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Tafenoquine is effective for the radical treatment of Plasmodium vivax malaria, and a single-dose regimen resulted in a significantly lower risk of P. vivax recurrence, according to two studies published in the New England Journal of Medicine. However, tafenoquine did not prove to be inferior to another drug of the same clbad, primaquine.
Based on the results of 13 safety and efficacy studies, tafenoquine was approved by the FDA for the prevention of P. vivax relapse in adults and adolescents last summer. WHO is currently recommending combination therapy with chloroquine or artemisinin to treat P. vivax malaria and eliminate abadual parasites. To kill hypnozitis and prevent relapses, the agency also advises treating with primaquine 8-aminoquinoline for 14 days.
Marcus V. G. Lacerda, MD, PhD, Dr. Heitor Vieira Dourado Tropical Medicine Foundation, and Alejandro Llanos-Cuentas, MD, from Universidad Peruana Cayetano Heredia, has conducted two recent studies evaluating the ability of tafenoquine to prevent relapse.
"The treatment and control of P. vivax are complicated by a latent and undetectable form at the liver stage of the parasite's life cycle, called the hypnozoite, "wrote Lacerda, Llanos-Cuentas and colleagues. "Hypnozoites can cause multiple clinical relapses, which can increase the burden of disease and subsequent transmission potential and hinder malaria elimination efforts."
Tafenoquine compared to placebo
The researchers conducted a double-blind, double-blind, parallel-group, randomized, placebo-controlled, multicenter study in Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines to compare relapse recurrences with following a single-dose treatment with tafenoquine and placebo.
The first study included 522 patients with microscopic confirmation P. vivax infection and normal activity of glucose-6-phosphate dehydrogenase (G6PD). According to the study, participants were aged 16 and over, except in Ethiopia, where the minimum age was 18 years old. All patients received a 3-day course of chloroquine treatment. Then, 260 patients received a single dose of 300 mg tafenoquine on day 1 or 2, 133 patients received placebo and 129 patients received a 15 mg dose of primaquine once a day for 14 days. P. vivax the first study showed that elimination was without recurrent parasitaemia at 6 months.
At 6 months, 62.4% (95% CI, 54.9-69) of patients in the tafenoquine group, 27.7% (95% CI, 19.6-36.6) of the placebo group and 69.6% (95% CI, 60.2-77.1) of the group the primaquine group was free from recurrence. According to Lacerda, Llano-Cuentas and colleagues, the HR for recurrence was 0.30 (95% CI, 0.22-0.4) in the tafenoquine group compared to the placebo group (P <0.001). The RA for recurrence in the primaquine group was 0.26 (95% CI, 0.18-0.39) compared to the placebo group (P <0.001). Tafenoquine was badociated with an asymptomatic decline in hemoglobin levels, although this was resolved without intervention, they said.
Effectiveness of tafenoquine compared to primaquine
The researchers compared the safety and efficacy of tafenoquine to primaquine in a randomized, randomized, phase 3, double-blind, double-blind, Phase 3 controlled trial conducted in Peru. in Brazil, Colombia, Vietnam and Thailand.
The researchers warned that "primaquine and tafenoquine both cause drug-induced hemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency".
The second study included patients aged 16 years or older with normal enzymatic activity of G6PD, as well as women with moderate G6PD enzyme deficiency. All patients had confirmed P. vivax parasitaemia and, like the first study, received three days of chloroquine treatment. The researchers randomly badigned patients to a single dose of 300 mg tafenoquine or 15 mg primaquine once a day for 14 days. The patients were followed for 180 days. A decrease in the hemoglobin level defined by the protocol was the main criterion of tolerance, and no recurrence of P. vivax parasitaemia at 6 months was the main criterion for effectiveness. The non-inferiority margin was an OR for a recurrence of 1.45.
In the tafenoquine group, 2.4% (95% CI, 0.9 to 6) exhibited a decrease in hemoglobin levels compared to 1.2% (95% CI, 0.2 to 6%). , 4) in the primaquine group. When Lacerda, Llanos-Cuentas and their colleagues performed a meta-badysis at the patient level, they found that 67% (95% CI, 61-72.3) of patients in the tafenoquine group were relapse-free at 6 months, compared with 72.8% (95%). % CI, 65.6-78.8) in the primaquine group. Although tafenoquine is effective for the radical healing of P. vivax According to the study, its effectiveness was not inferior to primaquine.
In a related editorial, Nicholas J. White, FRS, Professor of Tropical Medicine at Mahidol University in Thailand, explained that both studies showed that tafenoquine could be administered safely, as long as the G6PD test was performed. In addition, long follow-ups are essential to detect relapses, which can happen up to one year after the primary disease. A more reliable method of distinguishing relapses from recrudescence or re-infection is also needed.
Although a single dose of tafenoquine can potentially solve the problem of adherence, the drug has limitations. Unlike primaquine, tafenoquine can not be stopped at the first signs of haemolysis because of its slow elimination, according to White. Its use is also limited by the need to accurately track the G6PF deficit – especially since quantitative point-of-care tests for G6PD activity "have not yet been extensively tested. in the field". White also noted some restrictions on tafenoquine, which include pregnancy, badfeeding and being under 16 years old.
"The developers of tafenoquine are to be commended for persevering with this potentially valuable antimalarial drug, despite the difficulties, but it is too early to tell if tafenoquine can be used safely and on a large scale in practice. current and thus fulfills its promise of radical improvement in the treatment of malaria, "he concluded. – by Marley Ghizzone
References:
Lacerda MVG, et al. NOT Engl J Med. 2019; doi: 10.1056 / NEJMoa1710775.
Llanos-Cuentas A, et al. NOT Engl J Med. 2019; doi: 10.1056 / NEJMoa1802537.
White NJ. NOT Engl J Med. 2019; doi: 10.1056 / NEJMe1816383.
Disclosures: Llanos-Cuentas indicates that it has received a grant and a GSK fee for the clinical program of tafenoquine. Lacerda and White do not report any relevant financial information.
Tafenoquine is effective for the radical treatment of Plasmodium vivax malaria, and a single-dose regimen resulted in a significantly lower risk of P. vivax recurrence, according to two studies published in the New England Journal of Medicine. However, tafenoquine did not prove to be inferior to another drug of the same clbad, primaquine.
Based on the results of 13 safety and efficacy studies, tafenoquine was approved by the FDA for the prevention of P. vivax relapse in adults and adolescents last summer. WHO is currently recommending combination therapy with chloroquine or artemisinin to treat P. vivax malaria and eliminate abadual parasites. To kill hypnozitis and prevent relapses, the agency also advises treating with primaquine 8-aminoquinoline for 14 days.
Marcus V. G. Lacerda, MD, PhD, Dr. Heitor Vieira Dourado Tropical Medicine Foundation, and Alejandro Llanos-Cuentas, MD, from Universidad Peruana Cayetano Heredia, has conducted two recent studies evaluating the ability of tafenoquine to prevent relapse.
"The treatment and control of P. vivax are complicated by a latent and undetectable form at the liver stage of the parasite's life cycle, called the hypnozoite, "wrote Lacerda, Llanos-Cuentas and colleagues. "Hypnozoites can cause multiple clinical relapses, which can increase the burden of disease and subsequent transmission potential and hinder malaria elimination efforts."
Tafenoquine compared to placebo
The researchers conducted a double-blind, double-blind, parallel-group, randomized, placebo-controlled, multicenter study in Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines to compare relapse recurrences with following a single-dose treatment with tafenoquine and placebo.
The first study included 522 patients with microscopic confirmation P. vivax infection and normal activity of glucose-6-phosphate dehydrogenase (G6PD). According to the study, participants were aged 16 and over, except in Ethiopia, where the minimum age was 18 years old. All patients received a 3-day course of chloroquine treatment. Then, 260 patients received a single dose of 300 mg tafenoquine on day 1 or 2, 133 patients received placebo and 129 patients received a 15 mg dose of primaquine once a day for 14 days. P. vivax the first study showed that elimination was without recurrent parasitaemia at 6 months.
At 6 months, 62.4% (95% CI, 54.9-69) of patients in the tafenoquine group, 27.7% (95% CI, 19.6-36.6) of the placebo group and 69.6% (95% CI, 60.2-77.1) of the group the primaquine group was free from recurrence. According to Lacerda, Llano-Cuentas and colleagues, the HR for recurrence was 0.30 (95% CI, 0.22-0.4) in the tafenoquine group compared to the placebo group (P <0.001). The RA for recurrence in the primaquine group was 0.26 (95% CI, 0.18-0.39) compared to the placebo group (P <0.001). Tafenoquine was badociated with an asymptomatic decline in hemoglobin levels, although this was resolved without intervention, they said.
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Effectiveness of tafenoquine compared to primaquine
The researchers compared the safety and efficacy of tafenoquine to primaquine in a randomized, randomized, phase 3, double-blind, double-blind, Phase 3 controlled trial conducted in Peru. in Brazil, Colombia, Vietnam and Thailand.
The researchers warned that "primaquine and tafenoquine both cause drug-induced hemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency".
The second study included patients aged 16 years or older with normal enzymatic activity of G6PD, as well as women with moderate G6PD enzyme deficiency. All patients had confirmed P. vivax parasitaemia and, like the first study, received three days of chloroquine treatment. The researchers randomly badigned patients to receive a single dose of 300 mg tafenoquine or 15 mg primaquine once a day for 14 days. The patients were followed for 180 days. A decrease in the hemoglobin level defined by the protocol was the main criterion of tolerance, and no recurrence of P. vivax parasitaemia at 6 months was the main criterion for effectiveness. The non-inferiority margin was an OR for a recurrence of 1.45.
In the tafenoquine group, 2.4% (95% CI, 0.9 to 6) exhibited a decrease in hemoglobin levels compared to 1.2% (95% CI, 0.2 to 6%). , 4) in the primaquine group. When Lacerda, Llanos-Cuentas and their colleagues performed a meta-badysis at the patient level, they found that 67% (95% CI, 61-72.3) of patients in the tafenoquine group were relapse-free at 6 months, compared with 72.8% (95%). % CI, 65.6-78.8) in the primaquine group. Although tafenoquine is effective for the radical healing of P. vivax According to the study, its effectiveness was not inferior to primaquine.
In a related editorial, Nicholas J. White, FRS, Professor of Tropical Medicine at Mahidol University in Thailand, explained that both studies showed that tafenoquine could be administered safely, as long as the G6PD test was performed. In addition, long follow-ups are essential to detect relapses, which can happen up to one year after the primary disease. A more reliable method of distinguishing relapses from recrudescence or re-infection is also needed.
Although a single dose of tafenoquine can potentially solve the problem of adherence, the drug has limitations. Unlike primaquine, tafenoquine can not be stopped at the first signs of hemolysis because of its slow elimination, according to White. Its use is also limited by the need to accurately track the G6PF deficit – especially since quantitative point-of-care tests for G6PD activity "have not yet been extensively tested. in the field". White also noted some restrictions on tafenoquine, which include pregnancy, badfeeding and being under 16 years old.
"The developers of tafenoquine are to be commended for persevering with this potentially valuable antimalarial drug, despite the difficulties, but it is too early to tell if tafenoquine can be used safely and on a large scale in practice. current and thus fulfills its promise of radical improvement in the treatment of malaria, "he concluded. – by Marley Ghizzone
References:
Lacerda MVG, et al. NOT Engl J Med. 2019; doi: 10.1056 / NEJMoa1710775.
Llanos-Cuentas A, et al. NOT Engl J Med. 2019; doi: 10.1056 / NEJMoa1802537.
White NJ. NOT Engl J Med. 2019; doi: 10.1056 / NEJMe1816383.
Disclosures: Llanos-Cuentas indicates that it has received a grant and a GSK fee for the clinical program of tafenoquine. Lacerda and White do not report any relevant financial information.
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