Table A1.

(A) Therapeutic approaches targeting effector IgE⁺ and IgE producing cells. Randomised Control Trial (RCT), Adverse Event (AE). (B) Therapeutic approaches targeting effector IgE⁺ and IgE producing cells. Randomised Control Trial (RCT), Adverse Event (AE).

A	Approach	Biological Effect	Study Design	Disease Target	Subjects	Length of Observation	Outcome	Current Phase	References
Strategies targeting IgE	Immuno adsorption	Removal of circulating IgE or total Ig through Plasmapheresis	RCT	Allergic Asthma	N = 15	16 weeks	↓Total IgE ↓ basophil activation	Pre-Clinical	[13]
			RCT	Atopic Dermatitis	N = 50	8 weeks	Less AE in IgE group vs pan Ig	Pre-Clinical	[20]
	Omalizumab	Monoclonal antibody against Fc portion of IgE—prevents receptor binding	RCT	Allergic Asthma	N = 317	20 weeks	↓IgE ↓Steroid use	Marketed	[17]
	CMAB007	Biosimilar to Omalizumab developed by China	RCT	Allergic Asthma	N = 400	24 weeks	Not yet completed	Phase III NCT03468790	[163]
	DARPins	Ankyrin repeat domains that affect stability and function of target protein	In vitro study	Allergy	Isolated basophils	N/A	Removal of IgE from basophils + ↓ basophil activation	Pre-Clinical	[168]
	MEDI4212	Monoclonal antibody against Fc portion of IgE—prevents receptor binding	RCT	Allergy/Atopy	N = 86	12 weeks	Greater ↓total IgE vs Omalizumab worse half life	Phase I NCT01544348	[166]
	MEDI4212 Variant	Monoclonal antibody against Fc portion of IgE and Fc potion of monoclonal antibody binds to inhibitory receptor FcγRIIIa on B-cells	In vitro study	Allergy	Cell lines and human B cells	N/A	Elimination of IgE expressing B cells	Pre-Clinical	[178]
	IgE Peptide Vaccine	Induction of autoantibodies against Fc region of IgE	In vitro study	Allergy	FcεRI–ELISA	N/A	Autoantibodies block IgE binding to FcεRI	Pre-Clinical	[171]
	QGE031 (Ligelizumab)	Monoclonal antibody against Fc portion of IgE—prevents receptor binding	RCT	Allergic Asthma	N = 37	10 weeks	QGE031 > Omalizumab	Phase II NCT01703312	[164]
B	Approaches	Biological Effect	Study Design	Disease Target	Subjects	Length of Observation	Outcome	Current Trail Phase	References
Strategies targeting IgE production or effector cells	Quilizumab	Monoclonal antibody targeting M1-prime segment of membrane bound IgE expressed on IgE switched B cells leading to cell depletion	RCT	Allergic Asthma	N = 578	36 weeks with 48 week safety follow-up	Acceptable safety and reduced serum IgE but no clinically meaningful benefit in clinical outcome parameters	Phase II NCT01582503	[23]
	DARPins	Ankyrin repeat domains that affect stability and function of target protein	In vitro study	Allergy	Human basophils	N/A	Targets FcγIIB and inhibits basophil degranulation	Pre-Clinical	[169]
	Bsc-IgE/CD3 Construct	Monoclonal antibody binding to cells with membrane bound IgE and targets T-cell cytotoxic activity towards them	In vitro study	Allergy	Cells isolated from allergic human donors	N/A	Bsc-IgE/CD3 effective at eliminating IgE+ B cells without inducing degranulation of mast cells	Pre-Clinical	[176]
	Anti-FcεRI Fab-conjugated celastrol-loaded micelles	Fusion with cell membrane and induction of apoptosis of FcεRI expressing cells	In vitro study	Allergy	Mast cell line	N/A	Efficient induction of apoptosis of mast cells and reduction of allergic inflammation in mouse model	Pre-Clinical	[21]
	CTLA4Fcε Fusion Protein	Binds FcεRI and CD23, prevents CD23 cleavage, and blocks CD80/CD86 costimulation	In vitro study	Allergy	Cell line and human PBMC samples	N/A	Reduces sCD23 and lymphocyte proliferation	Pre-Clinical	[22]
	Maternal Anti-IgE Vaccination	IgG anti IgE antibodies transferred from mother to fetus and prevent onset of allergy by targeting IgE memory B cells	In vivo mouse study	Allergy	N/A	9 weeks after birth	Reduced IgE levels in mouse offspring	Pre-Clinical	[180]