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Effective combination therapy for acne requires addressing all four of this condition's causes while avoiding bothersome side effects and minimizing antibiotic resistance, according to an expert.
Buenos Aires, Argentina - With topical and oral acne treatments, successful combination therapy demands picking agents that will maximize efficacy while minimizing antibiotic resistance and undesirable side effects, an expert says.
"Outside the United States," says Emil Tanghetti, M.D., "a large preponderance of topical therapy is monotherapy - either benzoyl peroxide (BPO), a BPO/clindamycin combination or a retinoid."
However, he says single-agent therapies with retinoids or even combination products address only one or two of acne's contributing factors; namely, excess sebum production, follicular hyperkeratinization, proliferation of Propionibacterium acnes and inflammation.
Single-agent therapy, regardless of agent, tends to achieve about a 50 percent improvement in comedones and inflammatory lesions.
"But when one combines topical agents," he says, "patients get closer to two-thirds or three-quarters clearance. So using combination topical therapy makes sense."
For noninflammatory lesions, well-controlled studies of retinoid monotherapy show that tazarotene 0.1 percent creams and gels reduce median lesion count between 50 and 75 percent, Dr. Tanghetti says.
Conversely, adapelene gel 0.1 percent achieves median noninflammatory lesion count reductions of about 52 percent, while the corresponding figure for adapelene cream is about 38 percent.
Neither Retin-A Micro 0.1 percent (tretinoin, OrthoNeutrogena) or tretinoin gel 0.025 percent achieves noninflammatory lesion count reductions greater than 45 percent (Leyden JJ, et al. Cutis. 2002;69(2 Suppl):12-19. Shalita A, et al. J Drugs Dermatol. 2005;4:153;58. Webster GF, et al. Cutis. 2001;67(6 Suppl):4-9. Webster GF, et al. Cutis. 2002;69(2 Suppl):4-11). In the same trials, these drugs achieved similar reductions in inflammatory lesion counts, Dr. Tanghetti says.
In a 12-week study of tretinoin 0.025 percent plus topical clindamycin 1 percent versus tretinoin or clindamycin monotherapy, the combination treatment achieved 45 percent and 37 percent reductions in noninflammatory and inflammatory lesion counts, respectively.
The closest comparator in terms of noninflammatory lesions was tretinoin 0.025 percent, which achieved a 38 percent reduction (Leyden JJ, et al. Poster presented at 63rd Annual American Academy of Dermatology/AAD Meeting; February 18-22, 2005; New Orleans, La.).
Similarly, a recent randomized, blinded multi-center trial pitted tazarotene cream 0.1 percent plus clindamycin 1 percent gel versus tretinoin 0.025 percent plus clindamycin 1 percent gel. At 12 weeks, the tazarotene/clindamycin combination achieved a mean improvement of nearly two grades (on a six-point scale) versus slightly more than one grade for tretinoin/clindamycin in terms of overall disease severity (Tanghetti EA, et al. Poster presented at 65th Annual AAD Meeting; February 2-6, 2007; Washington, D.C.).
Choosing the right combination
A topical antibiotic adds another dimension to topical combination therapy. However, Dr. Tanghetti says, "An important subtext is that one must pick the right combination."
If one chooses to use a retinoid and clindamycin product, he says, "Over a period of time, one will see issues with resistance problems. The most important issue in acne treatment today is preventing the spread of drug resistant P. acnes and other cutaneous bacteria, including Staphylococcus aureus, which in my community accounts for 75 percent of cutaneous infections I treat."
Fortunately, Dr. Tanghetti says, BPO helps prevent resistance, while also providing anti-inflammatory activity and exerting faster and greater anti-propionibacterial activity than topical antibiotics.