MAUI, HAWAII – Combination therapy for severe acne, with a trio of familiar, well tolerated agents, knocked down the skin disease severity in a phase IV study such that 80% of patients deemed candidates for isotretinoin at baseline no longer qualified for the powerful oral retinoid 12 weeks later, Dr. Guy F. Webster reported at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
These data provide welcome news for patients who can’t take isotretinoin or don’t want to, as well as for the many physicians reluctant to prescribe the drug because of the considerable regulatory hassles and potentially serious side effects, including teratogenicity.
The treatment regimen in this open-label multicenter study consisted of an oral antibiotic, a topical antibiotic/retinoid agent, and benzoyl peroxide. More specifically, the 97 study participants aged 12-29 years, all with grade 3-4 moderate to severe facial acne by Investigator’s Global Assessment (IGA), were placed on once-daily minocycline HCL extended release at about 1 mg/kg, clindamycin phosphate 1.2%/tretinoin 0.025% gel, and 6% benzoyl peroxide foaming cloths. Patients were evaluated at weeks 0, 2, 4, 8, and 12.
Dr. Guy F. Webster
At week 2, 44% of subjects already had at least a 1-grade improvement in IGA; by week 12, 89% did. Moreover, 56% of patients had at least a 2-grade improvement in IGA.
At least a 1-grade improvement on the Global Aesthetic Improvement Scale was documented in 83% of subjects at week 2 and 96% at week 12.
"With this therapy, you can get patients with really bad acne from bad to really mild without resorting to big-time drugs," observed Dr. Webster, professor of dermatology and internal medicine at Thomas Jefferson University, Philadelphia.
Week 12 mean facial inflammatory lesion counts fell by 62%, and noninflammatory lesion counts decreased by 49% from baselines of 33 and 44 lesions, respectively.
At baseline, 69 patients were judged by three blinded assessors of clinical photos to have acne sufficiently severe for them to be candidates for isotretinoin therapy. By week 12, this number had dwindled to 14 patients. In other words, 80% of patients were no longer deemed to be candidates for isotretinoin.
Eight patients experienced treatment-related adverse events consisting of transient mild to moderate irritation and/or redness, burning, stinging, and dry skin.
The results of this Phase-4 study are consistent with studies of other multidrug regimens for acne, albeit mostly conducted in less severely affected patients.
"The general paradigm is that mixed therapies are useful because other than isotretinoin and maybe spironolactone, no one drug is strong enough to stop acne effectively. If you just hit the [Propionibacterium acnes] hard, you can’t get it down to where there’s no P. acnes. If you blunt the immune response, you’re still just blunting it, not turning it off. And if you’re addressing the plug in the follicle, it’s not a complete or rapid response," the dermatologist explained.
In clinical practice, Dr. Webster said he typically stops the oral antibiotic cold at about 12 weeks to avoid pigmentary changes and other side effects of long-term antibiotic therapy. At least 75% of patients can maintain their gains with topical therapy alone.
Compliance is often an issue with combination therapy. Patients need to understand that if they don’t use all of the medications consistently from day 1 they won’t get better.
"It’s tough with kids because kids expect to get better overnight. They see it on the Proactiv commercials and wonder why in the world they’re not better in 2 days," the dermatologist observed.
In this phase IV study, however, patient compliance was consistently excellent, perhaps because of the high disease severity. The treatment compliance rate was 91% at week 2 and 86% at week 12.
Dr. Webster is a consultant for several pharmaceutical companies, including Valeant, whose subsidiary Medicis sponsored the phase IV study.
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*This story was updated March 1, 2013.