Safety Of Ingenol Mebutate Gel Research Articles

Efficacy and safety of ingenol mebutate gel in field treatment of actinic keratosis on full face, balding scalp, or approximately 250 cm2 on the chest: A phase 3 randomized controlled trial

Ingenolmebutate (IngMeb) 0.015% or 0.05% is approved for actinic keratosis (AK) areas of 25cm2 or less; some patients require treatment of larger fields. To determine efficacy and safety of IngMeb 0.027% in areas of AK of up to 250cm2 during an 8-week initial assessment period and extended 12-month follow-up. This phase 3, randomized, double-blind, vehicle-controlled trial (NCT02361216) enrolled adult patients with 5 to 20 AK lesions on the face/scalp (25-250cm2) or chest (approximately 250cm2). Patients received once-daily IngMeb or vehicle for 3 consecutive days on the full face, full balding scalp, or approximately 250cm2 on the chest. The primary endpoint was complete AK clearance (AKCLEAR 100; week 8). Additional endpoints included partial AK clearance (AKCLEAR 75), recurrence, patient satisfaction, cosmetic outcome, and safety. IngMeb was superior to vehicle for complete AK clearance (21.4% vs 3.4%, P<.001) and AK clearance of 75% or greater (59.4% vs 8.9%, P<.001) at week 8. Probability of sustained clearance during the 12-month follow-up was 22.9% for patients treated with IngMeb. Increased treatment satisfaction and cosmetic outcomes were observed with IngMeb versus vehicle. No unexpected safety signals were identified. Localized skin responses hindered maintenance of double-blinding. IngMeb 0.027% was superior to vehicle for treatment of AK areas of up to 250cm2. The safety profile of IngMeb was as expected.

An open-label exploratory study evaluating the efficacy and safety of ingenol mebutate gel 0.05% for the treatment of verruca vulgaris

An open-label exploratory study evaluating the efficacy and safety of ingenol mebutate gel 0.05% for the treatment of verruca vulgaris

Prospective Pilot Evaluation of the Efficacy and Safety of Topical Ingenol Mebutate Gel for Localized Patch/Plaque Stage Mycosis Fungoides

Background: Mycosis Fungoides (MF) is the most frequent type of the primary cutaneous NK/T-cell lymphomas. Ingenol mebutate (IM) displays in vitro pro-apoptotic properties on neoplastic lymphocytes. Objectives: To evaluate the efficacy and safety of IM gel as topical treatment for MF. Materials and Methods: Ten male patients with longstanding classic type MF (n=9) and follicular MF (FMF; n=1), T2bN0M0B0, stage Ib, resistant to systemic methotrexate or acitretin therapies for at least 3 months, were included in this pilot study. In these patients, 11 target patch/plaque stage lesions with an area ≤ 25 cm2 were selected for IM therapy (0,05%, 2 weekly applications). The primary endpoint was the improvement of the CAILS scores. Biopsies were performed before and after treatment from 10 target lesions. Relapse rates were evaluated at 6 months. Results: The mean CAILS score of treated target lesions was reduced by 58.2%. The mean erythema, scaling and plaque elevation scores were improved by 73.6%, 93.9% and 97.9% (p&lt;0.0001), respectively, while the lesion size remained unchanged (p=0.34). A complete or partial clearance of histological and immunohistochemical features was observed in 6/10 (60%) and 4/10 (40%) of the MF or FMF target lesions, respectively. Monoclonal TCR rearrangement was evidenced in 100% (7/7) of the patients and in 3/7 (43%) after treatment. The relapse rate at 6 months was 18%. All the patients experienced burning sensations, oozing and crusting. Conclusion: IM gel warrants further investigation and development as a potential topical treatment for localized patch/plaque stage MF and FMF.

Pharmacokinetics of ingenol mebutate gel under maximum use conditions in large treatment areas

Purpose: Actinic keratoses (AKs) exist on a continuum with squamous cell carcinoma and can occur as sub-clinical and clinically visible lesions in cancerized fields on sun-damaged skin. Ingenol mebutate effectively treats AKs on areas up to 25 cm2, but actinic keratosis can affect larger areas of skin. This trial evaluated systemic exposure and safety of ingenol mebutate gel on larger areas of skin under maximum use conditions.Methods: Phase I, multicenter, open-label, uncontrolled, non-randomized trial. Patients received ingenol mebutate gel for three consecutive days on approximately 250 cm2 of sun-damaged skin on the full face (0.027%), the scalp (0.027%), or arm (0.06%).Results: Of 61 patients, 10 (face =8; arm =2) had ingenol mebutate in whole blood at subnanomolar levels (0.235–0.462 nM). The assayed metabolites were below the lower limit of quantification. Local skin responses increased during Days 1–4 and declined thereafter, approaching baseline by Day 16. Most adverse events were pain/pruritus of mild or moderate intensity.Conclusions: Subnanomolar systemic exposure to ingenol mebutate was measured after application of the gel to approximately 250 cm2 on the full face, scalp, or arm under maximum use conditions. No clinically relevant systemic adverse reactions were observed, and local skin responses were manageable.