Table 2.

Summary of findings from included studies of crizanlizumab (Adakveo).

Source (Country)	Outcome Measured	Study Design	Age, Years	Group, n	Summary of Findings
Clinical Efficacy
Ataga 2017, USA	Primary: rate of sickle-cell pain crises Secondary: hospitalizations, time to first and second hospitalizations, annual rates of uncomplicated crises, ACS, patient-reported outcomes	RCT (SUSTAIN trial)	Median 29, range 16–63	198	-Median rate of crises 1.63 with high-dose vs. 2.98 with placebo (45.3% lower, p = 0.01) -Median time to first crisis longer with high-dose crizanlizumab than with placebo (4.07 vs. 1.38 months, p = 0.001) -Median time to second crisis longer (10.32 vs. 5.09 months, p = 0.02) -Median rate of uncomplicated crises per year 1.08 with high-dose crizanlizumab, 2.91 with placebo (62.9% lower, p = 0.02) -Adverse events in 10% of either active treatment group and at least twice than in the placebo group: arthralgia, diarrhea, pruritus, vomiting, and chest pain
Ataga 2019, USA	Annual rate of hospitalization, time to first hospitalization	Post hoc of SUSTAIN data	Median 29, range 16–63	198	-46% of patients in treatment group were not hospitalized vs. 35% in placebo arm -54% in treatment group had ≥1 hospitalization vs. 65% in placebo arm -Median time to first hospitalization 6.3 in treatment vs. 3.2 months
Kutlar 2019, USA	Secondary endpoints of SUSTAIN	Post hoc of SUSTAIN data	Median 29, range 16–63	198	- % with no crises: 35.8% in 5/kg group crisis-free, 18.2% in 2.5 mg/kg, and 16.9% in placebo ○ 5–10 crises in last year: 28.0% vs. 4.2% ○ HbSS: 31.9% vs. 17.0% ○ Taking HU: 33.3% vs. 17.5% - In almost all subpopulations, crizanlizumab 5.0 mg/kg significantly (p < 0.05) increased time to first event by 2× or greater ○ 5–10 crises: 2.43 vs. 1.03 months (HR 0.47) ○ HbSS genotype: 3.7-fold increase (4.07 vs. 1.12 months; HR: 0.50) ○ HU use: 2.43 vs. 1.15 (HR 0.58)
Smith 2020, USA	Days of opioid use	Post hoc of SUSTAIN data	Median 29, range 16–63	198	-Absolute reduction of 4 days of opioid use in crizanlizumab vs. placebo (relative reduction: 57%, p = 0.162) -Reduction in IV use: absolute reduction 2.01 days (relative reduction: 50%, p = 0.047)
Shah 2019, USA	Pain crises events, treatment patterns, health care resources	Retrospective cohort review of SUSTAIN 1 year following study	≥18 years old, median 37	6	-Patients with placebo: 4 VOC events, w/2.5/kg: 5, with 5/kg: 0–2 -4 patients with HU use during and after -All used opioids after -2 patients had transfusions -5 used healthcare resources, 1 did not and had 0 VOC events
Side Effects and Prescribing Data
Kanter 2019, USA	Safety, side effects	Pooled Phase 2 trial data (SUSTAIN + SOLACE-adults) SUSTAIN: RCT SOLACE-adult: PK/PD	Median 29, range 16–65	111 (SUSTAIN n = 66, SOLACE n = 45)	-84.7% had ≥1 adverse event -21.6% had serious AEs, 5.4% thought to be due to crizanlizumab -Headache (19.8%), nausea (16.2%), back pain (15.3%) most common -25.2% discontinued treatment prematurely -45.9% had infection: 11.7% URI, 9.9% UTI -1.8% infusion-related reaction -No clinically relevant laboratory (hematology, biochemistry, liver) or ECG abnormalities, or vital sign changes
Kanter 2021, USA	Insurance approval, adherence	Retrospective multi-center review	≥16	297 prescribed, 238 received infusion	-12% denied by insurance -32% discontinued therapy -64% do not automatically use pre-medications -Reasons for discontinuing: lack of improvement or feeling pain was increased, transportation issues, infusion pain
Kanter 2021, USA	Infusion-related reaction	Retrospective review of safety database	Median 23 (range 16–38)	28	-From Novartis database, 28 patients had infusion-related reaction presenting as pain event, RR of 1.67 cases per 100 point-years -86% experiences at 1st or 2nd infusion, majority recovered within 3 days -6 (21%) had reactions on subsequent infusions -71% were hospitalized for further treatment, 32% reported SCD complications after reaction (ACS, fat embolism, hemolytic crisis, pneumonia, multi-organ failure) -82% had crizanlizumab discontinued after reaction occurrence
Li 2021, USA	Side effects	Case report	20 and 48	2	-2 patients developed acute febrile painful episodes on 2nd infusion of crizanlizumab despite pre-medications