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1.
N Engl J Med ; 390(6): 510-521, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38324484

ABSTRACT

BACKGROUND: The use of monoclonal antibodies has changed the treatment of several immune-mediated inflammatory diseases, including psoriasis. However, these large proteins must be administered by injection. JNJ-77242113 is a novel, orally administered interleukin-23-receptor antagonist peptide that selectively blocks interleukin-23 signaling and downstream cytokine production. METHODS: In this phase 2 dose-finding trial, we randomly assigned patients with moderate-to-severe plaque psoriasis to receive JNJ-77242113 at a dose of 25 mg once daily, 25 mg twice daily, 50 mg once daily, 100 mg once daily, or 100 mg twice daily or placebo for 16 weeks. The primary end point was a reduction from baseline of at least 75% in the Psoriasis Area and Severity Index (PASI) score (PASI 75 response; PASI scores range from 0 to 72, with higher scores indicating greater extent or severity of psoriasis) at week 16. RESULTS: A total of 255 patients underwent randomization. The mean PASI score at baseline was 19.1. The mean duration of psoriasis was 18.2 years, and 78% of the patients across all the trial groups had previously received systemic treatments. At week 16, the percentages of patients with a PASI 75 response were higher among those in the JNJ-77242113 groups (37%, 51%, 58%, 65%, and 79% in the 25-mg once-daily, 25-mg twice-daily, 50-mg once-daily, 100-mg once-daily, and 100-mg twice-daily groups, respectively) than among those in the placebo group (9%), a finding that showed a significant dose-response relationship (P<0.001). The most common adverse events included coronavirus disease 2019 (in 12% of the patients in the placebo group and in 11% of those across the JNJ-77242113 dose groups) and nasopharyngitis (in 5% and 7%, respectively). The percentages of patients who had at least one adverse event were similar in the combined JNJ-77242113 dose group (52%) and the placebo group (51%). There was no evidence of a dose-related increase in adverse events across the JNJ-77242113 dose groups. CONCLUSIONS: After 16 weeks of once- or twice-daily oral administration, treatment with the interleukin-23-receptor antagonist peptide JNJ-77242113 showed greater efficacy than placebo in patients with moderate-to-severe plaque psoriasis. (Funded by Janssen Research and Development; FRONTIER 1 ClinicalTrials.gov number, NCT05223868.).


Subject(s)
Antibodies, Monoclonal , Psoriasis , Receptors, Interleukin , Humans , Double-Blind Method , Interleukin-23/immunology , Peptides/administration & dosage , Peptides/adverse effects , Peptides/therapeutic use , Psoriasis/drug therapy , Psoriasis/immunology , Severity of Illness Index , Treatment Outcome , Receptors, Interleukin/antagonists & inhibitors , Administration, Oral , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Dose-Response Relationship, Drug
2.
Adv Ther ; 40(11): 5090-5101, 2023 11.
Article in English | MEDLINE | ID: mdl-37737889

ABSTRACT

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory condition characterized by sterile pustules on the palms and soles. This study evaluated the epidemiology of PPP using claims and electronic health record (EHR) databases. METHODS: Patients coded for PPP in the United States (US) and Japan from 2016 to 2020 were identified. Several PPP definitions were evaluated; the specific definition (≥ 2 visits coded for PPP, the second 31-730 days after diagnosis) was chosen for characterizing PPP epidemiology. Baseline characteristics and pre- and post-diagnosis treatments were summarized. Prevalence and incidence rates were analyzed by calendar year, sex, age, and database. RESULTS: Prevalence and incidence of PPP were higher in Japan than the US. PPP prevalence increased over time. PPP occurred predominantly in adulthood and was more common among women. Features of metabolic syndromes, anxiety, and depression were more common among US PPP patients. Consistently high baseline use of anti-bacterial, anti-inflammatory/anti-rheumatic, and obstructive airway disease treatments was observed among PPP patients. Potential miscoding or misclassification of PPP limited this analysis. Prevalence estimates from databases may differ from field- and population-based approaches. CONCLUSIONS: The burden of PPP was greater in Japan than in the US. Additional studies are needed to further elucidate PPP epidemiology worldwide.


Subject(s)
Electronic Health Records , Psoriasis , Humans , Female , Psoriasis/epidemiology , Chronic Disease , Acute Disease , Insurance, Health
3.
JAAD Int ; 12: 124-132, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37409312

ABSTRACT

Background: Hidradenitis suppurativa (HS) is a chronic, debilitating, inflammatory disease. Contemporaneous real-world data can be used to elucidate the clinical treatment of pediatric patients and how treatment strategies compare with adult hidradenitis suppurativa patients. Objective: The objective of this study is to evaluate clinical and treatment characteristics of pediatric and adult HS patients. Methods: HS adult and pediatric patients were identified in 3 the United States administrative claims databases during the study period between 2016 to 2021. Patients were required to have 2 diagnostic codes for HS and have at least 365 days of prior observation time to the first HS diagnosis. Results: Pediatric and adult HS treatments were similar. The proportions of subjects treated with topical and oral antibiotic or oral antibiotic alone or topical medication alone or surgery alone covered 90% of the treated pediatric subjects and 91% of treated adult subjects. The remaining proportion of subjects received other treatment combinations. Limitations: The databases represent subjects with commercial or government insurance coverage and thus do not necessarily represent the broader US population. The databases do not capture information about medications obtained without insurance. Conclusions: Although subtle differences exist, this study confirms that topical and systemic therapeutic treatment of HS in adults and adolescents is very similar.

4.
Pediatr Dermatol ; 38(4): 967-969, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34060128

ABSTRACT

Topical sirolimus has become a crucial treatment option for many dermatologic disorders. Because an FDA-approved topical formulation is not commercially available, sirolimus creams, ointments, and gels are professionally prepared by compounding pharmacies. Also, the topical use of a commercially available sirolimus solution approved for oral administration is described regularly. To better guide providers in their decision-making when topical sirolimus is being considered, this article highlights the substantial pharmaceutical and clinical differences between commercial oral solution and compounded preparations specifically designed for topical therapy.


Subject(s)
Immunosuppressive Agents , Sirolimus , Administration, Topical , Gels , Humans , Ointments
6.
Pediatr Dermatol ; 38(3): 585-590, 2021 May.
Article in English | MEDLINE | ID: mdl-33742460

ABSTRACT

BACKGROUND: In their early phase, infantile hemangiomas (IH) can sometimes be difficult to differentiate from port-wine birthmarks (PWB). Until recently, inexpensive diagnostic tools have not been readily available. OBJECTIVE: To determine the diagnostic utility of widely available colorimetric technology when differentiating PWB from IH in photographs of infants less than 3 months old. METHODS: Multi-center, retrospective analysis of RGB (red, green, and blue) and HSL (hue, saturation, lightness) values collected using electronic colorimeters from images of clinically confirmed untreated IH or PWB. Subgroup analysis of flat vascular birthmarks was subsequently performed. RESULTS: Images of 119 IH (specifically, 45 flat IH) and 59 PWB were identified. PWB had significantly (P < .001) higher RGB values of all primary colors, most notably for blue and green (mean difference: >50), irrespective of thickness. RGB or RGB with HSL values had an excellent accuracy (90%), sensitivity (92%), specificity (98%), and positive predictive value (98%) when discriminating PWB from flat IH. IH could be distinctly clustered from PWB when combining their RGB with HSL values. CONCLUSION: Electronic colorimeters with emphasis on blue and green values, are able to differentiate PWB from IH, irrespective of thickness, with a high degree of accuracy. A larger scale evaluation is now required.


Subject(s)
Hemangioma, Capillary , Pigmentation Disorders , Port-Wine Stain , Humans , Infant , Pilot Projects , Port-Wine Stain/diagnosis , Retrospective Studies
11.
Pediatr Dermatol ; 38(1): 296-298, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33099783

ABSTRACT

Dermatologically, FGFR3 mutations can lead to acanthosis nigricans (AN), epidermal nevi, and seborrheic keratosis. A recent case report found that topical rapamycin (sirolimus) can improve FGFR3-induced epidermal nevi with AN features in children, specifically with Fitzpatrick skin type (FST) I/II, and we would like to expand these findings to skin plaques with extensive AN-like features in the FST IV/V adolescent population. An 18-year-old female with FST IV/V and FGFR3-induced hypochondroplasia presented to our clinic with extensive AN-like plaques. Significant improvement with lightening and thinning of the plaques was observed after applying 1% topical rapamycin cream twice daily. Topical rapamycin should be considered as a treatment option for AN, particularly in FST IV/V adolescents with FGFR3-induced AN.


Subject(s)
Acanthosis Nigricans , Dwarfism , Nevus , Skin Neoplasms , Acanthosis Nigricans/diagnosis , Acanthosis Nigricans/drug therapy , Adolescent , Child , Female , Humans , Sirolimus/therapeutic use
12.
Dermatol Ther ; 33(6): e13907, 2020 11.
Article in English | MEDLINE | ID: mdl-32594609

ABSTRACT

Angiokeratomas are benign vascular neoplasms that arise as solitary or multiple lesions, most commonly treated with excision, electrodessication, cryotherapy, or laser therapies. This case presents a young female whose solitary angiokeratoma was treated with topical 1% sirolimus cream, improving the appearance, symptoms, and size of the lesion. Topical sirolimus cream may be a noninvasive treatment option for angiokeratomas with fewer risks than standard therapy that may be feasible and preferable for some patients.


Subject(s)
Angiokeratoma , Laser Therapy , Skin Neoplasms , Angiokeratoma/diagnosis , Angiokeratoma/drug therapy , Female , Humans , Sirolimus/adverse effects , Skin Neoplasms/drug therapy
13.
J Cosmet Laser Ther ; 22(3): 128-129, 2020 Apr 02.
Article in English | MEDLINE | ID: mdl-32496930

ABSTRACT

Brachioplasty, in addition to several nonsurgical interventions (e.g. cryolipolysis, noninvasive radiofrequency, and intense-focused ultrasound) have been described as efficacious in the elimination of excess skin laxity from the upper arms. Recently, fractional CO2 ablation has gained attention for its ability to reduce rhytids and improve skin texture on the face, neck, and hands. In this article, we report the first successful case of fractional CO2 ablation for upper arm contouring.


Subject(s)
Arm , Body Contouring , Lasers, Gas , Photothermal Therapy , Face , Humans , Lasers, Gas/therapeutic use , Neck
14.
J Lasers Med Sci ; 11(4): 395-404, 2020.
Article in English | MEDLINE | ID: mdl-33425289

ABSTRACT

Introduction: Darier disease (DD) is a chronic disease with high morbidity and limited treatment options. Laser efficacy in the treatment of DD remains understudied. Methods: A literature search conducted between 07/21/2017 and 05/05/2018 identified all original cases of DD treated with laser therapy. Results: Outcomes from 24 patients were reviewed, 22 patients were identified in the literature and 2 cases are included from our institution. Five types of lasers were identified [CO2 laser, Er:YAG laser, pulse dye laser [PDL], diode laser, erbium-doped fiber laser], with CO2 (46%) and PDL (42%) being the most common. Seventy-nine percent of patients were treated with more than one procedure (average, 3 procedures). The estimated body surface treated with each session ranged from 5%-50%. The most common adverse events came from CO2 and Er:YAG lasers and included dyspigmentation, pain, and post-laser erythema and edema. The time to response (mode, 1 month) was only reported in half of the studies. Conclusion: Laser treatments appear to be a promising alternative to standardized therapies in DD.

16.
Dermatol Surg ; 46(3): 402-410, 2020 03.
Article in English | MEDLINE | ID: mdl-30893164

ABSTRACT

BACKGROUND: Studies investigating the efficacy of lasers to minimize early surgical scars are low powered and report variable results. To further examine the evidence, the authors performed a systemic review and meta-analysis. OBJECTIVE: To present the evidence of randomized controlled trials investigating the efficacy of laser modalities in minimizing surgical scars when applied <1 month after operation. MATERIALS AND METHODS: A literature search of PubMed, EMBASE, Northern Light Life Sciences Conference Abstracts, and Cochrane Library was performed between November 6, 2015, and November 20, 2015. After assessing for inclusion, data extraction used the PRISMA checklist. Assessment for quality, validity, and risk of bias applied a scale devised by Jadad and colleagues, the Oxford Pain Validity Scale, and the RevMan risk of bias assessment tool, respectively. The GRADEpro application graded overall quality, and statistical analysis was performed with RevMan. RESULTS: Approximately 4,373/4,397 abstracts and 16/24 full articles were excluded using predefined criteria, leaving 8 articles in the systematic review and 4 in the meta-analysis. The primary outcome reached statistical significance favoring the intervention group with standardized mean difference 0.39 (95% confidence interval, 0.05-0.74) and p = .03. CONCLUSION: The outcome supports the efficacy of lasers in minimizing primarily closed surgical scars when treated <1 month after surgery.


Subject(s)
Cicatrix/therapy , Laser Therapy/methods , Postoperative Complications/therapy , Humans , Pain Measurement , Randomized Controlled Trials as Topic
17.
Pediatr Dermatol ; 37(1): 190-191, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31769049

ABSTRACT

A 15-year-old girl presented with leg wounds that were sustained after waxing and subsequent chemical depilation. History revealed prior usage of chemical depilatories without irritation. Given this finding, we suspect that waxing disrupted the epidermal barrier and, therefore, rendered the patient more susceptible to severe irritant contact dermatitis upon depilation. While there are reported cases of irritant contact dermatitis and chemical burns secondary to waxing or depilatory cream use in adults, a literature review found no reported cases of chemical burns in a pediatric patient or adult consequent to using these methods in tandem.


Subject(s)
Burns, Chemical/etiology , Dermatitis, Irritant/etiology , Hair Removal/adverse effects , Adolescent , Female , Humans , Leg , Skin Cream/adverse effects
19.
Pediatr Dermatol ; 36(3): 411-413, 2019 May.
Article in English | MEDLINE | ID: mdl-30907021

ABSTRACT

We report a pediatric case of extensive, progressive benign cephalic histiocytosis (BCH) involving the face, trunk, and extremities with response of facial lesions to treatment with topical 1% rapamycin. A split-face model was used to demonstrate improvement on the treated side versus the untreated side. After physician and parental perception of effectiveness, based in part on photodocumentation, subsequently both cheeks were treated with continued improvement.


Subject(s)
Facial Dermatoses/diagnosis , Facial Dermatoses/drug therapy , Histiocytosis/diagnosis , Histiocytosis/drug therapy , Immunosuppressive Agents/therapeutic use , Sirolimus/therapeutic use , Administration, Cutaneous , Child, Preschool , Humans , Male , Ointments
20.
Pediatr Dermatol ; 35(6): e406-e407, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30152558

ABSTRACT

Sirolimus has emerged as a promising treatment for complex congenital vascular malformations but is limited because of systemic side effects. Topically compounded formulations, which have been found to be successful in the treatment of several other conditions, are a preferred drug delivery system to provide local therapy. We report a case of a venolymphatic malformation in an adolescent girl treated with topical 1% sirolimus cream leading to improvement in appearance and associated symptoms.


Subject(s)
Immunosuppressive Agents/administration & dosage , Sirolimus/administration & dosage , Vascular Malformations/drug therapy , Administration, Topical , Adolescent , Female , Humans , Treatment Outcome
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