Kircik Leon H., Papp Kim A., Stein Gold Linda, Harris Susan, Pharm Tina Lin, Pillai Radhakrishnan
J Drugs Dermatol. 2019 Mar 1;18(3):279-284..
Background: Fixed combinations are commonplace in dermatology, providing significant efficacy and tolerability benefits. In some cases, two active ingredients complement each other providing a cumulative or additive effect. In rarer cases, a synergistic effect may be seen where the sum of the two active ingredients combined action is greater than the sum of the efficacy of the constituent parts. Objective: To determine whether a novel halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) fixed combination lotion provides a synergistic effect in the treatment of moderate-to-severe plaque psoriasis. Methods: Post hoc analysis of 212 patients with moderate-to-severe plaque psoriasis randomized (2:2:2:1) to HP/TAZ lotion, HP, TAZ or vehicle once-daily for 8 weeks, with a 4-week posttreatment follow-up. Treatment success was evaluated based on two outcomes: percent of patients achieving at least a 2-grade improvement in Investigator Global Assessment (IGA) and IGA score equating to ‘clear’ or ‘almost clear’; and percent change from baseline in the IGAxbody surface area (BSA) score, an alternative to assessing response to therapy that is more sensitive to area change than the Psoriasis Area Severity Index (PASI). In addition, a clinically meaningful outcome was reported in patients who achieved a 75% reduction in IGAxBSA. Synergy was established when the benefit of combination HP/TAZ lotion was greater than benefit of HP plus TAZ, with a ratio (HP/TAZ divided by HP+TAZ) >1.0. Results: HP/TAZ lotion was synergistic at week 8, and four weeks posttreatment. At week 8, treatment success with HP/TAZ lotion relative to vehicle was 42.8% compared with 32.5% for HP plus TAZ (ratio 1.3); and percent change from baseline in IGAxBSA score relative to vehicle was 51.6% compared with 40.6% for HP plus TAZ (ratio 1.3). At week 12, treatment success with HP/TAZ lotion relative to vehicle was 31.3% compared with 20.0% for HP plus TAZ (ratio 1.6). Percent change from baseline in IGAxBSA score relative to vehicle was 47.3% compared with 34.2% for HP plus TAZ (ratio 1.4). HP/TAZ lotion also provided synergistic benefits in terms of achieving a clinically meaningful outcome, with a ratio of 1.3 and 2.0 at weeks 8 and 12. Conclusions: Halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) fixed combination lotion provides a synergistic benefit in the treatment of moderate-to-severe plaque psoriasis. In addition, by combining two agents into one once-daily formulation, this novel formulation reduces the number of product applications and may help patient adherence. J Drugs Dermatol. 2019;18(3):279-284.
固定复方在皮肤科很常见，具有显著的疗效和耐受性优势。在某些情况下，两种活性成分相互补充，产生累积或相加效应。在更罕见的情况下，可能会出现协同效应，即两种活性成分联合作用的总和大于各组成部分疗效之和。目的：确定新型0.01%丙酸氯倍他索和0.045%他扎罗汀（HP/TAZ）固定复方洗剂在治疗中重度斑块状银屑病时是否具有协同效应。方法：对212例中重度斑块状银屑病患者进行事后分析，将其随机分为（2:2:2:1）四组，分别使用HP/TAZ洗剂、HP、TAZ或赋形剂，每日一次，共8周，并在治疗后进行4周随访。基于两个结果评估治疗效果：达到研究者整体评估（IGA）至少改善2级且IGA评分等于“清除”或“几乎清除”的患者百分比；以及IGA×体表面积（BSA）评分相对于基线的变化百分比，这是一种评估治疗反应的替代指标，比银屑病面积和严重程度指数（PASI）对面积变化更敏感。此外，报告IGA×BSA降低75%的患者的具有临床意义的结果。当复方HP/TAZ洗剂的益处大于HP加TAZ的益处时，即比值（HP/TAZ除以HP+TAZ）>1.0时，确定为协同效应。结果：HP/TAZ洗剂在第8周和治疗后4周具有协同效应。在第8周，HP/TAZ洗剂相对于赋形剂的治疗成功率为42.8%，而HP加TAZ为32.5%（比值1.3）；IGA×BSA评分相对于赋形剂从基线的变化百分比为51.6%，而HP加TAZ为40.6%（比值1.3）。在第12周，HP/TAZ洗剂相对于赋形剂的治疗成功率为31.3%，而HP加TAZ为20.0%（比值1.6）。IGA×BSA评分相对于赋形剂从基线的变化百分比为47.3%，而HP加TAZ为34.2%（比值1.4）。HP/TAZ洗剂在实现具有临床意义的结果方面也具有协同益处，在第8周和第12周的比值分别为1.3和2.0。结论：0.01%丙酸氯倍他索和0.045%他扎罗汀（HP/TAZ）固定复方洗剂在治疗中重度斑块状银屑病时具有协同益处。此外，通过将两种药物组合成一种每日一次的制剂，这种新型制剂减少了用药次数，可能有助于提高患者的依从性。《药物皮肤病学杂志》。2019年；18（3）：279 - 284。
