AIM:Given the chronic nature of acne, two 6-month studies were conducted to evaluate the long-term efficacy and tolerability of clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB)-the only approved triple-combination acne topical-and its effects on scarring/dyspigmentation in participants with moderate to severe acne. MATERIALS AND METHODS:Data were pooled from 2 identical, open-label, single-center studies conducted in participants (N = 50) aged ≥12 years with Investigator's Global Assessment (IGA) score of 3/4. Endpoints included change from baseline in IGA score, inflammatory/noninflammatory lesions, skin appearance (dryness, postinflammatory hyperpigmentation [PIH], postinflammatory erythema [PIE]), and scarring. Adverse events and tolerability (itching, burning, redness, swelling) were assessed. RESULTS:At week 24, 67% of participants achieved treatment success, and significant reductions from baseline in inflammatory (88%) and noninflammatory (68%) lesions were observed (p < 0.001, both). Significant reductions in scarring (33%), investigator- and participant-assessed PIH (71%; 78%, respectively), and PIE (77%; 77%, respectively) were demonstrated (p < 0.001, all). Most participants (>70%) reported no tolerability issues throughout the studies. Seven adverse events occurred; 4 were related to CAB, and 3 led to study discontinuation (BPO allergy [n = 2], irritant contact dermatitis to BPO [n = 1]). CONCLUSIONS:These findings suggest that CAB is an appropriate and effective topical option for the long-term treatment of acne vulgaris.
Introduction Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel—the only approved triple-combination acne topical—was efficacious and well tolerated in 12-week clinical trials and in 24-week studies. Acne presentation and sequelae vary by skin type, requiring long-term management strategies to account for differences in skin pigmentation. This post hoc analysis assessed long-term efficacy and tolerability of acne treatment with CAB gel in participants with Fitzpatrick skin phototypes IV-VI. Methods Data were pooled from 2 identical, postmarketing, 24-week, single-center, open-label studies of once-daily CAB gel in 50 participants ≥12 years with moderate to severe acne (Investigator’s Global Assessment [IGA] score=3 or 4). Endpoints included changes from baseline in IGA score and inflammatory/noninflammatory lesions at week 24. Scarring (assessed using the Goodman Qualitative Scar Scale), skin appearance (dryness, postinflammatory hyperpigmentation [PIH], postinflammatory erythema [PIE]), tolerability (itching, burning, redness, swelling), and adverse events (AEs) were evaluated. Results Of 24 participants with Fitzpatrick skin types IV-VI, 22 completed the studies. Participants were a mean age of 26.6 years and 86.4% were female. At week 24, 73% of participants achieved treatment success (≥2-grade reduction from baseline in IGA score and clear/almost clear skin), with reductions in inflammatory and noninflammatory lesions of 90% and 66%, respectively. PIH, PIE, and scarring improved from baseline by 71%, 87%, and 32%, respectively. No participants reported tolerability issues at week 24 and all had skin dryness scores of 0 (none). One participant experienced an AE (bronchitis), which was deemed unrelated to study product. Conclusions In participants with darker skin phototypes, 6 months of once-daily CAB gel use led to 73% treatment success and inflammatory lesion reductions of 90%. These improvements are higher than those seen at week 12 in the pivotal trials and support the long-term use of CAB gel in patients with darker skin phototypes.
ABSTRACTObjectivesThis work highlights the methods used to develop a multi‐pulse 1726 nm laser system combined with bulk air‐cooling for selective sebaceous gland (SG) photothermolysis using thermal imaging and software algorithms. This approach enables treating to a desired tissue temperature and depth to provide a safe, effective, reproducible, and durable treatment of acne.MethodsWe designed and built a 1726 nm laser system with a 40 W maximum power output, a highly controlled air‐cooling device, and a thermal camera in the handpiece, which permits real‐time temperature monitoring of the epidermis. IRB‐approved safety and efficacy trials demonstrated SG damage at depth, resulting in safe, efficacious, and durable clinical outcomes. Bioheat transfer and light transport modeling confirmed that the pulsing protocols could produce therapeutic temperatures at various SG depths, while protecting the epidermis and dermis with bulk air‐cooling. Similarly, we employed clinical observations and photothermal modeling to identify pain mitigation opportunities while maintaining therapeutic efficacy. Biopsies were subsequently taken for histological evaluation.ResultsClinical and histological data, confirmed with modeling, demonstrated that multi‐pulse laser delivery with bulk air‐cooling selectively increased SG temperature compared to surrounding dermis and at depths unachievable by a single pulse. Subjects showed an average 71% ILC reduction at 3 months posttreatment. We identified two different pulsing protocols with similar selective photothermolysis (SP) of the SG with very different pain responses. Thus, changing the pulsing protocols allowed for pain mitigation and eliminated the need for injectable anesthetic. Histology confirmed the selective damaging of the SG at depth and the preservation of the surrounding dermis and the epidermis.ConclusionsThe multi‐pulse 1726 nm laser with bulk air‐cooling, thermal monitoring, treat‐to‐temperature (and depth) control, and a unique pulsing protocol, is capable of selectively damaging SGs at depth without damage to the surrounding dermis or the epidermis. The system offers two different protocols that were developed with different levels of discomfort allowing for two different methods for pain mitigation (injectable vs. topical anesthesia).
BACKGROUND:Nonablative lasers treat photoaged skin and stimulate new collagen formation while sparing epidermal damage. OBJECTIVE:To evaluate the effectiveness and safety of nonablative fractional diode combination laser skin resurfacing treatment (1440 and 1927 nm) in mild-to-moderate photoaged skin. MATERIALS AND METHODS:The entire face was treated with both 1440-nm and 1927-nm wavelengths per treatment, with a total of 4 treatments spaced 1 month apart. Follow-up occurred at 1 and 3 months post-treatment. Outcomes were improvement in the appearance of ≥1 measure of photodamage (rhytides, skin texture, dyschromia/pigment, skin radiance, pore size, and overall appearance) at the 3-month (primary) and 1-month (secondary) follow-up visits. Safety was monitored throughout the study. RESULTS:Participants ( N = 28; 89% female; mean age, 40 years) experienced significant mean improvement from baseline in all measures of photodamage with combination laser treatment at 1 and 3 months post-treatment (all p < .001). No serious adverse events occurred. Post-treatment erythema and edema were minimal, and pain levels remained consistent throughout treatment. Most participants (96.4%) considered their overall appearance as improved and expressed satisfaction with treatment outcomes. CONCLUSION:Nonablative combination laser skin resurfacing treatment was well tolerated and significantly improved measures of photodamage in photoaged skin across diverse skin types.
Background: Topical treatment of acne—particularly with retinoids—often incurs a transient period of dermal irritation characterized by erythema, scaling, and other dermal changes that may reflect the same mechanisms of action by which acne pathophysiology is addressed. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel demonstrated efficacy in the treatment of acne, with a safety/tolerability profile typical of topical acne treatment. The objective of this post-hoc analysis is to determine whether CAB efficacy was related to occurrence of cutaneous safety/tolerability events. Methods: Data were pooled from 4 double-blind, 12-week studies of participants with moderate-to-severe acne. Efficacy endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of 0 or 1 [clear/almost clear]) and reductions from baseline in inflammatory (IL) and noninflammatory lesions (NIL). Cutaneous safety/tolerability assessments of erythema and scaling (investigator-assessed) and itching, burning, and stinging (participant-assessed) were graded on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe). To determine if CAB efficacy was associated with cutaneous events, efficacy endpoints at week 12 were compared for CAB-treated participants who experienced no increase versus ≥1-grade (any) increase in any safety/tolerability score at weeks 2, 4, or 8. Results: At week 12, CAB-treated participants experiencing any safety/tolerability event (n=411) had significantly greater rates of treatment success and IL reductions, and numerically greater NIL reductions, than those without events (n=188; treatment success: 55.0% vs 43.0%; P<0.01; IL reductions: 79.1% vs 72.3%; P<0.001; NIL reductions: 73.1% vs 68.1%). At weeks 2, 4, and 8, IL/NIL reductions were significantly greater among participants experiencing any cutaneous event than those without events (P<0.05, all). Overall, improved efficacy appeared to be driven by events of scaling, itching, and burning. Conclusions: Across four clinical studies, CAB-treated participants who experienced safety/tolerability events at weeks 2, 4, or 8 also experienced greater lesion reductions across 12 weeks of treatment and greater rates of treatment success at week 12. These findings are consistent with the theory that early instances of cutaneous irritation during topical acne treatment may reflect therapeutic mechanisms of action. Setting patient expectations regarding the potential for transient irritation during treatment may contribute to greater adherence and efficacy with CAB gel. Funding: Ortho Dermatologics
