An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women

Our objective was to determine the optimal duration of treatment with imiquimod for external genital warts over 4, 8, 12 or 16 weeks. A total of 120 women with a history of genital warts for a median of 3-6 months and prior alternative treatments in 73% were evaluated for total clearance rates. There was no statistically significant difference in complete clearance rates after 16-week follow-up across treatment groups: four weeks (40.0%), eight weeks (48.4%), 12 weeks (39.3%) and 16 weeks (51.6%). Imiquimod was well tolerated, and in those treated for four weeks there was a lower incidence of local skin reactions such as erythema and erosion, and no incidences of pain. These preliminary results suggest that a four-week treatment course of imiquimod applied thrice weekly for women with external genital warts may provide a reasonable approach with comparable efficacy and compliance, and minimal adverse events, drug costs and clinic visits.     

Safety and efficacy of imiquimod 5% cream in the treatment of penile genital warts in uncircumcised men when applied three times weekly or once per day

This dose-escalation study was performed to evaluate safety and efficacy of imiquimod 5% cream in the treatment of uncircumcised men with penile warts associated with the foreskin. The cream was applied 3 times/week (n=34) or once per day (n=30) over 8+/-2 h. Imiquimod 5% cream was safe in both treatment groups. However, the 3 times/week regimen was better tolerated with a lower incidence of local skin reactions. In both groups, the 2 most frequently reported local skin reactions were erythema and erosion; they were more severe with the once-daily dosing. The most frequently reported application site reactions were burning, pruritus and irritation or pain (once-daily patients only). Total clearance was achieved in 62% of the patients in the 3 times/week group and by 57% in the once-daily group. Thus, imiquimod 5% cream administered 3 times/week was the optimal dosing regimen in the treatment of penile warts in uncircumcised men.     

Topical imiquimod cream 5% for resistant perianal warts in a renal transplant patient

Renal transplant recipients represent a patient subgroup for whom the effective treatment of genital warts poses a significant problem in genitourinary medicine. This case demonstrates the safe and effective treatment of resistant perianal warts in a male renal transplant recipient using imiquimod.     

Topical imiquimod cream 5% for resistant perianal warts in a renal transplant patient

Renal transplant recipients represent a patient subgroup for whom the effective treatment of genital warts poses a significant problem in genitourinary medicine. This case demonstrates the safe and effective treatment of resistant perianal warts in a male renal transplant recipient using imiquimod.     

Treatment of rheumatoid arthritis with ornidazole. A randomized, double-blind, placebo-controlled study

SIR, In many previous studies, rheumatoid arthritis (RA) hasbeen found at high frequencies in individuals with periodontitis,and RA resembles periodontitis in many pathological aspects[1, 2]. HLA-DR4 tissue antigens are found at high frequenciesboth in patients with periodontitis and in those with RA. HLA-DR4tissue antigens and their subtypes are directly associated witheach disease [3, 4]. High levels of oral anaerobic bacterial antibodies and heat-shockproteins have been found in the     

A double-blind, placebo-controlled cytogenetic study of oral acyclovir in patients with recurrent genital herpes

The antiherpes drug acyclovir breaks chromosomes in vitro at millimolar concentrations and at highly toxic doses in rodents but does not induce single-gene mutations. Recurrent genital herpes patients were examined to determine if such chromosomal damage occurs in peripheral lymphocytes during acute or chronic acyclovir therapy. Patients were randomly assigned to receive acyclovir suppressively and for recurrences, placebo suppressively and acyclovir for recurrences, or placebo suppressively and for recurrences (n greater than or equal to 20 for each group; all treatment double-blind). Normal volunteers and acyclovir-treated cultures served as additional controls. Cytogenetic analyses were done at enrollment (pretreatment), on day 5 of acute acyclovir or placebo treatment for the first postenrollment recurrence (postacute), and at the end of a year on study (postchronic). Cells in metaphase, 150 for each patient, were examined at each time point for structural and numerical chromosomal abnormalities. No cytogenetic effects of chronic or acute oral acyclovir treatment were found relative to lifestyle controls, pretreatment controls, or placebo treatment.     

A comparison of topical application of penciclovir 1% cream with acyclovir 3% cream for treatment of genital herpes: a randomized, double-blind, multicentre trial

Genital herpes simplex virus (HSV) infection, a sexually transmitted disease (STD), is the commonest cause of ulcerative genital infections among the young and adult population. The significant association of genital ulceration and transmission of human immunodeficiency virus (HIV) has been shown in many studies. To explore the potential efficacy of topical treatment of genital herpes with penciclovir cream, a randomized, double-blind, multicentre, acyclovir-controlled Phase II clinical trial of penciclovir 1% cream 5 times daily up to 7 days for suppression of genital herpes was conducted in China. A total of 205 patients aged 20-59 years (mean age 36.0+/-8.8 years for acyclovir and 34.8+/-8.4 years for penciclovir) with a clinical diagnosis of genital herpes were randomly allocated to one of the 2 parallel treatment groups and used for analysis. Clinical assessment were made before treatment and followed up at every visit during the study. Our results show that there was an encouraging improvement simultaneously in the 2 groups although no significant differences in clinical efficacy with respect to clinical cure rate, and times to healing, resolution of all symptoms, absence of blisters, cessation of new blisters, crusting, and loss of crust between penciclovir and acyclovir groups in terms of primary, non-primary and total patients were found. However a significantly shorter time to crusting was found in primary penciclovir group when compared with primary acyclovir group. Adverse experience was generally infrequent and mild, and was comparable in the 2 treatment groups. Based on these preliminary clinical findings, further evaluation of penciclovir 3% cream for topical treatment of genital herpes is planned.     

Efficacy and safety of 5% ibuprofen cream treatment in knee osteoarthritis. Results of a randomized, double-blind, placebo-controlled study

OBJECTIVE: To investigate the efficacy and safety of a cream containing 5% ibuprofen (Dolgit) cream) in primary knee osteoarthritis (OA) in a double-blind, randomized, placebo-controlled, parallel-group study using an adaptive sequential design. METHODS: Patients of both sexes aged 40-75 years, with a visual analog scale (VAS) score for pain on motion of >or= 40 mm, a Lequesne index score of 5-13, and a Kellgren-Lawrence radiographic score grade II-III were enrolled between January 2001 and July 2001. Study medication was applied in a 10-cm strip tid for 7 days on the more painful knee. Each strip of the active treatment contained approximately 200 mg ibuprofen. The primary efficacy variable was the treatment response rate compared between the 2 groups. Response was defined as a reduction of pain on motion, self-assessed on VAS, of >or= 18 mm or >or= 23% compared to baseline. RESULTS: The second interim analysis scheduled post-inclusion of 2 25 patients revealed a response rate of 21 patients (84.0%) in the ibuprofen group and of 10 patients (40.0%) in the placebo group (p = 0.0015). The study was then terminated. All secondary endpoints such as pain at rest, overall pain, Lequesne index, and global assessment of efficacy also showed the superiority of ibuprofen. No adverse event was recorded. CONCLUSION: The efficacy and safety of ibuprofen cream in treatment of primary knee OA were statistically significant and clinically relevant compared to placebo.     

An audit of patients who have received imiquimod cream 5% for the treatment of anogenital warts

With the licensing of the new drug Imiquimod cream 5% (Aldara 3M Health Care) for the treatment of anogenital warts and its inclusion into clinic guidelines, a case note review audit was performed of its use. The treatment of 52 patients was audited. Results showed that clinic guidelines were being followed and that patient outcomes in terms of clearance were at least as good as the quoted rates in the literature. Significant issues included firstly patient education-especially for those who had previously received ablative therapy. Secondly the length of time that therapy would be continued before a patient was deemed to be a non-responder to Imiquimod cream 5%, and if this was the case should the frequency of application be amended from the manufacturer's recommended regime of 3 times a week.     

5% Imiquimod cream for external anogenital warts in HIV-infected patients under HAART therapy

The efficacy of imiquimod in the treatment of external genital warts in HIV positive subjects was compared to a group of patients with normal immune function. Imiquimod 5% cream was applied by patients three times a week until resolution for a maximum of 16 weeks. Assessment for response and the occurrence of side effects was performed every four weeks. Thirty-one per cent of 75 HIV positive patients achieved a complete clearance, a partial response was obtained in 24% of subjects while in 45% we observed no clinical response. In the control group a total clearance was obtained in 62% of subjects, a partial response in 24% and no response in 14%. Recurrences occurred in 4/23 HIV patients and 2/31 immunocompetent patients within three months of follow-up. Side effects were minor to moderate. We conclude that imiquimod 5% cream has an acceptable efficacy and safety on HIV patients.     

Randomized, double-blind, placebo-controlled, clinic-initiated, Canadian multicenter trial of topical edoxudine 3.0% cream in the treatment of recurrent genital herpes. Canadian Cooperative Study Group

Treatment for recurrent genital herpes using edoxudine 3% cream for 5 days was evaluated in 200 patients in a randomized, multicenter, double-blind, placebo-controlled, clinic-initiated trial. Lesion tenderness was predictive of and more sensitive and longer-lasting than the symptom of pain. Among patients receiving placebo, times to crusting (P = .043), cessation of investigator-observed signs (P = .005), lesion-associated signs (P = .02), and groin signs (P = .05) were longer in women. Edoxudine reduced viral shedding in men (mean 2.7 vs. 3.4 days, P = .009) and women (2.0 days vs. 3.5 days, P = .0001). Loss of investigator-observed signs (4.4 vs. 6.2 days, P = .002), investigator-observed lesion tenderness (P = .01), lesion signs (P = .02), groin adenopathy (P = .01), and tenderness (P = .01) occurred earlier in women taking edoxudine. Edoxudine was well-tolerated and reduced several signs of herpes in women. Its clinical role in recurrent genital herpes remains to be fully determined.     

Effectiveness,satisfaction and compliance with imiquimod in the treatment of external anogenital warts

This study aims to evaluate the effectiveness of imiquimod treatment of external anogenital warts and analyse its possible relationship with patient treatment satisfaction and compliance under conditions of routine clinical practice. An observational, prospective and multi-centre study was conducted in a cohort of 559 patients with external anogenital warts. Imiquimod 5% cream was administered three times a week until the end of treatment (complete wart clearance or up to a maximum of 16 weeks). Effectiveness and compliance were evaluated at four weeks and again at the end of treatment, when satisfaction was also assessed. Complete wart clearance was experienced by 66.6% of patients at the end of treatment and a 50% or greater reduction in total wart area occurred in 79.5%. Imiquimod was more effective in patients who were more satisfied and compliant with treatment. Under conditions of routine clinical practice, imiquimod is an effective treatment for external anogenital warts.     

Genivir (DIP-253) 1% cream versus placebo cream in the treatment of recurrent genital herpes: a double-blind study

A total of 100 heterosexual adults of either sex with frequent episodes of recurrent genital herpes were allocated to treatment with either Genivir (DIP-253) 1% cream or placebo cream. All patients had genital herpes previously verified by a positive viral culture. The study was carried out as a double-blind parallel group trial. Fifty patients were allocated to each of the two treatment groups. The treatment was initiated within 24 hours after the first sign of a recurrence, and at the pretreatment examination all patients had developed typical lesions with blisters and/or sores. At baseline a sample for herpes virus culture and typing was obtained. The creams were applied four times daily for five days. Follow-up examinations were carried out on days 1, 2, 4 and if needed on days 7, 10 and 14. The major factor used for assessment of efficacy was the time to complete healing of all lesions. Duration of pruritus and pain were also recorded. In the group of patients treated with Genivir cream the time to complete healing was 3.3 days and in the placebo group 6.1 days. The difference was statistically significant (P less than 0.001). The mean duration of pain was 1.3 days in the Genivir group and 2.5 days in the placebo group: this difference also reached significance (P less than 0.01). The duration of pruritus was about the same in both groups. The active agent in Genivir, DIP-253, is a heterocyclic aromatic complex with confirmed anti-herpetic activity and with evidence of a local immunomodulatory effect. It was concluded that the efficacy of topical application of DIP-253 may be due to combined antiviral and immunomodulatory activities.     

Management of intravaginal warts in women with 5-fluorouracil (1%) in vaginal hydrophilic gel: a placebo-controlled double-blind study

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.     

Treatment of primary fibrositis/fibromyalgia syndrome with ibuprofen and alprazolam. A double-blind, placebo-controlled study

A multidimensional evaluation of 78 patients with primary fibrositis/fibromyalgia syndrome (PFS) revealed no significant relationship between clinical measures of physical discomfort and psychological measures. This observation provided evidence against the notion that the pain of PFS has a psychological etiology. The same patients were randomized into 4 groups for treatment with ibuprofen and/or alprazolam in a randomized, double-blind, double-dummy, placebo-controlled pilot trial. Clinical improvement in patient rating of disease severity and in the severity of tenderness upon palpation was most apparent in the subgroup of patients who were receiving both ibuprofen and alprazolam. An 8-week, open-label study in which 52 patients received both drugs further documented improvement in outcome measures. These data indicate that treatment with a combination of ibuprofen and alprazolam can be beneficial for some patients with PFS.     

Management of psoriasis with Aloe vera extract in a hydrophilic cream: a placebo-controlled,double-blind study*

The purpose of this double-blind, placebo-controlled study was to evaluate the clinical efficacy and tolerability of topical Aloe vera extract 0.5% in a hydrophilic cream to cure patients with psoriasis vulgaris. Sixty patients (36M/24F) aged 18–50 years (mean 25.6) with slight to moderate chronic plaque-type psoriasis and PASI (Psoriasis Area and Severity Index) scores between 4.8 and 16.7 (mean 9.3) were enrolled and randomized to two parallel groups. The mean duration of the disease prior to enrolment was 8.5 years (range 1–21). Patients were provided with a precoded 100 g tube, placebo or active (with 0.5%Aloe vera extract), and they self-administered trial medication topically (without occlusion) at home 3 times daily for 5 consecutive days per week (maximum 4 weeks active treatment). Patients were examined on a weekly basis and those showing a progressive reduction of lesions, desquamation followed by decreased erythema, infiltration and lowered PASI score were considered healed. The study was scheduled for 16 weeks with 12 months of follow-up on a monthly basis. The treatment was well tolerated by all the patients, with no adverse drug-related symptoms and no dropouts. By the end of the study, the Aloe vera extract cream had cured 25/30 patients (83.3%) compared to the placebo cure rate of 2/30 (6.6%) (P<0.001) resulting in significant clearing of the psoriatic plaques (328/396 (82.8%) vs placebo 28/366 (7.7%), P<0.001) and a decreased PASI score to a mean of 2.2. The findings of this study suggest that topically applied Aloe vera extract 0.5% in a hydrophilic cream is more effective than placebo, and has not shown toxic or any other objective side-effects. Therefore, the regimen can be considered a safe and alternative treatment to cure patients suffering from psoriasis.     

Evaluation of amitriptyline in primary fibrositis. A double-blind, placebo-controlled study

Seventy patients with primary fibrositis satisfying Smythe's criteria were studied in a 9-week double-blind trial comparing 50 mg amitriptyline with placebo. Fifty-nine patients completed the trial: 27 were treated with amitriptyline, and 32 took a placebo. The patients who received amitriptyline improved significantly in their morning stiffness and pain analog scores at 5 and 9 weeks, compared with baseline scores, whereas no changes were noted in these parameters in the placebo group. Fibrocytic point tenderness did not improve significantly in either of the treatment groups. When compared with the placebo group, the amitriptyline group improved significantly with respect to sleep pattern and patient and physician global assessments. Our data indicate that amitriptyline has some therapeutic benefit in patients with primary fibrositis.