The Dutch MAKI study was a multicenter, double-blind, randomised, placebo-controlled exploratory study which investigated the potential causal role of respiratory syncytial virus (RSV) infection in the pathogenesis of wheezing illness during the first year of life, using the monoclonal antibody palivizumab (Synagis™) against RSV.
Healthy preterm infants (gestational age, 33 to 35 weeks) aged 6 months or younger at the start of the RSV season were randomised to either palivizumab (15 mg /kg; n=214) or matching placebo (n=215). The primary outcome was number of parent-reported wheezing days (daily log) in the first year of life.
After a median follow-up of 10 months, the following results were reported:
• The primary endpoint was lower in the RSV-prevention group than in the placebo group (930 of 53,075 days [1.8%] and 2309 of 51,726 days [4.5%], respectively), for a relative reduction of 61% (95% confidence interval [CI], 56 to 65).
• The proportion of patients with serious adverse events was lower in the RSV-prevention group than in the placebo group.
• There were fewer hospitalisations in the RSV-prevention group compared to the placebo groups (12.6% vs 21.9%; P=0.04).
• The effect of RSV prevention on the number of wheezing days persisted during the post-prophylaxis period (i.e., starting at 2 months after the last injection; secondary outcome), for a relative reduction of 73% (95% CI, 66 to 80).
The authors concluded that the administration of palivizumab for RSV prevention reduced the total number of wheezing days in the first year of life in preterm infants and further confirm the role that RSV plays in the pathogenesis of recurrent wheeze.
A related editorial discusses the limitations of using wheezing as a primary outcome measure which is identified as a limitation by the study coordinators.
This population for which palivizumab is currently recommended is not representative of the study population. The Department of Health currently recommends the passive immunisation with palivizumab (Synagis) in the following groups:
• Pre-term infants who have chronic lung disease (CLD) at the chronological ages at the start of the RSV season and gestational ages at birth.
• Pre-term infants who have haemodynamically significant, acyanotic congenital heart disease (CHD) at the chronological ages at the start of the RSV season and gestational ages.
Furthermore they recommend that passive immunisation should be considered during the RSV season for the following groups of infants:
• all children under the age of 24 months who have severe combined immunodeficiency syndrome (SCID), until immune reconstituted and;
• all children who are on long term ventilation (LTV) aged under 12 months at the start of the RSV season and,
• all children who are on LTV aged under 24 months at the start of the RSV season with additional co-pathology (heart disease/pulmonary hypertension, intrinsic lung disease (as reflected by oxygen dependency).