ObjectiveThis phase 3 study was undertaken to investigate the efficacy and safety of lenabasum, a cannabinoid type 2 receptor agonist, in patients with diffuse cutaneous systemic sclerosis (dcSSc)... Show moreObjectiveThis phase 3 study was undertaken to investigate the efficacy and safety of lenabasum, a cannabinoid type 2 receptor agonist, in patients with diffuse cutaneous systemic sclerosis (dcSSc).MethodsA multinational double-blind study was conducted in 365 dcSSc patients who were randomized and dosed 1:1:1 with lenabasum 20 mg, lenabasum 5 mg, or placebo, each twice daily and added to background treatments, including immunosuppressive therapies (IST).ResultsThe primary end point, the American College of Rheumatology combined response index in dcSSc (CRISS) at week 52 for lenabasum 20 mg twice a day versus placebo, was not met, with CRISS score of 0.888 versus 0.887 (P = 0.4972, using mixed models repeated measures [MMRM]). The change in the modified Rodnan skin thickness score (MRSS) at week 52 for lenabasum 20 mg twice a day versus placebo was −6.7 versus −8.1 (P = 0.1183, using MMRM). Prespecified analyses showed higher CRISS scores, greater improvement in MRSS, and lower decline in forced vital capacity in patients on background mycophenolate and those who were taking IST for ≤1 year. No deaths or excess in serious or severe adverse events related to lenabasum were observed.ConclusionA benefit of lenabasum in dcSSc was not demonstrated. Most patients were treated with background IST, and treatment with mycophenolate mofetil in particular was associated with better outcomes. These findings support the use of IST in the treatment of dcSSc and highlight the challenge of demonstrating a treatment effect when investigational treatment is added to standard of care IST. These findings have relevance to trial design in SSc, as well as to clinical care. Show less
Zheng, B.Y.; Wang, M.B.; McKenna, K.; Shapiro, L.; Silver, R.; Csuka, M.E.; ... ; Canadian Scleroderma Res Grp 2022
Objective Diffuse cutaneous systemic sclerosis (SSc) is a highly heterogeneous disease. A provisionally approved Composite Response Index in diffuse cutaneous SSc (CRISS) was developed as a 1-year... Show moreObjective Diffuse cutaneous systemic sclerosis (SSc) is a highly heterogeneous disease. A provisionally approved Composite Response Index in diffuse cutaneous SSc (CRISS) was developed as a 1-year outcome measure for clinical trials. Our goal was to further validate the CRISS by examining agreement between CRISS definitions for improved/non-improved with physicians' evaluation of disease. Methods Patient profiles from a large observational cohort were created for 50 random diffuse cutaneous SSc patients of <5 years disease duration with improved CRISS scores after 1 year and 50 with non-improved CRISS scores. Profiles described disease features used during the initial CRISS development at baseline and at 1 year. Each profile was independently rated by 3 expert physicians. Majority opinion determined whether a patient was improved or not improved, and kappa agreement with the CRISS cutoff of 0.6 was calculated. Results Patients had mean +/- SD disease duration of 2.2 +/- 1.3 years. There was substantial agreement between the physician majority opinion about each case and the CRISS (kappa = 0.76 [95% confidence interval (95% CI) 0.64-0.88]). The agreement between each individual physician opinion and the CRISS was also substantial (kappa = 0.70 [95% CI 0.62-0.78]). All CRISS non-improvers were also rated as non-improved by physician majority; however, 12 CRISS improvers were rated as non-improved by physicians. Conclusion There was substantial agreement between the dichotomous CRISS rating and physician assessment of diffuse cutaneous SSc patients after 1 year. This supports the use of a CRISS cutoff at 0.6 for improvement versus non-improvement, although the CRISS tended to rate more patients as improved than did physicians. Show less
Objective: Contagious disease outbreaks and related restrictions can lead to negative psychological outcomes, particularly in vulnerable populations at risk due to pre-existing medical conditions.... Show moreObjective: Contagious disease outbreaks and related restrictions can lead to negative psychological outcomes, particularly in vulnerable populations at risk due to pre-existing medical conditions. No randomised controlled trials (RCTs) have tested interventions to reduce mental health consequences of contagious disease outbreaks. The primary objective of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Trial is to evaluate the effect of a videoconference-based program on symptoms of anxiety. Secondary objectives include evaluating effects on symptoms of depression, stress, loneliness, boredom, physical activity, and social interaction.Methods: The SPIN-CHAT Trial is a pragmatic RCT that will be conducted using the SPIN-COVID-19 Cohort, a sub-cohort of the SPIN Cohort. Eligible participants will be SPIN-COVID-19 Cohort participants without a positive COVID-19 test, with at least mild anxiety (PROMIS Anxiety 4a v1.0 T-score >= 55), not working from home, and not receiving current counselling or psychotherapy. We will randomly assign 162 participants to intervention groups of 7 to 10 participants each or waitlist control. We will use a partially nested RCT design to reflect dependence between individuals in training groups but not in the waitlist control. The SPIN-CHAT Program includes activity engagement, education on strategies to support mental health, and mutual participant support. Intervention participants will receive the 4-week (3 sessions per week) SPIN-CHAT Program via video-conference. The primary outcome is PROMIS Anxiety 4a score immediately post-intervention.Ethics and dissemination: The SPIN-CHAT Trial will test whether a brief videoconference-based intervention will improve mental health outcomes among at-risk individuals during contagious disease outbreak. Show less
