Cutaneous Lupus Erythematosus Disease Area And Severity Index Research Articles

Efficient topical treatments of cutaneous lupus erythematosus: A systematic review and network meta-analysis.

Although cutaneous lupus erythematosus (CLE) has been treated with topical agents, there was no high-quality evidence of which agents were more effective, and which clinical scores were more suitable. On December 22nd, 2023, a search was conducted across five databases to identify randomized controlled trials (RCTs). Two authors independently screened the titles and abstracts of articles based on predetermined criteria. Selected articles were then assessed for inclusion in a blinded manner, with any disagreements resolved through consensus. Data were abstracted in duplicate, and a random-effects model was utilized for network meta-analysis. The certainty of the evidence was evaluated according to PRISMA guidelines, using the Grading of Recommendations Assessment, Development and Evaluation approach. The analysis was finalized in January 2024, with the primary outcome focused on the change in cutaneous lupus erythematosus disease area and severity index (CLASI) from baseline. Seven RCTs involving 231 participants were analyzed. The network meta-analysis (NMA) revealed that 4% nicotinamide demonstrated the highest probability of achieving the intended outcomes, with a mean difference (MD) of 3.10 and a 95% confidence interval (CI) of 1.99-4.21. Additionally, 0.05% clobetasol, 2% nicotinamide, and 0.1% tacrolimus also exhibited statistically significant differences, with MDs of 2.30 and 95% CIs of 0.73-3.88; 2.30 and 0.97-3.63; and 1.30 and 0.03-2.57, respectively. As data with a high level of evidence, NMAs demonstrated that 4% nicotinamide, 0.05% clobetasol, 2% nicotinamide, and 0.1% tacrolimus are statistically significant topical agents. CLASI may be an appropriate outcome to evaluate drug efficacy in CLE.

Anifrolumab for systemic lupus erythematosus with multi-refractory skin disease: A case series of 18 patients.

Skin involvement is common in systemic lupus erythematosus (SLE), but may be resistant to conventional treatment. We sought to evaluate the efficacy of anifrolumab (ANI) in refractory cutaneous manifestations of SLE. Case series of patients with refractory cutaneous SLE from three Rheumatology Departments in Greece. Outcome measures were improvement in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), physician global assessment (PGA) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Clinically relevant improvement in skin was defined as decrease ≥50% (CLASI50) from baseline values. Eighteen patients received ANI; all had active skin involvement at baseline. Mean (SD) SLEDAI and PGA at ANI initiation were 7.4 (2.7) and 1.4 (0.5), respectively, with a mean prednisone dose 4.9 (4.5) mg/day. Mean CLASI (Activity/Damage) at baseline was 13.9 (9.7)/2.9 (4.6). Patients were refractory to a mean 6.3 (1.5) immunomodulatory agents (including hydroxychloroquine and glucocorticoids) before the initiation of ANI. After a mean 8.5 (4.6) months, 89% (n = 16/18) of patients demonstrated significant improvement in general lupus and cutaneous disease activity, and glucocorticoid tapering. Mean SLEDAI and mean CLASI at last visit were 3.4 (1.9) and 2.1 (2.4)/1.4 (2.2), respectively, and mean daily prednisone dose decreased to 2.4 (2.2). Of note, in this group of highly refractory patients CLASI50 was achieved in 16/18 (89%) patients. One patient discontinued ANI after 4 infusions due to a varicella-zoster virus infection and one patient, who initially responded to treatment with ANI, experienced a skin flare due to temporary discontinuation due to Covid 19 infection. DORIS remission and LLDAS were attained in two (11.1%) and eleven (61.1%) patients, respectively. Anifrolumab is highly effective in various skin manifestations of SLE, even after prior failure to multiple treatments.

Mezagitamab in systemic lupus erythematosus: clinical and mechanistic findings of CD38 inhibition in an autoimmune disease

ObjectiveTo evaluate safety and mechanism of action of mezagitamab (TAK-079), an anti-CD38 monoclonal antibody, in patients with moderate to severe systemic lupus erythematosus (SLE).MethodsA phase 1b double-blind, placebo-controlled, multicentre study...

Evaluation of RNase therapy in systemic lupus erythematosus: a randomised phase 2a clinical trial of RSLV-132

BackgroundCirculating, extracellular RNA is the primary trigger of type I interferon in systemic lupus erythematosus (SLE), and interferon is known to play a central pathogenic role in the disease. RSLV-132...

Dermoscopic Characteristics of Cutaneous Lupus Erythematosus According to Subtype, Lesion Location, Lesion Duration, and CLASI Score.

Dermoscopic findings are used to diagnose and evaluate disease activity in patients with cutaneous lupus erythematosus (CLE). This study aimed to characterize the dermoscopic features of discoid LE (DLE) and LE tumidus (LET) by lesion duration and CLE Disease Area and Severity Index (CLASI) scores and to examine the dermoscopic findings of lesions in different locations in DLE patients. Dermoscopic findings (follicular features, perifollicular surface, interfollicular features, and vessel pattern) were assessed and lesion duration (≤12 and >12 months) and CLASI scores (grouped as mild or moderate) were calculated. DLE lesion locations were categorized as, non-scalp, scalp and lip. Forty-eight dermoscopic images from 35 DLE and 4 LET patients were analyzed. The most common dermoscopic findings in non-scalp DLE were follicular keratotic plugs (82.8%) and white scales (69%). In scalp DLE (n=9), the most common findings were absent follicular openings (77.8%), white structureless areas (77.8%), and perifollicular scaling (66.7%). All LET patients had pink-white background and linear vessels. Follicular plugs, peripheral pigmentation, and polymorphous vessels were lower in patients with mild CLASI activity than moderate activity (P = 0.036, 0.039, and 0.019, respectively). Fibrotic white dots, honeycomb pigment pattern, and blue-gray dots/globules were lower in those with mild CLASI damage scores than moderate damage (P = 0.010, 0.010, and 0.020, respectively). Peripheral pigmentation was more common in patients with lesion duration ≤12 months, while blue-gray dots/globules were more common with lesion durations >12 months. Certain dermoscopic features may facilitate the differential diagnosis of DLE and LET.

Dermatoscopic Patterns in Indian Patients with Discoid Lupus Erythematosus and Correlation to the duration of Disease and Cutaneous Lupus Erythematosus Disease Area and Severity Index

Abstract Dermatoscopic patterns of discoid lupus erythematosus (DLE) have recently been described in the literature. A temporal correlation of certain dermatoscopic features has also been proposed. There is sparse literature on dermatoscopic features seen in Indian/Asian patients with DLE and the correlation of these features with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score. A few of the patients of DLE coming to the dermatology outpatient department of our center in South India were evaluated by dermoscopy. Demographic details, duration of illness, location of plaques, and the CLASI scores were collected. A total of 26 plaques from 12 patients were evaluated by dermoscopy. Hair follicle effacement (n = 20) was the most common feature, followed by patchy pigmentation (n = 18), telangiectasia (n = 13), perifollicular pigmentation (n = 13), and perifollicular scaling (n = 10). There was a statistically significant difference in disease activity (CLASI) in patients with perifollicular scale and telangiectasia compared to patients without the above features. There was a significant difference in the duration of disease among patients with and without follicular red dots.

Anifrolumab for systemic lupus erythematosus: A clinical study of Japanese patients in Kanazawa University Hospital.

We investigated the effectiveness of anifrolumab in treating systemic lupus erythematosus (SLE). We treated seven patients with SLE (age range, 31-68 years; median age, 48 years); one male and six females) with anifrolumab between January 2022 and February 2023 at Kanazawa University Hospital. The period between the onset and initiation of anifrolumab treatment was 60-276 months (median, 234 months), and the SLE disease activity index-2000 (SLEDAI-2 K) before treatment was 2-6 months (median, 3 months). Five patients experienced skin rashes or alopecia, and their cutaneous lupus erythematosus disease area and severity index (CLASI) activity scores were 2-9 (median, 4). Six patients continued treatment with anifrolumab, but one did not because of uncontrolled pleurisy and pericarditis. Our results demonstrated that anifrolumab was effective in treating SLE and reducing both SLEDAI-2 K and CLASI activity scores (median decrease, 100%). Furthermore, the oral corticosteroid dosage could be reduced in all patients who were able to continue treatment. Our findings indicate that anifrolumab is effective not only for reducing disease and eruption activities, but also facilitates tapering of corticosteroid dosage.

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.

Assessment of cutaneous disease activity in early lupus and its correlation with quality of life: a cross-sectional study.

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with varied dermatological manifestations that are almost universal. Overall, lupus disease has a major effect on the quality of life in these patients. We assessed the extent of cutaneous disease in early lupus and correlated it with the SLE quality-of-life (SLEQoL) index and disease activity measures. Patients diagnosed as SLE with the skin involved were recruited at the first presentation and were assessed for cutaneous and systemic disease activity using the cutaneous lupus erythematosus disease area and severity index (CLASI) and the Mexican-SLE disease activity index (Mex-SLEDAI), respectively. Quality of life was assessed with the SLEQoL tool while systemic damage was captured by the SLICC damage index. Fifty-two patients with SLE who had cutaneous involvement were enrolled (40, 76.9% females) with a median disease duration of 1month (1-3.7). The median age was 27.5years (IQR: 20-41). Median Mex-SLEDAI and SLICC damage index were 8(IQR: 4.5-11) and 0 (0-1), respectively. The median CLASI activity and damage scores were 3 (1-5) and 1 (0-1), respectively. Overall, there was no correlation between SLEQoL with CLASI or CLASI damage. Only the self-image domain of SLEQoL correlated with total CLASI (ρ = 0.32; p = 0.01) and CLASI-D (ρ = 0.35; p = 0.02). There was a weak correlation of CLASI with the Mexican-SLEDAI score (ρ = 0.30; p = 0.03) but not with the SLICC damage index. In this cohort of early lupus, cutaneous disease activity in lupus had a weak correlation with systemic disease. Cutaneous features did not appear to influence the quality of life except in the self-image domain.

Rapid efficacy of anifrolumab across multiple subtypes of recalcitrant cutaneous lupus erythematosus parallels changes in discrete subsets of blood transcriptomic and cellular biomarkers.

Observations with rituximab suggest B-cell independent mechanisms of cutaneous lupus erythematosus (CLE) in systemic lupus erythematosus (SLE), especially discoid lupus erythematosus (DLE). Type-I interferon receptor blockade with anifrolumab shows efficacy in SLE, but efficacy for cutaneous disease of specific morphologies has not been studied. Interferon has pleotropic immune effects and it is unknown which of these are critical to therapeutic response. We evaluated clinical efficacy and quality-of-life impact of type-I interferon-blockade in: (i) rituximab-refractory CLE; (ii) DLE and other morphologies and (iii) transcriptomic and flow cytometric biomarkers. We conducted a prospective single-centre study of anifrolumab in refractory mucocutaneous SLE. CLE Disease Area and Severity Index (CLASI) activity score, health-related quality of life, 96-probe TaqMan® gene expression analysis capturing key SLE blood transcriptome signatures, and eight-colour flow cytometry were undertaken at baseline, 1, 3 and 6 months. Seven patients [DLE (n = 5), chilblain lupus erythematosus (n = 1), subacute CLE (n = 1)] were evaluated. The median number of prior therapies was six (range 3-15), including rituximab in six of seven patients. Median CLASI-A showed rapid and sustained improvement from 17 at baseline to 6 (P = 0.016) at 1 month and 0 (P < 0.001) by 3 months. The median percentage reduction in CLASI-A at 3 months was 60%. Significant improvements were observed in Dermatology Life Quality Index scores (P < 0.001), EuroQol 5D visual analogue scale (P = 0.002) and LupusQoL fatigue, image and planning domains (P ≤ 0.05). One patient discontinued treatment owing to severe herpes zoster. Clinical responses paralleled discrete suppression of interferon-stimulated genes (ISGs) from SLE blood transcriptome module M1.2 with more varied downregulation in other interferon modules. Myeloid and inflammation-annotated genes remained upregulated throughout treatment. Intermediate monocytes (CD14++CD16+) reduced to normal levels during therapy (P = 0.014), while other flow subsets showed no substantive changes. These data indicate rapid efficacy of anifrolumab in DLE and rituximab-resistant CLE. Response is associated with suppression of a subset of ISGs and decline in intermediate monocytes. Suppression of all ISGs or the wider SLE blood transcriptome is not required for response.

Advancements in the Treatment of Cutaneous Lupus Erythematosus and Dermatomyositis: A Review of the Literature.

BackgroundCutaneous lupus erythematosus (CLE) and dermatomyositis (DM) are autoimmune diseases that present with a wide variety of cutaneous manifestations. In both cases, first-line therapy includes topical corticosteroids. Patients may present with more widespread disease requiring systemic treatments, including corticosteroids, traditional immunosuppressants, or antimalarials. Due to their complex nature, both CLE and DM remain difficult to treat and continue to cause significant distress to patients.ObjectiveTo summarize the most recent literature on the safety and efficacy of novel treatment modalities for CLE and DM.MethodsA literature search was conducted on PubMed using search terms “(dermatomyositis) AND (treatment)” and “(cutaneous lupus) AND (treatment)”. Additional search terms included specific names of biologic agents, phosphodiesterase inhibitors (apremilast), and JAK inhibitors.ResultsJAK inhibitors, PDE-4 inhibitors, and biologics have shown promise in reducing cutaneous symptoms of both CLE and DM, including reduction in SLE Disease Activity Index 2000 (SLEDAI-2K), Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), British Isles Lupus Assessment Group (BILAG), Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), and Disease Activity Score (DAS).ConclusionWhile there have been recent advancements in the treatment for CLE and DM, further research and clinical trials are required to better elucidate which therapy is best for individual patients.

Clinicohistological and immunopathological features of patients with cutaneous lupus erythematosus at tertiary dermatology centre in Malaysia

Cutaneous lupus erythematosus (CLE) is a chronic, autoimmune skin disease with a wide spectrum of clinical presentations in different populations. To study the clinicohistological and immunological features of CLE in a multiethnic population and to identify the predictive factors of disease severity based on the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). This was a cross-sectional study of CLE conducted from March 2019 to February 2020. In total, 111 patients were recruited with a female/male ratio of 4.9 : 1. Acute CLE contributed 47.7%, followed by chronic CLE at 46.9% and subacute CLE at 5.4%. A large majority (84%) of patients had systemic lupus erythematosus. Of patients with chronic CLE, about 67.3% developed systemic involvement. Antinuclear antibody (ANA) was detected in 90.0%. Skin biopsy was taken from 42 patients and showed perivascular lymphocytic infiltration (95.2%), epidermal atrophy (47.6%) and hydropic degeneration of the basal layer (47.6%). Immunoglobulin deposition at the dermoepidermal junction was seen in > 40% of patients, predominantly in a granular pattern. Mean CLASI Total was 6.44 ± 7.70, while CLASI Activity (CLASI-A) was 2.75 ± 4.10 and CLASI Damage (CLASI-D) was 3.71 ± 4.76. Involved body surface area (BSA) was found to be an independent predictive factor for CLASI-A (OR = 1.34, P < 0.02). For CLASI-D, positive predictive factors were involved BSA (OR = 4.14, P < 0.001), discoid lupus erythematosus subtype (OR = 13.10, P = 0.001), cutaneous vascular disease (OR = 26.59; P = 0.014), scalp involvement (OR = 8.7, P < 0.01) and hypocomplementaemia (OR = 5.71, P < 0.5). Mean Dermatology Life Quality Index was 5.91 ± 5.34 and correlated significantly with disease severity. We observed a high percentage of patients with CLE with systemic manifestations and positive ANA result. More aggressive treatment of patients with positive predictive factors for severe disease combined with significant clinical activity may be warranted.

Iberdomide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled, ascending-dose, phase 2a study

ObjectiveTo evaluate safety, pharmacokinetics, pharmacodynamics and efficacy of iberdomide in patients with SLE. Iberdomide is a high-affinity cereblon ligand that targets the hematopoietic transcription factors Ikaros and Aiolos for proteasomal...

Clinico-Pathological Profile of Cutaneous Lupus Erythematosus Patients: A Report from A Tertiary Care Center of Chattogram

Background : Nearly all epidemiologic studies have involved patients with Systemic Lupus Erythematosus (SLE). Few authors have investigated the characteristics of patients with Cutaneous Lupus Erythematosus (CLE). We aim to describe the epidemiologic, clinical, and immunologic characteristics of a series of patients diagnosed with CLE.&#x0D; Materials and methods : This is a descriptive retrospective cross-sectional study carried out using the register records of total 218 patients attending the ‘Lupus Clinic’ in Chittagong Medical College Hospital during the period 2010 and 2020. The disease activity and damage of CLE were assessed according to the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI).&#x0D; Results : There were 187 females (86%) and 31 males (14%) with the female: male ratio being 6.1:1. The mean age was 28 ± 10.06 (mean ± SD) ranging between 11 and 65 years. The Chronic Cutaneous Lupus Erythematosus (CCLE) patients accounted 154 (71%) followed by Acute Cutaneous Lupus Erythematosus (ACLE) 46 (21%) and Subacute Cutaneous Lupus Erythematosus (SCLE) 18 (8%). On the basis of CLASI score, 91 (42%) patients were in mild form, 85 (39%) in moderate form and 42 (19%) in severe state. In LE specific skin lesions, common manifestation was photosensitivity 198 (91%) followed by discoid rash 154 (71%) and maculo-papular lupus rash 55 (25%). Oral ulcer was seen in 49 (22%) patients and malar rash in 46 (21%) patients. Other observed LE specific skin manifestations were papulo squamous rash 11 (5%), Toxic epidermal necrolysis like lesions 7 (3%) and lichenoid lesions 6 (3%). Among LE nonspecific skin lesions, common manifestation was nonscarring alopecia 123 (56%) followed by Raynaud’s phenomenon 17 (8%) livedo reticularis 17 (8%) Vasculitis 15 (7%) Periungual telangiectasia 7 (3%) erythema multiforme 6 (3%) and leg Ulcer 5 (2%). Antinuclear Antibody (ANA) 132 (61%) was the most common autoantibody followed by anti-ds DNA 91 (42%) anti-Sm antibody 2 (1%) anti-phospholipid antibodies 9 (4%) and anti-RNP 3 (1%). Hematological manifestations were seen in 161 (73.85%) where erythrocyte sedimentation rate was the most common hematological abnormality 161(73.85%) followed by lymphopenia 126 (57.80%) leucopenia 113 (51.80%) thrombocytopenia 107 (49.10%) anemia 92 (42%) monocytopenia 37 (16.97%). Conclusions: CCLE was the most common subtypes of CLE. Patients with different subtypes of CLE have distinct clinical and pathological characteristics. The onset or concurrence of SLE mandates the involvement of other disciplines depending on organ involvement. In the absence of consensus on a definition that makes it possible to differentiate cutaneous forms of LE from SLE, the dermatologist’s role in the correct diagnosis and classification of such patients is fundamental.&#x0D; Chatt Maa Shi Hosp Med Coll J; Vol.20 (2); July 2021; Page 79-84

British Association of Dermatologists guidelines for the management of people with cutaneous lupus erythematosus 2021.

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of cutaneous lupus erythematosus (CLE) in the presence or absence of systemic lupus erythematosus (SLE) in adults, young people and children. The document aims to: offer an appraisal of all relevant literature up to December 2020, focusing on any key developments address important, practical clinical questions relating to the primary guideline objective. provide guideline recommendations and if appropriate research recommendations.

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.

Efficacy of hydroxychloroquine for treating annular erythema associated with Sjögren's syndrome.

Annular erythema is one of the cutaneous manifestations of Sjögren's syndrome (SS). Topical corticosteroids and tacrolimus, and oral corticosteroids, have been used as treatments for this condition. However, the safety and efficacy of these treatments remains unsatisfactory, and further development of therapies are desired. In this study, we performed a retrospective analysis of 16 annular erythema associated with SS (AESS) patients treated with hydroxychloroquine (HCQ). Disease activity was assessed using a modified version of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), which we termed the modified CLASI (m-CLASI). HCQ treatment improved AESS lesions in all 16 patients. The mean m-CLASI score was reduced by 85.6% at the 12-week follow-up relative to baseline (p<0.01). Notably, 60% (6/10 cases) of patients with AESS lesions limited to the facial area achieved complete remission within 4weeks. In the analysis of six patients who had taken oral prednisolone before starting HCQ, all were able to reduce the dose within 52weeks without relapse. Particularly, 75% (3/4 cases) of patients with prednisolone dose of more than 5mg/day could reduce their dose to less than 5mg/day in combination with HCQ. For the safety concerns, two patients experienced grade 1 diarrhea during the 52-week observation period. However, neither serious adverse events nor adverse events requiring discontinuation of treatment occurred. The results of the present study suggest that HCQ may not only be highly effective as a single agent, but may also be useful as a steroid-sparing agent in refractory case requiring long-term steroid administration, making it a good treatment option for AESS.

POS0701 ANIFROLUMAB, AN ANTI-INTERFERON-Α RECEPTOR MONOCLONAL ANTIBODY IN SYSTEMIC LUPUS ERYTHEMATOSUS- A META ANALYSIS

Background:Type I interferons such as Anifrolumab have been implicated in Systemic lupus erythematosus (SLE) pathogenesis on the basis of increased interferon-stimulated gene expression and genetic susceptibility. Little is known regarding its efficacy and safety profile.Objectives:To assess the efficacy and safety of Anifrolumab in patients with SLE.Methods:Electronic databases (PubMed, Embase, Scopus, Cochrane) were searched from inception until December 15th, 2020. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p&lt;0.05. The primary outcome of interest was British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). Secondary outcomes included the proportion of patients who achieved an SLE responder index of 4 (SRI-4) reduction of 50% or more in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), reductions in the glucocorticoid dose and adverse effects.Results:A total of three studies1,2,3 with 839 participants (Anifrolumab=372, Placebo=467) were included in our analysis. Follow-up duration was at week 52. A statistically significant different was observed in the Anifrolumab arm in terms of BICLA response (OR 0.44 95%CI 0.34-0.59;p &lt; 0.00001, I2=4), ≥50% reduction in CLASI activity score (OR 0.36 95%CI 0.21-0.60;p=0.0001, I2=0), glucocorticoid reduction (OR 0.41 95%CI 0.28-0.59;p&lt;0.00001; I2=0) and SRI-4 response (OR 0.52 95% CI 0.30-0.90; p=0.02, I2=75). However, Adverse events were less likely in the placebo arm as compared to Anifrolumab (OR 1.54 95%CI 1.05-2.25; p=0.03; I2=0).Conclusion:Anifrolumab was found to be more effective than placebo for the management of SLE, but may also cause more severe adverse effects.

POS0695 KZR-616, A SELECTIVE IMMUNOPROTEASOME INHIBITOR FOR THE TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS FROM THE COMPLETED DOSE ESCALATION PHASE 1B PORTION OF THE MISSION STUDY

Background:KZR-616 is a first-in-class selective inhibitor of the immunoproteasome, which is active in &gt;15 autoimmune disease models, including murine models of systemic lupus erythematosus (SLE)/lupus nephritis (LN).1,2,3 Selective inhibition of the immunoproteasome modulates both innate and adaptive immune effector cells, resulting in reduced inflammatory T helper cell subsets (Th1 and Th17), increased regulatory T cells, and decreased plasma cells and autoantibodies. KZR-616 was well tolerated in two healthy volunteer studies of 100 subjects receiving up to 75 mg subcutaneously (SC). Target levels of immunoproteasome inhibition were observed at doses ≥30 mg.3,4 KZR-616 is currently in Phase 2 studies for several autoimmune indications, including the ongoing Phase 2 portion of the MISSION Study (KZR-616-002; NCT0339013) in patients with LN.Objectives:Results of the completed MISSION Phase 1b dose escalation portion of the study are reported.Methods:In the open-label, multicenter, dose escalation Phase 1b portion, SLE patients (per SLICC Classification Criteria) with SLEDAI ≥4 despite stable background immunosuppressant, anti-malarial, and/or corticosteroid therapy were administered weekly KZR-616 subcutaneously at doses of 45 mg (cohort 1), 60 mg (cohort 2), 60 mg following step-up doses of 30 mg and 45 mg (cohort 2a), 60 mg following a step-up dose of 30 mg (cohorts 2b, 2c) or 75 mg following a step-up dose of 30 mg (cohort 3) for 13 weeks with follow-up through Week 25 (W25); a lyophilized formulation was used for cohorts 2b, 2c and 3. The disease activity measures assessed were: SLEDAI-2K, Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), 28 tender and swollen joint counts, Physician and Patient Global Assessments, and Patient Assessment of Pain. Safety and tolerability were assessed in the safety population (patients receiving at least one dose of KZR-616).Results:The Phase 1b portion of MISSION enrolled 47 SLE patients, including 2 patients with active proliferative LN. The most common treatment-emergent adverse events (TEAE) were injection site reactions, which were mostly mild. Infections occurred at a low rate, and there were no reports of peripheral neuropathy, prolonged hematologic AEs, or clinically significant laboratory abnormalities. No discontinuations were observed in cohorts 2b and 2c; no serious AEs were reported in cohort 3 and TEAEs were consistent with those reported in earlier cohorts. Mean values of all measures of disease activity improved in evaluable patients who completed the 13-week treatment period, and improvements were generally maintained at W25. All patients with elevated anti-double-stranded DNA antibody (anti-dsDNA) levels at baseline (n=7) had a reduction in levels with 3 of 7 experiencing a &gt;50% reduction in their levels. Two of two patients with active proliferative LN had a &gt;50% reduction in UPCR and experienced reductions in SLEDAI-2K scores as well as anti-dsDNA levels. Exposure to KZR-616, similar to that reported in healthy volunteers, was dose-proportional across doses, and no accumulation was observed.Conclusion:KZR-616 SC, once weekly for 13 weeks up to 75 mg, appears to be safe and well-tolerated in patients with active SLE on stable background therapy in the MISSION Phase 1b. At doses ≥45mg, efficacy was noted, including improvements in proteinuria in two of two patients with LN and serologic improvement in all 7 patients with quantifiable levels of anti-dsDNA antibodies at baseline. KZR-616 60 mg SC weekly for 24 weeks is currently being evaluated in the MISSION Phase 2 in patients with LN. Based on the results of MISSION, inhibition of the immunoproteasome with KZR-616 represents a novel strategy to treat autoimmune diseases.