Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.

Effective Combination Therapy for Acne

Source: Thiboutot D, et al. An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl peroxide 2.5% for once-daily treatment of moderate to severe acne vulgaris: Assessment of efficacy and safety in 2813 patients. J Am Acad Dermatol 2008;59:792-800.

Topical agents, both as monotherapy and in combination, have shown efficacy in management of acne. Benzoyl peroxide (BPO) is one of the most commonly used agents, but despite excellent efficacy, the side effects of skin dryness, burning, erythema, and peeling are sometimes limiting effects of treatment.

Clinical trials of clindamycin phosphate (CMP) 1% plus BPO have demonstrated that the combination is more effective than either agent alone, but traditional BPO concentrations (5%-10%) have been associated with dryness and irritation. Monotherapy comparisons of BPO 2.5% with BPO 5%-10% indicate similar efficacy, with better tolerability. Hence, a clinical trial to establish the relative efficacy of CMP, BPO 2.5%, and the combination was a sensible next step.

Thiboutot et al randomized adolescents and adults (n = 2813) with moderate-to-severe acne to CMP 1%, BPO 2.5%, CMP + BPO, or placebo. Subjects were followed for 12 weeks. Outcomes included facial acne lesion counts as well as tolerability evaluation.

CMP + BPO was statistically significantly superior to CMP, BPO, and placebo at the conclusion of the trial. The tolerability of CMP + BPO was essentially the same as placebo (vehicle), and when adverse effects were reported, 97% were mild to moderate. My online search (Nov. 23, 2008) does not yet show availability of a CMP 1% + BMP 2.5% product, but FDA approval of this product (trade name Acanya™) occurred Nov. 20, 2008.

Genotypes Associated with CRP Elevations

Source: Zacho J, et al. Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med 2008;359:1897-1908.

It remains uncertain whether the observed relationship between elevated CRP levels and adverse cardiovascular outcomes is causal. The question remains whether elevated CRP simply reflects the presence of inflammation or instead is etiologic in increasing the risk of endpoints. One way to elucidate the relationship is to evaluate persons who have gene polymorphisms that lead to elevated CRP levels, the profile for which is established in youth and maintained throughout life.

Danish investigators identified genotypes associated with elevated CRP; a high-sensitivity CRP level of > 3.0 was defined as high. Several populations were available for comparison: the Copenhagen City Heart Study, a prospective population study (n = 10, 276); the Copenhagen General Population Study, a cross-sectional population study (n = 37,690); and the Copenhagen Ischemic Heart Disease Study, a cohort with documented ischemic heart disease (n = 2238).

Overall, an elevated CRP was associated with an increased risk of ischemic heart disease (2.2 relative risk). However, when the population of individuals with genetic polymorphisms leading to elevated CRP was evaluated, there was no increased CV risk identified. If elevated CRP levels were causal in CVD endpoints, one would expect that persons with genetically influenced elevations would show a similar risk relationship as study groups with known CVD. The concluding statement of the authors summarizes their findings: "...the risk of ischemic vascular disease associated with higher plasma CRP levels observed in epidemiologic studies may not be causal, but rather that increased CRP levels are simply a marker for atherosclerosis and ischemic vascular disease."

Benefits of Extending the Duration of Detox

Source: Woody GE, et al. Extended vs short-term buprenorphine-naloxone for treatment of opioid-addicted youth. JAMA 2008;300:2003-2011.

Misuse of pharmaceutical opioids is increasing. Data from 2004 indicate that as many as 10% of high school seniors acknowledge prescription opioid use in the prior year. Although the majority of opioid misuse is sporadic, a substantial minority of young adults suffer opioid addiction, for which short-term (14 days) buprenorphine combined with naloxone (s-B/N) has shown some detoxification benefit. Whether a more extended program (e-B/N) could reduce opioid addiction relapse was the object of this study.

Woody et al randomized opioid-addicted adults (n = 153) to either s-B/N (14 days) or e-B/N (12 weeks). The primary outcomes measure was the number of patients with opioid-positive urine drug testing (UDT) at week 12.

UDT was opioid-positive in 51% of s-B/N subjects, compared with 43% of the e-B/N group. Post-treatment outcomes at months 6, 9, and 12 showed no statistically significant difference in use of opioids, alcohol, or marijuana between the groups; on the other hand, cocaine use was approximately half as common in the e-B/N group. Extending the duration of treatment with buprenorphine combined with naloxone merits further study, based upon the favorable results of this trial.