Mosquirix (RTS,S)

A Novel Vaccine for the Prevention of Plasmodium falciparum Malaria

Kyle J Wilby BSP ACPR, PharmD; Tim TY Lau PharmD ACPR FCSHP; Samuel E Gilchrist MSc (Pharm), PhD; Mary HH Ensom PharmD FASHP FCCP FCSHP FCAHS

Disclosures

The Annals of Pharmacotherapy. 2012;46(3):384-393. 

In This Article

Adverse Events and Drug Interactions

Adverse Events

RTS,S appears to be well tolerated in infants and children, with >90% receiving all 3 doses across the 4 major trials described above.[10–13] Long-term follow-up studies have not reported increased rates of adverse events.[15–18] Preliminary results from the Phase 3 study have also shown similar rates of adverse events between groups, although a few cases of meningitis and seizures were reported within 7 days of vaccination.[14]

RTS,S AS01E had similar rates of minor adverse events when compared to the rabies vaccine, with the most common adverse events in both groups being gastroenteritis, pneumonia, and upper respiratory tract infections.[11] However, RTS,S was associated with fewer serious adverse events (SAEs; 11% [95% CI 8 to 14] RTS,S vs 18% [95% CI 15 to 22] rabies vaccine). Only one SAE, of a patient experiencing a febrile seizure, appeared to be associated with RTS,S. The seizure, however, terminated spontaneously and no neurologic abnormalities were noted. A subsequent safety analysis reporting on data from the extension follow-up study described similar results.[17] Fewer patients receiving RTS,S reported at least one SAE compared with the rabies vaccine group (11% [95% CI 9 to 15] vs 20% [95% CI 16 to 24]); this difference persisted when adjusted for malaria-related SAEs (11% [95% CI 8 to 15] vs 19% [95% CI 16 to 23]). While these results are promising, the study was not powered to detect rare SAEs.

The long-term follow-up study of RTS,S AS02A found fewer SAEs with RTS,S when compared to control vaccines (23.2% [95% CI 20.7 to 25.9] vs 32.3% [95% CI 29.4 to 35.3]).[16] The most common SAEs reported in both groups were malaria, anemia, gastroenteritis, and pneumonia. As these conditions are endemic to the region, they are not completely unexpected. In the initial trial assessing RTS,S AS02A, no SAEs were associated with RTS,S AS02A and local (injection site pain and swelling) and general (fever, irritability, drowsiness) adverse effects were infrequent and mild to moderate in nature. Similar results for RTS,S AS02D were found for infants.[12] However, an increased incidence in rash was seen in the RTS,S AS02D group when compared to the hepatitis B vaccine group (7.1% vs 0.6%). The most common adverse events in this population were fever and irritability (soon after dosing), cough, rhinorrhea, and pneumonia (in the 30-day postadministration period). However, rates of these adverse events were similar between treatment and control groups.

In the recent Phase 3 trial, patients developing at least one adverse event at 30 days after vaccination were similar between RTS,S and control groups (86% vs 87%, respectively).[14] In children aged 5–17 months, SAEs occurred in 17.6% (95% CI 16.7 to 18.6) of the RTS,S group versus 21.6% (95% CI 20.1 to 23.1) of the control group. For the children aged 6–12 weeks, SAE rates were 13.1% (95% CI 12.1 to 14.1) for RTS,S patients versus 13.4% (95% CI 12.0 to 15.0) for controls. Total adverse events reported were also similar between groups. Two SAEs, meningitis and seizure within 7 days of vaccination, were more common in RTS,S patients. Meningitis was reported in 11 of 5949 RTS,S patients and 1 of 2974 control patients in the older age group (5–17 months). In the younger group (6–12 weeks), meningitis was reported in 8 of 4358 RTS,S patients and 1 of 2179 control patients. No temporal relationship was seen according to vaccination. Generalized seizures within 7 days after vaccination were more common in the older children (incidence of 1.04 per 1000 doses [95% CI 0.62 to 1.64] RTS,S vs 0.57 per 1000 doses [95% CI 0.19 to 1.34] controls). All seizure episodes were associated with fever and all patients recovered with no sequelae.

Drug Interactions

To date, no drug interactions with the RTS,S vaccine have been reported. When vaccine-vaccine interactions were studied in a clinical trial in which RTS,S was administered with WHO EPI vaccines (tetanus, diphtheria, pertussis, and Hib), antibody titer levels were comparable (noninferior) between RTS,S and control groups.[12] This is an important finding, as the RTS,S vaccine could potentially be coadministered as part of a routine immunization schedule; however, Phase 3 trials are required to confirm efficacy in these particular situations.

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