Total eosinophil count as a biomarker for therapeutic effects of upadacitinib in atopic dermatitis over 48 weeks.

Background: Atopic dermatitis (AD) is a chronic skin disease characterized by type 2-skewed immune responses, and significantly influenced by cytokines dependent on Janus kinases (JAKs). Upadacitinib, a JAK1 inhibitor, is effective for moderate-to-severe AD. This study aims to identify biomarkers that reflect long-term therapeutic effects of upadacitinib 15 mg or 30 mg. Methods: A retrospective study from August 2021 to July 2023 included 213 AD patients treated with upadacitinib 15 mg and 70 AD patients with 30 mg. We analyzed eczema area and severity index (EASI), peak pruritus-numerical rating scale (PP-NRS), serum immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), and total eosinophil count (TEC) at weeks 0, 4, 12, 24, 36, and 48 of treatment. Results: Both treatments with upadacitinib 15 mg and 30 mg significantly reduced EASI and PP-NRS scores over week 4 to 48 compared to baseline. Upadacitinib 15 mg or 30 mg treatment significantly decreased TEC compared to baseline through week 4 to 36 or week 4 to 48, respectively. The percent reduction of TEC correlated with those of EASI and PP-NRS through week 4 to 48 of treatment with upadacitinib 15 mg, or through week 12 to 48 with 30 mg, respectively. After adjusting for % reductions of other laboratory markers, the significance of correlations was preserved at weeks 36 and 48 of 15 mg treatment, while at weeks 4 and 36 of 30 mg treatment. Conclusion: The % reduction of TEC correlated with those of EASI and PP-NRS during upadacitinib treatment, indicating its potential as a biomarker reflecting treatment responses to upadacitinib in AD patients. However, the variability of significant correlation during treatment indicates that further inspection is needed for its usefulness in monitoring responses to upadacitinib treatment for AD.

Sustained Effectiveness of Upadacitinib in Moderate-to-Severe Atopic Dermatitis: A 48-Week Real-World Study.

Clinical trials and real-world studies have shown the effectiveness of upadacitinib for treating rash and pruritus in patients with atopic dermatitis (AD). This study aimed to determine whether the early reduction in rash or pruritus at week 12 of upadacitinib treatment could be maintained at later treatment stages. This retrospective study involved 227 and 73 patients with moderate-to-severe AD treated with 15 and 30 mg upadacitinib daily, respectively. The eczema area and severity index (EASI) scores, peak pruritus numerical rating scale (PP-NRS), and investigator's global assessment (IGA) were analyzed. At week 12, patients were divided into achievers and non-achievers of EASI 75, 90, 100, absolute EASI ≤ 2, IGA0/1, PP-NRS4, or absolute PP-NRS ≤ 1. Achievement rates for each endpoint were assessed at later time points (weeks 24, 36, and 48) in both groups. Week 12 achievers largely maintained their endpoint achievements until week 48, regardless of dosage (15 mg or 30 mg). Week 12 non-achievers saw an increasing achievement rate of EASI 75 until week 48. The initial reduction in rash and pruritus at week 12 persisted until week 48 with upadacitinib treatment, suggesting potential benefits for patients requiring prolonged treatment despite not achieving EASI 75 at week 12.

Long-term effectiveness and safety of upadacitinib for Japanese patients with moderate-to-severe atopic dermatitis: a real-world clinical study.

BACKGROUND: Previous clinical trials presented efficacy and safety of Janus kinase 1 inhibitor upadacitinib through 52 weeks for moderate-to-severe atopic dermatitis (AD). OBJECTIVES: To assess the effectiveness and safety of upadacitinib through 48 weeks in real-world clinical practice for Japanese AD patients (aged ≥12 years). METHODS: This retrospective study included 287 patients with moderate-to severe AD treated with 15 mg (n = 216) or 30 mg (n = 71) of upadacitinib daily. Effectiveness was assessed using eczema area severity index (EASI) scores, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and investigator's global assessment (IGA). Safety was evaluated through the incidence of treatment-emergent adverse events. RESULTS: From baseline, EASI, ADCT, PP-NRS, and IGA rapidly reduced at week 4, and the reduction was maintained until week 48 of treatment with upadacitinib at both doses. Achievement rates of EASI 75, EASI 90, and EASI 100 at week 48 were 63.5, 30.2, and 7.9 in 15 mg group, and 77.4, 54.8, and 3.2% in 30 mg group, respectively. Acne and herpes zoster were frequent, but no serious adverse events occurred. CONCLUSIONS: Upadacitinib was therapeutically effective and tolerable for moderate-to-severe AD through 48 weeks in real-world clinical practice.

Effectiveness of Dose Increase in Upadacitinib from 15 mg to 30 mg for Patients with Moderate-to-Severe Atopic Dermatitis: A Real-World Clinical Practice in Japan.

BACKGROUND: Atopic dermatitis is characterized by persistent eczema and pruritus. Janus kinase inhibitors, including upadacitinib, are effective treatments for moderate-to-severe atopic dermatitis. If patients do not respond well to a certain dose of a Janus kinase inhibitor, increasing the dose may improve their treatment responsiveness. OBJECTIVES: We assessed the outcomes of a dose increase in upadacitinib from 15 mg to 30 mg for Japanese patients with moderate-to-severe atopic dermatitis. METHODS: In 23 patients who showed insufficient responses to upadacitinib 15-mg treatment, the dose of upadacitinib was increased to 30 mg. We evaluated total Eczema Area and Severity Index (EASI), EASI on the head and neck, trunk, upper, or lower limbs, EASI of erythema, edema/papulation, excoriation, or lichenification, and Peak Pruritus Numerical-Rating Scale at baseline (onset of upadactinib 15 mg), week 0 (time of increase), and weeks 4 and 12 after the increase. RESULTS: Total EASI, EASI on each anatomical site, EASI of each clinical sign, and Peak Pruritus Numerical-Rating Scale were markedly reduced at weeks 4 or 12 compared with week 0. After the dose increase, the achievement rates of EASI 75 and EASI 90 significantly improved; EASI 75 4.3%, 68.2%, and 66.7%; EASI 90 0%, 18.2%, and 38.1% at weeks 0, 4, and 12, respectively. CONCLUSIONS: These results suggest that upadacitinib 30 mg can ameliorate rash and pruritus insufficiently improved by upadacitinib 15 mg, and that the dose increase to 30 mg may be considered as a treatment option for patients with atopic dermatitis with a limited response to upadacitinib 15 mg.

Real-world effectiveness and safety of bimekizumab in Japanese patients with psoriasis: A single-center retrospective study.

Bimekizumab, which suppresses both interleukin (IL)-17A and IL-17F, has recently been approved as a biologic for psoriasis. We aimed to evaluate the real-world effectiveness and safety of bimekizumab for psoriasis and to identify predictive factors for its treatment responsiveness. We analyzed 36 Japanese patients with psoriasis (19 with psoriasis vulgaris and 17 with psoriatic arthritis) from May 2022 to September 2023. All patients received bimekizumab (320 mg every 4 weeks) until week 16. Seventeen patients (43.2%) had experienced bio-switch. The median (interquartile range) baseline total psoriasis area and severity index (PASI) was 6 (3.2-20.0). Total PASI rapidly and significantly decreased at week 4 by a median 79.8% from baseline, and gradually decreased thereafter. The PASI on the trunk, and upper and lower limbs rapidly and significantly decreased at week 4 compared to baseline and plateaued thereafter. The neutrophil-to-lymphocyte ratio and neutrophil number significantly decreased at week 16 compared to baseline. At weeks 4, 8, 12, and 16, the achievement rate of absolute PASI ≤2 was 72.2%, 80.6%, 92.9%, and 96.4%, respectively; that of absolute PASI ≤1 was 41.7%, 61.3%, 85.7%, and 82.1%; that of PASI 75 was 55.5%, 52.9%, 69.7%, and 75.8%; that of PASI 90 was 36.1%, 50.0%, 57.6%, and 62.9%; and that of PASI 100 was 19.4%, 38.2%, 51.5%, or 57.6%, respectively. Linear multivariate regression analysis revealed that younger age was associated with a higher percentage reduction of total PASI at weeks 4 and 8. There were no serious or fatal adverse events during treatment. In conclusion, bimekizumab rapidly and remarkably reduced the total PASI together with high achievement rates of absolute PASI ≤1 and ≤2, and with favorable safety in real-world clinical practice. Younger age may be a predictive factor for a good treatment response to bimekizumab.

Dietary habits in adult Japanese patients with vitiligo.

Vitiligo is an autoimmune skin disease with acquired depigmentation. Dietary habits may modulate the pathogenesis of vitiligo. We evaluated dietary habits in adult Japanese patients with nonsegmental vitiligo, and compared their results with those of age- and sex-matched controls. We also examined the relationship between dietary habits and Vitiligo Area Scoring Index (VASI), or vitiligo on different anatomical sites. The intakes of energy, nutrients, and foods in the participants were analyzed using a brief-type self-administered diet history questionnaire. Patients with vitiligo showed higher body mass index (BMI) and lower intakes of manganese, vitamin D, pulses, and confection, compared with controls. Multivariate logistic regression analysis showed that vitiligo was associated with high BMI. VASI was higher in males than in females, and negatively correlated with age or intakes of potatoes and vegetables other than green/yellow vegetables. Linear multivariate regression analysis showed that high VASI was associated with younger age. Multivariate logistic regression analysis showed that moderate to severe vitiligo (VASI ≥ 4.25) was associated with male sex and longer disease duration. Multivariate logistic regression analyses showed the following association with vitiligo on respective anatomical sites: high intake of eggs and dairy products and high VASI on the head or neck, high intake of oils and fats and high VASI on the trunk, high intake of cereals and high VASI on the upper limbs, male sex and high VASI on the lower limbs, and high BMI and high VASI on the hands or feet. In conclusion, the control of obesity might have prophylactic or therapeutic effects on vitiligo.

Predictive factors for responders to upadacitinib treatment in patients with atopic dermatitis.

BACKGROUND: Janus kinase 1 inhibitor upadacitinib is therapeutically effective for atopic dermatitis (AD). However, predictive factors for high responders to upadacitinib have not been established in real-world clinical practice. OBJECTIVES: To identify predictive factors for responders to upadacitinib 15 mg or 30 mg, defined as achievers of investigator's global assessment (IGA) 0/1 with ≥ 2-point improvement from basal IGA. METHODS: A retrospective study was conducted from August 2021 to July 2023 on 159 AD patients treated with upadacitinib 15 mg and 52 patients with 30 mg. Patients in each group were categorized into responders (achievers of IGA 0/1 at week 12) and non-responders (non-achievers). We compared baseline values of clinical and laboratory parameters between responders and non-responders. Logistic regression analysis was used to detect variables predicting responders. Receiver-operating characteristic curves were used for evaluating prediction capabilities of the variables. RESULTS: In logistic regression analysis, responders to 15 mg upadacitinib were associated with lower total EASI and higher age whereas responders to 30 mg were associated with lower LDH and lower IgE. CONCLUSIONS: Lower total EASI and higher age may predict responders to upadacitinib 15 mg while lower IgE and lower LDH may predict responders to 30 mg.

Effectiveness and safety of deucravacitinib treatment for moderate-to-severe psoriasis in real-world clinical practice in Japan.

BACKGROUND: Deucravacitinib is a selective oral tyrosine kinase 2 (TYK2) inhibitor recently approved for psoriasis. OBJECTIVES: We aimed to evaluate the real-world effectiveness and safety of deucravacitinib for psoriasis. METHODS: We analyzed 33 Japanese patients with psoriasis (23 with plaque psoriasis, eight with psoriatic arthritis, and two with erythrodermic psoriasis) from January 2023 to October 2023. All patients received deucravacitinib 6 mg daily until week 16. RESULTS: At week 8, 12, or 16, the achievement rate of PASI 75 was 60.9%, 73.9%, or 78.3%, that of PASI 90 was 13.0%, 39.1%, or 52.2%, that of PASI 100 was 0%, 8.7%, or 13.0%, that of absolute PASI ≤2 was 34.8%, 65.2%, or 78.3%, respectively. The achievement rate of dermatology life quality index 0/1 at week 16 was 42.9%. Fourteen patients (42%) complained pruritus. Peak pruritus-numerical rating scale in patients with pruritus decreased by median [interquartile] 71.4 [50-80] % of baseline at week 2. Adverse events occurred in 18.2% of patients, which were mild and manageable. CONCLUSIONS: Deucravacitinib for patients with psoriasis was well-tolerated and gave favorable therapeutic effects in the real-world practice. Deucravacitinib treatment rapidly reduced pruritus.

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

BACKGROUND: 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. OBJECTIVES: This study aims to determine if early itch relief by upadacitinib could predict complete skin clearance in later phases. METHODS: 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. RESULTS: 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. CONCLUSIONS: The achievement of week 2 PP-NRS ≤ 1 may predict later skin clearance in upadacitinib treatment.

Effectiveness of switching from baricitinib 4 mg to upadacitinib 30 mg in patients with moderate-to-severe atopic dermatitis: a real-world clinical practice in Japan.

BACKGROUND: Atopic dermatitis (AD) is a chronic eczematous disease with severe pruritus. Janus kinase (JAK) inhibitors, upadacitinib, baricitinib, and abrocitinib, are systemic treatments for AD. The outcomes of switching from one JAK inhibitor to another have not been examined. OBJECTIVES: We assessed the outcomes of switching from baricitinib 4 mg to upadacitinib 30 mg in Japanese patients with moderate-to-severe AD. METHODS: Twenty patients treated with baricitinib 4 mg, showing insufficient response or adverse events, were switched to treatment with upadacitinib 30 mg. We evaluated total eczema area and severity index (EASI), EASI at head and neck, trunk, upper, or lower limbs, EASI of erythema, edema/papulation, excoriation, or lichenification, and peak pruritus numerical-rating scale (PP-NRS) at baseline (start of baricitinib), weeks 0 (time of switching), and 4 and 12 after switching. RESULTS: Total EASI, EASI at each anatomical site, EASI of each clinical sign, and PP-NRS were markedly reduced at weeks 4 or 12 compared to week 0. Achievement rates of more than 75% or 90% reduction of EASI from baseline significantly improved after switching. CONCLUSIONS: Switching from baricitinib 4 mg to upadacitinib 30 mg effectively improved rash and pruritus.

Effectiveness and Safety of Upadacitinib in Combination with Topical Corticosteroids in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis.

Purpose: To investigate the therapeutic effectiveness and safety of Janus kinase 1 inhibitor upadacitinib in adolescent patients with atopic dermatitis (AD). Patients and Methods: This study examined therapeutic effectiveness and safety of upadacitinib for 39 Japanese adolescent patients (aged 12-17 years) diagnosed with moderate-to-severe AD from August 2021 to January 2023. The patients were treated with upadacitinib 15 mg/day plus twice daily topical corticosteroids. Total eczema area and severity index (EASI) or EASI on head and neck, upper limbs, lower limbs, and trunk or for erythema, edema/papulation, excoriation, or lichenification, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and laboratory indexes were assessed at weeks 0, 4, and 12 of treatment. Treatment-emergent adverse events were recorded. Results: Total EASI or EASI on 4 anatomical sites or for 4 rash types, ADCT, and PP-NRS were significantly reduced at week 4 and 12 compared to week 0. The achievement rates at weeks 4 or 12 were 64.1% or 62.5% for EASI 75, 93.5% or 73.1% for ADCT <7-point, and 80.6% or 60% for PP-NRS ≥4-point improvement, respectively, indicating their peak at week 4 and slight decrease at week 12. The percent reduction of EASI for excoriation was higher than that for lichenification or edema/papulation at week 4 or week 12, respectively. The percent reductions of EASI for erythema and edema/papulation on head and neck were lower than those on lower limbs at week 12. Total eosinophil counts (TEC) and IgE reduced at week 4 compared to week 0 while TARC, IgE, TEC, and LDH increased at week 12 compared to week 4. Conclusion: These results suggest therapeutic effectiveness and tolerability of upadacitinib and support its therapeutic usefulness for adolescent AD patients.

Dietary habits in Japanese patients with bullous pemphigoid: low intake of retinol.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. Dietary habits may modulate the pathogenesis of BP. OBJECTIVES: We evaluated dietary habits in Japanese patients with BP and compared their results to those of age- and sex-matched healthy controls. We also examined the relationship between dietary habits versus IgG anti-BP180NC16A antibody or parameters of BP disease area index (BPDAI); cutaneous blisters/erosions, cutaneous urticaria/erythema, and mucosal blisters/erosions. MATERIALS & METHODS: Dietary habits were assessed by the validated, Brief-type self-administered Diet History Questionnaire. Severity of disease was assessed with BPDAI. RESULTS: Patients with BP showed a lower intake of retinol (vitamin A1) and beverages, and a higher intake of seasoning/spices, compared to controls. The bivariate and multivariable logistic regression analysis showed that BP was associated with a low intake of retinol and beverages. There were no significant correlations between IgG anti-BP180NC16A antibody levels and intake of nutrients/foods. The BPDAI score for cutaneous blisters/erosions significantly positively correlated with intake of carbohydrate and negatively with intake of retinol, vitamin A, animal fat, cholesterol, phosphorus, and vitamin B2. The BPDAI score for cutaneous urticaria/erythema significantly negatively correlated with intake of vitamin A. BP patients with mucosal blisters/erosions had a higher intake of cholesterol, n-6 polyunsaturated fatty acid, and eggs, and lower intake of seasoning/spices, compared to patients without BP. CONCLUSION: The supplementation of vitamin A might have prophylactic and/or therapeutic effects on BP.

Dietary Fiber Inulin Improves Murine Imiquimod-Induced Psoriasis-like Dermatitis.

Psoriasis is a chronic skin disease with interleukin (IL)-17-dominated inflammation and hyperproliferation of epidermis. Dietary fiber is fermented by the gut microbiome into short-chain fatty acids (SCFAs) that manifest anti-inflammatory effects. We examined if feeding with an inulin-enriched high-fiber diet (HFD) might improve topical imiquimod-induced psoriasis-like dermatitis in mice. HFD reduced thickening and total severity scores of imiquimod-induced dermatitis and reduced epidermal thickness, inflammatory infiltrates, including Ly6G+ neutrophils, and epidermal Ki67+ proliferating cells. HFD reduced mRNA levels of IL-17A, IL-17F, IL-22, IL-1ß, tumor necrosis factor (TNF)-α, CXCL1, CXCL2, and keratin 16 and increased those of transforming growth factor (TGF)-ß1 and cyclin-dependent kinase inhibitor 1A in imiquimod-induced dermatitis. In 16S rRNA sequencing of the gut microbiome, imiquimod increased relative abundance of phylum Firmicutes, while HFD increased that of phylum Bacteroidota and genus Bacteroides. HFD increased serum and fecal concentrations of SCFA propionate. Oral propionate reduced inflammatory infiltrates and epidermal Ki67+ cells and reduced mRNA levels of IL-17A, IL-17F, IL-17C, IL-22, IL-1ß, IL-6, TNF-α, CXCL1, CCL20 and increased those of TGF-ß1and IL-10 in imiquimod-indued dermatitis. Dietary inulin supplementation improves imiquimod-induced psoriasis-like dermatitis partially via propionate, and may be a promising adjunctive therapy for psoriasis.

Therapeutic effectiveness of upadacitinib on individual types of rash in Japanese patients with moderate-to-severe atopic dermatitis.

Atopic dermatitis (AD) is a chronic eczematous disease with various types of rash, erythema, edema/papulation, excoriation, or lichenification. Janus kinase 1 inhibitor upadacitinib is effective for moderate-to-severe AD. We aimed to investigate the therapeutic effects of upadacitinib on each rash type in AD patients in real-world clinical practice. Seventy-two Japanese patients with moderate-to-severe AD were treated with oral upadacitinib 15 mg/day plus topical corticosteroids. The Eczema Area and Severity Index (EASI) scores for erythema, edema/papulation, excoriation, or lichenification on the whole body or on head and neck, upper limbs, lower limbs, or trunk were assessed at weeks 0, 4, and 12 of treatment. The proportions of patients who achieved resolution or at least 75% reduction of EASI from baseline (EASI 75) for individual rash types were calculated at weeks 4 and 12 on the whole body or each anatomical site. The resolution rates for excoriation, erythema, edema/papulation, or lichenification on the whole body were 38.3%, 23.7%, 21.7%, and 8.3% at week 4 and 18.3%, 18.6%, 11.6%, and 13.3% at week 12, respectively. The EASI scores for all rash types significantly decreased at weeks 4 and 12 compared to week 0. The achievement rates of EASI 75 for excoriation, erythema, edema/papulation, or lichenification on the whole body were 67.2%, 66.7%, 49.2%, and 37.7% at week 4 and 57.3%, 65%, 41%, and 41% at week 12, respectively. The achievement rate of EASI 75 for erythema on head and neck at week 4 (45.3%) was lower than that on upper limbs (71%) and on lower limbs (70.8%), and that on head and neck at week 12 (42.2%) was lower than that on lower limbs (69.2%). These results indicate that upadacitinib is effective for all AD rash types, especially for excoriation and erythema, while head-and-neck erythema might be less responsive to upadacitinib.

Background factors predicting the occurrence of herpes zoster in atopic dermatitis patients treated with upadacitinib.

Upadacitinib, an oral Janus kinase 1 inhibitor approved for treating atopic dermatitis (AD), can cause adverse events such as herpes zoster (HZ) and acne. We aimed to identify background factors predicting the occurrence of HZ and acne during upadacitinib treatment in patients with AD. From August 2021 to December 2022, 112 Japanese patients with moderate-to-severe AD (aged ≥12 years) were treated with upadacitinib 15 mg/day (78 patients) or 30 mg/day (34 patients) plus topical corticosteroids or delgocitinib limited to head and neck for 3-9 months. AD patients with the occurrence of HZ during upadacitinib treatment had higher incidences for history of HZ and of bronchial asthma than those without in the upadacitinib 15 mg, 30 mg, and whole groups. AD patients with occurrence of HZ had higher pretreatment values of lactate dehydrogenase and eczema area and severity index on head and neck compared to those without in the upadacitinib 15 mg and whole groups. Logistic regression analysis revealed that history of HZ was associated with the occurrence of HZ in the upadacitinib 15 mg and whole groups. The proportion of underage patients (<18 years) was higher in patients with occurrence of acne compared to those without in the upadacitinib 30 mg group, but no significant differences were found in the other background factors between the two patient populations. History of HZ may predict the occurrence of HZ during upadacitinib treatment in patients with AD.

Change in Serum KL-6 Level during Biologic Treatment for Psoriasis.

BACKGROUND: We previously analyzed data from blood examination screenings, including serum Krebs von den Lungen (KL) -6 level, before starting biologic treatment for psoriasis in a real-world setting. However, we did not follow change in KL-6 level after the initiation of biologics. Furthermore, there has been no follow-up study of certolizumab pegol, risankizumab, or tildrakizumab. This study evaluated change in serum KL-6 levels in patients during treatment with biologics, including certolizumab pegol, risankizumab, and tildrakizumab. METHODS: We analyzed data from 111 patients. Change in KL-6 level was regarded as significant if it increased to greater than 500 U/mL at least once and if the maximum level after treatment with biologics was at least 1.5 times that of the baseline level. RESULTS: KL-6 level significantly changed during treatment with TNF inhibitors, IL-17 inhibitors, and IL-23 inhibitors in 9 (20.9%), 2 (6.3%), and 2 (5.6%) patients, respectively. Mean age, mean baseline KL-6 level, and frequency of TNF inhibitor use were higher in patients with a significant change in KL-6 level than those in patients without a significant change. Ten patients had minor interstitial changes on chest CT scans but no clinical signs suggesting interstitial pneumonia. CONCLUSIONS: Older patients with psoriasis and high baseline KL-6 levels must be carefully monitored during treatment with biologics, especially TNF inhibitors. Monitoring of KL-6 level and chest CT scans is necessary to exclude the possibility of drug-induced interstitial pneumonia.

The differential effects of upadacitinib treatment on skin rashes of four anatomical sites in patients with atopic dermatitis.

BACKGROUND: Upadacitinib is an oral Janus kinase (JAK) 1 inhibitor approved in Japan for moderate-to-severe atopic dermatitis (AD), and it provides a high therapeutic efficacy. OBJECTIVES: We compared the therapeutic effects of upadacitinib on skin rashes of individual anatomical sites, head and neck, upper limbs, lower limbs, and trunk in patients with AD. METHODS: From August 2021 to December 2022, 65 Japanese patients with moderate-to-severe AD (aged ≥ 12 years) were treated with oral once daily upadacitinib 15 mg plus twice daily topical corticosteroids of moderate-to-strongest classes. RESULTS: The eczema area and severity indexes (EASIs) of individual sites decreased significantly at weeks 4, 12, and 24 compared to those at week 0 in parallel to total (whole body) EASI. The achievement rates of EASI 75 at week 24 and of EASI 90 at week 12 of lower limbs were significantly higher than those of trunk. The percent reductions of EASI of lower limbs at weeks 12 and 24 were significantly higher than those of head and neck and of trunk. CONCLUSIONS: Among the four anatomical sites, the treatment responsiveness to upadacitinib in lower limbs appeared the highest, while those in trunk and in head and neck appeared relatively lower.

Barrier Factors of Adherence to Dupilumab Self-Injection for Severe Allergic Disease: A Non-Interventional Open-Label Study.

Purpose: The status of dupilumab self-injection at home is not well understood. We therefore aimed to identify the barriers to adherence to dupilumab self-injection. Patients and Methods: This non-interventional open-label study was conducted between March 2021 and July 2021. Patients with atopic dermatitis, bronchial asthma, and chronic rhinosinusitis with nasal polyps receiving dupilumab, from 15 sites, were requested to complete a self-administered questionnaire regarding the frequency and effectiveness of dosing as well as their use and satisfaction with dupilumab. Barriers to adherence were assessed using the Adherence Starts with Knowledge-12. Results: We included 331 patients who used dupilumab for atopic dermatitis (n = 164), chronic rhinosinusitis with nasal polyps (n = 102), and bronchial asthma (n = 65). The median efficacy of dupilumab scored 9.3 on the visual analog scale. Overall, 85.5% of the patients self-injected dupilumab, and 70.7% perfectly complied with the established injection dates. The pre-filled pen was significantly superior to the conventional syringe in terms of usability, operability, ease of pushing the plunger, and patient satisfaction. However, the pre-filled pen caused more pain during self-injection than did the syringe. Multivariate logistic regression analysis showed that adherence decreased with longer dupilumab treatment duration (p = 0.017) and was not associated with age, sex, underlying disease, or device type. There was a difference in responses related to "inconvenience/forgetfulness" between the good and poor adherence groups. Conclusion: The pre-filled dupilumab pen was superior to the syringe in terms of usability, operability, ease of pushing the plunger, and satisfaction. Repetitive instructions are recommended for preventing poor adherence to dupilumab self-injection.