Examining the association between pruritus and quality of life in patients with atopic dermatitis treated with crisaborole.

BACKGROUND: Pruritus is a leading cause of reduced health-related quality of life (QoL) in atopic dermatitis (AD). Crisaborole ointment is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. In identical Phase 3 studies (NCT02118766, NCT02118792), crisaborole reduced disease and pruritus severity versus vehicle. OBJECTIVE: Quantify the relationship between pruritus and QoL using data from these studies. METHODS: Patients aged ≥2 years were randomly assigned 2 : 1 to receive crisaborole:vehicle twice daily for 28 days. QoL was measured at baseline and day 29 using the Dermatology Life Quality Index (DLQI; patients aged ≥16 years), the Children's Dermatology Life Quality Index (CDLQI; patients aged 2-15 years) and the Dermatitis Family Impact (DFI; caregivers of patients aged 2-17 years). Pruritus was measured using the Severity of Pruritus Scale (SPS), a 4-point scale from 0 ('no itching') to 3 ('bothersome itching/scratching that disturbs sleep'), and captured morning and evening via electronic diary. Data from crisaborole and vehicle arms were pooled for this analysis. A repeated-measures longitudinal model was used to estimate relationships between pruritus (SPS) and QoL (DLQI, CDLQI and DFI in separate analyses). RESULTS: One thousand five hundred and twenty two patients received crisaborole or vehicle. A linearity assumption for the relationship between SPS and DLQI (n = 294), CDLQI (n = 1200), and DFI (n = 1293) was appropriate. For DLQI, SPS score of 0 was associated with 'no negative effect on patient QoL'; SPS score of 1 was associated with 'small effect on patient QoL'; SPS score of 2 was associated with 'moderate effect on patient QoL'; and SPS score of 3 was associated with 'very large effect on patient QoL'. The pattern of relationships between SPS and CDLQI and DFI was similar. CONCLUSIONS: The relationships between SPS and DLQI, CDLQI and DFI substantiate the significant link between pruritus and patient/caregiver QoL in AD.

Tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: long-term safety and efficacy in an open-label extension study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. Final safety and efficacy data from an open-label extension study of tofacitinib in psoriasis are reported. OBJECTIVES: To evaluate the long-term safety and durability of efficacy of tofacitinib in adults with moderate-to-severe chronic plaque psoriasis. METHODS: Eligible patients who completed qualifying phase II/III tofacitinib studies received tofacitinib 10 mg twice daily (q12h) until month 3; subsequently, the dose could be adjusted by investigators to either 5 or 10 mg q12h. Adverse events (AEs) are reported up to month 66 and laboratory data up to month 54. Efficacy end points up to month 54 included Physician's Global Assessment of 'clear' or 'almost clear' (PGA response) and 75% improvement in Psoriasis Area and Severity Index (PASI 75). RESULTS: Overall, 2867 patients received tofacitinib, with a median treatment duration of 35·6 months. Adverse events (AEs) and serious AEs were reported in 82·5% and 13·7% of patients, respectively; 13·9% of patients discontinued owing to AEs; and 29 patients died. Incidence rates (patients with event/100 patient-years) were 1·16 for serious infections, 0·67 for malignancies and 0·26 for major adverse cardiovascular events. After initial changes in qualifying studies, most laboratory parameters were generally stable over 54 months. PGA response was achieved by 52-62% of patients and PASI 75 by 56-74% of patients at each study visit through month 54. CONCLUSIONS: In patients with psoriasis, the safety profile of tofacitinib over 66 months was similar to previous reports in phase III studies and efficacy was sustained through 54 months (NCT01163253).

Quantitative Evaluations of Time-Course and Treatment Effects of Systemic Agents for Psoriasis: A Model-Based Meta-Analysis.

Aggregate data model-based meta-analysis is a regression approach to compare the dose-response and/or time-course across different treatments using summary level data from the literature. Literature search and systematic review following the Cochrane approach yielded 912 sources for investigational and approved treatments for psoriasis. In addition, data for tofacitinib were obtained from an internal database. Tofacitinib is an oral Janus kinase inhibitor. Two mathematical models were developed for Psoriasis Area and Severity Index (PASI) response in moderate to severe psoriasis patients to quantify the time to maximum effect for PASI75 and to evaluate the dose-response relationship for PASI responders (PASI50, PASI75, PASI90, PASI100) at Week 12. Body weight exhibited an inverse effect on the placebo component of both models, suggesting that body weight affects the overall PASI response regardless of drug. This analysis provides a quantitative framework for efficacy comparisons across psoriasis treatments.

Prevalence of yeasts in beach sand at three bathing beaches in South Florida.

The abundance and types of yeasts in the wet and dry sand of three recreational beaches in South Florida were determined. Samples were collected on 17 occasions between August 2001 and July 2002. After analyzing 102 sand samples, a total of 21 yeast species were identified by molecular methods. These isolates comprised four Basidiomycetes and 17 Ascomycetes and included eight species that had previously been reported from humans. The most frequently encountered yeasts were Candida tropicalis and Rhodotorula mucilaginosa. A greater diversity of species (16 species) was found in the dry sand above the high tide mark compared with the wet sand in the intertidal zone (11 species). Densities were also highest in the dry sand relative to wet sand (20-fold higher at Hobie beach, 6-fold higher at Fort Lauderdale Beach and 1.3-fold higher at Hollywood beach). There were no clear temporal patterns in the data and overall densities were greatest at the busiest bathing beach (Hobie Beach) where total yeasts averaged 37,720 cfu 100g(-1) dry sand and 1852 cfu 100 g(-1) in the wet sand. This concentration of yeast was significantly higher than populations at the less populated beaches. Fort Lauderdale beach had a mean count of 4130 cfu 100 g(-1) dry sand and 705 cfu 100g(-1) in the wet sand while the least populated beach, Hollywood Beach averaged 1945 cfu 100g(-1) dry sand and 1483 cfu 100g(-1) wet sand. While definitive statements cannot be made, high levels of yeasts may have a deleterious bearing on human health and the presence of such a diverse aggregation of species suggests that yeasts could have a role as indicators of beach health.

Biodiversity and systematics of basidiomycetous yeasts as determined by large-subunit rDNA D1/D2 domain sequence analysis.

The molecular systematics of 337 strains of basidiomycetous yeasts and yeast-like fungi, representing 230 species in 18 anamorphic and 24 teleomorphic genera, was determined by sequence analysis of the D1/D2 region of the large-subunit rDNA. The data were compared with published sequences of other basidiomycetous fungi. The results demonstrated that the yeast species and genera are phylogenetically distributed among the Microbotryum, Sporidiobolus, Agaricostilbum and Erythrobasidium clades of the Urediniomycetes; the Tremellales, Trichosporonales ord. nov., Filobasidiales and Cystofilobasidiales clades of the Hymenomycetes; and the Ustilaginales, Microstromatales and Malasseziales clades of the Ustilaginomycetes. Genera such as Bensingtonia, Cryptococcus, Rhodotorula and Sporobolomyces are polyphyletic, i.e. they occur in two or more clades. In contrast, other genera, e.g. Bullera, Cystofilobasidium, Fellomyces, Filobasidiella, Filobasidium, Kondoa, Kurtzmanomyces, Leucosporidium, Rhodosporidium, Sporidiobolus and Udeniomyces, are monophyletic. The majority of the species can be identified using D1/D2 analyses, although the internal transcribed spacer region is required to distinguish closely related species. The intergenic spacer region is recommended for additional differentiation of species and strains.

Validation of the basidiomycetous yeast, Sporidiobolus microsporus sp. nov., based on phenotypic and molecular analyses.

The validation of Sporidiobolus microsporus Higham, nom. nud. is based on phenotypic characterization and molecular sequence analysis of a partial region of the large sub-unit ribosomal DNA. The species is compared, based on phenotypic and molecular characteristics, with other species of Sporidiobolus and the closely related Rhodosporidium fluviale.

Systematic placement of the basidiomycetous yeast Cystofilobasidium lari-marini comb. nov. as predicted by rRNA nucleotide sequence analysis.

Based on similarities in basidial morphology and nucleotide sequences of the V3 variable region in the large sub-unit ribosomal RNA, the yeast Leucosporidium lari-marini is considered phylogenetically related to the genus Cystofilobasidium. Therefore the new combination Cystofilobasidium lari-marini is proposed.

Partial rRNA sequences in marine yeasts: a model for identification of marine eukaryotes.

The V3 variable region of the large subunit rRNA was examined for nucleotide sequence signatures as potential taxonomic tools. Data are presented on 117 species, representing 23 genera of basidiomycetous yeasts. The results of nucleotide sequence alignments indicate that strains within species have identical base sequences and that species may differ from one another by one to more than 100 base positions. Phylogenetic analyses of the alignments indicates relationships among species, including the prediction of synonymous species and the clustering of species belonging to the Ustilaginales and Tremellales. These results suggest that species-specific nucleotide sequences can be used for the development of techniques for population analyses of a variety of marine and other microeukaryotes.