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July 20, 2007 (芝加哥) — 一篇发表于小儿皮肤科学会(Society for Pediatric Dermatology (SPD)) 第33届年会的研究显示，治疗12到18岁青少年的青春痘，含有1.2%clindamycin和0.025% tretinoin的一种外用凝胶，比这两种成分的单方制剂药物有效。
同一研究团队也对在今年稍早上市的这个新的抗生素-A酸凝胶 (Ziana, Medicis)进行了另外两个研究，发现此药对12到36岁病患耐受良好且有长期安全性。
两项重要小儿研究中一大群12到18岁的病患(n = 1710)参加了这个药物的试验，发表人是Medicis 公司执行副总裁暨主要科学组员Mitchell Wortzman博士，和同事研究clindamycin-tretinoin的效果 (n = 572) ，为期12周 ，和0.25% tretinoin凝胶 (n = 560)、1.2% clindamycin (n = 284)、或无药效的赋形剂 (n = 294)进行比较。
第12周时显示，复方药物在减少发炎、非发炎区域病灶，以及全部病灶上，明显比tretinoin或无药效的赋形剂更佳(P < .001)，在非发炎区域病灶以及全部病灶与clindamycin效果一样；至于发炎病灶区域，研究药物与clindamycin间则没有显著差异；对开始时任何程度的青春痘(轻度到严重) 之结果均一致。
耐受性研究中，作者治疗45位小孩和成人(平均年纪24.6岁)，以 clindamycin-tretinoin每天一次在脸之一侧治疗 21天，他们随机筛选病患，另一侧的脸接受0.1% adapalene 凝胶 (22位病患)或者0.1% tretinoin microsphere凝胶(23位病患)；评估者并不知道治疗疗程，且使用标准的4点距量表评估红斑和皮鳞。
Clindamycin-tretinoin者累积的红斑和皮鳞，以及病患自述的灼热、痒和刺痛显著比0.1% tretinoin microsphere凝胶者减少 (P 值未知)；研究者报告，第22天时，使用此一研究药物者不到20%的病患出现红斑或者皮鳞，使用tretinoin 有超过60%出现红斑，且超过50%有皮鳞；Adapalene 也有较高之累积的红斑(38.4%的病患)和皮鳞(53.8%)，clindamycin-tretinoin分别只有25.7%和 35.3%，不过，差异并未达统计上的显著差异。
Wortzman博士形容这个在去年11月获得美国食品药物管理局(FDA)核准的复方药物时表示，只有很少的皮肤发炎。
Wortzman博士提出许多新配方比0.1% tretinoin microsphere凝胶耐受更好的理由，他向Medscape表示，赋形剂是无酒精基剂，而tretinoin是以设计来延迟药物分布于皮肤的结晶形式；同时，复方药物的tretinoin浓度比0.1% tretinoin microsphere凝胶的tretinoin浓度低；Tretinoin microsphere 凝胶另外有0.04% 配方，但此一配方未包含在此研究中。
未参与此研究的SPD前总裁，维吉尼亚州Fairfax的开业小儿皮肤科医师Robert Silverman表示，tretinoin浓度越高，所预期的皮肤刺激就更大；但是，Silverman医师表示，clindamycin 和 tretinoin 复方有单纯治疗标准面疱和发炎青春痘的潜力，且就其本身而论，需改善病患的顺从性，不过，顺从性并未在这些研究之中被评估。
在安全性研究中，进行一个 52周的开放标签试验，Wortzman 医师和同事报告指出clindamycin-tretinoin 凝胶在655位病患安全且耐受良好(平均年纪20岁)，这些病患的青春痘程度从轻微到严重都有，是一个第3期随机双盲赋型剂控制的多中心临床试验中的一群病患，因为这是一个长期安全研究，Wortzman 医师表示，病患被允许合并使用药物，不过仅占30%。
根据摘要，在12个月的研究中，clindamycin-tretinoin 凝胶的病患超过90% 未报告有灼热、痒和刺痛；再者，因副作用而停用的比率不到1%。
根据Wortzman 医师所述，本研究未筛选抗生素阻抗菌株，他向Medscape表示，如果考虑到阻抗性，可以并用过氧化苯（Benzoyl peroxide）。
Silverman 向 Medscape 表示，此新药是昂贵的，要说它是否将改变临床实务，仍为时过早。
本研究接受Medicis资金赞助，Wortzman 医师为Ziana 的制造商Medicis工作，Silverman 医师的报告和Medicis没有相关财经关系。
小儿皮肤科学会第33届年会：海报2, 3,和 4。发表于2007年7月13-14日。
New Gel Formulation of Acne Drugs Is Effective for Adolescents
By
Medscape Medical News
July 20, 2007 (Chicago) — A gel that combines topical 1.2% clindamycin and 0.025% tretinoin treats acne vulgaris in children aged 12 to 18 years as or more effectively than either of its active ingredients alone, a study presented at the Society for Pediatric Dermatology (SPD) 33rd Annual Meeting shows.
The novel antibiotic-retinoid gel (Ziana, Medicis), which has been on the market since early this year, also was found in 2 other studies conducted by the same group to be tolerable and have long-term safety in patients aged 12 to 36 years.
The pediatric study was done in a large subgroup (n = 1710) of patients aged 12 to 18 years who participated in 2 pivotal trials of the study drug. Presenter Mitchell Wortzman, PhD, executive vice president and chief scientific officer of Medicis in Scottsdale, Arizona, and coauthors studied the efficacy of clindamycin-tretinoin (n = 572) during 12 weeks' treatment compared with 0.25% tretinoin gel (n = 560), 1.2% clindamycin (n = 284), or vehicle (n = 294).
At week 12 the combination medication showed significantly better (P < .001) reductions in both inflammatory and noninflammatory acne lesions and total lesions compared with tretinoin or vehicle and in noninflammatory and total lesions compared with clindamycin. For inflammatory lesions there was no statistically significant difference in efficacy between the study drug and clindamycin. Results applied to all baseline severities of acne (from mild to severe).
In the tolerability study, the authors treated 45 children and adults (mean age, 24.6 years) with clindamycin-tretinoin once daily on 1 side of the face for 21 days. They randomly selected patients to receive either 0.1% adapalene gel (22 patients) or 0.1% tretinoin microsphere gel (23 patients) on the opposite side. The evaluator was blinded to the treatment schedule and used a standard 4-point scale to assess erythema and skin scaling.
Cumulative erythema and skin scaling as well as patient-reported burning, itching, and stinging were significantly less with clindamycin-tretinoin than with 0.1% tretinoin microsphere gel (P not given). At day 22, less than 20% of patients had erythema or scaling using the study drug, whereas more than 60% of those receiving tretinoin had erythema and greater than 50% had scaling, the authors reported. Adapalene also had higher cumulative erythema (38.4% of patients) and scaling (53.8%) than clindamycin-tretinoin (25.7% and 35.3%, respectively), but the difference was not statistically significant.
"You get very little skin irritation," Dr. Wortzman said of the combination medication, which the US Food and Drug Administration approved last November.
Dr. Wortzman proposed several reasons why the new formulation may be more tolerable than 0.1% tretinoin microsphere gel. The vehicle has an alcohol-free water base, he told Medscape, and the tretinoin is in a crystalline form designed to slowly dispense the drug to the skin. Also, the combination drug has a lower concentration of tretinoin than 0.1% tretinoin microsphere gel, he noted. Tretinoin microsphere gel is also available in a 0.04% formulation, although this formulation was not included in this study.
"You would expect to get more irritation with [the higher strength of tretinoin]," said Robert Silverman, MD, a pediatric dermatologist in private practice in Fairfax, Virginia, and a past president of SPD. Dr. Silverman was not involved in the study.
"But the combination of clindamycin and tretinoin does potentially simplify treatment of standard comedonal and inflammatory acne," Dr. Silverman added, "and, as such, should improve patient compliance."
However, compliance was not evaluated in either of these studies.
In the safety study, a 52-week open-label trial, Dr. Wortzman and colleagues reported clindamycin-tretinoin gel to be safe and well tolerated in 655 patients (mean age, 20 years). These patients had acne vulgaris ranging from mild to severe and were a subgroup of patients from phase 3, randomized, double-blind, vehicle-controlled, multicenter clinical trials. Because it was a long-term safety study, Dr. Wortzman said patients were allowed to use concomitant medications, but only 30% did so.
More than 90% of patients treated with clindamycin-tretinoin gel reported no burning, stinging, or itching during the 12-month study, according to the abstract. Furthermore, the discontinuation rate resulting from adverse events was less than 1%.
The study did not screen for antibiotic-resistant organisms, according to Dr. Wortzman. He told Medscape, "If one is concerned about resistance, one can add the use of benzoyl peroxide."
Noting that the new drug is expensive, Dr. Silverman told Medscape it is too soon to tell whether it will change clinical practice.
The studies were funded by Medicis. Dr. Wortzman works for Medicis, the manufacturer of Ziana. Dr. Silverman reports no relevant financial relationship with Medicis.
Society for Pediatric Dermatology 33rd Annual Meeting: Posters 2, 3, and 4. Presented July 13–14, 2007.