Clinical endpoints in myositis: challenges and ways forward.

PURPOSE OF REVIEW: This review addresses the challenges and advances in clinical endpoints for myositis, with a particular focus on ensuring comprehensive assessment of both muscle and skin disease activity. The relevance of this review stems from recent developments in outcome measures and their implications for clinical trial design and patient inclusivity. While quality of life (QoL) and lung involvement are also important aspects of myositis, they are beyond the scope of this review and need to be addressed in future studies. RECENT FINDINGS: Traditional outcome measures like the Total Improvement Score (TIS) have limitations, especially for patients with skin-predominant dermatomyositis (DM). Recent studies highlight the importance of incorporating skin-specific measures such as the Cutaneous Disease Area and Severity Index (CDASI) and the novel composite measure, Dermatomyositis Outcomes for Muscle and Skin (DMOMS). These measures provide a more balanced assessment of disease activity. Clinical trial data analyzed using these measures have demonstrated significant benefits for patients with both classic and amyopathic DM, emphasizing the need for their broader adoption. SUMMARY: Advancements in outcome measures are crucial for inclusive and effective myositis clinical trials. Incorporating comprehensive tools like the DMOMS can enhance the assessment of both muscle and skin disease activities, potentially leading to better therapeutic strategies and improved patient outcomes. This shift is essential for addressing the needs of all Idiopathic inflammatory myopathy patients, including those with skin-predominant DM.

Two-Stage Syphilis Testing.

A 54-year-old woman presented with erythematous annular and indurated plaques on her face, trunk, and extremities and had false-positive syphilis test results during 2 pregnancies 25 and 22 years prior. What would you do next?

An update on clinical trials for cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) comprises dermatologic manifestations that may occur independently or with systemic lupus erythematosus (SLE). Despite advancements in refining CLE classification, establishing precise subtype criteria remains challenging due to overlapping presentations and difficulty in distinguishing morphology. Current treatments encompass preventive measures, topical therapies, and systemic approaches. Hydroxychloroquine and glucocorticoids are the sole US Food and Drug Administration (FDA)-approved medications for CLE, with numerous off-label treatments available. However, these treatments are often not covered by insurance, imposing a significant financial burden on patients. The exclusion of most CLE patients, particularly those without concurrent SLE, from trials designed for SLE has resulted in a lack of targeted treatments for CLE. To develop effective CLE treatments, validated outcome measures for tracking patient responsiveness are essential. The Cutaneous Lupus Erythematosus Disease Area and Severity Index is widely utilized for its reliability, validity, and ability to differentiate between skin activity and damage. In contrast, the FDA mandates the use of the Investigator's Global Assessment, a five-point Likert scale related to lesion characteristics, for skin-related therapeutic trials. It requires the disease to resolve or almost completely resolve to demonstrate improvement, which can be difficult when there is residual erythema or incomplete clearance that is meaningfully improved from a patient perspective. Various classes of skin lupus medications target diverse pathways, allowing tailored treatment based on the patient's lupus inflammatory profile, resulting in improved outcomes. Promising targeted therapeutic drugs include anifrolumab (anti-type 1 interferon), deucravacitinib (allosteric tyrosine kinase 2 inhibitor), litifilimab (plasmacytoid dendritic cell-directed therapy), iberdomide (cereblon-targeting ligand), and belimumab (B-cell directed therapy). Despite the significant impact of CLE on quality of life, therapeutic options remain inadequate. While promising treatments for cutaneous lupus are emerging, it is crucial to underscore the urgency for skin-focused treatment outcomes and the implementation of validated measures to assess therapeutic effectiveness in clinical trials.

Prevalence and Risk of Immunostimulatory Herbal Supplement Treatment Among Autoimmune Dermatology Patients.

OBJECTIVE: We assess the prevalence and patterns of herbal supplement treatment among patients with autoimmune skin diseases, particularly dermatomyositis (DM) and cutaneous lupus erythematosus (CLE), and identify commonly taken supplements and their associated risks. METHODS: This study screened 673 adult patients with clinicopathologic evidence of DM or CLE at the University of Pennsylvania's rheumatologic-dermatology clinic between January 2007 and February 2024. Demographic data, disease characteristics, and detailed information on herbal supplement treatment were collected. Predictors of supplement treatment were analyzed using chi-square tests and reported as odds ratios. RESULTS: The prevalence of herbal supplement treatment was 32% among the cohort. The relative frequency of herbal supplement treatment was significantly higher in younger patients (44% of patients ages 18-29 years, reference; 29% ages 50-64 years, P = 0.02; 23% ages ≥65 years, P = 0.003) and in Hispanic/Latino patients (58% vs 31% White, P = 0.009). No significant difference in herbal supplement treatment was seen by sex (33% of female participants, 29% of male participants, P = 0.49), race (31% White, P = reference; 31% Black, P = 1.0; 38% Asian, P = 0.55), or disease (30% of patients with DM, 36% of patients with CLE; P = 0.12). Among patients with DM, 31% experienced a disease onset or exacerbation after supplement treatment compared with 10% of patients with CLE. Elderberry treatment was associated with the highest risk of exacerbation in both disease cohorts (62% DM, 50% CLE). CONCLUSION: Herbal supplement treatment is prevalent among patients with autoimmune skin diseases, with immunostimulatory supplements posing a significant risk for immune dysregulation, particularly in DM. Providers should proactively screen and counsel patients regarding treatment with these supplements.

Application of Risk-Based Cancer Screening in Patients With Dermatomyositis.

This cohort study investigates the performance of the International Myositis Assessment and Clinical Studies Group cancer screening recommendations in a community setting.

Long-Term Safety and Efficacy of Lenabasum, a Cannabinoid Receptor Type 2 Agonist, in Patients with Dermatomyositis with Refractory Skin Disease: Follow-Up Data from a 3-Year Open-Label Extension Study.

Dermatomyositis (DM) is a rare autoimmune condition involving skin manifestations often resistant to standard treatments such as immunosuppressants and antimalarials. Biopsies show elevated inflammatory cells such as CD4+ T cells, dendritic cells, and cytokines. Lenabasum, a selective cannabinoid receptor 2 agonist, has demonstrated significant benefits in treating autoimmune skin diseases. OBJECTIVES: This study utilizes data from the open-label extension (OLE) phase of the lenabasum phase 2 trial and additional post-OLE follow-up data. Key aims include evaluating the drug's long-term effectiveness and assessing disease manifestation recurrence. METHODS: The phase 2 lenabasum trial enrolled patients with treatment-resistant, skin-predominant DM. The OLE consisted of a 3-year period during which 20 patients were on the drug for the entire duration, with assessments every 8 weeks to evaluate drug safety and efficacy. Subsequently, a follow-up retrospective chart review was performed on patients who completed the OLE as well as on control subjects with DM who did not participate in the lenabasum trial. RESULTS: By week 68, patients exhibited reductions in Cutaneous Dermatomyositis Disease Area and Severity Index activity score (-21.8), Patient Skin Activity Visual Analog Scale (-3.0), and Skindex-29 (-28.0) from OLE baseline. After OLE, 58.3% maintained stable disease, significantly higher than controls (P = .035), with 41.7% not experiencing flares compared with 91.6% of controls. In addition, 50% of patients reported sustained pruritus improvement. CONCLUSIONS: Data from OLE and subsequent follow-up periods demonstrate lenabasum's efficacy in maintaining disease stability, reducing flares, and improving DM symptoms, suggesting that it is a promising option for patients with treatment-resistant skin-predominant DM. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov, with NCT02466243. Study registration was first submitted on June 2, 2015.