Lack of Significant Anti-inflammatory Activity With Clindamycin in the Treatment of Rosacea: Results of 2 Randomized, Vehicle-Controlled Trials
Rosacea is a chronic inflammatory skin disease of the face. The objective of the studies described here was to evaluate the efficacy of clindamycin in the treatment of rosacea. Two multicenter, randomized, vehicle-controlled, phase 2 studies were conducted in participants with moderate to severe rosacea. Study A was a 12-week dose-comparison, 5-arm, parallel group comparison of clindamycin cream 1% or vehicle once or twice daily and clindamycin cream 0.3% once daily. Study B was a 2-arm comparison of twice daily clindamycin gel 1% versus vehicle gel. A total of 629 participants (study A, N=416; study B, N=213) were randomized. The results of these studies indicated that clindamycin cream 0.3% and 1% and clindamycin gel 1% were no more effective than the vehicle in the treatment of moderate to severe rosacea, suggesting clindamycin has no intrinsic anti-inflammatory activity in rosacea.
Practice Points
- Clindamycin cream 0.3% and 1% and clindamycin gel 1% were no more effective than their respective vehicles in the treatment of moderate to severe rosacea.
- Clindamycin may have no intrinsic anti-inflammatory activity in rosacea.
Results
Participant Disposition and Baseline Characteristics
Overall, a total of 629 participants were randomized across both studies. In study A, a total of 416 participants were randomized into 5 treatment arms, with 369 participants (88.7%) completing the study; 47 (11.3%) participants discontinued study A, mainly due to participant request (19/47 [40.4%]) or lost to follow-up (11/47 [23.4%]). In study B, a total of 213 participants were randomized to receive either clindamycin gel 1% (n=109 [51.2%]) twice daily or vehicle gel (n=104 [48.8%]) twice daily, with 193 participants (90.6%) completing the study; 20 (9.4%) participants discontinued study B, mainly due to participant request (6/20 [30%]) or lost to follow-up (4/20 [20%]). Participants in studies A and B were similar in demographics and baseline disease characteristics (Table). The majority of participants were white females.
Efficacy
No statistically significant difference was observed in all pairwise comparisons (clindamycin cream twice daily vs vehicle twice daily, clindamycin cream once daily vs vehicle once daily, clindamycin gel vs vehicle gel) for the primary end point of mean percentage change from baseline in inflammatory lesion counts at week 12 (Figure 1; P>.5 for all pairwise comparisons).
,
At week 12, the proportion of participants in study B deemed as a success (none/clear or mild/almost clear [investigator global rosacea severity score of 0 or 1]) in the clindamycin gel 1% and vehicle gel groups were 45% versus 38%, respectively (P=.347) (Figure 2).
For the secondary end point of mean investigator global rosacea severity assessment at week 12 (study A), there were no significant differences between the active and vehicle control groups (P>.5 for all pairwise comparisons)(Figure 3). Also, the proportion of participants with at least a moderate investigator global improvement assessment from baseline to week 12 ranged from 45% for clindamycin cream 1% twice daily to 56% for clindamycin cream 0.3% cream once daily and from 45% for vehicle cream once daily to 51% for vehicle cream twice daily (P>.5 for all pairwise comparisons).
There were no significant differences in the mean total erythema severity scores at week 12 for clindamycin cream 1% twice daily versus vehicle cream twice daily (6.3 vs 6.0; P>.5), clindamycin cream 1% once daily versus vehicle cream once daily (6.2 vs 6.0; P>.5), clindamycin cream 0.3% once daily versus vehicle cream once daily (5.9 vs 6.0; P>.5), and clindamycin gel 1% twice daily versus vehicle gel twice daily (6.7 vs 6.2; P>.5).
There were no relevant differences between any of the clindamycin cream groups and their respective vehicle group at week 12 for skin irritation, including desquamation, edema, dryness, pruritus, and stinging/burning.
Safety
In study A, the majority of AEs in all 5 treatment arms were nondermatologic, mild in intensity, and not considered to be related to the study treatment by the investigator. Overall, 12 participants had AEs considered by the investigator as possibly or probably related to the study treatment: 4.9% in the clindamycin cream 1% twice daily group, 4.6% in the clindamycin cream 1% once daily group, 3.7% in the vehicle cream twice daily group, 1.2% in the clindamycin cream 0.3% once daily group, and 0% in the vehicle cream once daily group. Two treatment-related AEs led to treatment discontinuation, including dermatitis in 1 participant from the clindamycin cream 1% once daily group and contact dermatitis in 1 participant from the clindamycin cream 1% twice daily group.
Comment
No evidence of increased efficacy over the respective vehicles was observed with clindamycin cream or gel, whatever the regimen, in the treatment of rosacea patients in either of these well-designed and well-powered, blinded studies. Slight improvements in the various efficacy criteria were observed, even in the vehicle groups, highlighting the importance of using a good basic skin care regimen in the management of rosacea.9 In contrast to our observations of lack of efficacy in the treatment of rosacea, clinical efficacy of clindamycin has been demonstrated in acne,10-12 albeit with low efficacy for clindamycin monotherapy.13 It is noteworthy that oral or topical antibiotics are no longer recommended as monotherapy for acne to prevent and minimize antibiotic resistance and to preserve the therapeutic value of antibiotics.14
Acne and rosacea are both chronic inflammatory disorders of the skin associated with papules and pustules, and they share some common inflammatory patterns.15-19 Furthermore, the intrinsic anti-inflammatory activity of clindamycin in addition to its antibiotic effects has been suggested by some authors as the main reason for treating acne with clindamycin.20 However, the relative contributions of antibacterial and/or anti-inflammatory properties remain to be fully elucidated, and evidence for direct anti-inflammatory effects of clindamycin remains heterogeneous.21,22 Several pathophysiological factors have been implicated in acne, including hormonal effects, abnormal keratinocyte function, increased sebum production, and microbial components (eg, hypercolonization of the skin follicles by Propionibacterium acnes).23,24 The antibiotic activity of clindamycin against P acnes may be the key factor responsible for the clinical effects in acne.25,26 Although clindamycin may have anti-inflammatory effects in acne via a different inflammatory pathway not shared by rosacea, a purely antibiotic mechanism of action of clindamycin also could explain why we observed no evidence of efficacy in the treatment of rosacea, as no causative bacterial component has been clearly demonstrated in rosacea.27
Conclusion
In these studies, clindamycin cream 0.3% once daily, clindamycin cream 1% once or twice daily, and clindamycin gel 1% twice daily were all well tolerated; however, they were no more effective than the vehicles in the treatment of moderate to severe rosacea.
Acknowledgment
The authors would like to thank Helen Simpson, PhD, of Galderma R&D (Sophia Antipolis, France), for editorial and medical writing assistance.
