Cutaneous Lupus Erythematosus Disease Area And Severity Index Activity Score Research Articles

BI16 (P41) An emerging role of interferon-targeted therapy for the treatment of cutaneous systemic lupus erythematosus: a prospective real-world evaluation of anifrolumab for refractory cutaneous lupus

Abstract Cutaneous lupus erythematosus (CLE), particularly discoid lupus erythematosus (DLE), is frequently unresponsive to standard therapies, including antimalarial and immunosuppressive therapies. Recent evidence has identified the importance of type-1 interferon (IFN-1) in the pathogenesis of disease. Anifrolumab is a monoclonal antibody that targets IFN-1 and has been licensed for the treatment of systemic lupus erythematosus (SLE). It is unclear which clinical subtypes of CLE are associated with an IFN-1 signature and may be responsive to anifrolumab therapy. We sought to evaluate the efficacy of anifrolumab on (i) DLE and (ii) rituximab-refractory CLE; and (iii) to compare IFN-specific biomarkers and (iv) early and late immunophenotypic and clinical responses. Anifrolumab was available through an early access to medicines scheme. Patients with SLE for whom the phenotype was predominantly cutaneous were treated with anifrolumab 300 mg intravenously every 4 weeks. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and Dermatology Life Quality Index (DLQI) were reported. Seven patients were enrolled (five with DLE, one with chilblain and one with subacute CLE). All patients were female (median age 46 years; median disease duration 17 years). The median number of failed therapies was six: rituximab in six, belimumab in two and thalidomide in four patients. Four patients required long-term oral prednisolone > 10 mg daily. Median baseline CLASI activity score was 17 and DLQI was 16/30. Median CLASI score reduced after 4 weeks to 6 (range 0–13; P = 0.016) with a median decrease from baseline of 60% (range 19–100%), which was maintained at 6 months. Clinical responses were associated with significant improvements in DLQI (P < 0.001) and EQ-5D visual analogue scale (P = 0.002) by 3 months. All patients had a marked suppression of IFN-stimulated genes at 4 weeks (mean difference 2.92; P < 0.01). Treatment was generally well tolerated with the exception of one patient who had shingles complicated by sensorineural hearing loss while on anifrolumab and prednisolone > 15 mg daily. This required prolonged aciclovir for effective management. This case series highlights the potential role for anifrolumab in managing treatment-resistant CLE with particular responses observed in DLE and chilblain lupus. The need for enhanced awareness of viral infections, particularly varicella-zoster virus, needs to be considered in higher-risk patients.

P41 An emerging role of interferon targeted therapy for the treatment of cutaneous systemic lupus erythematosus: a prospective real-world evaluation of anifrolumab for refractory cutaneous lupus

Abstract Cutaneous lupus erythematosus (CLE), particularly discoid lupus erythematosus (DLE), is frequently unresponsive to standard therapies, including antimalarial and immunosuppressive therapies. Recent evidence has identified the importance of type-1 interferon (IFN-1) in the pathogenesis of disease. Anifrolumab is a monoclonal antibody that targets IFN-1 and has been licensed for the treatment of systemic lupus erythematosus (SLE). It is unclear which clinical subtypes of CLE are associated with an IFN-1 signature and may be responsive to anifrolumab therapy. We sought to evaluate the efficacy of anifrolumab on (i) DLE and (ii) rituximab-refractory CLE and (iii) to compare IFN-specific biomarkers and (iv) early and late immunophenotypic and clinical responses. Anifrolumab was available through an early access to medicines scheme. Patients with SLE for whom the phenotype was predominantly cutaneous were treated with anifrolumab 300 mg intravenously every 4 weeks. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and Dermatology Life Quality Index (DLQI) were reported. Seven patients were identified (five with DLE, one with chilblain and one with subacute CLE were enrolled). All patients were female (median age 46 years; median disease duration 17 years). The median number of failed therapies was six: rituximab in six, belimumab in two and thalidomide in four patients. Four patients required long-term oral prednisolone > 10 mg daily. The median baseline CLASI activity score was 17 and DLQI was 16/30. The median CLASI score reduced after 4 weeks to 6 (range 0–13; P = 0.016) with a median decrease from baseline of 60% (range 19–100%), which was maintained at 6 months. Clinical responses were associated with significant improvements in DLQI (P < 0.001) and the EQ-5D visual analogue scale (P = 0.002) by 3 months. All patients had a marked suppression of IFN-stimulated genes at 4 weeks (mean difference 2.92; P < 0.01). Treatment was generally well tolerated with the exception of one patient who had shingles complicated by sensorineural hearing loss while on anifrolumab and prednisolone > 15 mg daily. This required prolonged aciclovir for effective management. This case series highlights the potential role for anifrolumab in managing treatment-resistant CLE with particular responses observed in DLE and chilblain lupus. The need for enhanced awareness of viral infections, particularly varicella-zoster virus, needs to be considered in higher-risk patients.

Efficacy and safety of deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, in patients with active systemic lupus erythematosus: Results from a phase 2, randomized, double-blind, placebo-controlled study

Introduction: Tyrosine kinase 2 (TYK2) mediates signaling of Type I interferons and IL-23, key cytokines involved in systemic lupus erythematosus (SLE) pathogenesis. Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in multiple countries for the treatment of adults with plaque psoriasis. This analysis assessed the efficacy and safety of deucravacitinib in patients with active SLE.
 Methods: This 48-week, double-blind, phase 2 trial (NCT03252587) randomized patients 1:1:1:1 to deucravacitinib (3 mg BID, 6 mg BID, 12 mg QD) or placebo. Oral corticosteroid tapering was required from weeks 8-20; further tapering was optional from weeks 32-40. The primary endpoint was the proportion of patients achieving SLE Responder Index-4 (SRI[4]) at week 32. Key secondary endpoints at week 48 included percentage of patients achieving SRI(4) and decrease of ≥50% from baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-50), in patients with baseline CLASI ≥10. Change from baseline in CLASI Activity Score (CLASI-A) over time was also assessed.
 Results: Of 363 randomized patients, 275 (76%) completed 48 weeks of treatment. Baseline demographic and disease characteristics were balanced across treatment groups, with baseline mean CLASI-A scores ranging from 8.0 to 8.6. The primary endpoint at week 32 was met, with significantly greater proportions of patients in deucravacitinib 3 mg BID and 6 mg BID groups vs placebo achieving SRI(4) responses (placebo: 34.4%; deucravacitinib 3 mg BID: 58.2%, P=0.0006; 6 mg BID: 49.5%, P=0.021; 12 mg QD: 44.9%, P=0.078). Patients treated with deucravacitinib demonstrated improvement across all secondary endpoints compared with placebo. In patients with CLASI ≥10 at baseline, greater mean changes from baseline in CLASI-A were observed in deucravacitinib vs placebo over 48 weeks of treatment (placebo: 16.7%; deucravacitinib 3 mg BID: 69.6%, P=0.0006; 6 mg BID: 56.0%, P=0.0058; 12 mg QD: 62.1%, P=0.0009). Rates of adverse events (AEs), serious AEs, and AEs of interest were similar between deucravacitinib and placebo groups. Most common AEs with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. No deaths, major adverse cardiac events, thrombotic events, systemic opportunistic infections, or active tuberculosis occurred.
 Conclusion: Deucravacitinib demonstrated sustained, meaningful clinical efficacy in SRI(4), improvement in mucocutaneous activity as measured by CLASI-A responses, and was well tolerated in patients with active SLE up to 48 weeks.

Research in Brief

Litifilimab, a humanised monoclonal antibody against blood dendritic cell antigen 2 (BDCA2), might be an effective treatment for cutaneous lupus erythematosus, according to a phase 2 trial by Victoria Werth and colleagues. 132 participants with cutaneous lupus erythematosus, with or without systemic manifestations, were randomly assigned, stratified by Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) score and presence of discoid lupus erythematosus, to receive 50 mg (n=26), 150 mg (n=25), or 450 mg (n=48) subcutaneous litifilimab or placebo (n=33) at weeks 0, 2, 4, 8, and 12. At week 16, the least-squares mean differences in change in CLASI-A score from baseline between litifilimab and placebo were −24·3% (95% CI −43·7 to −4·9) for 50 mg litifilimab, −33·4% (−52·7 to −14·1) for 150 mg, and −28·0% (−44·6 to −11·4) for 450 mg. A best-fitting dose–response model across the three drug doses showed a significant effect of litifilimab compared with placebo. Three cases of hypersensitivity, three oral herpes infections, and one herpes zoster infection occurred in patients taking litifilimab.

Correlation of whole blood hydroxychloroquine concentration with cutaneous lupus erythematosus and factors associated with it: First multicenter, cross-sectional analysis in Malaysia.

Hydroxychloroquine (HCQ) is the first-line systemic treatment for cutaneous lupus erythematosus (CLE). Whole blood HCQ concentration (WBHCQ) was found to correlate with CLE severity among Caucasians. However, studies on Asians are scarce. We aim to explore the relationship of WBHCQ with CLE disease activity among multi-racial Malaysians and the factors associated with WBHCQ. A cross-sectional study targeting patients with CLE was conducted from 1 June till 30 November 2019. Disease activity was assessed using Cutaneous Lupus Erythematosus Disease Area and Severity Index - Activity Score (CLASI-AS). Blood was analyzed for WBHCQ concentration using a high-performance liquid chromatography technique. Statistical analysis was done using R studio version 1.2.1335. A total of 88 subjects (male:female, 4.5:1) with a median age of 41years old were recruited. The median duration CLE was 5years. The majority had acute cutaneous lupus (n=45, 51.1%). The median WBHCQ was 946.8ng/mL. Indians were found to have the highest WBHCQ (median±interquartile range [IQR], 1515.4±1494.8ng/mL). Males had a lower WBHCQ (median±IQR, 733.5±573.8ng/mL) than females (995.5±925.1ng/mL). However, no statistically significant association between race and sex with WBHCQ was demonstrable (p=0.247, p=0.066). No correlation was demonstrated between WBHCQ and CLASI-AS (r=-0.02, p=0.851). A positive correlation was found between HCQ dosage (ideal bodyweight) and WBHCQ (r=0.24, p=0.027). No other factors were found associated with WBHCQ. Indians and females were observed to have higher WBCHQ; however, no significant correlation was identified. Further study is required to confirm the finding.

Correlation of plasma and urine Wnt5A with the disease activity and cutaneous lesion severity in patients with systemic lupus erythematosus

Reliable noninvasive biomarkers are needed to accurately assess disease activity and prognosis in patients with systemic lupus erythematosus (SLE). The purpose of this study was to investigate the clinical relevance of Wnt5A with disease activity and severity with cutaneous involvement in particular in SLE patients; its concentrations in plasma and urine were examined and analyzed. In the cross-sectional study, the clinical relevance of Wnt5A protein was evaluated in both plasma and urine of SLE patients and healthy cohorts using commercial enzyme-linked immunosorbent assays (ELISA). Significantly, more abundances of Wnt5A protein were determined in both of plasmas and urines of SLE patients compared to healthy cohorts (p < 0.0001), which were even higher in active disease (AD) SLE patients relative to low disease activity (LDA) SLE patients (p < 0.0001). Meanwhile, the ROC curve analysis demonstrated that the plasma and urine Wnt5A were potential candidate biomarkers for identifying the disease activity and severity in SLE patients. The discriminant function analysis further revealed that the plasma and urine Wnt5A were separated and distinct for AD SLE patients and healthy controls. In consistence, the disease severity was correlated with the plasma and urine Wnt5A as ascertained by CLASI activity score and the prevalence of serositis in SLE patients. These results suggest that Wnt5A, as a summary measure for different inflammatory processes, could be a potential biomarker for accessing the disease activity, and a noninvasive biomarker for evaluating the disease severity in terms of cutaneous involvement in SLE patients.

Preliminary definition of flare in cutaneous lupus erythematosus using the Cutaneous Lupus Erythematosus Disease Area and Severity Index

To the Editor: “Flare” in cutaneous lupus erythematosus (CLE) is a clinically significant increase in disease activity from baseline. While quantitatively defined for systemic lupus erythematosus and used as a clinical research end point, flare has not been defined for CLE. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) has been used to define improvement in CLE, but not worsening.1 To determine the change in CLASI activity (CLASI-A) score that corresponds to a meaningful flare in disease activity, we conducted a retrospective review of our institutional review board–approved prospective CLE database at the University of Pennsylvania.

Clinical characteristics of itch in cutaneous lupus erythematosus: A prospective, multicenter, multinational, cross-sectional study.

Pruritus is an important symptom frequently accompanying various inflammatory skin conditions and some recent data indicated that it may be associated with autoimmune connective tissue diseases. The aim of this study was to assess the frequency and clinical presentation of itch in CLE. A multinational, prospective, cross-sectional study was performed to assess the prevalence, intensity and clinical characteristic of pruritus in various subtypes of CLE. A total of 153 patients with active CLE lesions were included. Their age ranged between 17 and 82 years (mean 49.8 ± 15.4 years), and 115 patients (75.2%) were women. The disease activity and damage were assessed according to the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Pruritus severity was assessed with Numeric Rating Scale (NRS) and the 12-Item Pruritus Severity Scale. Dermatology Life Quality Index and EQ-5D questionnaire were used to measure quality of life. Pruritus was present in 116 (76.8%) of patients of whom half had NRS scoring equal or above 4 points indicating moderate or severe pruritus. Most commonly itch was localized on the scalp, face (excluding ears and nose) and arms (40.5%, 36.2%, 31.9%, respectively). Sensations connected with pruritus were most frequently described as burning, tingling and like ants crawling feeling, but 31.9% patients described it as "pure itch". More than half of patients reported that pruritus was present every day, and it was most frequent during the evenings. The pruritus scoring and the CLASI activity score were significantly correlated (r = 0.42, p = 0.0001), while no correlation was found with the CLASI damage score (p = 0.16). Both the maximum and average itch intensity were correlated with systemic lupus erythematosus (SLE) activity measured with the Systemic Lupus Erythematosus Disease Activity Index. Pruritus is a common, but frequently overlooked symptom of CLE. Its intensity correlates with the activity of CLE, but not with the skin damage. In more than a half of patients it occurs on a daily basis. The correlation between the intensity of pruritus and the activity of the skin lesions and the systemic involvement indicate that pruritus could be an individual indicator of both SLE and CLE activity.

Repository Corticotropin Injection for Persistently Active Systemic Lupus Erythematosus: Results from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

IntroductionWe assessed the efficacy and safety of repository corticotropin injection (RCI; Acthar® Gel) for persistently active systemic lupus erythematosus (SLE) despite use of moderate-dose glucocorticoids.MethodsThis multicenter, double-blind, randomized, placebo-controlled study enrolled patients ≥ 18 years with active SLE and moderate to severe rash and/or arthritis despite stable glucocorticoid doses (7.5–30 mg/day prednisone equivalent) and antimalarials for ≥ 4 weeks and/or immunosuppressants for ≥ 8 weeks before screening. Stable glucocorticoid doses were required through week 16 with optional taper from weeks 16 to 24. Patients were randomized (1:1) to 80 U RCI subcutaneously or placebo every other day to week 4, then twice weekly to week 24. Endpoints included the proportion of SLE Responder Index (SRI)-4 responders at week 16; changes from baseline to week 16 in 28 Swollen Joint Count/Tender Joint Count (28 SJC/TJC) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-Activity score; and changes from baseline to week 24 in inflammatory cytokines. Safety was assessed by adverse events.ResultsIn the modified intention-to-treat population (RCI, n = 84; placebo, n = 85), the proportion of SRI-4 responders at week 16 was not significantly different between groups (RCI, 47.6%; placebo, 43.5%; OR [95% CI] 1.2 [0.6 to 2.2]; p = 0.5762). RCI treatment resulted in a reduction from baseline to week 16 in 28 SJC/TJC and CLASI-Activity score and from baseline to week 8 in B-cell activating factor cytokine. Post hoc analyses demonstrated a greater proportion of BILAG-based Combined Lupus Assessment responders for RCI than placebo at weeks 4, 12, and 20 and greater SRI-4 response in RCI-treated patients with baseline SLE Disease Activity Index-2000 ≥ 10 and CLASI-Activity ≥ 11. No new safety signals were identified.ConclusionsDespite failure to achieve the primary endpoint, these results support the utility of RCI for treating persistently active SLE.Trial RegistrationClinicalTrials.gov identifier NCT02953821.Electronic Supplementary MaterialThe online version of this article (10.1007/s40744-020-00236-1) contains supplementary material, which is available to authorized users.

Serum galectin-3 and galectin-3 binding protein levels in systemic lupus erythematosus and cutaneous lupus erythematosus.

IntroductionThe roles of galectin-3 (Gal-3) and galectin-3 binding protein (G3BP) in systemic lupus erythematosus (SLE) are of ongoing interest, but the data are insufficient due to highly limited available studies. There are no data on cutaneous lupus erythematosus (CLE).AimTo assess serum Gal-3 and G3BP concentrations in SLE patients with and without LE-specific skin lesions, CLE patients and to correlate levels of proteins with clinical and laboratory parameters.Material and methodsThe study included 71 SLE patients with and without LE-specific skin lesions, 23 CLE patients and 40 controls. Gal-3 and G3BP were measured by specific enzyme-linked immunosorbent assays (ELISA).ResultsSerum Gal-3 and G3BP concentrations were significantly higher in SLE with and without LE-specific lesions compared to controls, but without differences between SLE groups. Gal-3 and G3BP levels were also elevated in CLE compared to controls (p = 0.001, p = 0.005; respectively). There was a positive correlation between G3BP level and CLASI activity score both in CLE (r = 0.55, p = 0.006) and in SLE patients with LE-specific lesions (r = 0.36, p = 0.02). G3BP and Gal-3 levels did not differ in SLE with LE-specific lesions and CLE. There was a positive correlation between serum G3BP level and the SLEDAI score in SLE patients (r = 0.26, p = 0.03).ConclusionsOur findings indicate that serum G3BP and Gal-3 are elevated in CLE. Additionally, G3BP might be associated with the extent of skin lesions. There are no differences between G3BP and Gal-3 concentrations in SLE with and without LE-specific skin lesions.

Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial

Summary Background Type I interferons are involved in systemic lupus erythematosus (SLE) pathogenesis. In a phase 2 trial, anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1, suppressed interferon gene signatures and substantially reduced SLE disease activity. Here, we sought to confirm the efficacy of anifrolumab versus placebo in a phase 3 trial of adult patients with SLE and moderate-to-severe disease activity despite standard-of-care treatment. Methods TULIP-1 was a double-blind, randomised, controlled, phase 3 trial done at 123 sites in 18 countries. Included patients were aged 18–70 years, with moderate-to-severe SLE, and ongoing stable treatment with either prednisone or equivalent, an antimalarial, azathioprine, mizoribine, mycophenolate mofetil or mycophenolic acid, or methotrexate. Patients were randomly assigned (2:1:2) to receive placebo, anifrolumab 150 mg, or anifrolumab 300 mg intravenously every 4 weeks for 48 weeks. Stable standard-of-care treatment continued except for mandatory attempts at oral corticosteroid tapering for patients receiving prednisone or equivalent of 10 mg/day or more at baseline. The primary outcome was the difference between the proportion of patients who achieved an SLE responder index-4 (SRI-4) response at week 52 with anifrolumab 300 mg versus with placebo. Key secondary outcomes were the difference between the anifrolumab 300 mg group and the placebo group in: proportion of patients in the interferon gene signature test—high subgroup who achieved SRI-4 at week 52; proportion of patients on 10 mg/day or more corticosteroids at baseline who achieved a sustained dose reduction to 7·5 mg/day or less from week 40 to 52; proportion of patients with a cutaneous lupus erythematosus disease area and severity index (CLASI) activity score of 10 or higher at baseline who achieved a 50% or more reduction in CLASI score by week 12; proportion of patients who achieved SRI-4 at week 24; and annualised flare rate through week 52. Other measures of disease activity were also assessed at week 52, including the British Isles Lupus Assessment Group-based composite lupus assessment (BICLA). Safety was also assessed. Efficacy and safety analyses were done in the population of patients who received at least one dose of study drug. This trial was registered at ClinicalTrials.gov (NCT02446912). Findings Between June 9, 2015, and June 16, 2017, 457 patients were randomly assigned to the anifrolumab 300 mg group (n=180), the anifrolumab 150 mg group (n=93), or the placebo group (n=184). The proportion of patients at week 52 with an SRI-4 response was similar between anifrolumab 300 mg (65 [36%] of 180) and placebo (74 [40%] of 184; difference −4·2 [95% CI −14·2 to 5·8], p=0·41). Similarly, proportions of patients with an SRI-4 response at week 24, and at week 52 in patients in the interferon gene signature test—high subgroup, did not differ between the anifrolumab and placebo groups. In patients with baseline oral corticosteroids of at least 10 mg/day, sustained dose reduction to 7·5 mg/day or less was achieved by 42 (41%) of 103 patients in the anifrolumab 300 mg group and 33 (32%) of 102 patients in the placebo group (difference 8·9 [95% CI −4·1 to 21·9]). In patients with CLASI activity score of at least 10 at baseline, at least 50% reduction by week 12 was achieved by 24 (42%) of 58 patients in the anifrolumab 300 mg group and 14 (25%) of 54 in the placebo group (difference 17·0 [95% CI −0·3 to 34·3]). Annualised flare rates were 0·60 for anifrolumab and 0·72 for placebo (rate ratio 0·83 [95% CI 0·60 to 1·14]). BICLA response was achieved by 67 (37%) of 180 patients receiving anifrolumab 300 mg versus 49 (27%) of 184 receiving placebo (difference 10·1 [95% CI 0·6 to 19·7]). Anifrolumab's safety profile was similar to that observed in phase 2, with similar proportions of patients having a serious adverse event between groups (25 [14%] of 180 for anifrolumab 300 mg, ten [11%] of 93 for anifrolumab 150 mg, and 30 [16%] of 184 for placebo). Interpretation The primary endpoint was not reached. However, several secondary endpoints, including reduction in oral corticosteroid dose, CLASI responses, and BICLA responses, suggest clinical benefit of anifrolumab compared with placebo. Conclusive evidence for the efficacy of anifrolumab awaits further phase 3 trial data. Despite the inherent limitations of a 1-year phase 3 study, such as incomplete knowledge of applicability to the general population and scarce detection of rare safety signals, in addition to complications from prespecified restricted medication rules, our results suggest that anifrolumab might have the potential to provide a treatment option for patients who have active SLE while receiving standard therapy. Funding AstraZeneca.

Validation of the Cutaneous Lupus Erythematosus Disease Area and Severity Index and pSkindex27 for use in childhood-onset systemic lupus erythematosus

ObjectiveTo determine the measurement properties of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the paediatric adaptation of the Skindex29 (pSkindex27) when used in childhood-onset SLE (cSLE).MethodsPatients...

Natural history of disease activity and damage in patients with cutaneous lupus erythematosus

Long-term studies characterizing disease course of cutaneous lupus erythematosus (CLE) patients on standard-of-care treatments are lacking. We characterized and compared disease course of CLE patients using Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). In total, 83 CLE patients with CLASI scores collected from ≥3 study visits within 2years had disease activity and damage trends calculated by average change scores (ACS). Trends were classified as improved (ACS ≤-3), worsened (ACS ≥3), or stable (-3<ACS<3). Linear regression models compared CLASI trends between groups. Most patients (72.73%) with initial CLASI activity (CLASI-A) scores >9 (N=33) had improved disease activity versus 14.00% of those with initial CLASI-A scores ≤9 (N=50). Linear regression analyses showed significant improvement in CLASI-A scores in patients of minority races (P<.05), with baseline CLASI-A scores >9 (P<.0001), baseline CLASI damage (CLASI-D) scores ≥10 (P=.0001), and CLE disease duration ≤1year (P=.01). Of 28 patients with baseline CLASI-D scores ≥10, 35.71% had improvements in damage, while 5.26% of patients with initial CLASI-D scores of 5-9 (N=19) and 0% with initial CLASI-D scores <5 (N=36) (P=.0005) had improvements. Limitations include small sample size. Baseline CLASI-A score >9, minority race, and short disease duration predict CLE diseaseactivity improvement. A baseline CLASI-D score ≥10 is associated with disease damage improvement.

Cytokines and Effector/Regulatory Cells Characterization in the Physiopathology of Cutaneous Lupus Erythematous: A Cross-Sectional Study.

We compared the presence of diverse cytokines and regulatory T and B cells in skin biopsies of discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). We included 19 patients with DLE, 13 with SCLE, 8 healthy controls, and 5 patients with hypertrophic scars. We assessed the CLASI activity score. To determine IL-22-producing cells and the subpopulation of CD4+/IL-17A+-, CD4+/IL-4+-, and CD4+/IFN-γ +-expressing T cells, CD123+/IDO+ pDCs, CD25+/Foxp3+ Tregs, and CD20+/IL-10+-producing B cells, an immunostaining procedure was performed. Also intracellular IL-22, IL-17, IL-4, IFN-γ, and Foxp3 in CD4 T cells, IL-10 in B cells, and IDO in pDCs were analyzed by flow cytometry in peripheral blood. The main cellular participation in both lupus groups was IL-17- and IL-22-producing cell responses both at skin and at peripheral blood but prevailed in DLE. The CLASI activity scores negatively correlated with Th22 subpopulation and positively correlated with CD25+/Foxp3+ Treg cells. In conclusion a proinflammatory and regulatory imbalance coexists in cutaneous lupus, both responses being more intense in DLE.

Influence of smoking on disease severity and antimalarial therapy in cutaneous lupus erythematosus: analysis of 1002 patients from the EUSCLE database

In recent years it has been controversially discussed in the literature if smoking is associated with the activity of cutaneous lupus erythematosus (CLE) and the efficacy of antimalarial agents. To investigate the influence of smoking on disease severity and antimalarial treatment in patients with CLE using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). A total of 1002 patients (768 female, 234 male) with different CLE subtypes were included in this cross-sectional study, which was performed in 14 different countries. Smoking behaviour was assessed by the EUSCLE Core Set Questionnaire in 838 patients and statistically analysed using an SPSS database. The results were correlated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the efficacy of antimalarial treatment. A high percentage (87·2%) of the 499 patients with CLE, who have ever smoked, had already smoked at the date of their first diagnosis. Patients with intermittent CLE have ever smoked significantly more often than patients with subacute CLE (P < 0·05) and chronic CLE (P < 0·05). The total CLASI activity and damage score of patients with CLE was 6·6 ± 7·1 and 2·6 ± 4·3, respectively, and was higher in patients who have ever smoked than in nonsmokers. Antimalarial treatment was successful in 84·3% of cases, with a significantly higher efficacy in nonsmokers than in patients with CLE who have ever smoked (P < 0·05). This analysis of a multicentre study population of 838 patients with CLE assessed by the EUSCLE Core Set Questionnaire confirms that smoking negatively influences CLE disease severity and the efficacy of antimalarial treatment.

Response to hydroxychloroquine in Japanese patients with lupus-related skin disease using the cutaneous lupus erythematosus disease area and severity index (CLASI)

Background Hydroxychloroquine (HCQ) is not available in Japan. To design a clinical trial of HCQ, we evaluated the response to HCQ in Japanese patients with lupus-related skin disease using the cutaneous lupus erythematosus disease area and severity index (CLASI).Methods Twenty-seven patients with lupus-related skin disease who started HCQ at four hospitals were included. Patients were categorized into responders by the CLASI response criteria. The points and the rate of improvement in the CLASI activity score after 16 weeks of treatment were analyzed, focusing on six parameters: systemic lupus erythematosus (SLE), skin manifestations, disease duration, prednisolone, smoking, and severity.Results Twenty-seven patients, including 17 with SLE (6 with SLE/Sjögren’s syndrome), were analyzed retrospectively. Twenty-three patients (85 %) were categorized as responders. The mean CLASI activity score improved from 10.1 to 4.5 (p < 0.0001). The improvement rate did not differ in these parameters except for that of annular erythema (81.6 versus 34.3 %, p = 0.036). On multivariate analysis, the baseline CLASI activity score (CLASI ≥ 9) correlated with the greatest decrease in CLASI activity score (F = 69.7, p < 0.0001).Conclusions CLASI is a reliable indicator to evaluate the efficacy of the drug, and HCQ is an effective treatment for Japanese patients with lupus-related skin disease.

Response to hydroxychloroquine in Japanese patients with lupus-related skin disease using the cutaneous lupus erythematosus disease area and severity index (CLASI)

Hydroxychloroquine (HCQ) is not available in Japan. To design a clinical trial of HCQ, we evaluated the response to HCQ in Japanese patients with lupus-related skin disease using the cutaneous lupus erythematosus disease area and severity index (CLASI). Twenty-seven patients with lupus-related skin disease who started HCQ at four hospitals were included. Patients were categorized into responders by the CLASI response criteria. The points and the rate of improvement in the CLASI activity score after 16 weeks of treatment were analyzed, focusing on six parameters: systemic lupus erythematosus (SLE), skin manifestations, disease duration, prednisolone, smoking, and severity. Twenty-seven patients, including 17 with SLE (6 with SLE/Sjögren's syndrome), were analyzed retrospectively. Twenty-three patients (85 %) were categorized as responders. The mean CLASI activity score improved from 10.1 to 4.5 (p < 0.0001). The improvement rate did not differ in these parameters except for that of annular erythema (81.6 versus 34.3 %, p = 0.036). On multivariate analysis, the baseline CLASI activity score (CLASI ≥9) correlated with the greatest decrease in CLASI activity score (F = 69.7, p < 0.0001). CLASI is a reliable indicator to evaluate the efficacy of the drug, and HCQ is an effective treatment for Japanese patients with lupus-related skin disease.

Response to hydroxychloroquine in Japanese patients with systemic lupus erythematosus using the cutaneous lupus erythematosus disease area and severity index (CLASI)

We evaluated the cutaneous lupus erythematosus disease area and severity index (CLASI) in Japanese patients with systemic lupus erythematosus (SLE) in order to design a clinical trial of hydroxychloroquine (HCQ) in Japan. Our prospective cohort study consisted of seven SLE patients with active skin disease who started HCQ at Tokyo Metropolitan Tama Medical Center. The therapeutic responses were assessed at 4 months. Patients were categorized as responders (improved) or non-responders (unchanged or worsened) using the criteria of a 4-point or 20% decrease in the CLASI activity score. We also assessed joint pain determined by patient visual analog scale (VAS), malaise (VAS), patient global assessment of SLE (VAS), and constitutional and musculoskeletal symptoms according to the British Isles Lupus Assessment Group (BILAG) disease activity index. Six patients (86%) were categorized as responders. The median (range) CLASI activity score of all patients at assessment had changed from 8.0 (2–22) to 4 (2–10). All five patients with joint pain and all five patients with malaise showed improvement in patient VAS but the BILAG findings failed to capture these improvements. In conclusion, the cutaneous aspects of SLE can be measured by the CLASI. The CLASI activity score may be a reasonable primary endpoint when performing a clinical trial of HCQ.

The study of Cutaneous Lupus Erythematosus Disease Area and Severity Index in Indian patients with systemic lupus erythematosus

The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a newly described tool used to assess the activity of and damage caused by cutaneous lupus erythematosus (CLE). There is a paucity of data on CLASI from the Indian subcontinent. We sought to determine the applicability of CLASI in specific lesions of CLE in patients with systemic lupus erythematosus (SLE) attending a tertiary care hospital in India. In this prospective, cross-sectional study, 93 patients of SLE with cutaneous lesions were recruited. CLASI activity and damage scores of lupus erythematosus (LE)-specific skin lesions were done in 75 patients with SLE. The mean CLASI activity score was 15.4 ± 9.4 (range 0-39) and the mean damage score was 6.87 ± 7.75 (range 0-30). Higher mean CLASI activity scores were seen in patients with a combination of acute, subacute and chronic CLE and in those with widespread lesions. Patients with longstanding disease and long duration of skin lesions had higher damage scores. This study shows that CLASI is an effective tool to assess cutaneous activity of LE-specific lesions, and the damage caused by them, in Indian patients.

Response to hydroxychloroquine in Japanese patients with systemic lupus erythematosus using the cutaneous lupus erythematosus disease area and severity index (CLASI)

We evaluated the cutaneous lupus erythematosus disease area and severity index (CLASI) in Japanese patients with systemic lupus erythematosus (SLE) in order to design a clinical trial of hydroxychloroquine (HCQ) in Japan. Our prospective cohort study consisted of seven SLE patients with active skin disease who started HCQ at Tokyo Metropolitan Tama Medical Center. The therapeutic responses were assessed at 4 months. Patients were categorized as responders (improved) or non-responders (unchanged or worsened) using the criteria of a 4-point or 20% decrease in the CLASI activity score. We also assessed joint pain determined by patient visual analog scale (VAS), malaise (VAS), patient global assessment of SLE (VAS), and constitutional and musculoskeletal symptoms according to the British Isles Lupus Assessment Group (BILAG) disease activity index. Six patients (86%) were categorized as responders. The median (range) CLASI activity score of all patients at assessment had changed from 8.0 (2-22) to 4 (2-10). All five patients with joint pain and all five patients with malaise showed improvement in patient VAS but the BILAG findings failed to capture these improvements. In conclusion, the cutaneous aspects of SLE can be measured by the CLASI. The CLASI activity score may be a reasonable primary endpoint when performing a clinical trial of HCQ.