Onset of Plaque Psoriasis Treatment Responses With Anti-IL-17/IL-23 Biologic Therapies.

BACKGROUND: The impact of psoriasis on quality of life arises from both physical symptoms, such as pain and pruritus, and the psychosocial effects of the often highly visible lesions. For patients with moderate-to-severe psoriasis seeking amelioration of these symptoms, time to onset of treatment response is an important consideration when determining an appropriate therapeutic approach with their healthcare provider. METHODS: In this review, we discuss the fluidity of the definition of rapid response and time-to-response expectations of patients with psoriasis receiving biologic therapies. Next, we focus on time to response of brodalumab, a human anti–interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe psoriasis, as measured by the psoriasis area and severity index and the psoriasis symptom inventory. Brodalumab previously exhibited efficacy and safety in treatment of moderate-to-severe psoriasis in three phase 3 trials (AMAGINE-1/-2/-3), warranting further characterization of its ability to meet patient needs regarding rapidity of treatment response. Finally, we place time to response of brodalumab in the context of the current treatment landscape of biologic therapies for psoriasis (particularly those targeting the interleukin-17/interleukin-23 axis). RESULTS: Direct and indirect comparisons with other interleukin-targeting drugs support brodalumab’s more rapid onset of treatment effects, including skin clearance and relief of itch and pain. CONCLUSION: Brodalumab induces a rapid treatment response in patients with moderate-to-severe psoriasis and may promote earlier improvements in quality of life. J Drugs Dermatol. 2022;21(8):854-860. doi:10.36849/JDD.6791.

Real-World Clinical Experience With the IL-17 Receptor A Antagonist Brodalumab

Psoriasis is a chronic, inflammatory, remitting/relapsing autoimmune dermatologic condition that manifests with scaly, erythematous plaques. It has a significantly negative effect on patient quality of life, as well as increasing their risk of numerous comorbid diseases. Patients are typically treated initially with topical steroids, retinoids, and vitamin D derivatives followed by phototherapy and systemic treatments, including oral, subcutaneous or intravenous immunomodulatory drugs, if needed. Psoriasis is driven by T-cell activation and associated with the secretion of proinflammatory cytokines and a dysregulated interleukin-23/T helper 17 (Th-17) inflammatory response. Eleven biologic therapies and 6 biosimilars that target the 3 main immunological pathways­tumor necrosis factor-α (TNF-α), interleukin 23 (IL-23), and IL-17, are approved for the treatment of plaque psoriasis. While most demonstrate similar effectiveness in clinical trials, patient response in real-world settings is varied. Thus, it is important that the clinician understand the mechanism of action of these drugs as well as their safety profile, unique benefits, and limitations. They must also consider the patient's disease presentation, severity, and comorbid conditions when determining the most appropriate therapy. This article focuses on the IL-17 inhibitors, secukinumab, ixekizumab, and brodalumab, highlighting their unique mechanisms of action and their efficacy and safety in a real-world clinical setting. J Drugs Dermatol. 2020;19(2)132-136. doi:10.36849/JDD.2020.4774

Oral Lichen Planus Treated With Apremilast.

Oral lichen planus is a very difficult condition to treat and causes patients to experience pain and difficulty eating. Therapeutic approaches focus on minimizing flares and relieving pain and discomfort to improve patient quality of life. Topical preparations are the mainstay of therapy, but they are often insufficiently efficacious for more severe cases. The use of systemic agents can be complicated by potentially serious adverse effects, the need for regular monitoring, suboptimal efficacy, and cost. Reported here are 3 recalcitrant cases of oral lichen planus that were effectively treated with apremilast, a drug recently approved for psoriasis and psoriatic arthritis.

J Drugs Dermatol. 2016;15(8):1026-1028.

Treatment of superficial basal cell carcinoma with ingenol mebutate gel, 0.05%.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in Caucasians. Surgical approaches are the most widely used and effective treatment strategies for well-defined BCC. However, for patients with low-risk, superficial BCCs (sBCCs), medical therapy may be a treatment option. In this small case series, we describe our experience in using topical treatment with ingenol mebutate gel, 0.05%, for patients who refused surgical treatment for sBCC. METHODS: We conducted a retrospective chart review of seven patients from our community dermatology practice for whom sBCC was treated with ingenol mebutate. The chart review extracted information on demography, dermatologic history, and prior treatment for actinic keratosis or skin cancer. Summary of the treatment outcome with ingenol mebutate included the size and location of the sBCCs, description of administration, local skin reactions, adverse events, and efficacy. RESULTS: Histopathologic analysis of a shave biopsy sample of suspicious lesions on the trunk confirmed nine sBCCs: a single sBCC in five patients and two well-separated lesions in each of the other two patients. Patients were treated at 10 to 14 days after shave biopsy; biopsy sites were not required to be fully healed. Lesions were either occluded using a standard adhesive bandage (n=6) or not occluded (n=3). All patients experienced local skin reactions that began on day 1 or 2 of treatment, peaked on days 2 to 7, and were largely resolved at 2 weeks. All sBCCs were clinically resolved on short-term follow-up at 2 to 4 weeks. Repeat biopsy of six lesion sites in four patients at 3 or 4 months confirmed histologic clearance. There were no clinically suspicious lesions in any patients at subsequent follow-up evaluations at 3-month intervals. The longest follow-up to date has been 14 months. CONCLUSION: Ingenol mebutate gel, 0.05%, was efficacious and well tolerated for the treatment of biopsy-confirmed sBCCs on the trunk in seven patients.

Tolerability of Ingenol Mebutate Gel, 0.05%, for Treating Patients with Actinic Keratosis on the Scalp in a Community Dermatology Practice.

OBJECTIVE: To describe the safety, tolerability, and efficacy of treatment of actinic keratosis on the scalp with two consecutive, once-daily applications of ingenol mebutate gel, 0.05%. DESIGN: Retrospective chart review. SETTING: Community dermatology practice. PARTICIPANTS: Male patients (N=78) with a long history of recurrent and relapsed scalp actinic keratosis. MEASUREMENTS: This chart review extracted non-identifying information on patients' medical history, pertinent history of actinic keratosis and skin cancer, and prior actinic keratosis treatments. Also collected was information on patients' treatment of scalp actinic keratosis with ingenol mebutate gel, 0.05%, including the occurrence of local skin reactions and their treatment, adverse events, and efficacy results at short-term and additional follow-up. RESULTS: In these patients, a significant proportion of the scalp had numerous actinic keratoses that were often recurrent and/or hyperkeratotic. Most patients (83%) received cryosurgery to visible scalp actinic keratoses two weeks before ingenol mebutate treatment. Local skin reactions developed on the first day of topical treatment, were predominantly mild or moderate in intensity, and generally were resolved by 10 to 14 days. Local skin reactions were treated with a topical moisturizing product in 44 percent of the patients. Nearly half (45%) of the patients experienced application-site reactions, described as a combination of burning, itching, pain, and/or tenderness; the reactions were mild or moderate in intensity and lasted only a few days. CONCLUSIONS: Ingenol mebutate gel, 0.05%, had a good safety and tolerability profile when used to treat scalp actinic keratosis in patients who had a prolonged history of actinic keratosis.

Effect of Field Treatment of Actinic Keratosis With Ingenol Mebutate Gel on the Identification of Lesions for Biopsy.

Actinic keratoses (AKs) are premalignant skin lesions caused by cumulative ultraviolet-light exposure that may progress to invasive squamous cell carcinoma (SCC). As the clinical presentation of AKs varies widely, only a histopathologic analysis of a biopsied sample can eliminate or confirm a diagnosis of invasive SCC. Reducing the burden of AK with a combination of lesion-directed and field-directed treatments may help to identify persistent, suspicious lesions that require further evaluation. We present 10 cases of SCC that were identified and histologically confirmed in 7 patients after complete or substantial clearance of AKs by sequential treatment of sun-damaged skin with cryosurgery and ingenol mebutate.

Use of ingenol mebutate gel for actinic keratosis in patients in a community dermatology practice.

BACKGROUND: Ingenol mebutate gel is a topical field treatment for actinic keratosis (AK) approved for a 2- or 3-day duration of application. OBJECTIVE: This chart review examined the efficacy and safety of ingenol mebutate gel for treatment of AK in patients from a community dermatology practice. METHODS: A retrospective chart review was conducted for all patients with AK treated with ingenol mebutate gel. RESULTS: A total of 135 patients with a prolonged history of AK were treated from April 2012 to January 2013. The majority received cryosurgery to all visible lesions, followed 2 weeks later by ingenol mebutate; areas treated with ingenol mebutate were typically >25 cm² in size. Local skin reactions, consisting of mild to moderate erythema and flaking/scaling, were significantly improved by 1 week after peak inflammation and were not treated in most patients. At 1 to 4 months after treatment of AKs on the face, nearly all patients (99%) achieved ≥75% clearance of baseline and emergent AKs. After treatment of AKs on the scalp or forearm and/or hand, >80% of patients demonstrated ≥75% clearance. LIMITATIONS: This was a retrospective chart review of patients from a single practice. CONCLUSION: Ingenol mebutate is an effective, well-tolerated topical treatment for AK in sun-damaged skin.