinogen	Hepatomegaly/Splenomegaly/Clinical and Biochemical parameter improvement	109
		Dexamethasone, Etoposide, Infliximab, Daclizumab,	HLH	EBV, CMV, HHV6	↑Fever, ↑Hepatomegaly, ↑Splenomegaly, ↓WBC, ↓PLT, ↑Ferritin, ↑sCD25, ↑TG, ↑AST, ↑ALT,	Clinical symptom improvement	110
JAK 1/2	Ruxolitinib	Prednisolone, Tocilizumab Methylprednisolone, Anakinra,	AOSD	–	↑Fever, ↑Hepatomegaly, ↑Ferritin, ↓PLT, ↑AST, ↑TG, ↓ Fibrinogen	Blood counts/Ferritin/CD25 levels normal range	111
	Baricitinib	Glucocorticoid, Immunoglobulin, Cyclophosphamide, MTX, Prednisolone	Nodular panniculitis, HLH	Prednisolone	↑Fever, ↑Hepatomegaly, ↑Splenomegaly, ↑Ferritin, ↓PLT, ↑AST, ↑TG, ↓ Fibrinogen, ↑sCD25	Abnormal laboratory all improvement	112
CD20	Rituximab	Metronidazole, Etoposide, Cyclosporine, Dexamethasone	SLE	–	↑Fever, ↑Splenomegaly, ↓WBC, ↓PLT, ↑Ferritin, ↓PLT, ↑AST, ↑TG, ↓ Fibrinogen	Blood counts/Ferritin/TG all normal range	113
		Methylprednisolone, Prednisone, Tacrolimus, Cyclosporine A	DM	Methylprednisolone	↑Fever, ↑AST, ↑ALT, ↓WBC, ↓PLT, ↑Ferritin	Pancytopenia improvement	114
		Methylprednisolone, Immunoglobulin, rituximab, Prednisolone	XLP	EBV	↑Fever, ↑Hepatomegaly, ↑Splenomegaly ↑WBC, ↑AST	Clinical symptom improvement	65
CD28	Abatacept	Anakinra, MTX, Corticosteroids, Methylprednisolone, IVIG, Cyclosporine	sJIA	Anakinra, Corticosteroids	Development of chronic low-grade MAS with concurrent cutaneous vasculitis	Fever improvement, ESR normal range	115