Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18–50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure.

Background:Iberdomide is a high-affinity cereblon ligand that promotes proteasomal degradation of Ikaros (IKZF1) and Aiolos (IKZF3), transcription factors involved in innate and adaptive immune cell development and homeostasis, and linked to the genetic risk for systemic lupus erythematosus (SLE). A phase 2, placebo-controlled study evaluated the efficacy and safety of iberdomide in patients (pts) with moderate to severe SLE.Objectives:To examine the effect of iberdomide on cutaneous manifestations in SLE pts.Methods:Adult autoantibody-positive SLE pts with a SLE Disease Activity Index 2000 (SLEDAI 2K) score ≥6 were randomized (2:2:1:2) to oral iberdomide (0.45, 0.3, 0.15 mg) or placebo once daily (QD) for 24 weeks while continuing standard background lupus medications. The Cutaneous Lupus Area and Severity Index Activity score (CLASI-A) was assessed every 4 weeks through week 24. As prespecified, exploratory analyses, change from baseline and the proportion of pts who achieved ≥50% reduction from baseline (CLASI-50) were evaluated for all pts, pts with baseline CLASI-A ≥8, and by cutaneous lupus subtypes (acute [ACLE], subacute [SCLE], chronic [CCLE]). CLASI-A outcomes were also evaluated post hoc for subgroups with high baseline expression of IKZF3 or the type 1 interferon (IFN) gene signatures in the blood.Results:Of 288 randomized pts, the mean and median (range) baseline CLASI-A scores were 6.9 and 5.0 (0-49), with 28% of pts having a score ≥8. 56% of pts had ACLE, 29% CCLE, and 16% SCLE. CLASI-50 responses were not significantly different comparing iberdomide to placebo in all pts and pts with baseline CLASI-A ≥8 at week 24, where high placebo response rates were observed (Table). Numerically greater mean improvement from baseline in CLASI-A scores in pts with baseline CLASI-A ≥8 was observed for iberdomide 0.45 mg vs placebo beginning at week 4, with continuous improvement through week 24. For pts with SCLE or CCLE, CLASI-50 response rates were significantly higher with iberdomide 0.45 mg vs placebo (P<0.04; Table). SCLE pts had significantly greater mean change and median percent improvement in CLASI-A from baseline with iberdomide 0.45 mg vs placebo at week 24 (P<0.03). Treatment differences in CLASI-A between iberdomide 0.45 mg and placebo were larger for SCLE and CCLE subgroups with high baseline IKZF3 or type 1 IFN gene signatures, with statistical significance achieved for SCLE pts but not CCLE pts (Figure).Table 1.CLASI-50 Response Rates by Subgroups at Week 240.15 mg QD0.3 mg QD0.45 mg QD(n=42)(n=82)(n=81)PlaceboSubgroup(n=83)0.15 mg QD vs Placebo0.3 mg QD vs Placebo0.45 mg QD vs Placebon/m (%)n/m (%)Str Diff in % (95% CI)P valuen/m (%)Str Diff in % (95% CI)P valuen/m (%)Str Diff in % (95% CI)P valueAll pts37/83 (44.6)19/42 (45.2)0.4 (-17.33, 18.55) P=0.96141/82 (50.0)5.3 (-9.93, 20.11) P=0.49945/81 (55.6)10.9 (-4.30, 25.51) P=0.163CLASI-A ≥810/20 (50.0)8/13 (61.5)15.9 (-17.42, 45.45) P=0.39913/24 (54.2)12.1 (-17.57, 39.97) P=0.45816/24 (66.7)15.1 (-15.51, 42.49) P=0.368ACLE23/50 (46.0)15/30 (50.0)4.8 (-17.22, 26.31) P=0.66220/43 (46.5)-3.3 (-22.95, 16.67) P=0.73817/38 (44.7)-3.0 (-23.20, 17.65) P=0.782SCLE9/17 (52.9)5/9 (55.6)2.6a (-33.04, 36.33) P=0.9663/9 (33.3)-6.6 (-38.98, 31.86) P>0.99911/12 (91.7)38.7a(4.54, 61.75) P=0.035CCLE5/18 (27.8)7/14 (50.0)22.2a (-10.51, 50.00) P=0.19810/23 (43.5)23.8 (-6.89, 48.88) P=0.12918/29 (62.1)34.1 (4.43, 56.16) P=0.029CI, confidence interval; Str Diff, stratified difference.aUnstratified difference.Conclusion:Iberdomide showed beneficial effects on skin manifestations in pts with SLE. Efficacy appears to be more pronounced in pts with SCLE and CCLE skin subtypes, and in pts with high IKZF3 or IFN gene expression signatures.Δ, treatment difference of adjusted means; CCLE, chronic cutaneous lupus erythematosus; CLASI-A, Cutaneous Lupus Erythematosus Disease Area and Severity Index-activity score; IFN, interferon; SCLE, subacute cutaneous lupus erythematosus.Acknowledgements:This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb.Disclosure of Interests:Victoria Werth Consultant of: Bristol Myers Squibb, Grant/research support from: Bristol Myers Squibb, Joan Merrill Consultant of: UCB, GlaxoSmithKline, AbbVie, EMD Serono, Remegen, Celgene/Bristol Myers Squibb, AstraZeneca, Lilly, Immupharma, Amgen, Janssen, Resolve, Alpine, Aurinia, Astellas, Alexion, and Provention, Grant/research support from: GlaxoSmithKline and AstraZeneca, Richard Furie Consultant of: Bristol Myers Squibb, Grant/research support from: Bristol Myers Squibb, Thomas Dörner Consultant of: support for clinical studies and honoraria for scientific advice: AbbVie, Bristol Myers Squibb Company, Celgene, Eli Lilly, Janssen, Novartis, Roche, Employee of: Charite Universitätsmedizin, Berlin and DRFZ Berlin, Germany, Ronald van Vollenhoven Speakers bureau: UCB, AbbVie, Galapagos, Janssen, Pfizer, Paid instructor for: support for educational programs: Pfizer, Roche, Consultant of: AstraZeneca, Biogen, Biotest, Celgene, Gilead, Servier, UCB, AbbVie, Galapagos, Janssen, Pfizer, Grant/research support from: Bristol Myers Squibb, GlaxoSmithKline, Eli Lilly, UCB, Peter Lipsky Employee of: RILITE Foundation, Michael Weiswasser Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Shimon Korish Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Peter Schafer Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Mark Stern Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Zhaohui Liu Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Shaojun Tang Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Nikolay Delev Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb