Partial Clearance Research Articles

Paring and intense pulsed light versus paring alone for recalcitrant hand and foot warts: A randomized clinical trial with blinded outcome evaluation

Treatment of recalcitrant viral warts remains a therapeutic challenge. Intense pulsed light (IPL) has been suggested effective to clear wart tissue. The objective was in a randomized controlled trial to assess the efficacy of paring followed by IPL versus paring alone for recalcitrant hand and foot warts. Eighty-nine patients with recalcitrant hand and foot warts were included and randomized (1:1) to three treatments at 3-week intervals with either paring of warts followed by IPL or paring of warts alone. IPL was given with the Ellipse Flex IPL system (Danish Dermatologic Development A/S, Hørsholm, Denmark, 400-950 nm, 5.5 millisecond pulse duration in double pulses with a 2 millisecond interval, 26.0-32.5 J/cm(2) repetitive passes). The primary outcome was complete and partial clearance of warts evaluated by blinded photo assessment at 6 weeks after final treatment. Secondary outcomes were treatment related pain and adverse reactions. We found no significant difference in clearance of warts between the two intervention groups (OR 1.64, 95% confidence interval 0.62-4.38). Paring followed by IPL resulted in complete or partial clearance of wart tissue in nine (22%) and five patients (12.2%) versus five (13.5%) and four patients (10.8%) from paring alone. Mostly plantar warts were treated (92.1%). The pain intensity after paring and IPL was moderate and significantly higher than the pain intensity after paring alone (P<0.0005). No adverse reactions were observed from the two interventions. Paring followed by IPL did not differ significantly from paring alone in clearance of recalcitrant hand and foot warts but caused significantly more pain.

Intralesional Pingyangmycin Treatment for Resistant Plantar Warts

Background: The diagnosis of viral warts is often straightforward, but their treatment is difficult and always takes a long time. Nowadays warts are usually treated with conventional methods including topical keratolytic agents, cryotherapy, electrosurgery and laser surgery. However, such treatments cause different complications, and the warts become recalcitrant. Objective: To investigate the effect of intralesional pingyangmycin injection for resistant plantar warts. Methods: From June 2006 to September 2008, we treated 66 patients with plantar warts by intralesional pingyangmycin injection after informed consent. Results: The lesions of 58 patients cleared (87.88%) after up to 4 treatments. The remaining 8 patients (12.12%) achieved partial clearance. No serious side effects were observed. Conclusion: Intralesional injection of pingyangmycin might be an effective, safe and generally well-tolerated treatment for plantar warts.

Generating Differentially Targeted Amyloid-β Specific Intrabodies as a Passive Vaccination Strategy for Alzheimer's Disease

Amyloid-beta (A beta) has been identified as a key component in Alzheimer's disease (AD). Significant in vitro and human pathological data suggest that intraneuronal accumulation of A beta peptides plays an early role in the neurodegenerative cascade. We hypothesized that targeting an antibody-based therapeutic to specifically abrogate intracellular A beta accumulation could prevent or slow disease onset. A beta 42-specific intracellular antibodies (intrabodies) with and without an intracellular trafficking signal were engineered from a previously characterized single-chain variable fragment (scFv) antibody. The intrabodies, one with an endoplasmic reticulum (ER) targeting signal and one devoid of a targeting sequence, were assessed in cells harboring a doxycycline (Dox)-regulated mutant human amyloid precursor protein Swedish mutant (hAPP(swe)) transcription unit for their abilities to prevent A beta peptide egress. Adeno-associated virus (AAV) vectors expressing the engineered intrabodies were administered to young adult 3xTg-AD mice, a model that develops amyloid and Tau pathologies, prior to the initial appearance of intraneuronal A beta. Chronic expression of the ER-targeted intrabody (IB) led to partial clearance of A beta 42 deposits and interestingly, in reduced staining for a pathologic phospho-Tau epitope (Thr231). This approach may provide insights into the functional relevance of intraneuronal A beta accumulation in early AD and potentially lead to the development of new therapeutics.

The clinical efficacy of topical methyl-aminolevulinate photodynamic therapy in moderate to severe actinic keratoses of the face and scalp

Introduction: Since actinic keratoses (AKs) often appear in areas with field cancerization, photodynamic therapy (PDT) may have significant advantages over the standard treatment options. Objectives: Clinical efficacy of PDT with topical methyl aminolevulinate (MAL-PDT) in field cancerization was evaluated with respect to the number of AKs and photodamage. Methods: A total of 14 patients with 223 AKs on the face or scalp were treated with MAL-PDT. Two treatments with a 3-monthly interval were given. At baseline, before the second treatment and 3 months after the end of therapy, the number of AKs were counted and photodamage was assessed with respect to skin roughness, hyperpigmentation, hypopigmentation, scarring, atrophy, telangiectasia and wrinkling. Results: Complete clearance was reached in patients with a moderate degree of actinic damage, whereas a severe degree of field cancerization demonstrated only partial clearance. The global score for photodamage improved significantly. After the follow-up period, none of the patients reaching clearance had developed relapsing or new AKs. Conclusions: MAL-PDT induces a high clearance rate of AKs, dependent on the degree of field cancerization, with a good improvement in photodamage and prevention of developing new AKs. Thus, more PDT sessions are needed in patients with a severe degree of field cancerization.

New Approach for Diagnosis of Candidemia Based on Detection of a 65-Kilodalton Antigen

Nosocomial candidiasis is a major concern in tertiary care hospitals worldwide. This infection generally occurs in patients with degenerative and neoplastic diseases and is considered the fourth most frequent cause of bloodstream infections. Diagnosis of candidemia or hematogenous candidiasis has been problematic because clinical signs and symptoms are nonspecific, leading to delays in diagnosis and, consequently, delays in appropriate antifungal therapy. We developed an inhibition enzyme-linked immunosorbent assay (ELISA) for detection of a 65-kDa antigen in an experimental model of candidemia and for diagnosis of patients in intensive care units (ICUs) with suspected candidemia. An anti-65-kDa monoclonal antibody was tested for detection of the 65-kDa antigen produced by Candida albicans, Candida tropicalis, and Candida parapsilosis in murine candidemia models. The 65-kDa antigen was detected in sera at concentrations ranging from 0.012 to 3.25 microg/ml. A total of 20 human patients with candidemia were then evaluated with the inhibition ELISA using sequential sera. Sixteen (80%) patients had the 65-kDa antigen in concentrations ranging from 0.07 to 5.0 microg/ml. Sequential sera from patients with candidemia presented three different patterns of antigenemia of the 65-kDa molecule: (i) total clearance of antigenemia, (ii) initial clearance and relapse of antigenemia, and (iii) partial clearance of antigenemia. Our results indicate detection of the 65-kDa protein may be a valuable tool for the diagnosis of candidemia by C. albicans, C. tropicalis, and C. parapsilosis.

Extracorporeal shock wave lithotripsy of large difficult common bile duct stones: Efficacy and analysis of factors that favor stone fragmentation

Difficult common bile duct stones (CBD) are those not amenable to extraction by the standard technique of sphincterotomy followed by use of a Dormia basket or balloon. The role of extracorporeal shock wave lithotripsy (ESWL) in stone fragmentation and clearance of difficult CBD stones and the factors which favor fragmentation were prospectively evaluated in the present study. A total of 283 patients with large CBD stones were subjected to ESWL. A maximum of 5000 shocks was delivered per session until CBD stones were fragmented to less than 5 mm diameter. CBD was cleared by biliary endotherapy using a basket or balloon. Outcome was assessed by CBD clearance. Total CBD clearance was achieved in 239 patients (84.4%) and partial CBD clearance in 35 patients (12.3%). Three or fewer sessions of ESWL were required in 74.6% of patients. Minor complications were seen in 45 patients (15.9%). There was no procedure-related mortality. Epidural anesthesia, shock frequency of 90/min, radiolucent calculi and presence of fluid around the calculus helped in better fragmentation. A high success rate, negligible complications and non-invasive nature of the procedure make ESWL a useful tool for removing large CBD stones.

Treatment of palmoplantar pustulosis with arotinoid ethylester

Palmoplantar pustulosis (PPP) is a chronic recurring and refractory pustular dermatosis. To investigate the efficacy and safety of arotinoid ethylester in patients with PPP, sixteen adult subjects with PPP, who had taken no systemic medications for three months, were enrolled. All the subjects received 0.03 mg of arotinoid ethylester once daily as initial dosage. The number of pustules and lesion area index (LAI) were measured pre- and post-treatment. Repeated measures of one factor ANOVA was used to statistically analyze the data. After 3 months of treatment, pustules disappeared completely in all patients (F = 15.04; p < .0001); LAI decreased significantly (F = 24.54; p < .0001). Complete clearance (100% reduction of LAI and complete disappear of pustules) and near complete clearance (75%-99%) occurred in 6 and 8 patients, respectively; the other two patients exhibited partial clearance (50%-74%). Side effects were observed in 10 patients, but were mild to moderate and well tolerated. Our study suggested that arotinoid ethylester is an effective therapy for PPP with minimal side effects.

Effect of dosing frequency on the safety and efficacy of imiquimod 5% cream for treatment of actinic keratosis on the forearms and hands: a phase II, randomized placebo-controlled trial

Clinical studies in cutaneous conditions other than actinic keratosis (AK) have revealed that the safety and efficacy profile of imiquimod is influenced by dosing frequency. To evaluate dosing frequency response of imiquimod 5% for treatment of AK. This was a phase II, multicentre, randomized, double-blind, placebo-controlled study. Adults with > or = 10 but < or = 50 clinical AKs, one of which was histologically confirmed, were randomized (4:1) to 2-6 packets of imiquimod or placebo cream applied to the dorsum of the forearms and hands once daily 2, 3, 5 or 7 times per week for 8 weeks. The primary endpoint was complete clearance of AKs in the treatment area at 8 weeks post-treatment. One hundred and forty-nine (94 men and 54 women) white subjects, with a mean +/- SD age of 71 +/- 10.2 years, were enrolled. Twenty-eight subjects (18.8%) discontinued from study: 0%, 3.1%, 6.9%, 30.0% and 33.3% withdrew for local skin reactions or adverse events in the combined placebo, and in the imiquimod 2, 3, 5 or 7 times per week groups, respectively. Seven serious adverse events occurred; none was related to the study drug. Median baseline lesions ranged from 38 to 40 for the treatment groups. Complete clearance was achieved in 0%, 3.2%, 6.9%, 3.3% and 6.7% of subjects, and partial clearance (> or = 75% lesion reduction) in 0%, 22.6%, 24.1%, 20.0% and 36.7% of subjects for the placebo and imiquimod 2, 3, 5 or 7 times per week regimens, respectively. Imiquimod 5% applied more frequently than 3 times per week to AKs was not well tolerated. Complete clearance rates were low; however, partial clearance rates increased with increased dosing frequency (P = 0.002).

Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis

There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis. Assess the efficacy and safety of ingenol mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis. Patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period. All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P < .0001 vs vehicle). The complete clearance rate was also significantly higher (P < or = .0006) for patients in the ingenol mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for ingenol mebutate gel compared with 13.3% for vehicle, P < .0001 to .0007 vs vehicle). The median percentage reduction in baseline actinic keratosis lesions for patients treated with ingenol mebutate gel ranged from 75% to 100% compared with 0% for vehicle gel (P < .0001 vs vehicle). Active treatment was well tolerated at all dosages. The mechanism of action of this agent is the localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, flaking/scaling, and crusting. There was no evidence of treatment-related scarring. Local skin responses may have suggested active treatment to investigators. Short-course, field-directed therapy with ingenol mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.

JS4-3 Evaluation of Increased Level of NT-proBNP in Viral Hepatitis Patients in China

negative patients with or without cardiac inflammation and constitutes the basis for any further specific treatment strategy. Results from non-controlled pilot studies and one recent randomized multicenter treatment trial (BICCstudy) have shown that a six months interferon-beta therapy improves the clinical course if patients have carefully been selected and characterized according to biopsy-based diagnostic criteria. Compared to placebo, virus elimination and/or virus load reduction were significantly higher in the interferon-b groups (odds ratio 2.33, p = 0.048). Complete entero-/adenovirus clearance but only partial parvovirus clearance occurred. Treatment was associated with significant clinical improvement as assessed by quality of life (total Minnessota score) (p = 0.032) and patient global assessment (p = 0.039). There were no safety concerns in association with the IFN-b therapy. The results demonstrate that IFN-b treatment leads to an effective virus clearance or reduction of virus load and significant clinical improvement in patients with CVC.

Saposin B-dependent Reconstitution of Arylsulfatase A Activity in Vitro and in Cell Culture Models of Metachromatic Leukodystrophy

Arylsulfatase A (ASA) catalyzes the intralysosomal desulfation of 3-O-sulfogalactosylceramide (sulfatide) to galactosylceramide. The reaction requires saposin B (Sap B), a non-enzymatic proteinaceous cofactor which presents sulfatide to the catalytic site of ASA. The lack of either ASA or Sap B results in a block of sulfatide degradation, progressive intralysosomal accumulation of sulfatide, and the fatal lysosomal storage disease metachromatic leukodystrophy. We studied the coupled Sap B-ASA reaction in vitro using detergent-free micellar and liposomal assay systems and in vivo using cell culture models of metachromatic leukodystrophy. Under in vitro conditions, the reaction had a narrow pH optimum around pH 4.3 and was inhibited by mono- and divalent cations, phosphate and sulfite. Bis(monoacylglycero) phosphate and phosphatidic acid were activators of the reaction, underscoring a significant role of acidic phosphoglycerolipids in sphingolipid degradation. Desulfation was negligible when Sap B was substituted by Sap A, C, or D. Up to a molar ratio between Sap B and sulfatide of 1:5, an elevation of Sap B concentrations caused a sharp increase of sulfatide hydrolysis, indicating the requirement of unexpected high Sap B levels for maximum turnover. Feeding of ASA-deficient, sulfatide-storing primary mouse kidney cells with ASA caused partial clearance of sulfatide. Co-feeding of Sap B or its precursor prosaposin resulted in the lysosomal uptake of the cofactor but did not promote ASA-catalyzed sulfatide hydrolysis. This suggests that Sap B is not a limiting factor of the coupled Sap B-ASA reaction in mouse kidney cells even if sulfatide has accumulated to unphysiologically high levels.

Dendritic cells and T cells deliver oncolytic reovirus for tumour killing despite pre-existing anti-viral immunity

Reovirus is a naturally occurring oncolytic virus currently in early clinical trials. However, the rapid induction of neutralizing antibodies represents a major obstacle to successful systemic delivery. This study addresses, for the first time, the ability of cellular carriers in the form of T cells and dendritic cells (DC) to protect reovirus from systemic neutralization. In addition, the ability of these cellular carriers to manipulate the subsequent balance of anti-viral versus anti-tumour immune response is explored. Reovirus, either neat or loaded onto DC or T cells, was delivered intravenously into reovirus-naive or reovirus-immune C57Bl/6 mice bearing lymph node B16tk melanoma metastases. Three and 10 days after treatment, reovirus delivery, carrier cell trafficking, metastatic clearance and priming of anti-tumour/anti-viral immunity were assessed. In naive mice, reovirus delivered either neat or through cell carriage was detectable in the tumour-draining lymph nodes 3 days after treatment, though complete clearance of metastases was only obtained when the virus was delivered on T cells or mature DC (mDC); neat reovirus or loaded immature DC (iDC) gave only partial early tumour clearance. Furthermore, only T cells carrying reovirus generated anti-tumour immune responses and long-term tumour clearance; reovirus-loaded DC, in contrast, generated only an anti-viral immune response. In reovirus-immune mice, however, the results were different. Neat reovirus was completely ineffective as a therapy, whereas mDC--though not iDC--as well as T cells, effectively delivered reovirus to melanoma in vivo for therapy and anti-tumour immune priming. Moreover, mDC were more effective than T cells over a range of viral loads. These data show that systemically administered neat reovirus is not optimal for therapy, and that DC may be an appropriate vehicle for carriage of significant levels of reovirus to tumours. The pre-existing immune status against the virus is critical in determining the balance between anti-viral and anti-tumour immunity elicited when reovirus is delivered by cell carriage, and the viral dose and mode of delivery, as well as the immune status of patients, may profoundly affect the success of any clinical anti-tumour viral therapy. These findings are therefore of direct translational relevance for the future design of clinical trials.

Spectrophotometric intracutaneous analysis as an early non‐invasive predictor of efficacy in the phototherapy of psoriasis

Phototherapy is generally effective for psoriasis but individual responsiveness and optimal treatment duration for disease clearance are unpredictable. However, easy, rapid and non-invasive plaque assessment by spectrophotometric intracutaneous analysis (SIAscopy), a novel multispectral skin imaging technique, may now make prediction feasible. The early prediction of psoriatic plaque clearance during phototherapy by SIAscopy. Sixteen psoriatic plaques in 10 psoriasis patients were serially assessed SIAscopically during phototherapy for punctate dots representing the dilated papillary dermal blood vessels characteristic of active psoriasis, and the results compared with the clinical findings. All plaques showing full SIAscopic clearance at early follow-up also showed complete or almost complete clinical clearance, and remained the same thereafter. All showing no SIAscopic clearance at early follow-up showed at most partial clinical clearance, and also remained the same thereafter. All showing only partial SIAscopic clearance at early follow-up also showed just partial clinical clearance, but then generally progressed to full SIAscopic and clinical clearance. SIAscopy of psoriatic plaques at early follow-up during patient phototherapy enables good prediction of likely later clinical clearance, thereby potentially avoiding unnecessary further treatment. A larger confirmatory study is now needed.

Multiple facial and axillary papules and pustules

Conflict of interest: none declared. A 46‐year‐old woman presented with a 3‐month history of an axillary rash and intermittent soreness. She had also developed papular lesions on her face at the same time. Physical examination revealed multiple orange‐brown papules and pustules in the axillae (2–3 mm in diameter) and a few similar lesions on the right upper cheeks 1,2). She was otherwise well with no relevant medical or drug history. There was no history of using antiperspirants containing aluminium or zirconium. A swab for microscopy and culture was negative. Serum angiotensin‐converting enzyme and calcium levels were normal, as was chest radiography. A T Spot TB test was negative, as was a patch test for aluminium using an empty Finn chamber. The patient was treated with topical mometasone furoate and oral lymecycline, to which she had good response, with partial clearance of the rash and no new lesions. ...

Spontaneous Regression of Hepatocellular Carcinoma: Three Case Reports and a Categorized Review of the Literature

Hepatocellular carcinoma (HCC) is the most frequent form of primary liver cancer and the fifth most prevalent cancer worldwide [1]. Spontaneous tumor regression was first defined by Cole and Everson [2] as complete or partial clearance of malignant cells in the absence of any specific treatment, particularly antineoplastic chemotherapy. However, it may also occur during or after therapy, a situation in which therapy could be endorsed with an undeserved antitumor effect. Spontaneous tumor regression was at first thought to be an extremely infrequent phenomenon, with an estimated incidence of 1 in 60,000–100,000 cases [3]. Its mechanism is largely unknown, however, it has important implications in clinical research and clinical practice. The number of cases of spontaneous regression reported in the literature is higher in HCC than in other neoplasms [4], possibly reflecting a higher incidence. However, due to its exceedingly low frequency it would probably not affect the results of any study on HCC therapy. Following our observation of two cases of spontaneous regression and one case of sustained, complete regression in the course of a chemotherapeutic regimen with marginal efficacy in the treatment of this tumor, we have searched the cases published in the English literature and reviewed the possible mechanisms involved in such remarkable events. We have retrospectively reviewed all the cases recorded in our liver unit in which an objective tumor remission was observed that could not be convincingly ascribed to a therapeutic effect of any rational intervention. These consist of tumor ablation, any sort of embolizing procedure performed in the hepatic artery or its branches (including intra-arterial injection of Lipiodol for diagnostic or staging purposes), or pharmacological therapy that might have a known antiproliferative effect. Medical records of these patients were thoroughly reviewed trying to find any possible event that may have triggered the observed remission.

A Community-Based Study of Acne-Related Health Preferences in Adolescents

To examine preferences for acne-related outcomes in adolescents. Community-based, cross-sectional survey study. Four public high schools in San Francisco, California. Volunteer sample of 266 adolescents with acne. Health utilities for current acne state and 3 hypothetical acne-related states (100% clearance, 50% clearance, and 100% clearance but with residual scarring) using time trade-off (TTO) and willingness to pay metrics. A self-administered written survey was used. The mean (median) utilities for current acne state using the TTO metric was 0.961 (0.985). One hundred percent acne clearance received a higher utility score (mean [median] score, 0.978 [0.994]) than 50% clearance (0.967 [0.992]; P < .001 by Wilcoxon signed rank test) and 100% clearance with scarring (0.965 [0.992]; P < .001). Although current acne state utility was not correlated with physician-rated severity (P = .23), a significant association with subject-rated severity was observed in both univariate analysis (P = .01) and after adjustment for duration of acne, having seen a physician for acne, and income (P = .05). Adolescents were willing to pay a median of $275 to have never had acne in their lifetime and were willing to pay significantly more for 100% clearance than for 50% clearance or 100% clearance but with scarring (P < .001 for both comparisons). We describe adolescents' acne-related health state utilities. Compared with current acne state utility, both partial and total clearance with scarring are substantially less preferable than total clearance. Subjects' self-rated disease severity correlates with current acne state utility, whereas physician-rated severity does not. A self-administered paper instrument can effectively assess adolescents' acne-related preferences in community-based samples.

Sinecatechins, a Defined Green Tea Extract, in the Treatment of External Anogenital Warts

To estimate the clinical efficacy of topical sinecatechins, a defined green tea extract, in the treatment of external genital and perianal warts. This was a randomized, double-blind, vehicle-controlled trial involving 502 male and female patients aged 18 years and older, with 2-30 anogenital warts ranging from 12 to 600 mm(2) total wart area. Patients applied sinecatechins ointment 15% or 10% or vehicle (placebo) three times daily for a maximum of 16 weeks or until complete clearance of all warts, followed by a 12-week treatment-free follow-up to assess recurrence. Complete clearance of all baseline and newly occurring warts was obtained in 57.2% and 56.3% of patients treated with sinecatechins ointment 15% and 10%, respectively, compared with 33.7% for vehicle (both P<.001). Significance was observed at weeks 4 and 6 and all subsequent visits. Numbers needed to treat were 4.3 and 4.4. Partial clearance rates of at least 50% were reported for 78.4% and 74.0% of patients in the sinecatechins ointment 15% and 10% groups compared with 51.5% of vehicle patients. During follow-up, recurrence of any wart was observed in 6.5%, 8.3%, and 8.8% in the sinecatechins ointment 15% group, sinecatechins ointment 10% group, and vehicle patients, respectively. A total of 3.7%, 8.3%, and 0.0% developed new warts, respectively. A total of 87.7% and 87.3% of patients in the sinecatechins ointment 15% and 10% groups, and 72.1% of vehicle patients experienced application site reactions; 49.2%, 46.2%, and 65.4% of those, respectively, were mild or moderate. Topical sinecatechins ointments 15% and 10% are effective and well-tolerated in the treatment of anogenital warts. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00449982. I.

A phase II dose-ranging study of topical resiquimod to treat actinic keratosis

Resiquimod, a toll-like receptor 7 and 8 agonist, may be effective as a topical treatment of actinic keratosis (AK). To evaluate the effect of resiquimod gel concentration on lesion clearance. Patients with AK lesions on the face or balding scalp were randomly assigned to resiquimod 0.01%, 0.03%, 0.06% or 0.1% gel applied once daily three times a week for 4 weeks to a contiguous 25-cm(2) area with four to eight lesions. Patients with persistent lesions received a second course after an 8-week treatment-free interval. Complete and partial lesion clearance was assessed 8 weeks after treatment for each course. For the 132 patients randomized, overall complete clearance rates were 77.1% (27/35), 90.3% (28/31), 78.1% (25/32) and 85.3% (29/34) and complete clearance rates after course 1 only were 40.0%, 74.2%, 56.3% and 70.6%, respectively, for the resiquimod 0.01%, 0.03%, 0.06% and 0.1% groups. During course 1, respectively 0%, 13%, 31% and 38% of patients discontinued treatment for adverse events or local skin reactions, for the resiquimod 0.01%, 0.03%, 0.06% and 0.1% groups. Possibly or probably related nonapplication site adverse events of severe intensity, including influenza-like symptoms, were reported by 0%, 3%, 13% and 12% of patients, respectively, for the resiquimod 0.01%, 0.03%, 0.06% and 0.1% groups. Efficacy in clearing AK lesions was similar between the resiquimod concentrations evaluated, but resiquimod 0.01% and 0.03% were better tolerated than the higher concentrations.

Open-Label Study to Assess the Safety and Efficacy of Imiquimod 5% Cream Applied Once Daily Three Times per Week in Cycles for Treatment of Actinic Keratoses on the Head

Local skin reactions are common during imiquimod treatment of actinic keratosis (AK). Cyclical application of imiquimod may improve tolerability while maintaining efficacy. To assess the tolerability of imiquimod and clearance rate of AK lesions after imiquimod application. Imiquimod 5% cream was administered three times per week for 4 weeks followed by 4 weeks of rest (cycle 1) to AK lesions on the head. If AK lesions remained visible at the end of cycle 1, a second treatment cycle was instituted. Fifty percent (30 of 60) of patients experienced complete clearance of AK lesions, and 75% (30 of 40) of patients experienced partial clearance of AK lesions after imiquimod treatment at the end of cycle 2. Moreover, 77% of patients who achieved complete clearance had no visible AK lesions 12 weeks post-treatment. Imiquimod was well tolerated. Imiquimod cycle therapy may be a safe and effective treatment option for AK lesions.

Multicentre, open-label study using imiquimod 5% cream in one or two 4-week courses of treatment for multiple actinic keratoses on the head

In the USA, Imiquimod 5% cream is approved for use 2-3 times per week over 16 weeks for the treatment of actinic keratoses (AKs). This study evaluated the efficacy of imiquimod in another treatment schedule, for AKs on the head. Open-label, phase IIIb. 180 dermatology clinics and practices in Germany. Patients were eligible if they had clinically typical, visible AK lesions located anywhere on the head, excluding the upper and lower eyelids, nostrils, lip vermilion, and inside the ears. Patients applied study cream to the treatment area once daily 3x/week for 4 weeks (course 1) followed by a 4-week post-treatment period. Patients with AK lesions remaining in the treatment area underwent a second 4-week treatment course. Primary variable was the complete clearance rate, defined as the proportion of patients with no clinically visible AK lesions in the treatment area at the course 1 or course 2 post-treatment visit. 829 patients entered the study. Overall, the complete clearance rate was 68.9% (571/829) and the partial clearance rate (percentage of patients with >/= 75% reduction in the number of baseline AK lesions) was 80.2%. Local skin reactions (LSRs) and application site reactions (ASRs) were the most commonly reported adverse events. Four patients discontinued from the study due to LSRs or ASRs. Shorter treatment regimen of imiquimod 5% cream can produce complete clearance rates similar to those seen with 16 weeks of treatment and has the advantage of lower drug exposure, resulting in a better benefit-risk profile for the patient.