A 72-hr, continuous intravenous infusion of rhIL-1ra failed to demonstrate a statistically significant reduction in mortality when compared with standard therapy in this multicenter clinical trial. If rhIL-1ra treatment has any therapeutic activity in severe sepsis, the incremental benefits are small and will be difficult to demonstrate in a patient population as defined by this clinical trial.

Objective. To preliminarily evaluate the safety and efficacy of different dose levels and dosing frequencies of recombinant human interleukin-1 receptor antagonist (rHuIL-1Ra) in the treatment of patients with rheumatoid arthritis (RA).Methods. One hundred seventy-five patients with active RA were enrolled in a randomized, double-blind trial of rHuIG1Ra administered by subcutaneous injection. There were 9 treatment groups in the trial. During the initial 3-week treatment phase, patients were treated with 20, 70, or 200 mg rHuIL-lRa, administered either once, 3 times, or 7 times per week, followed by a 4-week maintenance phase, during which all patients received the treatment-phase dose once per week. To maintain the blindness of the study, patients received daily injections of either rHuIL-1Ra or placebo on the days rHuIClRa was not administered.Results. Recombinant HuIL-1Ra was well tolerated. The most frequent adverse event was injection-site reactions, which were reported in 62% of patients and caused 8 patients (5%) to withdraw prematurely from the study. Five patients (3%) developed serious adverse reactions unrelated to dose or dosing frequency. Due to the lack of a placebo arm and to the multiple small treatment groups, a definitive statement regarding efficacy could not be made. However, by the end of the 3-week treatment phase, daily dosing appeared more effective than weekly dosing when assessed by the number of swollen joints, the investigator and patient asSupported by Synergen Inc.

Background The authors evaluated the efficacy of liposome bupivacaine in a femoral nerve block (FNB) after total knee arthroplasty. Methods Part 1: subjects received FNB with 20 ml liposome bupivacaine (67, 133, or 266 mg) or placebo. Part 2: subjects were randomized to FNB with liposome bupivacaine 266 mg or placebo. The primary outcome measure was area under the curve of the numeric rating scale score for pain intensity at rest through 72 h (AUC NRS-R0–72) with imputed scores after rescue medication. Results In part 1, FNB with liposome bupivacaine 266 mg (n = 24) resulted in analgesia similar to that obtained with 133 mg and was chosen for part 2. In part 2, least-squares mean (standard error) AUC NRS-R0–72 was lower with liposome bupivacaine 266 mg (n = 92) than with placebo (n = 91; 419 [17] vs. 516 [17]; P < 0.0001). This outcome remained unchanged in a post hoc analysis without score imputation (221 [12] vs. 282 [12]; P = 0.0005). Least-squares mean AUC NRS-R with imputed scores was lower with liposome bupivacaine during each 24-h interval (0 to 24, 24 to 48, and 48 to 72 h) after surgery; AUC NRS-R without imputed scores was lower during the 0- to 24-h and 24- to 48-h intervals. The liposome bupivacaine group had lower mean total opioid use (76 vs. 103 mg morphine; P = 0.0016). Pain was sufficiently severe to require second-step rescue with opioids via intravenously administered patient-controlled analgesia in 92% of liposome bupivacaine patients and 81% of placebo patients. With patient-controlled analgesia and other forms of rescue analgesia, mean NRS scores with activity were moderate in both liposome bupivacaine and placebo groups throughout the part 2 study period. Incidence of adverse events was similar between the groups (part 1: 90 vs. 96%; part 2: 96 vs. 96%, respectively). Conclusion FNB with liposome bupivacaine (266 mg) resulted in modestly lower pain scores and reduced opioid requirements after surgery, with an adverse event profile similar to placebo.

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