In the SUSTAIN clinical trial, infusion-related reactions (defined as occurring within 24 hours of infusion) were observed in 2 (3%) patients treated
The subgroup analyses should be interpreted with caution because the data are from a prespecified, noncomparative subgroup analysis of the primary end point and are not powered to detect statistical significance or superiority of ADAKVEO over placebo.3
ITT, intent to treat; HL, Hodges-Lehmann; CI, confidence interval; ER, emergency room.
*Annual rate of VOCs leading to a health care visit (ER, clinic, hospital, or local physician visit).1,4
The key secondary end point in the SUSTAIN study was defined as the annual rate of days a patient was hospitalized, including those related to VOCs. The range of days hospitalized for the ADAKVEO and placebo population was 0 to 131 days and 0 to 307 days, respectively.3
A patient was considered to not have experienced a VOC if the annualized VOC rate was zero, whether or not the patient completed the 12-month treatment period.2,3
An early separation of the time to first VOC was observed at Week 2 with ADAKVEO.
Time to first VOC
These analyses should be interpreted with caution as the data are from a noncomparative post hoc subgroup analysis and not powered to detect statistical significance or superiority of ADAKVEO over placebo.
HR, harzard ratio.
The efficacy of ADAKVEO® (crizanlizumab-tmca) was evaluated based on the annual rate of VOCs in patients (16 to 63 years of age) with SCD in a pivotal, phase 2, 52-week, randomized, multicenter, placebo-controlled, double-blind study.* The study included 198 patients evaluated at 60 study centers, the majority of which were located in the United States (51 centers with 151 study patients)1-3†
Prespecified, noncomparative subgroup analysis evaluated the annual rate of VOCs with or without hydroxyurea
(during previous 12 months)¶
References: 1. Adakveo [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2019. 2. Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376(5):429-439. 3. Data on file. Study NCT01895361. Novartis Pharmaceuticals Corp; 2016. 4. Bailey M, Thompson M, Brown S. The impact of crizanlizumab on VOC-related medical facility visits. Presented at: EHA Annual Congress; June 13-16, 2019; Amsterdam, Netherlands. Poster PF715. 5. Data on file. Novartis Pharmaceuticals Corp; November 2019. 6. Kutlar A, Kanter J, Liles DK, et al. Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: a SUSTAIN study analysis. Am J Hematol. 2019;94(1):55-61.
ADAKVEO® (crizanlizumab-tmca) is indicated to reduce the frequency of vaso-occlusive crises (VOCs) in adults and pediatric patients, aged 16 years and older, with sickle cell disease.
In the SUSTAIN clinical trial, infusion-related reactions (defined as occurring within 24 hours of infusion) were observed in 2 (3%) patients treated with ADAKVEO 5 mg/kg. Monitor patients for signs and symptoms of infusion-related reactions, which may include fever, chills, nausea, vomiting, fatigue, dizziness, pruritus, urticaria, sweating, or shortness of breath or wheezing. Discontinue ADAKVEO infusion for severe reactions and institute appropriate medical care.
Laboratory Test Interference: Platelet Counts
Interference with automated platelet counts (platelet clumping) has been observed following administration of ADAKVEO, in particular, when blood samples were collected in tubes containing EDTA.
Run blood samples within 4 hours of blood collection or collect blood samples in tubes containing citrate. When needed, estimate platelet count via peripheral blood smear.
Based on animal data ADAKVEO has the potential to cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. ADAKVEO should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the fetus.
Most Common Adverse Reactions
The most frequently reported adverse reactions (≥10%) in patients treated with ADAKVEO were nausea (18%), arthralgia (18%), back pain (15%), and pyrexia (11%).
Other Clinically Important Adverse Reactions
Clinically relevant adverse reactions (all grades) that were reported in <10% of patients treated with ADAKVEO included: oropharyngeal pain, abdominal pain (abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort, and abdominal tenderness), diarrhea, vomiting, pruritus (pruritus and vulvovaginal pruritus), musculoskeletal chest pain, myalgia, infusion-site reaction (infusion-site extravasation, infusion-site pain, and infusion-site swelling), and infusion-related reaction.
Please see full Prescribing Information.