A cost-effectiveness analysis of calcipotriol plus betamethasone dipropionate aerosol foam versus gel for the topical treatment of plaque psoriasis

Background: Calcipotriol 50 µg/g and betamethasone 0.5?mg/g dipropionate (Cal/BD) aerosol foam formulation provides greater effectiveness and improved patient preference compared with traditional Cal/BD formulations for the topical treatment of plaque psoriasis.

Objective: To determine the cost-effectiveness of Cal/BD foam compared with Cal/BD gel from the Australian perspective.

Methods: A Markov model was developed to evaluate the cost-effectiveness of topical Cal/BD foam and gel for the treatment of people with plaque psoriasis. Treatment effectiveness, safety, and utilities were based on a randomized control trial, resource use was informed by expert opinion, and unit costs were obtained from public sources. Outcomes were reported in terms of 1-year costs, quality-adjusted life years, and incremental cost-effectiveness ratios. All costs were reported in 2017 Australian Dollars.

Results: The model showed that patients using Cal/BD foam had more QALYs and higher costs over 1 year compared with patients using Cal/BD gel, resulting in a cost of $13,609 per QALY gained at 4-weeks. When 4 weeks of Cal/BD foam was compared with 8 weeks of Cal/BD gel treatment, Cal/BD foam was $8 less expensive and resulted in 0.006 more QALYs gained. Sensitivity analyses showed that, compared with Cal/BD ointment, Cal/BD foam was associated with an incremental cost of $15,091 per QALY gained.

Conclusion: Cal/BD foam is the most cost-effective Cal/BD formulation for the topical treatment of patients with plaque psoriasis.     

Fixed combination calcipotriol plus betamethasone dipropionate aerosol foam in the treatment of psoriasis vulgaris: rationale for development and clinical profile

Introduction: Psoriasis is a chronic, immune-mediated inflammatory disorder with a significant negative impact on quality of life. Most patients with mild-to-moderate psoriasis manage their disease with topical therapies; the most commonly used formulations contain corticosteroids and/or vitamin D3 analogues. However, adherence to topical treatment remains a significant issue as the daily treatment regimen can be cumbersome and time consuming and many patients do not obtain complete/almost complete clearance.

Areas covered: Published pre-clinical and clinical data evaluating calcipotriol 50 µg/g (Cal) and betamethasone 0.5 mg/g as dipropionate (BD) aerosol foam in patients with psoriasis.

Expert opinion: Cal/BD aerosol foam, a once-daily, alcohol-free, paraffin-based vehicle with emollient properties, was developed to increase the therapeutic options available to patients. Cal/BD aerosol foam is rapidly effective for treating psoriasis and the greater efficacy compared with the ointment and gel formulations is consistent and clinically relevant. This enhanced efficacy is due to improved skin penetration of the active ingredients following the formation of a stable supersaturated solution on the skin. Studies have shown increasing patient satisfaction with Cal/BD aerosol foam. It is hoped that this optimized formulation of Cal/BD will improve adherence and help to address the unmet medical needs of patients with mild-to-moderate psoriasis.     

Clobetasol propionate emollient formulation foam in the treatment of corticosteroid-responsive dermatoses

Background: Topical corticosteroids are the most common treatment modality for patients with psoriasis and atopic dermatitis; however, the efficacy of topical corticosteroids is often hampered by barriers to patient adherence, such as lack of efficacy, side effects and inconvenience. Recently published studies have investigated the safety and efficacy of a novel emollient foam (EF) formulation of clobetasol propionate (CP), a class I topical corticosteroid in psoriasis and atopic dermatitis. Objectives: To summarize recent literature on CP EF foam, and to evaluate recent Phase II and III clinical trials of CP EF foam in psoriasis and atopic dermatitis. Methods: The MEDLINE (1950 – January 2008) database was searched using the following terms: ‘clobetasol propionate foam’, ‘topical corticosteroids’, ‘topical glucocorticoids’, ‘psoriasis’ and ‘atopic dermatitis’. Results were evaluated for relevance and quality, and additional references were obtained from bibliographies of selected articles. Conclusion: CP EF foam appears to be safe and effective for corticosteroid-responsive dermatoses in adults and children ≥ 12 years of age. As compared to its hydroethanolic foam predecessor, CP EF presents a potential advance for patients who are less likely to tolerate alcohol-based foam. As alcohol-based foams can be irritating and cause stinging in non-hair-bearing areas, this new emollient formulation has the potential to widen the use of CP foam to more patients with atopic dermatitis and to more non-scalp body sites in patients with psoriasis.     

Tazarotene foam, 0.1%, for the treatment of acne

Introduction: Acne is a common skin condition of the pilosebaceous units that affects the young and old, ranges from moderate to severe and can be treated with an array of options. Topical retinoids are the initial treatment for acne due to their ability to treat comedones, the starting point of acne.

Areas covered: Tazarotene is a topical retinoid available as a cream, gel and foam. Tazarotene 0.1% foam was FDA approved in 2012 for the treatment of acne in patients ages ≥12 and is the first foam topical retinoid on the market. Phase I and III trials support the efficacy and safety of tazarotene foam for acne.

Expert opinion: The foam vehicles may increase compliance and satisfaction in some patients and as retinoids are commonly first line acne treatments, this new topical retinoid foam may be a useful option for some acne patients.     

Calcipotriene and betamethasone dipropionate for the topical treatment of plaque psoriasis

Introduction: Psoriasis affects an estimated 2% of the world's population, with higher rates in developed countries. 80% have mild-to-moderate disease and 50 to 80% have scalp involvement. Topical treatments are the mainstay of treatment.

Areas covered: Two-compound calcipotriene and betamethasone dipropionate (BD) is a common topical combination therapy consisting of a vitamin D analogue and a corticosteroid. It comes in ointment, gel/suspension, and foam formulations. Phase II and III clinical trials have consistently shown the two-compound formulation to be effective and safe, with no clinically significant skin atrophy, calcium level changes, or adrenal suppression were seen. Topical scalp solution was also safe and effective in treating scalp psoriasis in pediatric populations.

Expert commentary: Calcipotriene plus BD is more effective and safer than the individual ingredients in the same vehicle for treating body and scalp psoriasis. It should be considered a first line therapy for mild-to-moderate plaque psoriasis.     

Efficacy of a new aluminium salt thermophobic foam in the treatment of axillary and palmar primary hyperhidrosis: a pilot exploratory trial

ABSTRACT

Primary or idiopathic hyperhidrosis (PH) is a disorder of excessive eccrine sweating glands that mainly affects the axillae and the palms. The treatment options for PH involve a range of topical or systemic medication and/or surgical invasive techniques. The common topical treatments are aluminium salts which act by blocking the duct of the eccrine gland or by atrophying the secretory cells. Recently, a new low-residue thermophobic foam formulation (VersaFoam, Mipharm Spa, Milan, Italy), containing 20% of an aluminium salt (sesquichlorhydrate), has been developed. The foam is easy to apply especially in hairy body sites.

Objective: to evaluate the efficacy and the tolerability of the new aluminium salt foam in the treatment of axillary and palmar PH.

Patients and methods: Twenty patients were enrolled in a single-centre, open-label follow-up study. The Minor test score (range 0–3) and the Dermatology Life Quality Index (DLQI), were used to evaluate the amount of sweating and the impact on quality of life. The foam was applied to dry, clean skin, every night during the first week of treatment, and three times a week during the second week of treatment. Evaluation of the results was performed at baseline and at 7 and 15 days after treatment. Patients were monitored throughout the study for adverse events.

Results: All of the 20 enrolled patients completed the study. The foam resulted in a significant reduction of the Minor score in comparison with baseline values in both the axillary (?p = 0.0002) and palm regions (?p = 0.0047). By the end of treatment (day 15) the foam had reduced the amount of sweating in the axillae and palm regions by 50% (Minor score: 4.1 vs. 8.1) and 53% (Minor score: 4.0 vs. 8.5), respectively. Use of the foam showed a positive impact in the DLQI for patients with axillary but not palm hyperhidrosis. No side effects were reported during the study duration by the patients.

Conclusion: The new foam has been shown to be an effective topical treatment in reducing sweating in patients with axillary and palm PH. This formulation is well tolerated in the short term. Further studies are warranted to evaluate the efficacy and safety in the medium and long term.     

Efficacy of betamethasone valerate 0.1% thermophobic foam in seborrhoeic dermatitisof the scalp: an open-label,multicentre, prospective trial on180 patients

SUMMARY

Background: Seborrhoeic dermatitis (SD) is a common chronic inflammatory disease of the skin. Topical steroid creams and/or antifungal agents are commonly used in SD, but no resolutive therapies have been available up to now. Furthermore, little data have been available regarding clinical outcomes after cessation of topical treatments. A new formulation of betamethasone valerate 0.1% in a thermophobic, low-residue, foam vehicle (Bettamousse ^*) (BVM) has become available for the topical treatment of scalp dermatoses. No data have been published hitherto regarding efficacy, safety and patient acceptability of this new formulation for the treatment of SD of the scalp.

Study aim: To assess in an open-label, prospective, multicentre trial, the efficacy, safety and patient acceptability of BVM, as compared to baseline, in SD subjects with scalp involvement.

Patients and methods: A total of 180 patients with moderate-to-severe SD of the scalp were enrolled in the trial. Efficacy was evaluated by analysing SD lesions for erythema, scaling and itching using a five-point grading score (0?=?lesion completely cured; 1?=?mild; 2?=?moderate; 3?=?severe and 4?=?very severe lesion). The clinical global (sum) score was obtained adding the score of each item. Efficacy and safety were assessed at baseline, after 4 weeks of active treatment, followed by an 8-week follow-up period with no treatment.

Results: In comparison with baseline, BVM significantly improved SD lesions. The sum score was reduced from 6.3?±?1.8 to 1.4?±?1.4 at the end of the active treatment period, (p?<?0.0001) and to 1.7?±?1.8 at the end of the 8-week follow-up period (p?<?0.0001). After active treatment, 93% of the patients had a sum score of <3). At the end of 8-week of follow-up, 88% of patients maintained a sum score <3. In addition, 85% of patients considered BVM foam to be a better topical formulation both in terms of efficacy and acceptability compared with previous treatments used.

Conclusion: BVM is an effective and well-tolerated topical treatment of scalp SD. Its clinical effect is also maintained after a 2-month wash-out period.     

Topical delivery for the treatment of psoriasis

Importance of the field: Psoriasis is one of the most common human skin diseases. Topical therapy forms the cornerstone in the management of mild-to-moderate psoriasis. Topical therapies are also used as adjunctive to systemic therapy in moderate and severe forms of the disease.

Areas covered in this review: In this review, an overview of psoriasis pathogenesis, new topical medications for psoriasis, new targets and molecules, combination topical therapies and combination of topical and phototherapy is provided. Over the past decade several efficacious and acceptable treatment options have emerged from the age-old therapies. The development of sophisticated formulation options has led to an enhancement in the rate and extent of drug delivery across the skin, increasing therapeutic value and improving patient compliance.

What the reader will gain: Readers will learn about monotherapy and combination topical products as well as new topical drug delivery technology to achieve optimal clinical outcomes. This review will highlight the need to generate more dermal pharmacokinetic data for better understanding of the impact of formulation change on skin pharmacokinetics to help design improved topical drug delivery systems.

Take home message: New topical formulations have the potential to achieve better efficacy with improved safety profile.     

Evaluating the novel application of cyclosporine 0.1% in ocular surface disease

Introduction: Ocular surface disease (OSD) is a highly prevalent symptomatic condition caused by dry eye disease (DED), intrinsic, environmental, or iatrogenic causes. It affects patient’s visual function and quality of life. Its pathophysiology is centered on tear hyperosmolarity, inflammation, and epithelial damage. Current management is suboptimal and includes artificial tear supplementation and short-term use of topical steroids in severe cases. The recent approval of cyclosporine 0.1% has transformed management strategies of severe DED and moderate-to-severe OSD.

Areas covered: This review summarizes existing information on the efficacy, safety, and tolerability of the new cyclosporine 0.1% formulation.

Expert opinion: Topical cyclosporine A 0.1% represents a promising, novel medication for the management of DED, Meibomian gland dysfunction, and inflammatory OSD. It is primarily beneficial for those patients requiring topical immunomodulatory therapy. This topical formulation also has the potential to meaningfully improve the management of moderate-to-severe glaucoma therapy-related OSD. Currently there is limited published clinical data concerning the efficacy of topical cyclosporine. There are, however, theoretical advantages when comparing this cyclosporine formulation with other established commercial preparations. Future research is needed to delineate the precise role and value of this medication.     

Use of asenapine as add-on therapy in the treatment of bipolar disorder: a comprehensive review and case series

Introduction: Several randomized controlled trials (RCTs), conducted in schizophrenic and bipolar patients, have documented the efficacy and tolerability of asenapine as monotherapy both for short- and long-term treatment. However, evidence on its augmentative use is more limited and related to the manic/mixed phase of bipolar disorder (BD).

Areas covered: The present article reviews augmentative asenapine efficacy and safety/tolerability in the treatment of BD. It also includes some original cases of bipolar patients treated with add-on asenapine in the short- and long-term.

Expert opinion: To date, only a single RCT with manic/mixed patients with partial response to mood-stabilizer monotherapy supports the efficacy and safety/tolerability of augmentative asenapine to lithium/valproate, both in acute and long-term treatment. Additionally, two case reports confirm the overall effectiveness of augmentative asenapine to clozapine and valproate. Our case series, consisting of 4 bipolar patients treated with adjunctive asenapine to mood stabilizers and atypical antipsychotics – with treatment duration ranging from 1 to 14 months – provided clinical results that are consistent with literature data. Taken as a whole, available evidence seems to support the efficacy and safety of adjunctive asenapine in bipolar patients, though additional studies with active comparators are requested to confirm the current body of evidence.     

MAP0004: dihydroergotamine mesylate inhalation aerosol for acute treatment of migraine

Introduction: Dihydroergotamine mesylate (DHE) has been used as an acute migraine treatment since 1945, although tolerability with intravenous administration has limited its use. MAP0004 is a novel, orally inhaled, aerosol formulation of DHE that provides pulmonary drug delivery using a pressurized, metered dose inhaler for rapid absorption through lung alveoli. MAP0004 was developed to provide the anti-migraine efficacy of DHE, with fewer systemic effects than intravenous dosing.

Areas covered: This review discusses available literature describing the pharmacokinetics, tolerability and efficacy of MAP0004, including data from Phase II and Phase III clinical trials.

Expert opinion: MAP0004 aerosol DHE provides desirable activation of 5-HT1B/D receptors, resulting in effective anti-migraine effects. Unlike intravenous DHE, MAP0004 is less likely to bind with other serotonergic, adrenergic and dopaminergic receptors, resulting in fewer unwanted side effects. In addition, MAP0004 is less arterioconstrictive than intravenous DHE. Both Phase II and III clinical trials support anti-migraine efficacy with superior tolerability with MAP0004 compared with intravenous DHE. Inhaled rather than intravenous administration should also improve patient acceptance. These data support the future use of MAP0004 as a first-line acute migraine treatment.     

Drug safety evaluation of aripiprazole in bipolar disorder

Introduction: Safety and tolerability of medications are key variables to inform treatment choice for patients with bipolar disorder (BD). This review focuses on the overall tolerability and safety profile of aripiprazole when used for its bipolar disorder indications, which include acute treatment of manic and mixed episodes and maintenance treatment of bipolar I disorder for the oral formulation, agitation associated with bipolar mania for the injectable immediate-release formulation, and maintenance treatment of bipolar I disorder for the long acting once-monthly (AOM) formulation.

Areas covered: The authors reviewed aripiprazole safety in bipolar disorder according to product labeling. English language reports located through PubMed and information available on the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) websites, with a focus on the safety and tolerability of aripiprazole, were reviewed.

Expert opinion: Compared to many other antipsychotics, aripiprazole has a relatively favorable tolerability profile, with a lower risk for weight gain, dyslipidemia, diabetes, and hyperprolactinemia. Compared to first-generation antipsychotics, and similar to most second-generation antipsychotics, aripiprazole has a reduced propensity for extrapyramidal side effects and a better cardiovascular safety.     

Topical drug delivery systems: a patent review

Introduction: Topical administration is the favored route for local delivery of therapeutic agents due to its convenience and affordability. The specific challenge of designing a therapeutic system is to achieve an optimal concentration of a certain drug at its site of action for an appropriate duration.

Areas covered: This review summarizes innovations from the past 3 years (2012–2015) in the field of topical drug delivery for the treatment of local infections of the vagina, nose, eye and skin. The review also throws some light on the anatomy and physiology of these organs and their various defensive barriers which affect the delivery of drugs administered topically.

Expert opinion: Topical administration has been gaining attention over the last few years. However, conventional topical drug delivery systems suffer from drawbacks such as poor retention and low bioavailability. The successful formulation of topical delivery products requires the careful manipulation of defensive barriers and selection of a soluble drug carrier. Extensive research is required to develop newer topical drug delivery systems aiming either to improve the efficacy or to reduce side effects compared to current patented systems.     

Recent advances in aerosol gene delivery systems using non-viral vectors for lung cancer therapy

ABSTRACT

Introduction: Lung cancer commonly occurs at a high incidence worldwide. Application of aerosol gene delivery systems using various kinds of vectors can improve the patient’s quality of life by prolonging the survival rate.

Areas covered: This review provides a recent update on aerosol gene delivery strategies using various kinds of vectors and gene-modification technologies. Peptide-mediated gene therapy achieves specific targeting of cells and highly improves efficacy. Promoter-operating expression and the CRISPR/Cas9 system are novel gene therapy strategies for effective lung cancer treatment. Furthermore, hybrid systems with a combination of vectors or drugs have been recently applied as new trends in gene therapy.

Expert opinion: Although aerosol gene delivery has many advantages, physiological barriers in the lungs pose formidable challenges. Targeted gene delivery and gene-editing technology are promising strategies for lung cancer therapy. These strategies may allow the development of safety and high efficiency for clinical application. Recently, hybrid gene therapy combining novel and specific vectors has been developed as an advanced strategy. Although gene therapy for lung cancer is being actively researched, aerosol gene therapy strategies are currently lacking, and further studies on aerosol gene therapy are needed to treat lung cancer.     

Efficacy and safety of bromfenac 0.075% formulated in DuraSite for pain and inflammation in cataract surgery

ABSTRACT

Introduction: Bromfenac is a topical ophthalmic non-steroidal anti-inflammatory drug (NSAID) used to reduce pain and treat post-operative inflammation after cataract surgery. Bromfenac 0.075% in the DuraSite? vehicle is a newly-approved formulation which has been shown to be efficacious and safe for use in cataract surgery to reduce pain and treat inflammation. It has been shown to have a slightly better posterior segment ocular bioavailability compared to similar topical ophthalmic NSAIDs. However, there is a paucity of studies investigating its role in the prevention and treatment of post-operative pseudophakic cystoid macular edema.

Areas covered: In this review, the authors provide an overview of similar products available, describe the novelty of bromfenac 0.075% in the DuraSite vehicle, and discuss the relevant clinical studies to determine if the formulation is safe and efficacious.

Expert opinion: Bromfenac 0.075% in the DuraSite vehicle is a new topical ophthalmic medication which has been approved by the FDA for the prevention of pain and treatment of post-operative inflammation. It provides cataract surgeons with an additional medication for cataract surgery. However, no robust studies have been performed showing the effect that it has on the reduction or prevention of post-operative pseudophakic cystoid macular edema.     

Tafluprost for glaucoma

Introduction: Lowering intraocular pressure (IOP) is, at present, the only therapeutic approach to the treatment of glaucoma. Good compliance is essential in every chronic therapy; therefore, the development of IOP-lowering eye drops that are well tolerated and have an easy administration schedule is essential for the treatment of glaucoma. Prostaglandins are a first-choice drug class for the treatment of glaucoma.

Areas covered: This review provides a background on tafluprost, a newly synthesized prostaglandin analogue, and summarizes the existing data on its efficacy and safety, including comparative data with the other prostaglandin derivatives now available on the market. A review of the literature was performed.

Expert opinion: Current research focuses not only on the efficacy of the drugs but also on their tolerability. The importance of obtaining good compliance by the patient is increasingly relevant; therefore, new formulations are studied to provide fewer side effects and an easier schedule. Tafluprost is a new prostaglandin analogue that has been marketed in some European countries and in Japan for more than 2 years and was recently (July 2009) approved in 21 countries. Besides a well-demonstrated IOP-lowering effect, tafluprost is the first topical prostaglandin available as a preservative-free formulation.     

Recent advances in amphotericin B delivery strategies for the treatment of leishmaniases

ABSTRACT

Introduction: Among the drugs in clinical use for the treatment of leishmaniases, amphotericin B (AmB) is the most effective and has been the most extensively studied for the development of drug delivery strategies. Liposomal amphotericin B (AmBisome®) still represents the best therapeutic option for leishmaniases, however, its clinical efficacy depends on the patient immunological status and the endemic region. Moreover, the need for parenteral administration, its side effects and high cost significantly limit its use in developing countries.

Areas covered: This article provides insight into the novel drug delivery strategies that were investigated for AmB over the last 5 years and a final critical selection of emerging concepts and most promising approaches, based on the significance of preclinical antileishmanial and toxicity data.

Expert opinion: The feasibility of oral and topical delivery of AmB has been established in experimental models of leishmaniases. Highly effective AmB nanocarriers containing active targeting ligand and/or immunomodulatory component have also emerged. Translating these advances to the clinic still relies on the full demonstration of safety and efficacy in humans and on the viability and cost-effectiveness of large-scale industrial production.     

The discovery and development of prasugrel

Introduction: Prasugrel (CS-747, LY640315) is a third-generation thienopyridine, which gained approval by the FDA in 2009 for its use in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Areas covered: This article focuses on the preclinical profile of prasugrel. Using published preclinical and clinical studies, the authors summarize the pharmacokinetics, pharmacodynamics, and pharmacogenomics of prasugrel and their distinguishing features in efficacy and safety.

Expert opinion: Prasugrel has a more rapid, more potent antiplatelet effect with less interindividual response variability when compared to clopidogrel. Those therapeutic advantages are attributed to features of its chemical structure that favor the metabolic conversion of prasugrel to its active metabolite. However, the increased risk of bleeding has been associated with a greater antiplatelet effect and dosing profile; this is especially the case in those patients who are at a higher risk of bleeding complications. It is therefore important for an optimal dosing strategy of prasugrel to be identified to provide a formulation that has the best balance for efficacy and safety.     

A nanovesicle topical formulation of Bhut Jolokia (hottest capsicum): a potential anti-arthritic medicine

Objectives: Bhut Jolokia is a capsicum variety indigenous to Northeast India and is recognized as the hottest capsicum variety of the world. The ethnobotanical survey revealed that it has potential anti-arthritic activity but its topical adverse events restrict its usability. In the present study, the semipurified capsaicinoids extract of Bhut Jolokia was formulated as a topical formulation via ethosomal nanovesicle approach, which enhanced the acceptability.

Methods: Prepared formulation was optimized by surface response methodology and characterized for morphology, zeta potential, differential scanning calorimetry study and permeation and penetration studies. The experimental formulations were characterized on Freunds complete adjuvant-induced chronic arthritis model.

Results: Ethosomal nanovesicles prepared with the semipurified capsaicinoids extract demonstrated good anti-arthritic activity in rat model, superior to Thermagel (a marketed formulation of capsaicin) in the reduction of joint swelling and pain throughout the observation period. Nanovesicle formulation showed better tolerability and acceptance on both animal and human models. Results obtained from the study strengthen the potential application of Bhut Jolokia semipurified extract in an ethosomal nanovesicle carrier as a topical analgesic as well as an anti-arthritic.

Conclusion: The significant positive results, with reduced irritant effect of the semipurified capsaicinoids extract of Bhut Jolokia-loaded ethosomal nanovesicle carrier, suggest that it could be one of the choices for formulation development in anti-arthritic medicine.