-
Journal of the American Academy of... Mar 2022Difamilast is a selective phosphodiesterase 4 inhibitor. Phosphodiesterase 4 is involved in cytokine production linked with inflammatory disorders, including atopic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Difamilast is a selective phosphodiesterase 4 inhibitor. Phosphodiesterase 4 is involved in cytokine production linked with inflammatory disorders, including atopic dermatitis.
OBJECTIVE
To demonstrate the superiority of difamilast ointment 1% to vehicle in adult Japanese patients with atopic dermatitis.
METHODS
In this phase 3, randomized, double-blind trial, patients aged 15-70 years with an investigator global assessment score of 2 or 3 received topical difamilast ointment 1% (n = 182) or a vehicle (n = 182) twice daily for 4 weeks.
RESULTS
The success rate in investigator global assessment score at week 4 (primary endpoint)-the percentage of patients achieving an investigator global assessment score of 0 or 1 with ≥2-grade improvement-was significantly higher with 1% difamilast than with the vehicle (38.46% vs 12.64%, respectively, P < .0001). The success rates in ≥50%, ≥75%, and ≥90% improvement in overall eczema area and severity index score at week 4 followed the same trend. Difamilast at 1% provided significant mean percent improvement from baseline in overall eczema area and severity index score versus vehicle from week 1 to 4. Treatment-emergent adverse events were mostly mild or moderate and less frequent with difamilast.
LIMITATIONS
Study treatment was limited to 4 weeks.
CONCLUSION
Difamilast ointment 1% demonstrated superiority to the vehicle and favorable safety in adult Japanese patients with atopic dermatitis.
Topics: Adult; Benzamides; Dermatitis, Atopic; Double-Blind Method; Eczema; Emollients; Humans; Hyperplasia; Ointments; Phosphodiesterase 4 Inhibitors; Severity of Illness Index; Treatment Outcome
PubMed: 34710557
DOI: 10.1016/j.jaad.2021.10.027 -
American Journal of Clinical Dermatology Jul 2023Topical treatments for atopic dermatitis (AD) used reactively often fail to achieve lasting disease control; many of these therapies are associated with safety concerns... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Topical treatments for atopic dermatitis (AD) used reactively often fail to achieve lasting disease control; many of these therapies are associated with safety concerns that limit long-term use. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD that has potential as a long-term maintenance therapy.
OBJECTIVE
The aim was to evaluate the long-term efficacy and safety of crisaborole once daily (QD) compared to vehicle QD as a maintenance therapy to reduce the incidence of flares in patients with AD who previously responded to crisaborole twice daily (BID).
METHODS
CrisADe CONTROL was a randomized, double-blind, vehicle-controlled, 52-week, phase III study of patients aged ≥ 3 months with mild-to-moderate AD involving ≥ 5% treatable body surface area. Eligible patients received crisaborole BID during an open-label run-in period of up to 8 weeks. Responders were randomly assigned in the double-blind maintenance period to receive either crisaborole QD or vehicle QD. Responders were defined as patients who achieved Investigator's Static Global Assessment (ISGA) success (ISGA score of 0 [clear] or 1 [almost clear] with a ≥ 2-grade improvement) and ≥ 50% improvement in Eczema Area and Severity Index total score (EASI-50) from baseline. Patients who experienced a flare (ISGA score ≥ 2) during the double-blind maintenance period switched to crisaborole BID for up to 12 weeks. During this period, patients were assessed every 4 weeks; if the flare resolved (ISGA score ≤ 1), patients resumed their assigned treatment. The primary endpoint was flare-free maintenance until onset of the first flare. Key secondary endpoints were number of flare-free days, number of flares, and maintenance of pruritus response until onset of the first flare. The incidence of treatment-emergent adverse events was also analyzed.
RESULTS
Overall, 497 patients entered the open-label run-in period with crisaborole BID, of which 270 patients were randomized into the 52-week double-blind maintenance period of the study. Of the 270 patients, 135 were randomly assigned to the crisaborole QD group and 135 were randomly assigned to the vehicle QD group. Median time of flare-free maintenance was longer for patients who received crisaborole versus vehicle (111 vs 30 days, respectively; p = 0.0034). The mean number of flare-free days was higher for patients who received crisaborole versus vehicle (234.0 vs 199.4 days, respectively; p = 0.0346). The mean number of flares was lower for patients who received crisaborole versus vehicle (0.95 vs 1.36, respectively; p = 0.0042). No clear trend was observed in maintenance of pruritus response between crisaborole- and vehicle-treated patients. Crisaborole was well tolerated, with no new or unexpected safety findings when used as maintenance treatment.
CONCLUSIONS
Crisaborole QD was effective and well tolerated for long-term maintenance treatment and flare reduction in adult and pediatric patients with mild-to-moderate AD.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT04040192, 31 July 2019.
Topics: Adult; Humans; Child; Dermatitis, Atopic; Ointments; Boron Compounds; Pruritus; Double-Blind Method; Treatment Outcome; Severity of Illness Index
PubMed: 37184828
DOI: 10.1007/s40257-023-00780-w -
Journal of the American Academy of... Apr 2020Previous studies showed the potential effectiveness of delgocitinib ointment, a novel topical Janus kinase inhibitor, in atopic dermatitis (AD). (Randomized Controlled Trial)
Randomized Controlled Trial
Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: A phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study.
BACKGROUND
Previous studies showed the potential effectiveness of delgocitinib ointment, a novel topical Janus kinase inhibitor, in atopic dermatitis (AD).
OBJECTIVE
This study aimed to evaluate the efficacy and safety of delgocitinib 0.5% ointment.
METHODS
In part 1, a 4-week double-blind period, Japanese patients aged 16 years or older with moderate or severe AD were randomly assigned in a 2:1 ratio to delgocitinib 0.5% ointment or vehicle ointment. Eligible patients entered part 2, a 24-week extension period, to receive delgocitinib 0.5% ointment.
RESULTS
At the end of treatment in part 1, the least-squares mean percent changes from baseline in the modified Eczema Area and Severity Index score, the primary efficacy endpoint, were significantly greater in the delgocitinib group than in the vehicle group (-44.3% vs 1.7%, P < .001). The improvement in modified Eczema Area and Severity Index score was maintained in part 2. Most adverse events were mild and unrelated to delgocitinib across the study periods.
LIMITATIONS
Only Japanese patients were included. The vehicle-controlled period lasted only 4 weeks. In part 2, topical corticosteroids were allowed for the treatment of worsening of AD.
CONCLUSION
Delgocitinib ointment was effective and well tolerated in Japanese adult patients with moderate to severe AD for up to 28 weeks.
Topics: Adult; Dermatitis, Atopic; Dermatologic Agents; Double-Blind Method; Female; Humans; Janus Kinase Inhibitors; Male; Ointments; Pyrroles; Treatment Outcome; Young Adult
PubMed: 32029304
DOI: 10.1016/j.jaad.2019.12.015 -
Journal of Nippon Medical School =... 2017The guidelines for the treatment of atopic dermatitis (AD) issued by the Japanese Dermatological Association (JDA), which are basically designed for dermatologists, were... (Review)
Review
The guidelines for the treatment of atopic dermatitis (AD) issued by the Japanese Dermatological Association (JDA), which are basically designed for dermatologists, were first prepared in 2000 and revised in 2016. The guidelines for AD of the Japanese Society of Allergology (JSA), which are basically designed for allergologists, including internists, otorhinolaryngologists, ophthalmologists, and dermatologists, were first prepared in 2009 and revised in 2014. In this article, I review the definition, pathophysiology, etiology, epidemiology, diagnosis, severity classification, examination for diagnosis and severity assessment, and treatments for AD in Japan according to these two guidelines for AD (JDA and JSA). Based on the definition and diagnostic criteria for AD of the JDA, patients meeting three basic criteria, 1) pruritus, 2) typical morphology and distribution of the eczema, and 3) chronic or chronically relapsing course, are regarded as having AD. Treatment measures for AD basically consist of drug therapy, skin care, and elimination of exacerbating factors. Drugs that potently reduce AD-related inflammation in the skin are topical corticosteroids and tacrolimus. It is most important to promptly and accurately reduce inflammation related to AD by using these topical anti-inflammatory drugs. Proactive therapy refers to a treatment method in which, after inducing remission, a topical corticosteroid or tacrolimus ointment is intermittently applied to the skin in addition to skin care with moisturizers in order to maintain remission.
Topics: Administration, Topical; Adrenal Cortex Hormones; Allergy and Immunology; Dermatitis, Atopic; Humans; Japan; Ointments; Practice Guidelines as Topic; Societies, Medical; Tacrolimus
PubMed: 28331140
DOI: 10.1272/jnms.84.2 -
The Cochrane Database of Systematic... May 2022Corneal abrasion is a common disorder frequently faced by ophthalmologists, emergency physicians, and primary care physicians. Ocular antibiotics are one of the... (Review)
Review
BACKGROUND
Corneal abrasion is a common disorder frequently faced by ophthalmologists, emergency physicians, and primary care physicians. Ocular antibiotics are one of the management options for corneal abrasion. A comprehensive summary and synthesis of the evidence on antibiotic prophylaxis in traumatic corneal abrasion is thus far unavailable, therefore we conducted this review to evaluate the current evidence regarding this important issue.
OBJECTIVES
To assess the safety and efficacy of topical antibiotic prophylaxis following corneal abrasion. Our objectives were 1) to investigate the incidence of infection with antibiotics versus placebo or alternative antibiotics in people with corneal abrasion; and 2) to investigate time to clinical cure, defined as complete healing (re-epithelialization) of the epithelium, with antibiotics versus placebo or alternative antibiotics in people with corneal abrasion.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4), Ovid MEDLINE, Embase.com, PubMed, the Latin American and Caribbean Health Sciences Literature database (LILACS), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 25 April 2021.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing antibiotic with another antibiotic or placebo in children and adults with corneal abrasion due to any cause.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology and assessed the certainty of the body of evidence for the prespecified outcomes using the GRADE classification.
MAIN RESULTS
Our search of the electronic databases yielded 8661 records. We screened 7690 titles and abstracts after removal of duplicates. We retrieved 32 full-text reports for further review. We included two studies that randomized a total of 527 eyes of 527 participants in the review. One study was conducted in Denmark, and one was conducted in India. The two studies did not examine most of our prespecified primary and secondary outcomes. The first study was a parallel-group RCT comparing chloramphenicol ocular ointment with fusidic acid ocular gels (frequency was not clearly reported). This study enrolled 153 participants older than 5 years of age with corneal abrasion in Denmark with a one-day follow-up duration. No participants had secondary infection in the fusidic acid group, whereas three (4.1%) participants in the chloramphenicol group had a slight reaction (risk ratio [RR] 0.15, 95% confidence interval [CI] 0.01 to 2.79; 144 participants; very low certainty evidence). Thirty-one (44.3%) participants in the fusidic acid arm and 34 (46.6%) participants in the chloramphenicol arm were cured (defined as the area of abrasion zero and no infection) at day 1 (RR 0.94, 95% CI 0.65 to 1.34; 144 participants; very low certainty evidence). Without providing specific data, the study reported that the degree of pain was not affected by the interventions received. The most common adverse events reported were itching and discomfort of the eye, which occurred in approximately one-third of participants in each group (low certainty evidence). A second multicenter, two-arm RCT conducted in India enrolled 374 participants older than 5 years of age with corneal abrasion who presented within 48 hours after injury. This study investigated the effect of a three-day course of either ocular ointment combinations of chloramphenicol-clotrimazole or chloramphenicol-placebo (all three times daily). At day 3, 169 (100%) participants in the chloramphenicol-clotrimazole arm and 203 (99%) out of 205 participants in the chloramphenicol-placebo arm were cured without any complication, defined as complete epithelialization of the cornea without evidence of infection (RR 1.01, 95% CI 0.99 to 1.03; 374 participants; very low certainty evidence). Four participants assigned to the chloramphenicol-placebo arm experienced mild adverse events: two participants (1%) had mild chemosis and irritation, and two (1%) had small single sterile corneal infiltrates (low certainty evidence).
AUTHORS' CONCLUSIONS
Given the low to very low certainty of the available evidence, any beneficial effects of antibiotic prophylaxis in preventing ocular infection or accelerating epithelial healing following a corneal abrasion remain unclear. Moreover, the current evidence is insufficient to support any antibiotic regimen being superior to another. There is a need for a well-designed RCT assessing the efficacy and safety of ocular antibiotics in the treatment of corneal abrasion with a particular focus on high-risk populations and formulation of interventions.
Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Child; Chloramphenicol; Clotrimazole; Corneal Injuries; Fusidic Acid; Humans; Multicenter Studies as Topic; Ointments
PubMed: 35622535
DOI: 10.1002/14651858.CD014617.pub2 -
The Cochrane Database of Systematic... Feb 2015Pressure ulcers, also known as bedsores, decubitus ulcers and pressure injuries, are localised areas of injury to the skin or the underlying tissue, or both. Dressings... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pressure ulcers, also known as bedsores, decubitus ulcers and pressure injuries, are localised areas of injury to the skin or the underlying tissue, or both. Dressings are widely used to treat pressure ulcers and there are many different dressing options including hydrogel dressings. A clear and current overview of the current evidence is required to facilitate decision-making regarding dressing use for the treatment of pressure ulcers.
OBJECTIVES
To assess the effects of hydrogel dressings on the healing of pressure ulcers in any care setting.
SEARCH METHODS
We searched the following databases: the Cochrane Wounds Group Specialised Register (searched 19 June 2014); The Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5); Ovid MEDLINE (1946 to June Week 2 2014); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, 23 June 2014); Ovid EMBASE (1974 to 20 June 2014); and EBSCO CINAHL (1982 to 18 June 2014). There were no restrictions based on language or date of publication.
SELECTION CRITERIA
Published or unpublished randomised controlled trials (RCTs) comparing the effects of hydrogel dressings with alternative wound dressings or no dressing in the treatment of pressure ulcers (stage II or above).
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, risk of bias assessment and data extraction.
MAIN RESULTS
We included eleven studies (523 participants) in this review. Ten studies had two arms and one had three arms that were all relevant to this review. Three studies compared a hydrogel dressing with a basic wound contact dressing; three studies compared a hydrogel dressing with a hydrocolloid dressing; three studies compared a hydrogel dressing with another hydrogel dressing; one study compared a hydrogel dressing with a foam dressing; one study compared a hydrogel dressing with a dextranomer paste dressing and one study compared a hydrogel dressing with a topical treatment (collagenase). Limited data were available for analyses in this review: we conducted no meta-analyses. Where data were available there was no evidence of a difference between hydrogel and alternative treatments in terms of complete wound healing or adverse events. One small study reported that using hydrogel dressings was, on average, less costly than hydrocolloid dressings, but this estimate was imprecise and its methodology was not clear. All included studies were small, had short follow-up times and were at unclear risk of bias.
AUTHORS' CONCLUSIONS
It is not clear if hydrogel dressings are more or less effective than other treatments in healing pressure ulcers or if different hydrogels have different effects, Most trials in this field are very small and poorly reported so that risk of bias is unclear.
Topics: Bandages, Hydrocolloid; Collagenases; Dextrans; Humans; Hydrogels; Ointments; Pressure Ulcer; Randomized Controlled Trials as Topic
PubMed: 25914909
DOI: 10.1002/14651858.CD011226.pub2 -
The Yale Journal of Biology and Medicine Mar 2020Diltiazem is a calcium-channel blocker commonly used for the treatment of hypertension. Common adverse effects include dizziness, headache, and edema. Fewer than 20...
Diltiazem is a calcium-channel blocker commonly used for the treatment of hypertension. Common adverse effects include dizziness, headache, and edema. Fewer than 20 cases of diltiazem-associated photodistributed hyperpigmentation have been reported in the literature. Here, we present the case of a 71-year-old woman with new-onset facial hyperpigmentation 6 months after initiating treatment with diltiazem.
Topics: Aged; Biopsy; Calcium Channel Blockers; Dermatologic Agents; Diltiazem; Female; Humans; Hyperpigmentation; Hypertension; Ointments; Photosensitivity Disorders; Skin; Tacrolimus; Treatment Outcome; Withholding Treatment
PubMed: 32226335
DOI: No ID Found -
The British Journal of General Practice... Oct 2014
Topics: Alopecia; Decision Making; General Practice; Humans; Ointments; Physician-Patient Relations; Self Concept
PubMed: 25267042
DOI: 10.3399/bjgp14X681985 -
American Family Physician Aug 2014
Topics: Administration, Cutaneous; Anti-Bacterial Agents; Humans; Hygiene; Impetigo; Ointments
PubMed: 25251010
DOI: No ID Found -
BMJ Case Reports Sep 2018
Topics: Aged; Artifacts; Breast Diseases; Calcinosis; Diagnosis, Differential; Female; Humans; Mammography; Ointments; Zinc
PubMed: 30232076
DOI: 10.1136/bcr-2018-226536