Non-surgical local treatments of digital ulcers in systemic sclerosis: a systematic literature review.

INTRODUCTION: Digital ulcers (DUs) are difficult to treat in patients with systemic sclerosis (SSc) and systemic (i.e., pharmacological) therapy is currently considered the 'standard of care'. Our aim was to examine the safety and efficacy of local, non-surgical treatment for SSc-DUs. METHODS: A systematic literature review (SLR) of original research articles up to August, 29 2022 was performed according to the PICO framework. References were independently screened by two reviewers and risk of bias was assed using validated tools. Due to study heterogeneity narrative summaries are used to present data. RESULTS: Among 899 retrieved references, 14 articles were included (2 randomised trials (RTs), and 12 observational (OBS) studies). The most frequently studied procedure (5 studies) was botulin A toxin (hand or single finger) injection with a reported healing rate (HR) of 71%-100%. Amniotic and hydrocolloid membranes were examined in one study each and associated with a good HR. Tadalafil 2% cream was studied in a single study with a reduction in the number of DUs. Vitamin E gel was associated with a reduction in ulcer healing time. Low-level light therapy, hydrodissection and corticosteroid injection, extracorporeal shock wave (ESW) and photobiomodulation were evaluated in a single study each and showed a positive trend. Dimethyl sulfoxide was associated with significant local toxicity. CONCLUSIONS: A range of non-surgical, local treatments for SSc-DUs have been explored and showed efficacy to some extent. We have identified methodological flaws that should be avoided in the design of future studies to explore locally-acting treatments for SSc-DUs.

A randomised, double-blind, placebo-controlled phase 3 study of lenabasum in diffuse cutaneous systemic sclerosis: RESOLVE-1 design and rationale.

OBJECTIVES: The multi-systemic, heterogenous nature of diffuse cutaneous systemic sclerosis (dcSSc) presents challenges in designing clinical studies that can demonstrate a treatment effect on overall disease burden. We describe the design of the first Phase 3 study in dcSSc patients where the American College of Rheumatology (ACR) Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score was chosen prospectively as the primary outcome. The CRISS measures key clinical disease parameters and patient-reported outcomes (PROs). METHODS: RESOLVE-1 is a Phase 3, randomised, double-blind, placebo-controlled trial of dcSSc patients evaluating the efficacy and safety of lenabasum. Patients ≥18 years of age with dc-SSc and disease duration ≤6 years were eligible. Patients could continue stable background therapy for dcSSc, including stable immunosuppressive therapies. They were randomised to lenabasum 5 or 20 mg twice daily or placebo. The primary efficacy outcome was the mean change from baseline to 52 weeks in the ACR CRISS score. RESULTS: The study enrolled 365 patients over 1.5 years at 77 sites in 13 countries in North America, Europe, Israel, and Asia-Pacific, with the last patient first visit on May 1, 2019. CONCLUSIONS: RESOLVE-1 is the first Phase 3 interventional study to date in dcSSc to prospectively use the ACR CRISS as the primary efficacy outcome. Eligibility criteria allowed background therapy as might occur in clinical practice. This approach also facilitated timely patient enrolment. RESOLVE-1 provides a novel study design that may be used for future Phase 3 dcSSc studies to assess the holistic efficacy of therapy.

Is serum albumin a marker of malnutrition in chronic disease? The scleroderma paradigm.

BACKGROUND: Malnutrition is common in many chronic diseases, but physicians may rely on a low albumin value before deciding that malnutrition is present. OBJECTIVE: To determine the relationship between serum albumin and malnutrition in systemic sclerosis (SSc) as a paradigm for other chronic diseases. DESIGN: Cross-sectional, multicenter study of patients from the Canadian Scleroderma Research Group Registry. We used the Malnutrition Universal Screening Tool (MUST) to evaluate patients for malnutrition. Disease extent was measured in several ways, including physician global assessment. Multiple linear regression was performed to identify independent predictors of serum albumin. RESULTS: Two hundred fifty-eight patients were studied. The mean (SD) serum albumin level was 44.4 (4.2) g/L. Only 2% of the values were below normal and all these patients were in MUST category > or =2, or high risk for malnutrition, which included 21.3% of the cohort. MUST, shorter disease duration, greater disease severity (physician global assessment of disease severity and modified Rodnan skin score), and greater disease activity (physician global assessment of disease activity, C-reactive protein, and Scleroderma Disease Activity Index) all correlated significantly but weakly with albumin. Multivariate analysis demonstrated that a higher MUST score and worse disease severity were independently associated with lower serum albumin, but only 7% of the variance of albumin was explained in the adjusted model. CONCLUSIONS: Serum albumin is not useful as a marker for malnutrition in SSc and should not be assumed to be useful as a marker in other chronic diseases. More attention should be paid to clinical features of malnutrition, including assessment of body mass index and unplanned weight loss, and overall disease severity.

Health services costs and their determinants in women with fibromyalgia.

OBJECTIVE: Patients with fibromyalgia (FM) use health services extensively. Knowledge about costs of FM is limited because of non-inclusiveness in assessing direct costs, because attempts to assess indirect costs are largely absent, and because determinants of costs have yet to be identified. We investigated the 6-month costs (direct and indirect) in women with primary FM, and we identified determinants of direct costs. METHODS: Subjects (n = 180 women) completed a health resource questionnaire as well as measures of pain, psychological distress, comorbidity, and disability. Unit costs for resources were obtained from government, hospital, laboratory, and professional association sources. Regression modeling for 6-month direct cost included age, disability, comorbidity, pain intensity, psychological distress, education, and work status. RESULTS: The average 6-month direct cost was $CDN 2298 (SD 2303). The largest components were medications ($CDN 758; SD 654), complementary and alternative medicine (CAM; $CDN 398; SD 776), and diagnostic tests ($CDN 356; SD 580). Our most conservative estimate of average 6-month indirect cost was $CDN 5035 (SD 7439). Comorbidity and FM disability were statistically significant contributors to direct costs in the multivariate analysis. Costs increased by approximately 20% with each additional comorbid condition. CONCLUSION: Women with FM are high consumers of both conventional and CAM services. Our estimates of costs exceed those from most other studies; this may be due to our inclusion of a broader set of health services, medications, and indirect costs. Although in univariate analyses the number of comorbidities and indices of the effect of FM, psychological distress, and pain intensity were associated with higher direct cost, in a multiple regression analysis, only the measure of FM disability and the number of comorbidities were significant direct-cost determinants. FM also imposes important indirect costs, which were nearly 70% of the economic burden.