CollaGenex Pharmaceuticals, Inc.

Rosacea is a chronic, relapsing dermatologic condition that affects an estimated 14 million people in the U.S. However, there is little data in the literature on the healthcare utilization and costs of patients with rosacea in insured populations.

This retrospective, observational, cohort study used the MarketScan databases to identify a rosacea cohort of patients with medical and prescription drug claims between 2002 and 2005. Inclusion criteria were (1) age 30 years and older, (2) at least one medical claim with a primary or secondary diagnosis of rosacea (ICD-9-CM 695.3), (3) at least one pharmacy claim for a rosacea topical or systemic prescription drug, (4) a 6-month clean period prior to index drug and 12 months continuous enrollment after the index drug. Propensity score matching was used to match the rosacea cohort to a control group of patients without rosacea. Disease severity during the 6-month preperiod was assessed by the Charlson Comorbidity Index (CCI), the Chronic Disease Score (CDS), and the Elixhauser Index (EI). Healthcare utilization rates and costs were determined by the type of care for the 12-month postperiod. Costs were calculated for the 12-month post-period and adjusted to reflect 2005 costs. Healthcare utilization rates and costs were reported for inpatient hospital admissions, physician office visits, emergency room visits, other outpatient services, and outpatient pharmacy prescriptions. Both total healthcare and rosacea-related rates and costs were reported.

There were no rosacea-related inpatient admissions and very few emergency department visits. More rosacea patients had a specialist visit than a primary care physician visit. The average number of rosacea-related prescriptions, for all patients, was 3.4 (SD 2.7) per year. Total annual healthcare expenditures for the rosacea patient cohort were $735 more than for the matched controls ($6,458 vs. $5,723). Of the total healthcare costs, annual rosacea-related expenditures were $276; approximately 70% of rosacea-related expenditures were due to prescription drugs. Topical drugs were the index drugs for 77% of rosacea patients with branded metronidazole, which is the most common topical drug. Of the 23% of rosacea patients with an oral index drug, generic antibiotic dosage forms of tetracyclines were the most common oral index drug therapy.

This is the first extensive study of rosacea and its impact on healthcare utilization and costs in an insured population. Although rosacea is a common illness that does not have much financial impact on its sufferers, rosacea patients incurred slightly higher direct total healthcare costs than matched controls.

Lethal toxin, produced by the bacteriumBacillus anthracis, is a major contributor to morbidity and mortality in animals and humans who have contracted anthrax. One component of this toxin, lethal factor (LF), proteolytically inactivates members of the mitogen-activated protein kinase kinase (MAPKK or MEK) family. In this study we show that CMT-300, CMT-308, and Ilomastat, agents initially characterized as matrix metalloproteinase inhibitors which are in early stages of development as pharmaceuticals, effectively inhibit the zinc metalloproteinase activity of LF. All three inhibitors, CMT-300, CMT-308, and Ilomastat, inhibit LF-mediated cleavage of a synthetic peptide substrate based on the N-terminal domain of MEKs. Inhibition of LF-mediated MEK proteolysis by all three agents was also achieved using lysates of the human monocytoid line MonoMac 6 as sources of MAPKKs and visualization of the extent of cleavage after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by detection by Western blotting. Finally, we have demonstrated inhibition of intracellular MEKs in viable human monocytes and MonoMac 6 cells by these agents after incubation of the cells with a reconstituted preparation of recombinant lethal toxin. All three agents are effective inhibitors when incubated with LF prior to exposure to cells, while the CMTs, but not Ilomastat, are also effective when added after LF has already entered the viable cell targets. These results offer promise for strategies to combat effects of the lethal toxin ofB. anthracis.

The etiology of inflammatory disorders involves many cellular, plasmatic and humoral pathways of signaling culminating in the production of enzymatic and free radical mediated tissue damage. Multiple redundant pathways of initiation and elusive temporal expression of initiators pose formidable barriers to effective treatment. Nowhere is this more evident than in the adult respiratory distress syndrome (ARDS), a systemic inflammatory disorder leading to pulmonary failure where, despite significant advances in intensive care management, mortality has improved only 10% over the last decade. Tetracyclines, in addition to their anti-microbial properties, exhibit inhibitory activity toward several initiators of the inflammatory cascade and mediators of tissue damage. In this review we discuss how the broad spectrum anti-inflammatory properties of the tetracyclines make them attractive candidates for use in the prevention of acute lung injury.