Treatment with add-on IVIg in Myositis Early In the diSease course May be sUperior to Steroids alone for reaching CLinical improvEment (TIME IS MUSCLE): study protocol of a phase-2 double-blind placebo-controlled randomised trial.

INTRODUCTION: For idiopathic inflammatory myopathies (IIM) ('myositis') standard initial treatment is high-dosed glucocorticoids, which results in relatively slow improvement of muscle strength. Early immunosuppression or modulation by intensive treatment ('hit-early, hit-hard') may induce faster reduction of disease activity and prevent chronic disability due to disease-induced structural muscle damage. Intravenous immunoglobulin (IVIg) in addition to standard glucocorticoid treatment may be promising in this regard as was shown in various studies: add-on IVIg improved symptoms and muscle strength in refractory myositis patients and monotherapy IVIg improved outcomes after 9 weeks, in about half of treatment-naive patients. HYPOTHESIS: We hypothesise that early add-on IVIg leads to a greater clinical response after 12 weeks in patients with newly diagnosed myositis, in comparison to prednisone monotherapy. Second, we expect that early treatment with add-on IVIg leads to a faster time to improvement and sustained positive effects on multiple secondary outcomes. METHODS: The Time Is Muscle trial is a phase-2 double-blind placebo-controlled randomised trial. Forty-eight patients with IIM will be treated with IVIg or placebo at baseline (within 1 week after diagnosis) and after 4 and 8 weeks, in addition to standard therapy with prednisone. The primary outcome is the Total Improvement Score (TIS) of the myositis response criteria at 12 weeks. At baseline, and after 4, 8, 12, 26 and 52 weeks, relevant secondary outcomes will be assessed, including time to moderate improvement (TIS≥40), mean daily prednisone dosage, physical activity, health-related quality of life, fatigue and MRI muscle imaging parameters. ETHICS AND DISSEMINATION: Ethical approval was obtained from the medical ethics committee of the Academic Medical Centre, University of Amsterdam, the Netherlands (2020_180; including a first amendment approval at the 12 April 2023; A2020_180_0001). The results will be distributed through conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: EU Clinical trials register (2020-001710-37).

High Disease Burden Drives Indirect Costs in Employed Inflammatory Bowel Disease Patients: The WORK-IBD Study.

BACKGROUND: Work productivity (WP) loss includes absence from work (absenteeism) and productivity loss while working (presenteeism), which leads to high indirect costs in inflammatory bowel disease (IBD). Prior health economic analyses predominantly focused on absenteeism. Here we focus on presenteeism and assess predictors of WP loss, fatigue, and reduced health-related quality of life (HRQL). METHODS: Employed IBD patients completed the following surveys: Work Productivity and Activity Impairment, Multidimensional Fatigue Inventory, and Short Inflammatory Bowel Disease Questionnaire. Predictors were assessed using uni- and multivariable regression analyses. Annual costs were calculated using percentages of WP loss, hourly wages, and contract hours. RESULTS: Out of 1590 invited patients, 768 (48%) responded and 510 (32%) were included. Absenteeism, presenteeism, and overall WP loss were reported by 94 (18%), 257 (50%), and 269 (53%) patients, respectively, resulting in mean (SD) annual costs of €1738 (5505), €5478 (8629), and €6597 (9987), respectively. Disease activity and active perianal disease were predictors of WP loss (odds ratio [OR] = 6.6; 95% confidence interval [CI], 3.6-12.1); OR = 3.7; 95% CI, 1.5-8.7). Disease activity and arthralgia were associated with fatigue (OR = 3.6; 95% CI, 1.9-6.8; OR = 1.8; 95% CI, 1.0-3.3)) and reduced HRQL (OR = 10.3; 95% CI, 5.9-17.9; OR = 2.3; 95 % CI, 1.4-3.8). Fatigue was the main reason for absenteeism (56%) and presenteeism (70%). Fatigue and reduced HRQL led to increased costs compared with absence of fatigue and normal HRQL (mean difference = €6630; 95% CI, €4977-€8283, P < 0.01; mean difference = €9575; 95% CI, €7767-€11,384, P < 0.01). CONCLUSIONS: Disease activity and disease burden lead to WP loss in approximately half of the employed IBD population, driving indirect costs. Fatigue is the most important reason for WP loss.