Table 3.

Relevant clinical trials in HES, EGPA, and CRSwNP.

Author	Year	Study design	Condition	Study population	Drug	Dose	Primary outcome	Secondary outcome
Rothenberg39	2008	Multicenter RDBPC	HES	-85 patients with PDGFRA negative HES (defined as AEC >1500/μl for ≥6 months with organ involvement and no secondary cause requiring 20–60 mg prednisone)	Mepolizumab	750 IV every 4 weeks for 32 weeks	-Reduction of prednisone dose to ≤10 mg for ≥8 consecutive weeks	-AEC <600/μL ≥8 consecutive weeks -Time to treatment failure -Prednisone dose <7.5 mg -No prednisone use for 1+ days -Mean prednisone dose at week 36 -Prednisone dose ≤10 mg by week 20 AND for ≥8 consecutive weeks
Roufosse41	2020	Phase 3 multicenter RDBPC	HES	108 patients age 12+ with PDGFRA negative HES with ≥2 flares in previous year with AEC >1000/μl	Mepolizumab	-300 mg SC every 4 weeks for 32 weeks	-Proportion who had flare - Flare definition: 1) HES related clinical manifestation with increase in prednisone by ≥ 10 mg for 5 days or any increase/addition of additional HES therapy 2) Receipt of ≥2 blinded steroid courses given if AEC increased above pre-defined level	-Time to first flare -Proportion with flare during weeks 20–32 -Annualized rate of flares -Change in fatigue severity (BFI score) at week 32
Kuang42	2019	-Phase 2 single center trial -RDBPC for 12 weeks -Open label for 12 weeks -Open label extension for 24 weeks	HES	20 patients with symptomatic PDGFRA negative HES and AEC >1000-μl	Benralizumab	-30 mg SC every 4 weeks for 12 weeks -At week 12 all patients received 30 mg SC every 4 weeks -At week 24 patients with clinical or laboratory response could continue benralizumab	-% of patients with 50% reduction in AEC at week 12	-Reduction in AEC at 12 weeks -Adverse events -Changes in bone marrow and tissue eosinophilia -Reductions in concomitant therapy at week 48
Wechsler45	2017	Phase 3 multicenter RDBPC	EGPA	-136 patients age 18+ with relapsing or refractory EGPA on 7.5–50 mg prednisone at stable dose	Mepolizumab	-300 mg SC every 4 weeks for 52 weeks	-Accrued weeks of remission (BVAS 0 plus ≤4 mg prednisone) over 52 weeks -Proportion of patients in remission at weeks 36 and 48	-Time to first relapse -Average prednisone dose during weeks 48–52 -Proportion of patients with remission within first 24 weeks
Han49 (SYNAPSE)	2021	Phase 3 multicenter RDBPC	CRSwNP	-407 patients with severe bilateral nasal polyposis	Mepolizumab	-100 mg SC every 4 weeks for 52 weeks -All patients treated with intranasal mometasone	-Total endoscopic nasal polyp score at week 52 -Nasal obstruction VAS score during weeks 49–52	-% requiring surgery -Overall VAS score during weeks 49–52 -SNOT-22 at week 52 -% needing systemic steroids -Anosmia at weeks 49–52 -Composite VAS score at weeks 49–52
Bachert50 (OSTRO)	2021	Phase 3 multicenter RDBPC	CRSwNP	-413 patients with severe bilateral nasal polyposis	Benralizumab	-30 mg SC every 4 weeks for 12 weeks then every 8 weeks for 48 weeks total	-Total endoscopic nasal polyp score at week 40 -Nasal obstruction VAS score at week 40	-SNOT-22 at weeks 40 and 56 -Time to first surgery -% requiring surgery -% requiring systemic steroids -Time to first use, total duration, and number of courses of systemic steroids -DSS score -CT scan scores

Abbreviations: HES, hypereosinophilic syndrome; PDGFRA, platelet derived growth factor A; AEC, absolute eosinophil count; FEV1, forced expiratory volume in 1 s; RDBPC, randomized double-blind placebo controlled; CUP, compassionate use protocol; SC, subcutaneous; BFI, Big Five Inventory; EGPA, eosinophilic granulomatosis with polyangiitis; CBC, complete blood count; ESR, erythrocyte sedimentation rate; CRP, c-reactive protein; FeNO, fraction of exhaled nitric oxide; ACQ, Asthma Control Questionnaire; BVAS, Birmingham Vasculitis Activity; CRSwNP, chronic rhinosinusitis with nasal polyposis; PIF, peak inspiratory flow; AEC, absolute eosinophil count; VAS, visual analog scale; SNOT-22, Sino-Nasal Outcome Test 22; PFT, pulmonary function test; SC, subcutaneous; DSS, Difficulty with Sense of Smell; IV, intravenous Score; SC, subcutaneous; AEC, absolute eosinophil count; RDBPC, randomized, double-blind, placebo-controlled; SEA, severe eosinophilic asthma; ACT, Asthma Control Test; AQLQ, Asthma Quality of Life Questionnaire; SNOT-22, Sino-Nasal Outcome Test 22