When Do Efficacy Outcomes in Clinical Trials Correlate With Clinical Relevance? Analysis of Clindamycin Phosphate 1.2%–Benzoyl Peroxide 3.75% Gel in Moderate to Severe Acne Vulgaris
Acne vulgaris (AV) is a common skin disease that is challenging to successfully treat due to its complex underlying pathophysiology and chronicity. Unrealistic expectations based on the desire for rapid and complete clearance or local tolerability reactions related to topical medications often lead to incomplete adherence with therapy, premature treatment cessation, and poor therapeutic outcomes. Despite stressing to patients the importance of compliance and the lag time of several weeks before visible improvement may be noted with treatments for AV, data on evaluation of the time taken to achieve a clinically meaningful improvement of AV that may be perceived by clinicians and patients are limited. Clindamycin phosphate 1.2%–benzoyl peroxide 3.75% (clindamycin-BP 3.75%) gel has been shown in pivotal trials to be effective and well tolerated in patients with moderate to severe AV. This article reviews a new concept referred to as time to onset of action (TOA), which is described in detail and illustrated using the pivotal trial data with clindamycin-BP 3.75% gel for treatment of AV.
Practice Points
- Time to onset of action (TOA) refers to how long it takes after starting a therapy for a patient to perceive visible improvement.
- Time to onset of action has been determined based on data to date to correlate overall with a 25% lesion reduction.
- The TOA for clindamycin phosphate 1.2%–benzoyl peroxide 3.75% gel applied once daily based on analysis of pivotal trial data is 3 weeks or less depending on the severity of acne vulgaris at baseline.
There are limitations with this analysis. First, it is not possible to assess the contributions from each of the monads to the efficacy of clindamycin-BP 3.75% gel or TOA. Also, the data extraction method used assumes a linear progression model during the provided time points and was used to provide some comparison with calculations for other combination products.9 Although no strong deviations from the linear model are likely, calculations of TOA using other methodologies may give different results. The definition of a clinically meaningful benefit, defined here as a 25% reduction in the mean lesion count, has been used as a guide, but it has not been validated in clinical practice. It also is important to recognize that the initial visible perception of improvement of AV is likely to differ based on interpatient variability; that is, how different individuals perceive improvement. It also may be affected by differences in baseline severity of AV among different patients. Additionally, the TOA reflects an average duration of time, so it should not be described to patients as a suggestion of when they will definitely see visible improvement in their AV.
Conclusion
Unrealistic expectations of acne therapy or poor tolerability can lead to low adherence and poor clinical outcomes.1-4 The data on TOA reported here suggests that a clinically meaningful benefit with clindamycin-BP 3.75% gel may be seen in some patients within 2 to 3 weeks and maybe sooner in females or those with milder disease; however, longer durations may be required in some patients. This information can help clinicians and their staff in providing reasonable expectations and stress the importance of encouraging patients about the need to adhere to treatment.
Acknowledgments
The author thanks Brian Bulley, MSc (Inergy Limited, Lindfield, West Sussex, United Kingdom), for publication support. Valeant Pharmaceuticals North America, LLC, funded Inergy’s activities pertaining to this analysis. The author did not receive funding or any form of compensation for authorship of this publication.
