Tanweer A. Syed’s research while affiliated with University of North Carolina at Chapel Hill and other places

Methotrexate has been used as one of the first and systemic therapies for psoriasis. In general, 70% of patients with psoriasis prefer topical therapy as the treatment of choice. The purpose of this placebo-controlled double-blind study was to evaluate the clinical efficacy and tolerability of methotrexate 0.25% incorporated in a hydrophilic gel (hydroxyethylcellulose 1%) to treat patients afflicted with psoriasis vulgaris. Sixty patients (37M/23F) ranging between 18 and 70 years of age, with slight to moderate chronic plaque-type psoriasis and PASI (Psoriasis Area and Severity Index) scores between 5.3 and 17.5 joined the study. The mean duration of the disease at entry was 9.6 years (range 1-24 years). The diagnosis of psoriasis was established by clinical and histopathologic methods. Patients were sequentially randomized into two parallel groups. Each patient was allocated a precoded 100-g tube (active or placebo) with instructions on how to self-administer the trial medication topically (without occlusion) to their lesions two times daily for 5 consecutive days per week. The study lasted for 12 weeks with 4 weeks of active treatment. Patients were examined on a weekly basis and those showing total clearing or remission of lesions were considered effectively treated. By the end of the treatment, breaking the code disclosed that methotrexate 0.25% gel had significantly treated more patients than placebo (83.3% vs. 6.7%; p < 0.0001), reduced the PASI score to a mean of 2.2, and cleared more plaques (82.2% vs. 4.3%; p < 0.0001). Laboratory evaluations, including CBC with differential and platelet count, renal function, liver chemistry [SGOT (aspartate transaminase) and SGPT (alanine transaminase)], and serum creatinine, were within the normal limits. The treatment was well-tolerated by all the patients, with no adverse drug-related symptoms and no dropouts. The study was followed up for 12 months from the first day of the treatment; two cured patients had relapsed after 8 months. The findings of this study demonstrate that methotrexate 0.25% in a hydrophilic gel is well tolerated and significantly more effective than placebo as a patient-applied topical medication to treat psoriasis vulgaris.

Background Methotrexate has been used as one of the first and systemic therapies for psoriasis. In general, 70% of patients with psoriasis prefer topical therapy as the treatment of choice. Objective The purpose of this placebo-controlled double-blind study was to evaluate the clinical efficacy and tolerability of methotrexate 0.25% incorporated in a hydrophilic gel (hydroxyethylcellulose 1%) to treat patients afflicted with psoriasis vulgaris. Methods Sixty patients (37M/23F) ranging between 18 and 70 years of age, with slight to moderate chronic plaque-type psoriasis and PASI (Psoriasis Area and Severity Index) scores between 5.3 and 17.5 joined the study. The mean duration of the disease at entry was 9.6 years (range 1–24 years). The diagnosis of psoriasis was established by clinical and histopathologic methods. Patients were sequentially randomized into two parallel groups. Each patient was allocated a precoded 100-g tube (active or placebo) with instructions on how to self-administer the trial medication topically (without occlusion) to their lesions two times daily for 5 consecutive days per week. The study lasted for 12 weeks with 4 weeks of active treatment. Patients were examined on a weekly basis and those showing total clearing or remission of lesions were considered effectively treated. Results By the end of the treatment, breaking the code disclosed that methotrexate 0.25% gel had significantly treated more patients than placebo (83.3% vs. 6.7%; p < 0.0001), reduced the PASI score to a mean of 2.2, and cleared more plaques (82.2% vs. 4.3%; p < 0.0001). Laboratory evaluations, including CBC with differential and platelet count, renal function, liver chemistry [SGOT (aspartate transaminase) and SGPT (alanine transaminase)], and serum creatinine, were within the normal limits. The treatment was well-tolerated by all the patients, with no adverse drug-related symptoms and no dropouts. The study was followed up for 12 months from the first day of the treatment; two cured patients had relapsed after 8 months. Conclusion The findings of this study demonstrate that methotrexate 0.25% in a hydrophilic gel is well tolerated and significantly more effective than placebo as a patient-applied topical medication to treat psoriasis vulgaris.

Imiquimod (1-(2-methylpropyl)-1 H-imidazo[4,5-c]quinolin-4-amine) and its analogues are a class of non-nucleoside imidazoquinolinamines (hetero-cyclic amine) that activate the immune system through localised induction of cytokines, such as IFN-alpha, -beta, and a number of endogenous interleukins. The exact mechanism of its actions are still unexplored, although when tested in a number of cell culture systems, imiquimod demonstrated no inherent antiviral or antiproliferative activity in vitro, whereas, due to its reported ability to produce onsite stimulation and secretion of cytokines in various in vivo studies, such types of immune response modifiers have been shown to cause diverse biological functions, involving immunoregulatory, antiviral, antiproliferative and antitumour activities. These data support a rational justification to consider imiquimod as an innovative topical agent to treat various cutaneous diseases. Since its synthesis in 1980,several studies using animal models and human subjects have been reported substantiating its usefulness as a treatment option for various skin disorders such as genital warts, genital herpes, molluscum contagiosum, basal cell carcinoma and psoriasis. Imiquimod is insoluble in water but in most of the clinical studies its incorporation from 1 - 5% by weight in an oil-into-water cream emulsion has been reported as being well-tolerated with mild-to-moderate drug-related side effects, such as itching, burning sensation, pain, erythema, erosion and oedema. As a potent immune response modifier and an agent stimulating cell-mediated immune responses, imiquimod appears to be a promising drug to treat many skin disorders, infections and neoplasms.

The purpose of this double-blind, placebo-controlled study was to evaluate the safety, clinical efficacy and tolerability of imiquimod (2%) in cream to cure external genital warts in males. Preselected male patients (n=60) ranging between 18 and 50 years of age (mean 24.2) harbouring 558 lesions (mean 9.3) with clinical, histopathological and polymerase chain reaction (PCR) confirmed diagnosis of human papilloma virus (HPV) infection were randomized to two parallel groups. Each patient was allocated a precoded 25g tube, and instructions on how to apply the trial medication to their lesions at home once daily for three consecutive days per week (max. 12 application in 4 weeks). To evaluate the safety, clinical efficacy and tolerance, patients were exa-mined on a weekly basis. Cure was defined as the total elimination of treated warts with PCR, and Southern blot hybridization confirmed negative HPV DNA. By the end of the treatment, 40% (24/60) patients and 49.8% (278/558) warts were cured. Breaking the code revealed that imiquimod cream had cured 70% (21/30) patients and 86.8% of warts, while placebo healed three subjects and 28 warts (P=0.0001). Eleven patients (18.3%), predominantly in the imiquimod cream group, experienced mild to moderate, non-objective, drug-related side effects with no dropouts. The study was followed up for 18 months from the first day of the treatment, and among the 26 cured patients, one in the imiquimod cream group and two in the placebo had a relapse after 14 months. The study demonstrated that 2% imiquimod in cream with mild non-objective side effects is safe, tolerable and significantly more effective than placebo in curing external genital warts in males.

The purpose of this placebo-controlled, double-blind study was to determine the safety, tolerability and clinical efficacy of 5-fluorouracil (1%) in a vaginal hydrophilic gel (hydroxyethylcellulose, 1%) to cure intravaginal papillomas in women. Pre-selected, 60 women ranging between 18 and 50 years of age (mean 24.6), having 312 vaginal condylomas (mean 5.2) joined the study. The diagnosis of human papillomavirus (HPV) was established with clinical, histopathological and polymerase chain reaction (PCR) techniques. Subjects were randomized into 2 parallel groups. Each patient was allocated a pre-coded tube 15 g (active or placebo) with graduated vaginal applicators (disposable), and instructions how to insert 4 g of the trial medication deep into the vagina once at bedtime on every other day (1, 3 and 5) per week, to visit the clinic on day 7 for clinical evaluations and to receive the same pre-coded replacement to continue the regimen for another week. A maximum 12 applications were to be used in 4 weeks. Cure was defined as absence of clinical signs of infection, re-confirmed by PCR and Southern blot hybridization negative HPV DNA. By the end of the treatment 48.4% patients and 51.9% lesions were cured. Breaking the code revealed that 5-fluorouracil (1%) gel had cured 83.3% patients and 87% intravaginal warts. Placebo resolved 13.3% patients and 14% condylomas; (active gel versus placebo; P < 0.001). Twelve patients (20%) mostly in the active gel experienced mild erythema, erosion and oedema, with no drop-outs. Among cured patients 3 had a relapse after 16 months. In conclusion, the clinical results of the study demonstrate that 5-fluorouracil (1%) in a vaginal hydrophilic gel is safe, tolerable and significantly more effective than placebo to cure intravaginal warts in women.

Objective: To compare the clinical efficacy and tolerability of butenafine 1% in cream with terbinafine 1% in cream in the treatment of plantar or moccasin-type tinea pedis (athlete’s foot). Design and Setting: This was a placebo-controlled, double-blind study. Patients and Participants: 60 men aged between 18 and 60 years (mean 35.4 years) with a mean duration of disease of 28.4 weeks, positive mycology and culture-confirmed tinea pedis participated in the study. Methods: The participants were sequentially randomised into three parallel groups (butenafine cream, terbinafine cream and placebo). Each patient was given a precoded 25g tube and instructed to apply the trial medication to all tinea pedis lesions once daily at bedtime for 5 consecutive days per week (maximum of 2 weeks’ active treatment). Patients were examined on a weekly basis. Cure was defined as negative potassium hydroxide test results and negative fungal culture (mycological cure). Participants cured during the treatment were allowed to discontinue the treatment. Results: By the end of the treatment 60% of all patients were cured. Butenafine cured 18 (90%) patients at 1 week and no further patients at 2 weeks. Terbinafine cured no patients at 1 week and 16 (80%) patients at 2 weeks. Placebo cured no patients at 1 week and 2 (10%) patients at 2 weeks (p < 0.0001, butenafine and terbinafine vs placebo at 2 weeks). None of the patients reported any drug-related adverse events and no patients discontinued treatment. Conclusion: Butenafine 1% in cream is well tolerated and comparatively better than terbinafine 1% in cream or placebo to cure plantar or moccasin-type tinea pedis in men. Further clinical studies appear warranted.

Butenafine, a derivative of benzylamine with potent fungicidal activity is a new generation of antimycotic compound that has shown to be extremely effective against experimentally-induced tinea pedis in the guinea-pig, a situation that resembles synergetic pathology similar to that of tinea pedis in humans. Butenafine, (N-4-tert-butylbenzyl-N-methyl-1-naphthalenemethyl-amine hydrochloride) with a chemical structure and mode of action similar to those of the allylamines, demonstrates superior fungicidal activity in vitro against dermatophytes and superior fungistatic activity toward Candida albicans that of naftifine and terbinafine. In vitro, pharmacodynamic data has shown that the geometric mean of minimum inhibitory concentration values for butenafine were comparatively lower than those of naftifine and clotrimazole against clinical isolates for many dermatophytes. It inhibits sterol synthesis by blocking the squalene epoxidation stage in fungi. In phramacokinetic assessments butenafine achieves and maintains high concentrations and long retention time in skin, with associated anti-inflammatory activity in vivo. In controlled clinical trials when applied topically, butenafine appears to be well tolerated with a subjective mild burning sensation at the application site. There were no withdrawals from the study. Butenafine is sparingly soluble in water but readily soluble in methanol, ethanol, dichloromethane and chloroform. If incorporated properly in semisolid topical preparations, with a balanced vehicle, butenafine hydrochloride potentially exhibits as a promising alternative antimycotic agent for the treatment of tinea pedis.