Early itch relief with upadacitinib predicts later skin clearance in Atopic dermatitis

Though Janus kinase inhibitors such as upadacitinib rapidly relieve itch in atopic dermatitis (AD) patients, how early itch relief impacts later skin clearance is not examined. This study aims to determine if early itch relief by upadacitinib could predict complete skin clearance in later phases. This retrospective study involved 105 patients with moderate-to-severe AD treated with upadacitinib 15 mg/day. Eczema area and severity index (EASI), atopic dermatitis control tool, and achievement rate of EASI 100 were evaluated at weeks 4, 12, and 24. The threshold of early peak pruritus-numerical rating scale (PP-NRS) predicting later skin clearance was assessed by area under the receiver-operating characteristic curve, and predictors for EASI 100 achievement were determined by logistic regression analysis. The rate of achieving EASI 100 at week 24 was extremely higher in patients who achieved week 2 PP-NRS ≤ 1 (42.9%) than in non-achievers (1.4%). The logistic regression analysis showed that the achievement of week 2 PP-NRS ≤ 1 and low body mass index were associated with achievement of EASI 100 at weeks 12 and 24. The achievement of week 2 PP-NRS ≤ 1 may predict later skin clearance in upadacitinib treatment.</p

Correlation Analysis of Clinician- and Patient-Reported Outcomes Among Japanese Adults with Atopic Dermatitis

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Pairwise linkage disequilibrium between 34 SNPs.

<p>LD was measured by D′/LOD (upper) and r² (lower) estimated using the Haploview 4.2 program (<a href="http://www.broad.mit.edu/mpg/haploview/" target="_blank">http://www.broad.mit.edu/mpg/haploview/</a>). Boxed variants were genotyped in this study.</p

Frequencies of polymorphisms of the <i>CCL22</i> gene.

<p>*Numbering according to the genomic sequence of <i>CCL22</i> (AC003665). Position 1 is the A of the initiation codon.</p>‡<p>Minor allele frequencies (MAF) in the screening population (N = 12).</p>†<p>NCBI, number from the dbSNP of NCBI (<a href="http://www.ncbi.nlm.nih.gov/SNP/" target="_blank">http://www.ncbi.nlm.nih.gov/SNP/</a>).</p>§<p>SNPs were genotyped in this study.</p

Genotype counts and case-control association test results for SNPs rs4359426, rs170360 and rs223823.

<p><i>P</i> values of the two populations were calculated by logistic regression analysis under an additive model.</p><p>The combined <i>P</i> values were calculated using the inverse variance method. OR, odds ratio; CI, confidence interval.</p

Clinical characteristics of the subjects.

<p>Clinical characteristics of the subjects.</p

Genotype counts and case-control association test results of seven tag SNPs.

<p><i>P</i> values of the two populations were calculated by logistic regression analysis under an additive model. The combined <i>P</i> values were calculated using the inverse variance method. OR, odds ratio; CI, confidence interval; -, not significant.</p

Allelic imbalance of gene expression of <i>CCL22</i> in EBV-transformed cells with heterozygous genotypes.

<p>(<b>A</b>) Genomic structures, locations and LD of the two SNPs. (<b>B</b>) Haplotypes for the two SNPs in the 1^st population. (<b>C</b>) The allelic ratio of PCR products from individuals. Heterozygous (left) and homozygous (right) at rs4359426. *Two-tailed <i>P</i> = 0.0000006 by the Mann-Whitney U test.</p

Electrophoretic mobility shift assays of rs223821.

<p>EMSA was performed using nuclear extracts from THP-1 cells stimulated with LPS (1.0 µg/ml) for 1 hour. DIG-labeled oligonucleotides corresponding to the G allele (lanes 1–5) and A allele (lanes 6–10) were used as probes. Three independent experiments were performed with similar results.</p

Pairwise linkage disequilibrium (r²) among eight SNPs in strong LD with rs4359426 in 94 control subjects.

<p>Two tag SNPs, rs170360 and rs223823, were selected for further association study. Underlined SNPs were examined.</p