Biosimilars in dermatology: identifying myths and knowledge gaps.

Biosimilars are beginning to gain regulatory approval in the United States. Biosimilars are structurally near identical to the innovator and must demonstrate identical pharmacokinetics via the same binding affinity and biological function on assays. However, biologics are so complex that even the innovator company cannot produce exact duplicates; there is batch-to-batch variation. The International Psoriasis Council has outlined a biosimilarity index, which aims to standardize preclinical definitions of biosimilarity. Such an index, paired with post-approval monitoring, could provide a transparent, quantitative definition of biosimilarity. Such an index could increase trust in biosimilar medicines and the preclinical assessment process without increasing costs. As preclinical analyses are critical to biosimilar approval, manufacturers should devote proportionate resources to completing them. Dermatologists, who might reflexively look for indication-specific clinical data, might also shift their focus to preclinical variables. Finally, it should be noted that biosimilars provide more evidence of similarity than we have for different batches of the innovator product. Thus, any clinical testing standards, or lack thereof, for different batches of innovator products should also apply to biosimilars.

Oversight of in-office dispensing and samples in dermatology.

The provision of samples and in-office dispensing of products and medications to patients are important, yet often controversial, practices in dermatology. Opinions on the practices of sampling and in-office dispensing vary greatly among dermatologists. Ultimately, there are several advantages and disadvantages associated with each practice, and common topics of discussion include ethics, costs, safety, and adherence. Many of the concerns associated with the practices of sampling and dispensing in dermatology may be mitigated by careful consideration and action by prescribers. Providers should be aware of their current practices surrounding these issues and, if used, methods by which these practices can be improved to optimize patient care. With careful consideration, it may be possible to practice sampling and dispensing of products and medications safely, ethically, and to the patients' advantage as an integral part of the dermatology practice.

Percutaneous Egression: What Do We Know?

BACKGROUND: The process by which drugs leave the bloodstream to enter the skin compartments is important in determining appropriate routes of delivery and developing more efficacious medications. We conducted a general literature review on percutaneous egression mechanisms. SUMMARY: Studies demonstrate that the stratum corneum (SC) is a compartment for systemically delivered drugs. Upon reviewing the available literature, it became apparent that there may be multiple mechanisms of percutaneous egression dependent upon drug physiochemical properties. These mechanisms include, but are not limited to, desquamation, sebum secretion, sweat transport, and passive diffusion. While drugs often utilize one major pathway, it is possible that all mechanisms may play a role to varying extents. KEY MESSAGES: Available literature suggests that hydrophilic substances tended to travel from blood to the upper layers of the skin via sweat, whereas lipophilic substances utilized sebum secretion to reach the SC. Upon reaching the skin surface, the drugs spread laterally before penetrating back into the skin as if they were topically administered. More data are warranted to identify additional percutaneous egression mechanisms, precise drug action sites, and accelerate drug development.

An overview of adapalene and benzoyl peroxide once-daily topical gel as a therapeutic option for acne.

INTRODUCTION: Acne vulgaris is the most common skin condition worldwide, and it is associated with substantial psychological comorbidity. Topical therapies - including retinoids, antibiotics, and benzoyl peroxide - are the cornerstones of treatment for patients with acne. The main barriers to care in the treatment of acne are poor adherence to therapy and lack of tolerability. AREAS COVERED: Herein, the authors review the safety and efficacy of adapalene/benzoyl peroxide combination gel (0.1%/2.5% and 0.3%/2.5%), as well as its specific mechanisms of action that target acne vulgaris. The authors also offer an expert opinion on the use of adapalene/benzoyl peroxide gel compared with other topical therapies. EXPERT OPINION: Adapalene/benzoyl peroxide gel is safe and highly effective in the treatment of acne vulgaris. Its efficacy, tolerability, and ease-of-use are superior to other topical acne therapies, and its use does not contribute to antibiotic resistance. However, the cost of adapalene/benzoyl peroxide gel and lack of available generics may prohibit its use.

Topical calcipotriol plus betamethasone dipropionate for the treatment of plaque psoriasis: a drug evaluation.

Introduction: Psoriasis is an inflammatory skin disease affecting approximately 3.2% of adults in the United States. The mainstay treatment for mild-to-moderate plaque psoriasis (the most common subtype and severity) is topical therapy.Areas covered:The fixed combination calcipotriol plus betamethasone dipropionate (BD) is an effective topical treatment for plaque psoriasis. Two therapies with separate actions - a Vitamin D analog and a high-potency topical corticosteroid - combined into a single medication allows for better efficacy and patient adherence. The treatment is available in ointment, gel, suspension, foam, and cream formulations. The authors elaborate on this and provide their expert perspectives.Expert opinion: Combination calcipotriol/BD offers several advantages over its separate product monotherapies, including better efficacy, safety, and ease of use. Newer calcipotriol/BD formulations include less messy vehicles, thus promoting improved adherence. Further data are needed on whether combination calcipotriol/BD will be cost-effective and whether insurers will place it in the treatment coverage algorithm. Due to its higher price, calcipotriol/BD will likely remain a second-line treatment option after generic topical corticosteroids.

Clascoterone: How the Novel Androgen Receptor Inhibitor Fits Into the Acne Treatment Paradigm.

Many patients with acne remain unsatisfied with results from the various topical treatments available and often do not improve, because of poor adherence. Even if topical clascoterone, a safe and effective treatment, were more potent than existing topicals, it could face the same poor adherence hurdle as existing treatments. Real-life efficacy will likely not reflect trial results because, for several reasons, adherence is better in trials than in real-life practice. Although topical clascoterone may be exciting initially for its promise to improve acne outcomes, the long-term place in therapy may be another topical option that minimally enhances patients' treatment outcomes.

A Comparison of the Histopathologic Growth Patterns Between Non-Merkel Cell Small Round Blue Cell Tumors and Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine cutaneous malignancy that shares cytologic, histopathologic, and immunohistochemical features with other small round blue cell (SRBC) tumors. Although the trabecular pattern is anecdotally associated with MCC, objective data are lacking. METHODS: This was a retrospective institutional review board-approved observational study conducted on microscopic images of 79 MCCs and 74 other SRBC tumors (desmoplastic small round cell tumor, primitive neuroectodermal tumor, neuroblastoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, synovial sarcoma, carcinoid, metastatic small cell lung cancer, non-Hodgkin small cell lymphoma, retinoblastoma, medulloblastoma, nephroblastoma, small cell osteosarcoma, and round cell liposarcoma). An expert dermatopathologist evaluated blinded and randomized microscopic specimens and recorded histologic patterns (diffuse, infiltrative, large anastomosing nests, small islands, any trabecular, focal trabecular, mixed trabecular, and predominately trabecular). RESULTS: Trabecular features were identified in over 72% of MCCs but only rarely in non-MCC SRBC tumors. The presence of any amount of a trabecular pattern favored a diagnosis of MCC over SRBC tumors with a sensitivity of 72.2% and a specificity of 87.8%. If "any" and "focal" trabecular patterns were discounted, specificity rose to 93.2%. CONCLUSION: The presence of a trabecular pattern helps to differentiate MCC from other SRBC tumors, and specificity approaches that achieved with immunostaining.