SAATELLITE dishes out positive signals for pneumonia
The novel human monoclonal antibody suvratoxumab yielded a trend toward reducing the incidence of Staphylococcus aureus pneumonia (SAP) in high-risk, mechanically-ventilated intensive care unit (MV ICU) patients with an acceptable safety profile, according to data from the phase II SAATELLITE* trial presented at ECCMID 2019.
A total of 196 critically ill patients without pneumonia (mean CPIS**, 3.0) requiring prolonged ventilation (≥3 days) were enrolled and tested by PCR*** to identify SA colonization in the lower respiratory tract. Subjects were randomized 1:1 to receive either a single intravenous infusion of 5,000 mg suvratoxumab or placebo. Ninety percent of the patients had not received any anti-SA antibiotics prior to enrolment. All radiographic, clinical, and microbiologic criteria needed to be met to fulfil the primary endpoint, which was the incidence of SAP within 30 days post-dose. [ECCMID 2019, abstract L0013]
SAP incidence was markedly reduced in the suvratoxumab vs the placebo arm (17.7 percent vs 26.0 percent), generating a relative risk reduction (RRR) of 31.9 percent (90 percent confidence interval [CI], -7.5 to 56.8 percent; p=0.166).
“Even if we did not reach the predefined statistical significance (50 percent reduction), [the 30-percent reduction] was a positive effect,” said investigator Dr Bruno François from the Centre Hospitalier Universitaire de Limoges in Limoges, France. “[The incidence of SAP] in the placebo group [is what] we had exactly … expected, so this is a [good] finding for us.”
The lower SAP incidence among suvratoxumab vs placebo recipients was consistent across other pneumonia subgroups (20.8 percent vs 30.0 percent, RRR, 30.6 percent for all-cause pneumonia and 32.3 percent vs 42.0 percent, RRR, 23.1 percent for all-cause pneumonia or death).
The RR of SAP was almost halved among patients aged ≤65 years (RRR, 47.4 percent) with lower SAP incidence in the suvratoxumab vs placebo arm (15.3 percent vs 29.0 percent), more so among participants with low bacterial colonization load as evidenced by the PCR value (RRR, 66.7 percent; 11.1 percent [suvratoxumab] vs 33.3 percent [placebo]).
“[Patients] with the lowest bacterial load [are] in the early colonization phase [and may just be developing the infection],” said François. “[These patients appear to] respond best to the drug, which makes sense when compared to those with high bacterial load.”
Suvratoxumab use also led to shorter hospitalization stays throughout the 90-day post-dose stage (mean days saved/subject, 2.7 and 2.0 days for hospital and ICU, respectively [overall population] and 8.8 and 3.3 days, respectively [≤65 years]), as well as shorter MV utilization (mean days saved/subject, 1.1 and 1.9 days).
While a majority of patients had at least one adverse event (AE) with suvratoxumab at days 30 and 90 (90.6 percent and 92.7 percent, respectively), incidences of treatment-emergent (6.3 percent for both) and serious AEs (1.0 percent for both) were low.
“We are confident in terms of safety events … [as these] were well-balanced between the two groups,” said François. There was no mortality signal, and the findings were consistent with previous evidence, he added.
Addressing the paradigm shift
SA remains one of the most common causes of pneumonia in ICU patients, who are at high risk for pneumonia and poor outcomes including death, hence the need for rapid intervention. [Respir Care 2013;58:1220-1225; Crit Care Med 2014;42:601-609]
“[We] usually target [hospital-acquired/ventilator-associated pneumonia (HAP/VAP)] in the ICU … Now, we are [shifting our targets earlier as] … respiratory tract colonization precedes VAP in 94 percent of cases,” explained François, highlighting the importance of diagnosing patients at the time of colonization, which they refer to as the ‘pre-emption phase’. “[The objective is to] target a population which has not yet developed the disease but [with a] much higher risk of developing HAP/VAP.”
“[Overall, our findings showed that] suvratoxumab prevented SAP using multiple pneumonia case definitions, with greater efficacy in the younger population,” said François. “[Moreover, the] PCR-based enrichment strategy successfully identified an intubated population … [suggesting that this] is a good approach to identify populations at risk of developing VAP in the ICU.”
The shorter hospitalization/ICU duration and ventilator utilization could translate to potential cost-savings, added François, further boosting the potential of suvratoxumab in this setting.