Incorporating a Prognostic Gene Expression Profile Test into the Management of Cutaneous Squamous Cell Carcinoma: An Expert Consensus Panel Report.

BACKGROUND:  Cutaneous squamous cell carcinoma (cSCC) is a growing health concern with a rapidly increasing incidence. Disease-specific mortality is typically preceded by a metastasis, but current staging systems have significant limitations in predicting this event. The 40-gene expression profile (40-GEP) test is a validated method of further stratifying patients based on the risk of regional or distant metastasis, but limited guidelines exist for incorporating this test into clinical practice. OBJECTIVE:  To review the available literature on the use of gene expression profile (GEP) testing to assess prognosis in cSCC and create consensus statements to guide dermatology clinicians on its use. METHODS:  A comprehensive literature search of PubMed, EMBASE, and Scopus was completed for English-language original research articles on the use of GEP testing to assess cSCC prognosis. A panel of 8 dermatologists with significant expertise in diagnosing and managing cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS:  The literature search produced 157 articles that met the search criteria. A thorough screening of the studies for relevance to the research question resulted in 21 articles that were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 6 of which were given a strength of "A" and 1 of which was given a strength of "C". CONCLUSION:  The 40-GEP test provides accurate and independent prognostic information beyond standard staging systems that only incorporate pathologic data. Incorporation of GEP testing into national guidelines can help further stratify patients based on risk of metastasis and thus may improve morbidity and mortality. J Drugs Dermatol. 2023;22(12):54-60.   doi:10.36849/JDD.7691.

Incorporating a Prognostic Gene Expression Profile Test into the Management of Cutaneous Squamous Cell Carcinoma: An Expert Consensus Panel Report.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a growing health concern with a rapidly increasing incidence. Disease-specific mortality is typically preceded by a metastasis, but current staging systems have significant limitations in predicting this event. The 40-gene expression profile (40-GEP) test is a validated method of further stratifying patients based on the risk of regional or distant metastasis, but limited guidelines exist for incorporating this test into clinical practice. OBJECTIVE: To review the available literature on the use of gene expression profile (GEP) testing to assess prognosis in cSCC and create consensus statements to guide dermatology clinicians on its use. METHODS: A comprehensive literature search of PubMed, EMBASE, and Scopus was completed for English-language original research articles on the use of GEP testing to assess cSCC prognosis. A panel of 8 dermatologists with significant expertise in diagnosing and managing cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS: The literature search produced 157 articles that met the search criteria. A thorough screening of the studies for relevance to the research question resulted in 21 articles that were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 6 of which were given a strength of "A" and 1 of which was given a strength of "C". CONCLUSION: The 40-GEP test provides accurate and independent prognostic information beyond standard staging systems that only incorporate pathologic data. Incorporation of GEP testing into national guidelines can help further stratify patients based on risk of metastasis and thus may improve morbidity and mortality. J Drugs Dermatol. 2023;22(12): doi:10.36849/JDD.7691e.

High-Quality Lipoaspirate Following 1470-nm Radial Emitting Laser-Assisted Liposuction.

BACKGROUND: Laser-assisted liposuction (LAL) has been used to maximize viable adipocyte yields in lipoaspirates, although optimizing tissue processing methods is still a challenge. A high-quality lipoaspirate has been a key factor for extended graft longevity. OBJECTIVE: To assess the viability and potency of stromal vascular fraction (SVF) cells and adipose-derived stem cells (ASCs) in fat samples from lipoaspirates harvested with a novel 1470-nm diode, radial emitting LAL platform. Two processing methods, enzymatic and nonenzymatic, were compared. METHODS: Laser-assisted liposuction lipoaspirates harvested from 10 subjects were examined for cell viability after processing by enzymatic or nonenzymatic methods. Isolated SVF cells were cultured with an ASC-permissive medium to assess their viability and proliferation capacity by cell proliferation assay. Flow cytometric analysis with ASC-specific markers, gene expression levels, and immunofluorescence for ASC transcription factors were also conducted. RESULTS: Lipoaspirates showed high SVF cell viability of 97% ± 0.02% and 98% ± 0.01%, averaged SVF cell count of 8.7 × 10 6 ± 3.9 × 10 6 and 9.4 × 10 6 ± 4.2 × 10 6 cells per mL, and averaged ASC count of 1 × 10 6 ± 2.2 × 10 5 and 1.2 × 10 6 ± 5 × 10 5 cells per mL in nonenzymatic and enzymatic methods, respectively. The ASC-specific markers, gene expression levels, and immunofluorescence for ASC transcription factors confirmed the adipose origin of the cells. CONCLUSIONS: The laser lipoaspirates provide a high yield of viable and potent SVF cells and ASCs through both nonenzymatic and enzymatic processes. Improved purity of the harvested lipoaspirate and high ASC content are expected to result in extended graft longevity. Furthermore, eliminating enzymatic digestion may provide advantages, such as reducing process time, cost, and regulatory constraints.

Guidelines of care for the management of actinic keratosis.

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. OBJECTIVE: This analysis examined the literature related to the management of AK to provide evidence-based recommendations for treatment. Grading, histologic classification, natural history, risk of progression, and dermatologic surveillance of AKs are also discussed. METHODS: A multidisciplinary Work Group conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations. LIMITATIONS: This analysis is based on the best available evidence at the time it was conducted. The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data. CONCLUSIONS: Strong recommendations are made for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are made for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.

Guidelines of care for the management of actinic keratosis: Executive summary.

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. Treatment options for AK include topical medications, photodynamic therapy, cryosurgery, and laser ablation. OBJECTIVE: This executive summary provides a synopsis of the 18 evidence-based recommendations for the treatment of AK detailed in the Guidelines of Care for the Management of Actinic Keratosis. METHODS: A multidisciplinary workgroup conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations Assessment, Development and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations, suggesting there are several effective treatments available for AK. LIMITATIONS: The analysis informing the recommendations was based on the best available evidence at the time it was conducted. The results of future studies may necessitate a revision of current recommendations. CONCLUSIONS: Strong recommendations are presented for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are presented for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.

Advances and Considerations in the Management of Actinic Keratosis: An Expert Consensus Panel Report.

BACKGROUND: Actinic Keratosis (AK) is a potentially pre-malignant tumor with a poorly defined risk of progression to invasive squamous cell carcinoma (SCC). Because of the typical need for recurrent cycles of AK treatment, outcomes can be limited by both therapeutic efficacy and patient adherence. OBJECTIVE: To synthesize the available and most current literature into overarching principles to provide guidance on the management of AKs, improving patient experiences and treatment outcomes. METHODS: A systematic review querying epidemiology, natural history, prognosis, management of AKs as well as the mechanism of action of and adherence to current AK therapy was conducted. After reviewing the literature, an expert consensus panel consisting of 10 expert dermatologists and dermatopathologists used a modified Delphi process to develop statements regarding the pathogenesis and management of AKs. Final statements were only adopted with a supermajority vote (≥7/10). RESULTS: The panel developed 7 consensus statements regarding AKs pathogenesis and management. CONCLUSION: The poorly defined risk for AK progression into invasive SCC without universally accepted clinical-histopathological factors highlights the importance of long-term efficacious treatment. To effectively counsel and treat patients with actinic keratoses, dermatologists must understand how newer therapeutic approaches with mechanisms of action that have more rapid onset of action, shorter treatment courses, and less intense local skin reaction (LSRs) may promote adherence and improve long-term outcomes. J Drugs Dermatol. 2021;20(8):888-893. doi:10.36849/JDD.6078 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL fTEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

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Ripple-Pattern Sebaceous Trichoblastoma.

A 28-year-old man of Middle-Eastern descent presented with a raised, pearly, slightly pigmented lesion on the right nasal ala. The lesion had been present for approximately 4 months. An excisional biopsy was taken, and the lesion measured 1.0 cm × 0.9 cm in dimension. The cut surface revealed a firm, white to tan nodule located within the dermis. The patient had no other significant medical history. After the initial excision, the lesion did not recur.

A Comparative Study to Evaluate Epidermal Barrier Integrity of Psoriasis Patients Treated With Calcipotriene/Betamethasone Topical Suspension Versus Betamethasone Dipropionate 0.05% Lotion.

BACKGROUND: Topical corticosteroids are known to impair the epidermal barrier, even after short-term use, whereas topical vitamin D analogues can have a reparative effect. Combination products using corticosteroids and vitamin D analogues have gained popularity in recent years and may provide a means to minimize skin atrophy in patients treated with topical corticosteroids. OBJECTIVE: To compare epidermal barrier function and cutaneous atrophy after 4 weeks of calcipotriene 0.005% and betamethasone dipropionate 0.064% topical suspension (Taclonex® TS) versus betamethasone dipropionate 0.05% lotion (Diprosone®). METHODS: Ten subjects with moderate plaque psoriasis were enrolled. Patients were randomized to apply calcipotriene 0.005%/betamethasone dipropionate 0.064% once daily to psoriasis plaques on one side of the body and betamethasone dipropionate 0.05% lotion twice daily to plaques on the other side. Biopsies were performed at baseline and after four weeks of treatment to evaluate for epidermal and dermal changes. RESULTS: Treatment with betamethasone lotion resulted in significant decreases in epidermal thickness and dermal thickness. In contrast, treatment with calcipotriene/betamethasone did not lead to significant decreases in epidermal thickness or dermal thickness. Comparing betamethasone and calcipotriene/betamethasone, there was a significantly greater reduction in epidermal thickness with betamethasone lotion versus calcipotriene/betamethasone (P less than .0001). Relative differences in dermal thickness and transepidermal water loss (TEWL) did not reach statistical significance. CONCLUSION: This study is the first to demonstrate that treatment of plaque psoriasis with a combination topical corticosteriod and calcipotriene product results in greater preservation of the skin layers relative to topical corticosteroid use alone. These results hold important ramifications for minimizing cutaneous atrophy in patients receiving treatment with topical corticosteroid .

Incidence and prevalence of basal cell carcinoma (BCC) and locally advanced BCC (LABCC) in a large commercially insured population in the United States: A retrospective cohort study.

BACKGROUND: Accurate evaluation of basal cell carcinoma (BCC) in the United States was not possible before the 2011 release of BCC-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes. OBJECTIVE: We sought to describe BCC (including locally advanced BCC [LABCC]) incidence/prevalence and the characteristics of patients in a commercially insured US population. METHODS: This retrospective cohort study used Truven Health MarketScan database insurance claims. Patients, aged 18 years or older with 2 or more BCC claims at least 30 days apart from October 1, 2011, to September 30, 2012, were continuously enrolled in medical and pharmacy benefits for 12 months before and after the index claim. A specific algorithm was used to classify patients with LABCC. RESULTS: A total of 56,987 patients with BCC were identified (39,035 incident cases; 17,952 prevalent cases). Age-adjusted BCC incidence and prevalence were 226.09 and 342.64 per 100,000 persons, respectively. These values project to 542,782 patients (incidence) and 822,593 patients (prevalence) in the 2012 US population. LABCC was uncommon (471 cases identified; projected US incidence and prevalence: 4399 and 7940 patients, respectively). LIMITATIONS: Use of medical claims data and retrospective analysis are limitations. CONCLUSION: In a study designed to distinguish patients with LABCC from the general BCC population based on BCC-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes, 0.8% were found to have LABCC, the majority having pre-existing disease.

Therapies to improve the cosmetic symptoms of rosacea.

Rosacea is a commonly encountered chronic inflammatory skin disease with a predilection for highly visible areas of the skin such as the face. The cosmetic symptoms of rosacea can be substantial and may greatly reduce a patient's quality of life. Although there is no definitive cure for rosacea, effective treatment of symptoms can mitigate the deleterious effects of this condition and improve quality of life. In this article, we review both existing and emerging cosmetic treatments for rosacea, including topical medications, systemic pharmacologic therapies, light-based modalities, and procedural interventions, and assess their ability to improve the cosmetic symptoms of rosacea.

New systemic therapies for psoriasis.

Over the last decade, expanded understanding of psoriasis pathogenesis has led to the development of new systemic agents such as biological drugs that have revolutionized the treatment of psoriasis. Small molecule inhibitors also have been studied and offer patients options for oral administration. This article reviews recently approved and in-the-pipeline biologics (IL-17 inhibitors and IL-23 blockers) as well as small molecule inhibitors (phosphodiesterase 4 [PDE4] and Janus kinase [Jak] inhibitors).

Acne scarring: a review of cosmetic therapies.

Acne vulgaris is one of the most commonly encountered skin conditions and frequently is seen in both adolescent and adult populations. Scarring is a common result of acne and may take the form of atrophic or hypertrophic scars. Acne scarring often occurs in highly visible areas such as the face, thus resulting not only in an un-desirable cosmetic appearance but also potential impairment of mental health, social functioning, and overall well-being. There is a wide variety of medical and surgical therapies available for treatment of acne scarring. In this article, we review some of the most commonly used cosmetic therapies for acne scarring, including dermabrasion, laser resurfacing, radiofrequency (RF), subcision, skin needling, punch techniques, chemical peels, soft-tissue augmentation, intralesional therapy, cryotherapy, and silicone dressings, with a focus on cosmetic outcomes.

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: two phase 3, multicenter, randomized, double-blind, placebo-controlled studies.

BACKGROUND: Imiquimod 3.75% and 2.5% creams were studied for the treatment of actinic keratosis (AK) of the full face or balding scalp, to determine comparable efficacy and tolerability to imiquimod 5% cream. METHODS: In two identical multicenter, randomized, double-blind, placebo controlled studies. Adult subjects with 5 to 20 visible lesions, or palpable AKs in an area that exceeded 25 cm² on either the face or balding scalp were randomized to imiquimod 3.75%, 2.5% or vehicle cream (1:1:1) applied once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed 8 weeks posttreatment (End of Study Visit [EOS]). Primary efficacy was rate of complete clearance of AK lesions. Secondary efficacy endpoints were rate of partial clearance at EOS (≥ 75% reduction in number of AK lesions compared to baseline) and median percent decrease from baseline lesion count. Safety assessments included visual assessment of local skin reactions (LSRs), number and duration of study treatment rest periods required due to intolerant LSRs, adverse events (AEs) and clinical laboratory tests. RESULTS: Overall 479 patients were randomized to imiquimod 3.75%, 2.5%, or vehicle. Complete clearance rates were 35.6%, 30.6%, and 6.3% respectively (both P<.001 versus vehicle). The difference in complete clearance rates (imiquimod minus vehicle) was 29.3% and 24.3%, respectively. Partial clearance rates were 59.4%, 48.1%, and 22.6% respectively (both P<.001 versus vehicle). Median % reductions in AK lesions were 81.8%, 71.8%, and 25.0% respectively (P<.001 versus vehicle). All primary and secondary efficacy endpoints were greater in Study 1. Photodamage in the treatment area was 'much improved' with imiquimod 3.75%. Both active creams were well tolerated with few treatment-related discontinuations. CONCLUSIONS: In two well-controlled Phase 3 studies, both imiquimod 3.75% and 2.5% creams were more effective than vehicle and well tolerated when administered daily as a 2-week on/off/on regimen to treat AK. Reduction in AK lesions was comparable to that reported with imiquimod 5% with fewer local AEs.

A single-blinded randomized controlled study to assess the efficacy of twice daily application of sinecatechins 15% ointment when used sequentially with cryotherapy in the treatment of external genital warts.

OBJECTIVE: To evaluate the efficacy of sequential therapy of cryotherapy and sinecatechins 15% ointment BID versus cryotherapy alone in treatment of external genital warts (EGW). METHODS: Forty-two subjects with at least two EGW lesions underwent cryotherapy to all lesions. One week following cryotherapy, subjects were randomized 1:1 to receive either no additional treatment or treatment with sinecatechins 15% ointment BID up to 16 weeks or until complete clearance. The total number of visible baseline and new EGW were recorded at each visit. Subjects were followed for a total of 65 weeks post-treatment. RESULTS: There was a significant reduction in mean number of lesions from baseline after 16 weeks of treatment in the cryotherapy-sinecatechins ointment group compared to cryotherapy alone (-5.0 lesions vs -2.1 lesions respectively, P=0.07). CONCLUSION: Cryotherapy plus sinecatechins 15% ointment BID resulted in a significant improvement in the reduction of EGW compared to cryotherapy alone. Clinicaltrials.gov registration identifier: NCT02147353.

Efficacy and safety of ingenol mebutate 0.015% gel after cryosurgery of actinic keratosis: 12-month results.

INTRODUCTION: Recurrence rates of actinic keratosis (AK) lesions after cryosurgery are high, and this treatment does not address field cancerization. We investigated the efficacy and safety of field treatment of AKs with ingenol mebutate gel following cryosurgery. METHODS: In this phase 3, randomized, double-blind, vehicle-controlled study (NCT01541553), patients ≥18 years with four to eight clinically typical, visible, discrete AKs within a contiguous 25-cm2 treatment area on the face or scalp underwent cryosurgery followed 3 weeks later by once-daily ingenol mebutate 0.015% or vehicle gel for 3 consecutive days. Endpoints included complete clearance at week 11 and safety and efficacy over 12 months. RESULTS: In 329 randomized patients, complete clearance rates were greater with ingenol mebutate than vehicle (week 11: 60.5% vs 49.4%; P=.04; month 12: 30.5% vs 18.5%; P=.01). Fewer patients experienced the emergence of new lesions with ingenol mebutate than with vehicle (38.9% vs 51.9%; P =.02). At month 12, mean percentage reduction of AKs was higher with ingenol mebutate than with vehicle (68.2% vs 54.1%; P =.002). The probability of remaining free of lesions was sustained longer with ingenol mebutate compared with vehicle gel: 78% vs 68% at 6 months; 64% vs 57% at 9 months; 55% vs 40% at month 12, respectively. Ingenol mebutate 0.015% gel was well tolerated and no unexpected adverse events occurred; all adverse events resolved within 2 weeks of starting treatment. CONCLUSIONS: Field treatment with ingenol mebutate 0.015% gel following cryosurgery significantly enhanced clearance of baseline lesions, and was well tolerated. Furthermore, ingenol mebutate 0.015% gel following cryosurgery reduced development of new lesions in the treated field.

Efficacy and safety of ingenol mebutate 0.015% gel 3 weeks after cryosurgery of actinic keratosis: 11-week results.

INTRODUCTION: Cryosurgery is the most common treatment for actinic keratosis (AK) in the United States. Efficacy with cryosurgery is variable, and is a modality for treating individual, visible lesions while failing to treat subclinical lesions. METHODS: FIELD Study 1 (NCT01541553) is a phase 3, multicenter, randomized, double-blind study that evaluated the short- (11-week) and long- (12-month) term efficacy and safety of sequential AK treatment using cryosurgery with liquid nitrogen followed by ingenol mebutate gel, versus cryosurgery followed by vehicle. RESULTS: Overall, 329 patients were randomized to ingenol mebutate 0.015% gel (n=167) or vehicle (n=162) 3 weeks after cryosurgery. Baseline characteristics were balanced across groups. At week 11, complete clearance rate (100%) in the treatment area was higher for ingenol mebutate gel compared with vehicle (60.5% vs 49.4%, respectively; P=.04). Mean percentage reduction in number of AKs versus baseline was also numerically higher for ingenol mebutate gel (82.7% vs 75.6%). A general reduction from baseline lesion count was observed 3 weeks after cryosurgery. Treatment after cryosurgery was well tolerated. CONCLUSIONS: Short-term (11-week) AK clearance rates on the face or scalp with ingenol mebutate gel after cryosurgery were higher than with cryosurgery alone.

Identifying patients at risk for recurrent or advanced BCC.

Basal cell carcinoma (BCC) is a common skin cancer and its incidence is on the rise worldwide. Clinical presentation and histologic examination are used for diagnosis and to stratify BCCs as either low- or high-risk for recurrence or development of advanced disease. A number of surgical and nonsurgical options are available for BCC. BCC is most often managed with a surgical approach, but not all tumors and patients are suitable for surgery. Vismodegib is a recently approved first-in-class hedgehog pathway inhibitor that has expanded options for patients who have locally advanced or metastatic BCC.

Nonsurgical treatment options for basal cell carcinoma - focus on advanced disease.

Basal cell carcinoma (BCC) is the most common cancer in the world. It is typically slow growing and usually effectively managed with surgery. However, BCCs in some patients are unsuitable for surgery or the patient may prefer a nonsurgical treatment. Radiotherapy is a nonsurgical option for the primary treatment of either low- or high-risk BCCs. It is associated with high cure rates, albeit somewhat lower than those observed with Mohs micrographic surgery for high-risk BCCs. Not all patients with BCCs are suitable for radiotherapy. Superficial therapies for BCC include topical imiquimod or 5- fluorouracil and photodynamic therapy (PDT). These therapies are generally associated with somewhat lower clearance rates and/or higher recurrence rates than surgery or radiotherapy, although they may be suitable in patients with low-risk BCCs when surgery or radiotherapy are impractical or less appropriate. An appealing feature of PDT is excellent cosmesis, but PDT is not currently approved by the Food and Drug Administration (FDA), and regimens are not well standardized. Vismodegib is a first-in-class hedgehog pathway inhibitor and recent addition to the armamentarium for the treatment of advanced BCC.

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: two phase 3 multicenter, randomized, double-blind, placebo-controlled studies.

BACKGROUND: Imiquimod 3.75% and 2.5% creams were studied for the treatment of actinic keratosis (AK) of the full face or balding scalp, to determine comparable efficacy and tolerability to imiquimod 5% cream. METHODS: In two identical multicenter, randomized, double-blind, placebo controlled studies. Adult subjects with 5 to 20 visible lesions, or palpable AKs in an area that exceeded 25 cm² on either the face or balding scalp were randomized to imiquimod 3.75%, 2.5% or vehicle cream (1:1:1) applied once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed 8 weeks posttreatment (End of Study Visit [EOS]). Primary efficacy was rate of complete clearance of AK lesions. Secondary efficacy endpoints were rate of partial clearance at EOS (≥ 75% reduction in number of AK lesions compared to baseline) and median percent decrease from baseline lesion count. Safety assessments included visual assessment of local skin reactions (LSRs), number and duration of study treatment rest periods required due to intolerant LSRs, adverse events (AEs) and clinical laboratory tests. RESULTS: Overall 479 patients were randomized to imiquimod 3.75%, 2.5%, or vehicle. Complete clearance rates were 35.6%, 30.6%, and 6.3% respectively (both P<.001 versus vehicle). The difference in complete clearance rates (imiquimod minus vehicle) was 29.3% and 24.3%, respectively. Partial clearance rates were 59.4%, 48.1%, and 22.6% respectively (both P<.001 versus vehicle). Median % reductions in AK lesions were 81.8%, 71.8%, and 25.0% respectively (-<.001 versus vehicle). All primary and secondary efficacy endpoints were greater in Study 1. Photodamage in the treatment area was 'much improved' with imiquimod 3.75%. Both active creams were well tolerated with few treatment-related discontinuations. CONCLUSIONS: In two well-controlled Phase 3 studies, both imiquimod 3.75% and 2.5% creams were more effective than vehicle and well tolerated when administered daily as a 2-week on/off/on regimen to treat AK. Reduction in AK lesions was comparable to that reported with imiquimod 5% with fewer local AEs.