Aesthetic Implantation of Calcium Hydroxylapatite Does Not Interfere With Radiological Assessment of Bones in the Dorsum of the Hands.

BACKGROUND: Calcium hydroxylapatite (CaHA) is a radiopaque dermal filler used to provide volume correction in the dorsum of the hand. OBJECTIVES: The aim of this study was to evaluate whether CaHA implantation in the dorsum of the hand interferes with radiological assessment by obscuring the bones. METHODS: This 2-year, prospective, single-center, open-label study enrolled 20 subjects with Merz Hand Grading Scale (MHGS) grades ranging from moderate (MHGS 2 or 3; n = 10) to very severe (MHGS 4; n = 10). All subjects received an initial CaHA treatment and were offered up to 3 retreatments to provide volume correction in the dorsum of the hands, over a period of 18 months. Bone obscuration was assessed by blinded, licensed radiologists responsible for interpreting plain radiographs (X-rays). RESULTS: CaHA was seen to be present in 100% of hands in Month 1 X-rays and in 83.3% in Month 24 X-rays, but no bone obscuration was reported in any X-rays at any evaluated time point. CONCLUSIONS: According to blinded radiologists, treatment with CaHA in the dorsum of the hand does not obscure radiographic assessment of the bones seen on X-rays up to 24 months after initial injection. The safety of CaHA retreatment was also demonstrated by the lack of bone obscuration after multiple retreatments.

Effectiveness and Safety of Calcium Hydroxylapatite With Lidocaine for Improving Jawline Contour.

BACKGROUND: One of the early signs of aging is loss of jawline contour. Not all cases require surgical intervention and soft-tissue augmentation with injectable fillers may restore the profile and youthful appearance of the jawline. OBJECTIVE: To demonstrate the effectiveness and safety of calcium hydroxylapatite with lidocaine [CaHA (+); Radiesse® (+)] to improve the contour of jawline after deep (subdermal and/or supraperiosteal) injection. METHODS: Healthy eligible patients with moderate or severe ratings on the Merz Jawline Assessment Scale (MJAS) were randomized 2:1 to treatment with CaHA (+) or to control. Patients in the control group remained untreated until week 12, then received delayed treatment. Touch-ups were allowed in both groups, and re-treatment was allowed in the treatment group only. Effectiveness was evaluated on the MJAS, patient and investigator Global Aesthetic Improvement Scales, and FACE-Q™ questionnaires. Adverse events were recorded over a 60-week period. RESULTS: Treatment response rate (≥1-point MJAS improvement) was 93/123 (75.6%) for the treatment group and 5/57 (8.8%) for the control/delayed-treatment group at week 12. The difference between response rates was statistically significant (P<0.0001), showing superiority of treatment over control. Satisfaction with aesthetic improvement was reported by patients and treating investigators throughout the study. A total of 76/113 (67.3%) patients who responded to treatment 12 weeks after initial injection also demonstrated persistent improvement 48 weeks after initial treatment. The study demonstrated a favorable safety profile, with no reported unexpected adverse events. CONCLUSIONS: CaHA (+) is a safe and effective treatment for improving the contour of the jawline. J Drugs Dermatol. 2021;20(11): 1231-1238. doi:10.36849/JDD.6442.

Observational Study of Clindamycin Phosphate and Tretinoin Gel for the Treatment of Acne

INTRODUCTION: Acne vulgaris can cause pain/discomfort and have a negative impact on quality of life (QOL). Clin-RA is an acne treatment consisting of clindamycin phosphate 1.2% and tretinoin 0.025%, which has been proven effective and well tolerated in clinical studies. This prospective, non-interventional study aimed to capture data on previous treatment, acne severity, and QOL in patients with acne treated with Clin-RA and assess the efficacy and tolerability of Clin-RA in routine clinical practice. METHODS: The study was performed at 18 centers in Sweden and enrolled patients aged ≥15 years with acne, who were prescribed Clin-RA for the first time. The observation period was ~12 weeks. The primary objective was to assess the patient's perception of their facial acne severity before and during Clin-RA treatment using a visual analog scale (VAS; 100 mm scale). Secondary objectives included QOL evaluation before and after treatment, using the Dermatology Life Quality Index (DLQI) questionnaire. RESULTS: 84 patients were enrolled and eligible for analyses (79.8% female; mean age 22.6 years). Patient-assessed VAS scores for acne severity decreased continuously during the study, indicating improvement: the median percentage reduction from baseline for VAS score was 17.6% at week 4 and 63.8% at week 12, with changes from baseline being statistically significant (P=0.0004 at week 4; P<0.0001 at weeks 8 and 12). Overall, QOL improved after Clin-RA treatment, reflected by a decrease in the mean (standard deviation) DLQI sum score from 8.8 (5.8) on day 0 to 4.9 (4.2) at week 12. Seventy percent of patients were satisfied/very satisfied with treatment. Clin-RA was well tolerated, with no serious adverse drug reactions reported. CONCLUSIONS: Treatment with Clin-RA resulted in continuous improvement of facial acne over the course of 12 weeks, along with improved QOL and a tolerable safety profile, supporting the use of Clin-RA in clinical practice. J Drugs Dermatol. 2019;18(4):328-334.

Study of the Atopic March: Development of Atopic Comorbidities.

BACKGROUND: Atopic dermatitis (AD) is often the first step in the atopic march leading to the development of asthma or allergic rhinitis. The goal of this study was to determine whether early intervention with pimecrolimus limits the atopic march in infants with AD and to evaluate its efficacy and safety. METHODS: This was a 3-year double-blind study in which patients were randomized to pimecrolimus or vehicle and then open-label pimecrolimus for a planned further 3 years. Rescue topical corticosteroid was permitted if 3 days of study medication led to no improvement; investigators made decisions on rescue medication until week 14 and caregivers thereafter. Efficacy assessments included disease-free days, Eczema Area and Severity Index, and body surface area affected. RESULTS: Infants ages 3 to 18 months with recent-onset AD (≤3 months) were observed for a mean of 2.8 years (N = 1,091). No significant differences between pimecrolimus- and placebo-treated groups were found in the percentage of patients with AD who developed asthma (10.7%) or other allergic conditions (allergic rhinitis, 22.4%; food allergy, 15.9%; allergic conjunctivitis, 14.1%; one or more atopic comorbidities, 37.0%) by study end. Allergic rhinitis, food allergy, and having one or more atopic comorbidities (but not asthma or allergic conjunctivitis alone) developed significantly more often in infants with greater AD severity at baseline. Pimecrolimus was significantly more effective than vehicle for AD treatment at week 14. Adverse event incidences were similar. CONCLUSIONS: This longitudinal observation of infants with AD provides evidence of the atopic march. Pimecrolimus was safe and effective in infants with mild to moderate AD.

Efficacy and Safety of Imiquimod 3.75% from Lmax in Actinic Keratosis According to Fitzpatrick Skin Type.

BACKGROUND: Imiquimod 3.75% is an effective actinic keratosis (AK) treatment that detects and clears clinical and subclinical lesions across an entire sun-exposed field such as the full face or balding scalp. OBJECTIVE: To determine the efficacy and safety of imiquimod 3.75% according to patients' Fitzpatrick skin type. METHODS: Data were pooled from two identical 14-week, double-blind studies. Patients were randomized to imiquimod 3.75% or placebo and applied study medication to the full face or balding scalp each day for 2 two-week treatment cycles separated by a two-week treatment-free interval. End of study (EOS) was eight weeks after the last treatment application. Patients were subgrouped according to whether they had Fitzpatrick skin types I or II (FST I/II), or types III or IV (FST III/IV). Efficacy was analyzed using the reduction in lesions from Lmax (maximum lesion count during treatment) to EOS. This assesses whether clinical lesions, and subclinical lesions which become detectable during treatment, are cleared. Safety was assessed by monitoring local skin reactions. RESULTS: In total, 173 patients with FST I/II and 142 with FST III/IV were included. The median percentage reductions in lesions from Lmax to EOS were similar in patients treated with imiquimod 3.75% with FST I/II and FST III/IV (94.2% and 89.7%, respectively) as were the median absolute reductions in lesions from Lmax to EOS (19.0 and 17.0, respectively). These reductions were significantly greater with imiquimod 3.75% versus placebo in the two respective FST subgroups (P<0.0001). The frequency of local skin reactions was similar in the two imiquimod 3.75% FST subgroups. CONCLUSIONS: Imiquimod 3.75% is well tolerated and effective at clearing clinical and subclinical lesions across large areas of sun-exposed skin in patients with FST I-IV, and so can be considered for AK patients with any of these skin types.

Safety and efficacy of pimecrolimus in atopic dermatitis: a 5-year randomized trial.

BACKGROUND AND OBJECTIVES: Atopic dermatitis (AD) primarily affects infants and young children. Although topical corticosteroids (TCSs) are often prescribed, noncorticosteroid treatments are needed because compliance with TCSs is poor due to concerns about their side effects. In this longest and largest intervention study ever conducted in infants with mild-to-moderate AD, pimecrolimus 1% cream (PIM) was compared with TCSs. METHODS: A total of 2418 infants were enrolled in this 5-year open-label study. Infants were randomized to PIM (n = 1205; with short-term TCSs for disease flares) or TCSs (n = 1213). The primary objective was to compare safety; the secondary objective was to document PIM's long-term efficacy. Treatment success was defined as an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear). RESULTS: Both PIM and TCSs had a rapid onset of action with >50% of patients achieving treatment success by week 3. After 5 years, >85% and 95% of patients in each group achieved overall and facial treatment success, respectively. The PIM group required substantially fewer steroid days than the TCS group (7 vs 178). The profile and frequency of adverse events was similar in the 2 groups; in both groups, there was no evidence for impairment of humoral or cellular immunity. CONCLUSIONS: Long-term management of mild-to-moderate AD in infants with PIM or TCSs was safe without any effect on the immune system. PIM was steroid-sparing. The data suggest PIM had similar efficacy to TCS and support the use of PIM as a first-line treatment of mild-to-moderate AD in infants and children.

Efficacy and safety of clindamycin phosphate 1.2%/tretinoin 0.025% formulation for the treatment of acne vulgaris: pooled analysis of data from three randomised, double-blind, parallel-group, phase III studies.

BACKGROUND: The efficacy and safety of clindamycin phosphate 1.2%/tretinoin 0.025% (Clin-RA) were evaluated in three 12-week randomised studies. OBJECTIVES: To perform a pooled analysis of data from these studies to evaluate Clin-RA's efficacy and safety in a larger overall population, in subgroups of adolescents and according to acne severity. MATERIALS & METHODS: 4550 patients were randomised to Clin-RA, clindamycin, tretinoin and vehicle. Evaluations included percentage change in lesions, treatment success rate, proportions of patients with ≥50% or ≥80% continuous reduction in lesions, adverse events and cutaneous tolerability. RESULTS: In the overall population, the percentage reduction in inflammatory, non-inflammatory and total lesions and the treatment success rate were significantly greater with Clin-RA compared with clindamycin, tretinoin and vehicle alone (all p<0.01). The percentage reduction in all types of lesions was also significantly greater with Clin-RA in the adolescent subgroup (2915 patients, p<0.002) and in patients with mild/moderate acne (3662 patients, p<0.02) versus comparators. In patients with severe acne (n = 880), the percentage reduction in all lesion types was significantly greater with Clin-RA versus vehicle (p<0.0001). A greater proportion of Clin-RA treated patients had a ≥50% or ≥80% continuous reduction in all types of lesions at week 12 compared with clindamycin, tretinoin and vehicle. Adverse event frequencies in the active and vehicle groups were similar. Baseline-adjusted mean tolerability scores over time were <1 (mild) and similar in all groups. CONCLUSION: Clin-RA is safe, has superior efficacy to its component monotherapies and should be considered as one of the first-line therapies for mild-to-moderate facial acne.

Reduction in lesions from Lmax: a new concept for assessing efficacy of field-directed therapy for actinic keratosis. Results with imiquimod 3.75%.

BACKGROUND: Current parameters for assessing the efficacy of actinic keratosis (AK) treatments compare clinical lesions at the start and end of a study. However, the sun-exposed field also contains subclinical lesions which may become detectable during treatment. Lmax, the maximum lesion count during treatment, is a new concept to better assess the efficacy of field-directed AK therapies. Measuring efficacy using the reduction in lesions from Lmax includes for the first time the clearance of both subclinical and clinical lesions. OBJECTIVES: To evaluate the reduction of lesions from Lmax to study end and compare the results with traditional efficacy endpoints using imiquimod 3.75% (IQ3.75%) as an example of field-directed AK therapy. MATERIALS & METHODS: Pooled analysis of data from two 14-week, vehicle-controlled, double-blind studies of IQ3.75%. RESULTS: With IQ3.75%, the median number of lesions increased from 10 at baseline to an Lmax of 22. The median absolute reduction in lesions to study end was 18 from Lmax versus 7 from baseline. The median percentage reduction in AK lesions to study end was 92.2% from Lmax compared with 81.8% from baseline. CONCLUSIONS: The reduction in lesion count from Lmax is a novel efficacy parameter that should become the new way of evaluating field-directed AK therapies since it enables their efficacy against both clinical and subclinical lesions to be accurately determined. Together, the Lmax concept and IQ3.75% represent a new approach for the management of AK across a large sun-exposed field.