Topical Monotherapy Research Articles

Clinical efficacy and IL-17 targeting mechanism of Indigo naturalis as a topical agent in moderate psoriasis

BackgroundIndigo naturalis is a Traditional Chinese Medicine (TCM) ingredient long-recognized as a therapy for several inflammatory conditions, including psoriasis. However, its mechanism is unknown due to lack of knowledge about the responsible chemical entity. We took a different approach to this challenge by investigating the molecular profile of Indigo naturalis treatment and impacted pathways.MethodsA randomized, double-blind, placebo-controlled clinical study was conducted using Indigo naturalis as topical monotherapy to treat moderate plaque psoriasis in a Chinese cohort (n = 24). Patients were treated with Indigo naturalis ointment (n = 16) or matched placebo (n = 8) twice daily for 8 weeks, with 1 week of follow-up.ResultsAt week 8, significant improvements in Psoriasis Area and Severity Index (PASI) scores from baseline were observed in Indigo naturalis-treated patients (56.3% had 75% improvement [PASI 75] response) compared with placebo (0.0%). A gene expression signature of moderate psoriasis was established from baseline skin biopsies, which included the up-regulation of the interleukin (IL)-17 pathway as a key component; Indigo naturalis treatment resulted in most of these signature genes returning toward normal, including down-regulation of the IL-17 pathway. Using an in vitro keratinocyte assay, an IL-17-inhibitory effect was observed for tryptanthrin, a component of Indigo naturalis.ConclusionsThis study demonstrated the clinical efficacy of Indigo naturalis in moderate psoriasis, and exemplified a novel experimental medicine approach to understand TCM targeting mechanisms.Trial registrationNCT01901705.

Topical Carmustine as Monotherapy or as Multimodality Therapy for Folliculotropic Mycosis Fungoides.

Folliculotropic mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma with distinct clinical and histological features that is less responsive to therapy than the classic epidermotropic subtype of MF (1, 2). At any given stage, the folliculotropic variant has a worse prognosis than the epidermotropic variant. Due to the (peri) follicular nature of the neoplastic cells in folliculotropic MF, the T-cell infiltrate is thought to be too deep for penetration of many skin-directed treatments. Topical monotherapy is not currently recommended in the current National Comprehensive Cancer Network (NCCN) (3) guidelines as a mainstay treatment option even in patients with a low burden of disease. There is limited evidence that carmustine topical therapy (also known as bis-chlorethylnitrosourea or BCNU) may be beneficial in the treatment of folliculotropic MF. In this study, we hypothesized that topical carmustine would be a safe and effective treatment option for patients with stages I–III folliculotropic MF.

Adjuvant treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review.

In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).

European evidence-based (S3) guideline for the treatment of acne - update 2016 - short version.

European evidence-based (S3) guideline for the treatment of acne - update 2016 - short version.

Onychomycosis: local pharmacokinetics and the future of topical antifungals

Topical treatment for onychomycosis gains momentum in dermatological practice as well as in antifungal formulations research pipeline. Decades of clinical use of internationally available antifungals bring no consensus on real clinical efficacy of topical monotherapy of fungal nail infection. Recommendations of national societies and expert bodies offer no clear guidance on principles and practice of combination therapy with systemic and topical antifungals. Clinical trials conducted to date indicate evidence-based superiority of naftifine 1% topical formulations in management of tinea pedis and onychomycosis. Recently, Russian and international authors evaluated the benefits of antifungal solutions in treatment of onychomycosis. New data on pathophysiology of fungal nail infection and local pharmacokinetics of drugs inside the affected nail elucidate the success of 1% solution of naftifine in topical treatment of onychomycosis.

Oral Antifungal Drugs in the Treatment of Dermatomycosis.

Oral antifungal drugs are used primarily to treat tinea unguium; however, they are also useful for other types of tinea. For example, a combination of topical and oral antifungal drugs is effective in hyperkeratotic tinea pedis that is unresponsive to topical monotherapy. In cases of tinea facialis adjacent to the eyes, ears, or mouth, or widespread tinea corporis, or tinea cruris involving the complex skin folds of the external genitalia, it is difficult to apply topical drugs to all the lesions; therefore, oral antifungal drugs are necessary. Oral antifungal drugs are also useful not only for tinea but for widespread pityriasis versicolor and Malassezia folliculitis, candidal onychomycosis, and candidal paronychia and onychia. Topical antifungal drugs are in fact unsuitable for some mycoses. In tinea capitis, for example, irritation by topical drugs is likely to enhance inflammation; therefore, oral antifungal drug monotherapy is preferable. In interdigital tinea pedis with erosion or contact dermatitis, topical drugs are difficult to use because they tend to cause irritant dermatitis, resulting in exacerbation of the condition. In such cases, treatment should begin with a combination of topical corticosteroid therapy and oral antifungal drugs active against dermatophytes. Topical antifungal drugs are used after the complications resolve. A combination of topical and oral antifungal drugs can shorten the treatment period, thus improving patient adherence to topical treatment. Oral antifungal drugs are useful because of their wide range of applications in the treatment of dermatomycosis.

Tafluprost/Timolol: A Review in Open-Angle Glaucoma or Ocular Hypertension.

A once-daily preservative-free fixed combination ophthalmic solution containing tafluprost 0.0015% and timolol 0.5% (hereafter referred to as tafluprost/timolol) [Taptiqom(®)] has been developed to lower intraocular pressure (IOP) whilst avoiding damage to the ocular surface associated with preservatives such as benzalkonium chloride. Tafluprost/timolol is available in various EU countries for the reduction of IOP in adults with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical monotherapy with β-adrenergic receptor antagonists or prostaglandin analogues and require a combination therapy, and who would benefit from preservative-free eye drops. In two multinational, phase III studies, tafluprost/timolol was superior to monotherapy with either preservative-free tafluprost 0.0015% once daily or preservative-free timolol 0.5% twice daily, and noninferior to concomitant therapy with preservative-free tafluprost 0.0015% once daily plus preservative-free timolol 0.5% twice daily in lowering IOP in adults with open-angle glaucoma or ocular hypertension. Tafluprost/timolol was well tolerated in these studies, with a tolerability profile consistent with that of its individual components and with no new adverse reactions observed. Thus, preservative-free fixed combination tafluprost/timolol is an effective treatment option for the reduction of IOP in adults with open-angle glaucoma or ocular hypertension, providing a useful alternative for those patients who would benefit from preservative-free eye drops.

Dexamethasone Intravitreal Implant for Chronic Diabetic Macular Edema Resistant to Intravitreal Bevacizumab Treatment

Purpose: To evaluate the safety and efficacy of intravitreal dexamethasone implant (Ozurdex) in patients with chronic diabetic macular edema (DME) resistant to prior intravitreal bevacizumab (IVB) treatment.Materials and Methods: Thirty eyes of 30 patients were administered intravitreal Ozurdex and examined at baseline and 1, 3, and 6 months postinjection in this prospective study. Main outcomes were the best corrected visual acuity (BCVA, logMAR), central foveal thickness (CFT), mean cube volume (MCV), and intraocular pressure (IOP). Patients had a CFT over 275 µm (measured by OCT) and were unresponsive to 3 consecutive IVB injections. All data are presented as mean ± standard deviation.Results: The mean BCVA significantly increased from 0.56 ± 0.38 to 0.41 ± 0.27 (p < 0.001), and 0.44 ± 0.28 (p = 0.008) at 1 and 3 months, respectively. At months 1, 3, and 6, the mean CFT significantly decreased from 517 ± 136 µm at baseline, to 290 ± 60 µm (p < 0.001), 314 ± 88 µm (p < 0.001) and 411 ± 126 µm (p = 0.01), respectively. However, the mean CFT (p < 0.001) and MCV (p = 0.01) significantly increased and BCVA significantly decreased (p = 0.04) at 6 month compared to 3 month. Compared to baseline, IOP increased significantly at 1 week (p = 0.01), 1 month (p = 0.01) and 3 months (p = 0.04). However eyes with IOP higher than 21 mmHg were treated and well controlled with topical anti-glaucoma monotherapy. Macular edema recurrence occurred in 25 eyes (CFT ranged from 321 µm to 800 µm) at 6 months.Conclusion: Dexamethasone intravitreal implant may be an effective and safe alternative in treatment of chronic DME nonresponsive to regular IVB. However, its therapeutic efficacy decreases between the third and sixth months following the injection.

Drug Prescribing Pattern in Dermatophytosis at the Medical Outpatient Clinic of a Tertiary Healthcare in Karnataka, India

Abstract Aim of this study is to ascertain the drug prescribing pattern of the patients with Tinea infections attending a tertiary care teaching centre. This retrospective study conducted at a tertiary care teaching hospital in the Dakshina Kannada district, Karnataka for a period of one year. 158 prescriptions were audited to find generic/ brand names of drugs, number of drugs, dosage, forms, frequency, and duration of treatment. The age and sex distributions of patients and disease distribution were also studied. 72 (45.57%) patients were males and 86 (54.43%) were females. Terbinafine, Ketoconazole, Sertaconazole were prescribed as topical monotherapy .Clobetasone butyrate, Sertaconazole and Miconazole were prescribed as topical polytherapy. Terbinafine, Fluconazole and anti histaminics were prescribed as systemic monotherapy and polytherapy. Statistical analysis revealed p-value was > 0.05. Prescription patterns were in consensus with the general guidelines. Keywords: Dermatophytoses, medical audit, tertiary healthcare

The effectiveness of topical antihistamine monotherapy in the patients presenting with the manifestations of seasonal allergic rhinitis

The objective of the present study was to evaluate the effectiveness and safety of monotherapy with the use of allergoferon gel composed of topical recombinant human interferon-α-2β and loratadine. A total of 105 patients at the age varying from 18 to 55 years presenting with the manifest form of seasonal allergic rhinitis were available for the examination. They were given the topical treatment in the recommended standard doses. The patients included in group 1 (n=65) were treated with allergoferon while those comprising group 3 (n=40) received mometasonefuorate (nasonex). Changes in the clinical symptoms were recorded on days 3, 7, 14, 21, and 28. The best results of the treatment were documented in the patients of group 1 on day 3 afterthe onset of therapy; this effect was attributed to the rapid beginning of the drug action that was apparent within15 minutes after the topical application of the medication. There were no significant difference between the manifestations of the symptoms on days 7 and 14 in the patients of both groups. None of the patients in group 1 refused to continue therapy up to day 28. Two patients in group 2 (5%) wished to discontinue the treatment due to side effects. It is concluded that the treatment with the allergoferon gel for the topical and external applications extends the possibilities for efficacious and safe therapy of the clinical manifestations of seasonal allergic rhinitis.

Antifungal therapy for onychomycosis in children

Onychomycosis is a chronic infection of the nail unit, and its prevalence increases with age. Treatment options for children are similar to those for adults and include both oral and topical therapies. Oral agents, such as terbinafine, itraconazole, and fluconazole have been reported to have good efficacy and a low rate of side effects in children. Topical therapies, such as amorolfine and ciclopirox, can also be used as monotherapy or combined with oral agents to treat onychomycosis. Due to their thinner, faster-growing nails, children are more likely to respond to topical monotherapy than adults. There is currently insufficient data comparing emerging medical devices, such as laser therapy, with standard therapeutic options to recommend their use in children.

Topical therapy for toenail onychomycosis: an evidence-based review.

Managing toenail onychomycosis with topical treatments is challenging. It is difficult for topical medication to penetrate the nail plate, and this is reflected in lower cure rates with topical treatment than with oral treatment. However, oral medications may not be suitable for some patients, because of drug interactions; therefore, topical treatments are critical in managing the disease in certain patient populations. This paper reviews the quality and content of the scientific literature on topical treatments for toenail onychomycosis. PubMed, Ovid (Medline and Embase), Scopus, Cochrane library, and clinicaltrials.gov databases were searched for original clinical reports of topical monotherapy for microscopy and/or culture-confirmed toenail onychomycosis in adults. Studies were evaluated using an onychomycosis study quality scale, which was based on the CONSORT guidelines. Twenty-five publications (28 studies) were identified and met the inclusion criteria. Thirteen studies scored high ratings on the quality scale. These were randomized controlled trials or randomized comparative trials. Low-quality studies were nonrandomized, open studies that prevented statistical analysis. Most studies reported clinical and mycological cure. The most variation was observed with reporting outcomes of clinical improvement. Amorolfine, ciclopirox, tavaborole, and efinaconazole produced clinical and mycological cure in patients with mild to moderate toenail onychomycosis (<50-65 % nail involvement), with efinaconazole showing the highest rates. Treatments were generally applied daily for 24-48 weeks, with longer treatment and follow-up showing better outcomes. Topical treatment with amorolfine, ciclopirox, tavaborole, or efinaconazole is appropriate for cases of mild to moderate toenail onychomycosis due to dermatophyte or mixed dermatophyte/Candida infection.

Ocular Surface Squamous Neoplasia

To evaluate the current standard of care of ophthalmologists who are likely to encounter ocular surface squamous neoplasia (OSSN) in their practices and to compare this with data gathered in 2003. Invitations to a web-based survey were sent to members of the Ocular Microbiology and Immunology Group. In addition, the survey was posted to the Cornea Society Listserv, Keranet. The survey contained questions regarding the surgical and medical management of OSSN and postcare follow-up. The results of this survey were compared with the results of a 2003 survey, where possible, to identify the areas of change in the standard of care. Eighty-one ophthalmologists participated in the survey. Seventy-nine percent of the responders thought that there was enough evidence for topical monotherapy in OSSN, but only 58% reported ever using topical agents as monotherapy. First-line topical therapy was interferon α2b (56%) followed by mitomycin C (MMC) (37%). A shift from surgical excision alone to excision followed by topical therapy was seen when comparing the 2012 survey to the 2003 survey. The preferred postexcision topical agent was MMC. Seventy-five percent of responders evaluate their patients every 2 to 4 months during the first 2 years. Topical agents were being used more in 2012, either in combination with surgical excision or as monotherapy, compared with those used in 2003. Interferon has replaced MMC as the agent most used for topical monotherapy, possibly because of a favorable safety and tolerance profile. Prospective randomized trials are needed to better define the ideal practice patterns.

Efficacy of acne topical treatment using the isotretinoin solution

Goal. To assess the efficacy and safety of isotretinoin 0.025% in the form of a solution for external use for the treatment of patients with common acne. Materials and methods. Topical monotherapy with Retasol® (isotretinoin 0.025% solution for external application) was administered to 190 patients suffering from acne aged 12-30. Most of the patients (160 out of 190) suffered from the papulopustular acne while others suffered from the comedonal form. The solution was applied to the skin twice a day; the treatment duration was 3 months. Reduction in the amount of pimple components (comedones, papules, pustules, nodes and spots) and sebum secretion were considered as the key treatment efficacy indices. The drug safety was assessed based on subjective and objective data about any adverse events. Results. Application of the Retasol® drug produced a positive therapeutic effect in 170 patients out of 190 while complete clinical recovery was observed in 25 subjects. Application of the drug resulted in a substantial regression in all of the acne manifestations, in particular, comedones and excessive sebum secretion. Topical treatment with Retasol® did not entail any adverse events (except of the exacerbation reaction characteristic of any retinoid) or changes in blood and urine test. Conclusion. Retasol® (isotretinoin 0.025% solution for external application) is a highly efficient topical retinoid for the treatment of patients with comedonal and papulopustular acne forms and is characterized by a good safety profile.

Ocular surface evaluation in patients treated with a fixed combination of prostaglandin analogues with 0.5% timolol maleate topical monotherapy: a randomized clinical trial

OBJECTIVES:To compare ocular surface changes induced via glaucoma treatment in patients using fixed combinations of prostaglandin analogues (travoprost, latanoprost and bimatoprost) with 0.5% timolol maleateMETHODS:A prospective, multicenter, randomized, parallel group, single-blind clinical trial was performed in 33 patients with ocular hypertension or open angle glaucoma who had not been previously treated. The ocular surface was evaluated prior to and three months after treatment, with a daily drop instillation of one of the three medications. The main outcome measurements included the tear film break-up time, Schirmer's test, Lissamine green staining, the Ocular Surface Disease Index questionnaire, impression cytology using HE and PAS and immunocytochemistry for interleukin-6 and HLA-DR. Ensaiosclinicos.gov.br: UTN - U1111-1129-2872RESULTS:All of the drugs induced a significant reduction in intraocular pressure. Decreases in the Schirmer's test results were observed with all of the drugs. Decreases in tear-film break-up time were noted with travoprost/timolol and latanoprost/timolol. An increase in the Lissamine green score was noted with travoprost/timolol and bimatoprost/timolol. The Ocular Surface Disease Index score increased after treatment in the travoprost/timolol group. Impression cytology revealed a significant difference in cell-to-cell contact in the same group, an increase in cellularity in all of the groups and an increase in the number of goblet cells in all of the groups. The fixed combinations induced an increase in IL-6 expression in the travoprost/timolol group, in which there was also an increase in HLA-DR expression.CONCLUSIONS:All of the fixed combinations induced a significant reduction in intraocular pressure, and the travoprost/timolol group showed increased expression of the inflammatory markers HLA-DR and interleukin-6. All three tested medications resulted in some degree of deterioration in the ocular surface after three months of glaucoma treatment.

Treatment-Refractory Actinic Keratoses Successfully Treated Using Simultaneous Combination Topical 5-Fluorouracil Cream and Imiquimod Cream: A Case–Control Study

Most actinic keratoses (AKs) respond to standard treatments, but a subset persist and require further intervention. We report a series of 10 patients with AKs that failed to respond to conventional treatment with cryotherapy and topical monotherapy but responded completely to simultaneous therapy with topical 5-fluorouracil (5-FU) and imiquimod creams. To report the success of this combination therapy in refractory AKs and to determine whether any clinical or histologic features predict for treatment resistance. Case-control study with two control groups matched to each patient according to lesion location and sex. Mean lesion diameter (p < .001), lesion diameter greater than 1 cm (p < .001), and the presence of pain (p = .01) were statistically associated with failure of cryotherapy and topical monotherapy. None of the histologic features evaluated were found to be statistically significant, although thicker epidermis was nearly so (p = .054). In patients who have failed standard therapy for AKs, combination treatment using topical 5-FU and imiquimod cream may be an effective alternative therapeutic strategy. Larger lesion diameter, specifically greater than 1 cm, and the presence of pain predict conventional treatment resistance.

Early symptomatic response and mucosal healing with mesalazine rectal suspension therapy in active distal ulcerative colitis - additional results from two controlled studies

Rapid resolution of symptoms and endoscopic inflammation in ulcerative colitis (UC) represent important treatment goals. To establish times to bleeding cessation and endoscopic healing for topical and oral mesalazine in active distal UC, a post hoc analysis of two published studies was performed. Study I (Sutherland 1987) compared mesalazine rectal suspension to placebo, while Study II (Safdi 1997) compared topical suspensions, either alone or in combination with oral mesalazine, and oral alone. Cessation of rectal bleeding (RB) was defined as absence of bleeding on four consecutive days. Endoscopic remission was defined as DAI mucosal healing (MH) subscore=0 and clinical remission as MH subscore =0-1 and ≥ 1-point improvement, plus RB subscore = 0. Study I: By Day 2, 31.4% of subjects using topical monotherapy reported no RB vs. 5.5% in the placebo arm (P<0.0006); median time to RB cessation was 8 days. Significantly higher rates of endoscopic (25.0% vs. 7.8%, P<0.005) and clinical remission (48.6% vs. 9.6%, P<0.0001) were observed at Week 3. Study II: A significantly higher proportion of subjects achieved RB cessation with combination therapy vs. oral therapy, commencing by Day 8. By Week 3, a significantly higher proportion of subjects using combination therapy achieved clinical remission compared to oral therapy alone (57.9% vs. 18.2%, P<0.05). Topical mesalazine suspension, either alone or in combination with oral mesalazine, led to earlier rectal bleeding cessation and mucosal healing. These data support use of topical therapy for more rapid treatment benefit in active distal ulcerative colitis.

Is Topical Monotherapy Effective for Localized Pyoderma Gangrenosum?

In May 2008, a 32-year-old woman was seen with a painful infiltrated erythematous lesion 11 cm in diameter, studded with purulent necrotic pits, on the anterior right shin (Figure, A). It had started as an erythematous infiltrated lesion 3 months previously and had been stable for 1 month. Pyoderma gangrenosum was diagnosed based on the clinical appearance, negative findings on bacterial culture, and histologic examination of a skin biopsy specimen. No systemic underlying disease was found during investigations, including a colonoscopy. There is little evidence on the efficacy of PG treatment because there is only 1 randomized controlled trial to date comparing the effects of infliximab vs placebo. Systemic corticosteroids and cyclosporine are usually recommended as first-line treatments. Given the stability of this solitary lesion, we decided to consider the option of topical monotherapy for our patient. The objective of this article was to determine from the available evidence whether a topical agent would be an effective and safe treatment in this setting. Literature Search

Combination therapy in the treatment of psoriasis

In addition to topical monotherapy for mild and systemic monotherapy for moderate to severe psoriasis, combination therapy plays an important role in daily practice. Although clinical trials almost exclusively evaluate monotherapy regimens, in real life psoriasis patients are usually treated with combination therapies. All combinations are used, topical/topical, topical/UV-light, topical/systemic or UV-light/systemic. Often not only two but more drugs/therapies are combined. Not every combination provides additive or synergistic effects. Some combinations are not possible and may be regarded as contraindications. Data on a benefit-risk-assessment are much more sparse in medical literature as compared to monotherapies. We summarize current knowledge about the use of combination therapies in psoriasis on the basis of published literature in the form of a table to show which combinations are possible, useful or which can not be recommended. This provides a quick overview of available options.

A platform for predicting and enhancing model drug delivery across the human nail plate

Purpose: The objective of the present study was to assess the effect of pretreatment using chemical etchants on the delivery of terbinafine hydrochloride (TH) and 5-fluorouracil (5-FU) into and across the human nail plate. Methods: The TranScreen-N method was used to screen five potential etchants. Based on these results, the dorsal surface of nails was pretreated with chemical etchants, 1% or 10% (w/w) phosphoric acid (PA) or 10% (w/w) lactic acid (LA) gels, for a period of 60 seconds. The nail pretreated with a plain gel formulation (no PA or LA incorporated) was used as the control. Results: Despite the differences in physicochemical properties between TH (log P = 3.3) and 5-FU (log P = −0.83), the in vitro permeation as well as drug load of these drugs in the nail plate was enhanced because of pretreatment with the PA gels, whereas LA pretreatment failed to enhance the drug load and permeation. Optical microscopic and atomic force microscopy studies revealed that the PA enhanced the trans-ungual drug delivery by decreasing the keratin density of the dorsal layer of the nail plate and by microstructural alterations. Conclusions: This study demonstrated that pretreatment of the nail plate with PA (1% or 10%, w/w) for a short duration could be a potential method of improving the efficiency of topical monotherapy treatment for nail diseases.