The Effect of Anti-L-Selectin (Aselizumab) on the Posttraumatic Inflammatory Response in Multiply Traumatized Patients

Abstract

European Journal of Trauma Ab stractPurpose: This prospective phase II parallel-group, double-blind, randomized, placebo-controlled clinical trial was meant to evaluate the effect of a humanized monoclonal anti-L-selectin antibody (aselizumab) on the posttraumatic inflammatory response in severely injured patients. Patients and Methods: To be eligible for the study, patients had to have sustained a trauma due to a blunt or penetrating injury, which involved at least two organ systems according to the Abbreviated Injury Scale (AIS) resulting in a total Injury Severity Score (ISS) of ¹ 25. Included patients (n = 84) received either placebo or 0.5 mg/kg, 1.0 mg/kg, or 2.0 mg/kg of aselizumab within 6 h of the traumatic event. Parameters representing the posttraumatic inflammatory response were monitored for 10 days, patients' general records were monitored for 14 days and discontinuously until day 42. Results: The incidence of multiple organ failure (MOF) defined as a median value of the total Goris MOF score of ¹ 5 on ¹ 2 consecutive days within the first 14 days was not significantly different for the placebo and the 0.5-mg/kg, 1.0-mg/kg, and 2.0-mg/kg groups. The cytokine interleukin-(IL-)6 and IL-10 serum levels as well as neutrophil elastase serum concentrations revealed the well-described posttraumatic acute response which resolved from day 3 after trauma in all four study groups.Also complement factor C3a and procalcitonin followed the same pattern. There were no statistically significant differences between placebo and patients having received anti-L-selectin at different dosages. Conclusion: For all of the measured variables, IL-6, IL-10, elastase, C3a and procalcitonin, there were only a few trends but no significant differences between all study groups indicating that the effect of the administered anti-L-selectin antibody on the posttraumatic inflammatory response was similar to that of placebo.

A systematic review of randomized controlled trials exploring the effect of immunomodulative interventions on infection, organ failure, and mortality in trauma patients

“…By checking references of the relevant studies, three other relevant studies were found that were missed in the computerized search because the keywords were not included in the titles or abstracts [13-15]. Two articles by Seekamp et al [16,17] and two articles by Dries et al [13,18] report on the same study. Therefore, 18 unique RCTs that met the inclusion and exclusion criteria were available for analysis.…”

“…Three of the trials were phase II trials primarily powered to test dosage and safety, not efficacy [16,23,24]. Patient ages ranged between 13 and 90 years, with the mean age in the 30 s or low 40 s for all studies except those of Rizoli et al [27] and Seekamp et al [16,17] in which the mean age was nearer 50 years. Similarly, the ISS ranged from 0 to 75, with the mean ISS in the 20 s or low 30 s for most studies.…”

“…Most of the control groups were given a placebo [ 15 - 18 , 20 , 22 , 23 , 25 - 32 ] and four received only standard treatment [ 14 , 19 , 21 , 24 ]. The interventions were administered intravenously [ 14 - 17 , 19 - 21 , 23 , 25 , 27 - 30 , 32 ], subcutaneously [ 18 , 22 , 31 ], or via inhalation [ 24 , 26 ]. Interventions were initiated as soon as possible after injury by ambulance personnel [ 19 ] or as late as 145 hours after hospital admission [ 30 ].…”

“…These were not the most recently published or largest studies, nor the studies with the longest follow-up, and did not differ from the other studies regarding the ages or ISS of the patients. Besides the test intervention, only the duration of the test intervention distinguished the studies that reported a significant efficacy in preventing adverse clinical outcome from those that did not; none of the single-dose interventions proved efficacious [ 16 , 17 , 19 , 23 , 27 ].…”

Endothelial Cell Adhesion Molecules- (un)Attainable Targets for Nanomedicines

“…Clinical trial results showed a lack of efficacy, even though the saturation of leukocyte L-selectin was 89%. Possible explanations could be that the remaining 10% of L-selectin could still be sufficient to mediate adhesion or that other CAMs could compensate for L-selectin blockage ( 45 , 46 ). The murine anti-ICAM-1 mAb, enlimomab, reached clinical-stage development for stroke treatment, following the rationale that ICAM-1 blockade inhibits reperfusion-induced inflammation with neuronal injury after stroke.…”