Library

Notes: Pressure ulcers are associated with significant rates of morbidity and mortality, particularly in the geriatric and spinal cord–injured populations. Newer pharmacologically active therapies include the use of topically applied recombinant human platelet-derived growth factor-BB (becaplermin), the active ingredient in REGRANEX® (becaplermin) Gel 0.01%, which has been approved in the United States for treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply. In this study, the efficacy of becaplermin gel in the treatment of chronic full thickness pressure ulcers was compared with that of placebo gel. A total of 124 adults (≥ 18 years of age) with pressure ulcers were assigned randomly to receive topical treatment with becaplermin gel 100 μg/g (n = 31) or 300 μg/g (n = 32) once daily alternated with placebo gel every 12 hours, becaplermin gel 100 μg/g twice daily (n = 30), or placebo (sodium carboxymethylcellulose) gel (n = 31) twice daily until complete healing was achieved or for 16 weeks. All treatment groups received a standardized regimen of good wound care throughout the study period. Study endpoints were the incidence of complete healing, the incidence of ≥ 90% healing, and the relative ulcer volume at endpoint (endpoint/baseline). Once-daily treatment of chronic pressure ulcers with becaplermin gel 100 μg/g or 300 μg/g significantly increased the incidences of complete and ≥ 90% healing and significantly reduced the median relative ulcer volume at endpoint compared with that of placebo gel (p 〈 0.025 for all comparisons). Becaplermin gel 300 μg/g did not result in a significantly greater incidence of healing than that observed with 100 μg/g. Treatment with becaplermin gel was generally well tolerated and the incidence of adverse events was similar among treatment groups. In conclusion, once-daily application of becaplermin gel is efficacious in the treatment of chronic full thickness pressure ulcers.

Notes: Topically applied recombinant human platelet-derived growth factor-BB (becaplermin) is a new pharmacologically active therapy for chronic, neuropathic, lower extremity diabetic ulcers. In previous studies, becaplermin gel was administered once daily but dressings were changed twice daily. In the present study of 134 patients with diabetes mellitus and full thickness lower extremity ulcers, dressings were changed only once per day, simplifying the treatment regimen. Efficacy criteria included the percentage of patients achieving complete healing within the 20-week treatment period, the time to achieve complete healing, the rate of ulcer recurrence during the 6-month period following healing, and treatment compliance. Complete healing of ulcers was achieved in 57.5% of patients, with a mean time to closure of 63 days and a recurrence rate of 21% at 6 months. Of the potential factors affecting ulcer healing, only drug compliance (p 〈 0.001), dressing compliance (p 〈 0.01), the presence of infection (p 〈 0.01), baseline ulcer area (p 〈 0.05), and baseline total wound evaluation score (p 〈 0.05) were significantly associated with healing. Results of this study further confirm the efficacy and safety of becaplermin gel for the treatment of lower extremity diabetic ulcers.

Notes: The results of a combined analysis and separate analyses of four multicenter, randomized, parallel group studies that evaluated the effects of once-daily topical administration of becaplermin gel for the treatment of chronic, full thickness, lower extremity diabetic ulcers are presented. The four studies included a total of 922 patients with nonhealing lower extremity diabetic ulcers of at least 8 weeks' duration. Following initial complete sharp debridement of the ulcer, patients were randomized to receive a standardized regimen of good ulcer care alone, good ulcer care plus placebo gel, or good ulcer care plus becaplermin gel-30 μg/g, or good ulcer care plus becaplermin gel-100 μg/g, with various combinations of regimens used in the four studies. Safety was assessed by monitoring adverse events and by clinical laboratory evaluations. Meta-analytic statistical techniques were used in the combined analysis to establish homogeneity of treatment comparisons across studies. Based on an analysis of patients with baseline ulcer area common to all trials (≤ 10 cm2), representing 95% of all patients, becaplermin gel-100 μg/g significantly increased (p = 0.007) the probability of complete healing compared with placebo gel. It was determined that for the median ulcer area of these patients, which was 1.5 cm2, the becaplermin gel-100 μg/g treatment group showed a 39% increase in complete healing compared with that of the placebo gel treatment group (50% vs. 36%, respectively, p = 0.007). Becaplermin gel-100 μg/g significantly decreased (p = 0.01) the time to complete healing compared with placebo gel, with the 35th percentile of time to complete healing being reduced by 30% (14.1 weeks vs. 20.1 weeks, respectively). In patients with ulcers ≤ 5 cm2 at baseline (a more homogeneous group), becaplermin gel-100 μg/g also significantly increased the incidence of complete healing with a similar decrease in the time to healing. Adverse events reported during treatment or during a 3-month follow-up period were not unexpected for this patient population and were similar in nature and incidence across all treatment groups. We therefore conclude that treatment with becaplermin gel at a dose of 100 μg/g once daily, in conjunction with good ulcer care, is effective and well tolerated in patients with full thickness lower extremity diabetic ulcers.

Notes: [Auszug] To the editor: The news article “Lessons from Eprex for biogeneric firms” in the September issue (Nat. Biotechnol. 21, 956–957) cites an unpublished study conducted by Huub Schellekens and associates that proposes the hypothesis that the stabilizer polysorbate 80 led to the ...