Interventional studies targeting the prodromal or preclinical phase of immune-mediated disease to benefit patient outcomes: a scoping review

BACKGROUND: Immune-mediated diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and type 1 diabetes (T1D) often progress through prodromal or preclinical phases before classical symptom onset. These early stages present opportunity for preventative interventions, but evidence on their efficacy and safety has not been systematically synthesized. OBJECTIVE: This scoping review evaluated interventional studies targeting the prodromal/preclinical phases of MS, RA, SLE, and T1D, with a focus on efficacy and safety outcomes. METHODS: We systematically searched MEDLINE, EMBASE, and Web of Science for interventional studies published between January 2010 to June 2024. Studies assessing any intervention in individuals during the early phases of MS, RA, T1D, or SLE were included. RESULTS: Of 1455 screened studies, 23 met inclusion criteria: 13 for RA, 8 T1D, 2 MS, and none for SLE. For RA, abatacept lowered risk of disease onset in some trials (hazard ratio [HR] range = 0.14-0.61), while methotrexate and rituximab showed modest or subgroup-specific benefit. For T1D, teplizumab delayed clinical onset by over two years (median), preserved β-cell function and lowered risk of progression to T1D (adjusted HR = 0.41; 95% CI 0.22-0.78). For MS, teriflunomide (aHR = 0.28; 95% CI 0.11-0.71) and dimethyl fumarate (aHR = 0.07; 95% CI 0.01-0.45) lowered risk of clinical conversion in persons with radiologically isolated syndrome. Interventions demonstrated expected safety profiles. CONCLUSION: Interventions targeting preclinical or prodromal phases of immune-mediated diseases can delay clinical onset, particularly in RA, T1D, and MS. Progress will require harmonized preclinical definitions, improved risk stratification, longer follow-up, and dedicated efforts in underrepresented diseases such as SLE.