Lack of Significant Anti-inflammatory Activity With Clindamycin in the Treatment of Rosacea: Results of 2 Randomized, Vehicle-Controlled Trials

Figure 3. Study A mean investigator global rosacea severity score at baseline and week 12 for clindamycin cream 1% twice daily versus vehicle cream twice daily (A) and clindamycin cream 1% once daily and clindamycin cream 0.3% once daily versus vehicle cream once daily (B). All P values were not significant.

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