Partial Clearance Rates Research Articles

Microwave therapy for the treatment of resistant plantar warts: a randomized, placebo-controlled clinical trial.

Plantar warts, or verrucae plantares, are skin lesions on the soles of the feet caused by human papillomavirus (HPV). These warts are prevalent and affect up to 33% of children and 3.5% of adults. While they may regress spontaneously, plantar warts often persist and resist conventional treatments such as excision, cryotherapy, and laser procedures.This study investigated microwave-induced hyperthermia as a treatment for recalcitrant plantar warts. The study was conducted at a dermatology practice in Lübeck, Germany. Thirty-two adult patients with long-lasting, treatment-resistant plantar warts were randomly assigned to either a treatment or placebo group. The treatment group received microwave therapy (Swift®, Emblation Medical Ltd., UK), while the placebo group underwent sham treatment with a ruby laser (Sinon®, Alma Lasers Ltd., Israel). Treatments were administered every four weeks, for a total of 3 treatments, with a follow-up period of 3months after the third session. The primary outcome was complete wart clearance.Of the 32 participants, 6 dropped out, leaving 28 for analysis. Complete clearance was achieved in 27.3% of the treatment group (3/11) compared to 0% of the placebo group (p = 0.032). Six patients in the treatment group achieved a partial response ranging from 41.1 to 88.4% of the total wart area, with a partial clearance rate of 54.5% versus 13.3% in the placebo group. The average pain score for the microwave treatment group was 5.44.Microwave therapy has proven to be superior to placebo treatment. The clearance rate in this study was lower than that reported in previous uncontrolled studies, potentially due to differences in treatment protocols. The pain level and cost of consumables present challenges. However, further studies are needed to optimize the protocol and assess its efficacy in larger populations and for different wart types.

Tirbanibulin 1% Ointment Effectiveness for Actinic Keratosis Treatment Evaluated by Dynamic Optical Coherence Tomography

Background. Actinic keratosis (AK) is a common premalignant skin condition. Its diagnosis is based on a clinical and sometimes dermoscopic examination, but, in some situations, a skin biopsy may be necessary. Dynamic optical coherence tomography (D-OCT) can often bypass this need, by noninvasive evaluation of skin morphology. Early and effective treatment of AKs is important to prevent the progression to invasive squamous cell carcinoma (iSCC). Tirbanibulin 1% ointment, a new topical field therapy for AKs, has recently been introduced. Objectives. The aim of this study was to evaluate the efficacy and safety of tirbanibulin 1% ointment for the field treatment of nonhyperkeratotic, nonhypertrophic AKs (Olsen grade 1) on the face and/or scalp in adults, using D-OCT technology. Methods. Patients, presenting multiple, mild to moderate AKs on the face and scalp, in treatment with tirbanibulin 1% ointment for five consecutive days of an area measuring 25 cm2, were evaluated with videodermoscopy (V-track Vidix 4.0) and D-OCT (VivoSight Dx, Michelson Diagnostics Ltd., Kent, England, United Kingdom), as normal clinical practice. The lesions were staged according to the Olsen classification, excluding the most aggressive lesions. Results. We retrospectively evaluated 50 patients (27 males and 23 females, mean age 76 ± 7.9 years). At 57 days posttreatment, the complete clearance rate was 68% (n = 34) and partial clearance rate was 76% (n = 38). D-OCT showed markedly improved morphology, including a better recognizable dermal-epidermal junction (DEJ), associated with reduced inflammation. The most common adverse events reported were erythema and scaling, which were mostly mild and self-limiting. Conclusions. This study demonstrated that tirbanibulin may be considered an effective and well-tolerated treatment option for nonhyperkeratotic, nonhypertrophic AKs. It showed a favorable safety profile, with mostly mild adverse events. D-OCT can be considered a useful tool for personalizing AK treatment and monitoring.

Efficacy of sunscreen with photolyase or regular sunscreen associated with topical antioxidants in treating advanced photodamage and cutaneous field cancerization: a randomized clinical trial

BackgroundSeveral treatments are available for skin with advanced photodamage, which is characterized by the presence of actinic keratoses (AK). ObjectivesEvaluate the efficacy of using sunscreen with photolyase compared to regular sunscreen, as well as to compare the combination of a topical formulation of antioxidants versus placebo in the treatment of advanced photodamage. MethodsThis was a randomized, double-blind, factorial clinical trial. Participants with AKs on their forearms were randomized to apply regular sunscreen (SC) or sunscreen with photolyase (SC+P) on both forearms during the day. One of the forearms in each group was randomized again to receive topical antioxidants (AOx), and the other forearm received a placebo cream (both for night application). The four groups were SC/AOx, SC/placebo, SC+P/AOx, and SC+P/placebo. The duration of treatment was 8 weeks. Primary outcomes were total AK clearance, decrease in Forearm Photoaging Scale (FPS), and AK severity scores. Secondary outcomes were reduction in AK count, partial clearance rate, and safety. ResultsForty participants (80 forearms) were included. All groups showed significant improvement in outcomes at week eight. There were no significant differences between SC and SC+P for either outcome. AOx led to a significant reduction in AK count (22%; p < 0.05). Partial clearance was obtained in 18 (47.4%) forearms treated with AOx and in 9 (23.7%) treated with placebo (p < 0.05). All groups reduced the FPS score, without significant differences among them. Study limitationsShort interval of follow-up and absence of re-evaluation in the absence of treatment were limitations of the present study. ConclusionsThere is no difference in the treatment of advanced photodamage skin when comparing the use of sunscreen with photolyase and regular sunscreen, and topical antioxidants were more efficient in reducing AK count than placebo.

Interventions for Actinic Keratosis in Nonscalp and Nonface Localizations: Results from a Systematic Review with Network Meta-Analysis

Myriad interventions are available for the treatment of actinic keratosis located on the face or scalp. However, lesions located outside the head and neck have received little attention until now. We aimed to synthesize the current knowledge of interventions for actinic keratosis in nonscalp and nonface localizations. Randomized controlled trials reporting data for these localizations were searched in MEDLINE, Embase, and The Cochrane Library CENTRAL, as well as in pertinent trial registers until 25 March 2020. A total of 13 randomized controlled trials with 1,380 patients were included in a systematic review. Five treatment modalities were evaluated and compared with placebo in a frequentist network meta-analysis, including cryosurgery, ingenol mebutate, photodynamic therapy, colchicine, and 5-fluorouracil. In the network meta-analysis, cryosurgery showed the highest participant complete clearance rates (risk ratio, 7.73; 95% confidence interval= 3.21-18.61; 10 studies; I2= 20.3%; Grading of Recommendations Assessment, Development, and Evaluation,++--) and lesion clearance rates (risk ratio, 2.97; 95% confidence interval= 2.45-3.59; 4 studies; I2= 0%; Grading of Recommendations Assessment, Development, and Evaluation,++--) compared with placebo. Ingenol mebutate demonstrated the highest participant partial clearance rates compared with placebo (risk ratio, 7.12; 95% confidence interval= 4.36-11.64; 5 studies; I2= 0%; Grading of Recommendations Assessment, Development, and Evaluation,+++-). The mean reduction of lesions and occurrence of adverse events was poorly reported. The certainty of the evidence varied from very low to high and was limited by imprecision and study limitations.

Long-term efficacy of interventions for actinic keratosis: protocol for a systematic review and network meta-analysis

BackgroundActinic keratoses (AK) are common precancerous lesions of the skin due to cumulative sun exposure. A variety of interventions are available for the treatment; however, the majority of randomised controlled trials (RCTs) and meta-analyses focus on short-term efficacy outcomes. This network meta-analysis aims to investigate the long-term (> 12 months) efficacy of interventions for AK.MethodsTo identify relevant studies, we will perform a systematic literature research in MEDLINE, Embase, and CENTRAL and hand-search pertinent trial registers. Two authors will independently screen titles and abstracts for eligibility. We will include RCTs with an inter-individual (parallel arm) design. The study population includes patients with a clinical or histopathologic diagnosis of AK. Eligibility will be restricted to the following interventions: surgical approaches, cryosurgery, ablative laser treatment, topical drug treatment with 5-fluorouracil, imiquimod, ingenol mebutate, diclofenac, or photodynamic therapy. As outcomes, we will consider the following endpoints: (1) the participant complete clearance rate, (2) the participant partial clearance rate, (3) the lesion-specific clearance, (4) the mean lesion reduction per patient, and (5) the number of withdrawals due to adverse events after at least 12 months after the end of treatment. Monotherapy or placebo will serve as a comparison. Estimates of effects from individual studies will be pooled using a random-effects model. Heterogeneity will be evaluated based on I2 and chi-square test. The risk of bias will be estimated with the Cochrane Risk of Bias Tool by two review authors independently. The quality of evidence of the outcomes will be assessed with the GRADE approach. A network meta-analysis will be performed to combine direct and indirect evidence from the included RCTs.DiscussionThe potential of interventions to achieve a sustained clearance of AK has not been assessed to date. To investigate the long-term efficacy of interventions is important as the natural disease course is highly variable and relapses occur frequently even after initial lesion clearance. This review will help to set a framework for clinical decision making in patients with AK.Systematic review registrationCRD42018095903 (PROSPERO)

Efficacy of photodynamic therapy combined with topical interventions for the treatment of actinic keratosis: a meta-analysis.

Photodynamic therapy (PDT) is a highly effective treatment option for patients with actinic keratoses (AK). However, efficacy can be reduced by insufficient illumination or hyperkeratotic nature of lesions. To investigate if PDT combined with a topical intervention is superior to monotherapy in terms of efficacy and tolerability. A systematic literature research was conducted in Medline, Embase and CENTRAL. Pertinent trial registers were hand-searched for eligible randomized controlled trials (RCTs) until 20 August 2018. Results were pooled using a random effects model to calculate relative risks (RR) or mean differences. The risk of bias was assessed with the Cochrane Risk of Bias Tool. The quality of evidence was estimated for each outcome of interest according to GRADE. Out of 1800 references initially identified, 10 RCTs with a total sample size of n=277 were included. Four studies investigated a combination of PDT with imiquimod cream, three with 5-fluorouracil cream and one each with ingenol mebutate gel, tazarotene gel and calcipotriol ointment, respectively. Patients treated with a combination showed higher participant complete (RR 1.63; 95% CI 1.15-2.33; P=0.007) and partial clearance rates (RR 1.19; 95% CI 0.84-1.67; P=0.33). Similarly, the lesion-specific clearance was higher for PDT plus topical intervention compared to monotherapy (RR 1.48; 95% CI 1.04-2.11; P=0.03). A subgroup analysis was performed for PDT combined with imiquimod, revealing an increased participant complete clearance rate compared to monotherapy (RR 1.57, 95% CI 1.09-2.25, P=0.02). PDT-induced pain and local skin reactions after treatment were poorly reported. The studies were estimated at high risk for performance and detection bias. The combination of PDT with another topical drug intervention does improve AK clearance rates compared to either monotherapy alone. This study highlights that the sequential application of two field-directed treatments represents an efficient approach in patients with multiple AK and field cancerization.

Cryosurgery combined with topical interventions for actinic keratosis: a systematic review and meta‐analysis

Actinic keratoses (AKs) are early insitu carcinomas of the skin caused by cumulative sun exposure. Cryosurgery is an easy and practicable lesion-directed approach for treatment of isolated lesions. To investigate whether an upfront combination of cryosurgery with a topical intervention is superior to cryosurgery alone for treatment of AK. We performed a systematic literature search in MEDLINE, Embase and CENTRAL and hand searched pertinent trial registers for eligible randomized controlled trials until 17 July 2018. Results from individual studies were pooled using a random effects model. The risk of bias was estimated with the Cochrane Risk of Bias Tool and the quality of evidence of the outcomes with the GRADE approach. Out of 1758 records initially identified, nine studies with a total sample size of 1644 patients were included. Cryosurgery in combination with a topical approach showed significantly higher participant complete clearance rates than monotherapy [risk ratio (RR) 1·74, 95% confidence interval (CI) 1·25-2·43, I2 = 73%, eight studies]. The participant partial clearance rate was not statistically different (RR 1·64, 95% CI 0·88-3·03, I2 = 77%, three studies). The number of patients who completed the study protocol and did not withdraw due to adverse events was equal in both groups (RR 0·98, 95% CI 0·95-1·01, I2 = 75%, seven studies). The studies were estimated to have high risk for selective reporting bias. Our results suggest the superiority of a combination regimen for AK clearance, with equal tolerability. This study highlights the importance of a field-directed approach in patients with multiple AKs or field cancerization.

Efficacy and safety of topical SR-T100 gel in treating actinic keratosis in Taiwan: A Phase III randomized double-blind vehicle-controlled parallel trial

BackgroundCurrently available topical treatments for actinic keratosis (AK) are associated with substantial side-effects. ObjectivesTo evaluate the efficacy and safety of topical SR-T100 gel in treating AK. MethodsA multicenter, randomized, double-blinded phase III trial was conducted. Patients with at least two clinically visible AK were enrolled and a punch biopsy was performed on one of the AK to confirm the diagnosis. This study consisted of up to 16-week treatment and 8-week post-treatment periods. Medication was applied daily with occlusive dressing. Results123 subjects were recruited and 113 were randomized. 76 subjects were in the SR-T100 and 37 in the vehicle arms. In SR-T100 and vehicle groups, 32.39% and 17.14% of subjects achieved complete clearance, respectively. For 75% partial clearance of lesions, 71.83% and 37.1% of subjects achieved this goal in SR-T100 and vehicle group, respectively. When comparing SR-T100 to vehicle, the odds ratio of complete clearance was 2.14 (p = 0.111), and odds ratio of partial clearance was 4.36 (p < 0.001). Severe local reactions were reported by only one subject using SR-T100. ConclusionThe imitation of the study was that not all the treated AK lesions were confirmed by histopathology. The diagnostic uncertainty may contribute to the high partial clearance rate in the vehicle group since the clinical-diagnosed AK showed higher clearance rate compared to histopathology-confirmed AK. The use of occlusive dressing was another possible explanation for high placebo effects. The results suggested that topical SR-T100 gel may be an effective and safe treatment for field therapy of AK.

Ingenol mebutate gel: a guide to its use in actinic keratosis in the EU

Ingenol mebutate gel (Picato®) is indicated for the topical treatment of actinic keratosis. Field-directed therapy with topical ingenol mebutate (150 µg/g gel applied once daily for 3 consecutive days for actinic keratoses on the face or scalp, and 500 µg/g gel applied once daily for 2 consecutive days for actinic keratoses on the trunk or extremities) resulted in significantly higher complete and partial clearance rates at day 57 than treatment with vehicle gel. Clearance was generally sustained during 1-year follow-up. Moreover, relative to cryosurgery alone, a 3-day course of ingenol mebutate 150 µg/g gel applied to the face and scalp 3 weeks after cryosurgery improved clearance of actinic keratosis at 11 weeks. Transient local skin responses are very common after initiation of ingenol mebutate gel.

The efficacy and safety of topical 5% 5‐fluorouracil in renal transplant recipients for the treatment of actinic keratoses

Actinic keratoses (AK) occur more commonly and behave more aggressively in renal transplant recipients (RTR). Topical 5% 5-fluorouracil (5-FU) cream is a commonly used agent whose efficacy and safety have never been exclusively studied in the RTR population before. Eight RTR were enrolled and 5% 5-FU cream applied to AK lesions on their face twice daily for 3 weeks. They were reviewed at 2 and 8 weeks, and 12 months post-commencement of treatment. Their AK were counted and their cumulative surface areas measured. Patients completed surveys monitoring adverse effects and tolerability. Complete (100%) and partial clearance (≥ 75%) rates were measured, as well as mean percentages of the reduction in AK surface area. Patients had complete clearance rates of 63 and 0% at 8 weeks and 12 months, respectively. All (100%) patients had partial clearance at week 8 and 71% had partial clearance at 12 months. Patients had on average 15 AK at week 0 and 1 and 3 at 8 weeks and 12 months, respectively. The mean AK clearance rate was 98% at week 8 and 79% at 12 months. Common side-effects were erythema, itch and flaking or scaling, mostly mild in severity. 5-FU appears to be an efficacious and safe treatment for AK in RTR.

Ingenol Mebutate Gel 0.015% and 0.05%

Ingenol mebutate is the main active constituent of sap from the plant Euphorbia peplus, which has traditionally been used as a home remedy for various skin conditions. Ingenol mebutate gel is approved in the US, EU, Australia and Brazil for the topical treatment of actinic keratosis. A short course of field-directed therapy with topical ingenol mebutate gel was effective in the treatment of actinic keratoses on the face or scalp (ingenol mebutate gel 0.015% once daily for 3 consecutive days) and on the trunk or extremities (ingenol mebutate gel 0.05% once daily for 2 consecutive days), according to the results of four randomized, double-blind, vehicle-controlled, multicentre studies. Significantly higher complete clearance rates (primary endpoint) and partial clearance rates were seen at day 57 in patients receiving ingenol mebutate gel than in those receiving vehicle gel. Treatment with ingenol mebutate gel was generally associated with sustained clearance of actinic keratoses in the longer term. Topical ingenol mebutate gel was generally well tolerated in the treatment of patients with actinic keratoses on the face or scalp and on the trunk or extremities. Application-site conditions were the most commonly occurring adverse events.

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 3-week cycles

Imiquimod 5% cream is approved as a 16-week regimen for the treatment of actinic keratoses involving a 25-cm(2) area of skin. We sought to evaluate imiquimod 2.5% and 3.75% creams for short-course treatment of the entire face and scalp. In two identical studies, adults with 5 to 20 lesions were randomized to placebo, or imiquimod 2.5% or 3.75% cream (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 3-week treatment cycles, with a 3-week, no-treatment interval. Efficacy was assessed at 8 weeks posttreatment. In all, 490 subjects were randomized to placebo, or imiquimod 2.5% or 3.75% cream. Median baseline lesion counts for the treatment groups were 9 to 10. Complete and partial clearance rates were 5.5% and 12.8% for placebo, 25.0% and 42.7% for imiquimod 2.5%, and 34.0% and 53.7% for imiquimod 3.75% (P < .001, each imiquimod vs placebo; P = .034, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion count were 23.6%, 66.7%, and 80.0% for the placebo, imiquimod 2.5%, and imiquimod 3.75% groups, respectively (P < .001 each imiquimod vs placebo). There were few treatment-related discontinuations. Temporary treatment interruption (rest) rates were 0%, 17.1%, and 27.2% for the placebo, imiquimod 2.5%, and imiquimod 3.75%, respectively. Local effects of imiquimod, including erythema, may have led to investigator and subject bias. Both imiquimod 2.5% and 3.75% creams were more effective than placebo and had an acceptable safety profile when administered daily as a 3-week on/off/on regimen.

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles

The approved imiquimod 5% cream regimen for treating actinic keratoses requires a long treatment time and is limited to a small area of skin. We sought to evaluate imiquimod 2.5% and 3.75% for short-course treatment of the full face or balding scalp. In two identical studies, adults with 5 to 20 lesions were randomized to placebo, imiquimod 2.5%, or imiquimod 3.75% (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed at 8 weeks posttreatment. A total of 479 patients were randomized to placebo, or imiquimod 2.5% or 3.75%. Complete and partial clearance (> or =75% lesion reduction) rates were 6.3% and 22.6% for placebo, 30.6% and 48.1% for imiquimod 2.5%, and 35.6% and 59.4% for imiquimod 3.75%, respectively (P < .001 vs placebo, each; P = .047, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion counts were 25.0% for placebo, 71.8% for imiquimod 2.5%, and 81.8% for imiquimod 3.75% (P < .001, each active vs placebo; P = .048 3.75% vs 2.5%). There were few treatment-related discontinuations. Patient rest period rates were 0% for placebo, 6.9% for imiquimod 2.5%, and 10.6% for imiquimod 3.75%. Local pharmacologic effects of imiquimod, including erythema, may have limited concealment of treatment assignment in some patients. Both imiquimod 2.5% and 3.75% creams were more effective than placebo and were well tolerated when administered daily as a 2-week on/off/on regimen to treat actinic keratoses.

Effect of dosing frequency on the safety and efficacy of imiquimod 5% cream for treatment of actinic keratosis on the forearms and hands: a phase II, randomized placebo-controlled trial

Clinical studies in cutaneous conditions other than actinic keratosis (AK) have revealed that the safety and efficacy profile of imiquimod is influenced by dosing frequency. To evaluate dosing frequency response of imiquimod 5% for treatment of AK. This was a phase II, multicentre, randomized, double-blind, placebo-controlled study. Adults with > or = 10 but < or = 50 clinical AKs, one of which was histologically confirmed, were randomized (4:1) to 2-6 packets of imiquimod or placebo cream applied to the dorsum of the forearms and hands once daily 2, 3, 5 or 7 times per week for 8 weeks. The primary endpoint was complete clearance of AKs in the treatment area at 8 weeks post-treatment. One hundred and forty-nine (94 men and 54 women) white subjects, with a mean +/- SD age of 71 +/- 10.2 years, were enrolled. Twenty-eight subjects (18.8%) discontinued from study: 0%, 3.1%, 6.9%, 30.0% and 33.3% withdrew for local skin reactions or adverse events in the combined placebo, and in the imiquimod 2, 3, 5 or 7 times per week groups, respectively. Seven serious adverse events occurred; none was related to the study drug. Median baseline lesions ranged from 38 to 40 for the treatment groups. Complete clearance was achieved in 0%, 3.2%, 6.9%, 3.3% and 6.7% of subjects, and partial clearance (> or = 75% lesion reduction) in 0%, 22.6%, 24.1%, 20.0% and 36.7% of subjects for the placebo and imiquimod 2, 3, 5 or 7 times per week regimens, respectively. Imiquimod 5% applied more frequently than 3 times per week to AKs was not well tolerated. Complete clearance rates were low; however, partial clearance rates increased with increased dosing frequency (P = 0.002).

Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis

There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis. Assess the efficacy and safety of ingenol mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis. Patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period. All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P < .0001 vs vehicle). The complete clearance rate was also significantly higher (P < or = .0006) for patients in the ingenol mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for ingenol mebutate gel compared with 13.3% for vehicle, P < .0001 to .0007 vs vehicle). The median percentage reduction in baseline actinic keratosis lesions for patients treated with ingenol mebutate gel ranged from 75% to 100% compared with 0% for vehicle gel (P < .0001 vs vehicle). Active treatment was well tolerated at all dosages. The mechanism of action of this agent is the localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, flaking/scaling, and crusting. There was no evidence of treatment-related scarring. Local skin responses may have suggested active treatment to investigators. Short-course, field-directed therapy with ingenol mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.

Sinecatechins, a Defined Green Tea Extract, in the Treatment of External Anogenital Warts

To estimate the clinical efficacy of topical sinecatechins, a defined green tea extract, in the treatment of external genital and perianal warts. This was a randomized, double-blind, vehicle-controlled trial involving 502 male and female patients aged 18 years and older, with 2-30 anogenital warts ranging from 12 to 600 mm(2) total wart area. Patients applied sinecatechins ointment 15% or 10% or vehicle (placebo) three times daily for a maximum of 16 weeks or until complete clearance of all warts, followed by a 12-week treatment-free follow-up to assess recurrence. Complete clearance of all baseline and newly occurring warts was obtained in 57.2% and 56.3% of patients treated with sinecatechins ointment 15% and 10%, respectively, compared with 33.7% for vehicle (both P<.001). Significance was observed at weeks 4 and 6 and all subsequent visits. Numbers needed to treat were 4.3 and 4.4. Partial clearance rates of at least 50% were reported for 78.4% and 74.0% of patients in the sinecatechins ointment 15% and 10% groups compared with 51.5% of vehicle patients. During follow-up, recurrence of any wart was observed in 6.5%, 8.3%, and 8.8% in the sinecatechins ointment 15% group, sinecatechins ointment 10% group, and vehicle patients, respectively. A total of 3.7%, 8.3%, and 0.0% developed new warts, respectively. A total of 87.7% and 87.3% of patients in the sinecatechins ointment 15% and 10% groups, and 72.1% of vehicle patients experienced application site reactions; 49.2%, 46.2%, and 65.4% of those, respectively, were mild or moderate. Topical sinecatechins ointments 15% and 10% are effective and well-tolerated in the treatment of anogenital warts. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00449982. I.

Multicentre, open-label study using imiquimod 5% cream in one or two 4-week courses of treatment for multiple actinic keratoses on the head

In the USA, Imiquimod 5% cream is approved for use 2-3 times per week over 16 weeks for the treatment of actinic keratoses (AKs). This study evaluated the efficacy of imiquimod in another treatment schedule, for AKs on the head. Open-label, phase IIIb. 180 dermatology clinics and practices in Germany. Patients were eligible if they had clinically typical, visible AK lesions located anywhere on the head, excluding the upper and lower eyelids, nostrils, lip vermilion, and inside the ears. Patients applied study cream to the treatment area once daily 3x/week for 4 weeks (course 1) followed by a 4-week post-treatment period. Patients with AK lesions remaining in the treatment area underwent a second 4-week treatment course. Primary variable was the complete clearance rate, defined as the proportion of patients with no clinically visible AK lesions in the treatment area at the course 1 or course 2 post-treatment visit. 829 patients entered the study. Overall, the complete clearance rate was 68.9% (571/829) and the partial clearance rate (percentage of patients with >/= 75% reduction in the number of baseline AK lesions) was 80.2%. Local skin reactions (LSRs) and application site reactions (ASRs) were the most commonly reported adverse events. Four patients discontinued from the study due to LSRs or ASRs. Shorter treatment regimen of imiquimod 5% cream can produce complete clearance rates similar to those seen with 16 weeks of treatment and has the advantage of lower drug exposure, resulting in a better benefit-risk profile for the patient.

Vehicle-controlled, double-blind, randomized study of imiquimod 5% cream applied 3 days per week in one or two courses of treatment for actinic keratoses on the head

A shorter dosing regimen of imiquimod for the treatment of actinic keratosis may be effective, with long-term clinical benefits. Imiquimod in one or two shorter courses of treatment was evaluated. Patients with actinic keratosis lesions on the head applied imiquimod or vehicle cream 3x/wk for 4 weeks (course 1). Patients with remaining lesions received another course of treatment. Complete and partial clearance rates were evaluated after course 1, after course 2 (overall), and 1 year later. Complete clearance rates were 26.8% (course 1) and 53.7% (overall). Partial clearance rates were 36.6% (course 1) and 61.0% (overall). One-year follow-up recurrence rates were 39% (imiquimod) and 57% (vehicle). Blinded investigators may have been biased toward patients treated with imiquimod identified by treatment site reactions. Imiquimod 3x/wk in one or two courses of treatment appears to be effective for the treatment of actinic keratoses on the head, providing long-term clinical benefits. Some recurrences do occur, so long-term follow-up is recommended.

Treatment of multiple actinic keratoses with topical diclofenac 3% gel in organ transplant recipients: a series of six cases

Non-melanoma skin cancer (NMSC) represents a significant cause of morbidity in organ transplant patients; the relative risk of squamous cell carcinoma and actinic keratosis (AK) is 100 and 250 times higher, respectively, compared with immunocompetent patients. The aim of this study was to investigate the effects of 3% diclofenac gel on the clearance rates of multiple AKs in organ transplant recipients (OTRs). An open-label study was conducted in six patients (three kidney, one liver and two heart transplant patients) with histories of multiple NMSCs and extensive actinic keratoses (AKs). Patients were treated with diclofenac 3% gel, twice daily for 16 weeks. Complete and partial clearance rates of AKs were assessed after 16 weeks and biopsies were performed 4 weeks post-therapy on clinically typical AKs identified prior to the start of treatment. Three out of six patients showed complete clinical and histological clearance after 16 weeks of treatment with diclofenac 3% gel. Two further patients showed a marked (> or = 75% lesion reduction) improvement in their overall AK lesion count in the treatment area. One patient showed a 30% lesion reduction in the area treated. Local adverse events at the site of application were very mild and included mild erythema and marginal erosion. No systemic side effects were reported. Results suggest that diclofenac 3% gel may be useful in the treatment and control of multiple AK lesions in OTRs. Further studies are needed to investigate the efficacy and safety of this therapy for the local treatment of AK in greater numbers of immunosuppressed patients.

Dosing With 5% Imiquimod Cream 3 Times per Week for the Treatment of Actinic Keratosis

To evaluate the efficacy and safety of 5% imiquimod cream compared with vehicle in the treatment of actinic keratosis (AK). Two phase 3 randomized, double-blind, parallel-group, vehicle-controlled studies. Twenty-six ambulatory care offices, including dermatologists in private practice or research centers. Four hundred ninety-two patients, 18 years and older, with 4 to 8 AK lesions in a 25-cm(2) treatment area on the face or the balding scalp were randomized; an additional 162 patients underwent screening but were ineligible. Patients applied 5% imiquimod (Aldara) or vehicle cream to the treatment area once daily, 3 times per week, for 16 weeks, followed by an 8-week posttreatment period. Complete clearance rate (proportion of patients at the 8-week posttreatment visit with no clinically visible AK lesions in the treatment area), partial clearance rate (proportion of patients at the 8-week posttreatment visit with a >/=75% reduction in the number of baseline AK lesions in the treatment area), and frequency and severity of adverse events and local skin reactions were measured. Complete and partial clearance rates for imiquimod-treated patients (48.3% and 64.0%, respectively) were clinically and statistically significantly higher than for vehicle-treated patients (7.2% and 13.6%, respectively). The median percentage reduction of baseline lesions was 86.6% for the imiquimod-treated group and 14.3% for the vehicle-treated group. The 5% imiquimod cream dosed 3 times weekly for 16 weeks is safe and effective for the treatment of AK.