Prospectively stratifying Infectious risks in multiple sclerosis-first results of the InRIMS study

Introduction and Objectives: Long-term use of highly effective disease modifying treatments (DMT) can cause secondary immunodeficiency and consecutive, potentially life-threatening infectious complications. The main objective of this study is to identify factors for increased susceptibility to infections and to establish a prospective infection risk stratification tool for people with MS (pwMS). Methods: InRIMS is a monocentric, prospective, observational and comparative study, enrolling regularly followed pwMS from two cohort studies in Switzerland (SMSC and SUMMIT) since September 2019. Extending a validated infection questionnaire from the large population-based Airway Infection Susceptibility (AWIS) study, we developed an adapted survey with MS-specific items (MS-AWIS questionnaire). At baseline, all participants complete this MS-AWIS questionnaire, which allows calculating an infection risk (IR) score of weighted questionnaire items indicative for increased susceptibility to infections. In analogy to the AWIS study, IR scores ≤4, >4 to <17, and ≥17 correspond to a low, intermediate or high risk for airway infections, respectively. To assess the prognostic value of the IR score, frequency and severity of infections is prospectively recorded over two years using monthly, standardized infection diaries. In response to the SARS-COV2 pandemic, we also document cases of COVID-19 by an additive questionnaire. Results: By May 2021, 297 pwMS were enrolled in InRIMS (9 drop-outs). In a first interim-analysis we included 245 patients with baseline questionnaires (67% female, 87% under DMT, mean age of 48 years (SD ± 12,3 years), mean disease duration 13,3 years (SD ± 9,3 years), median BMI 21,5 (IQR 18,3:24,2)). The mean calculated IR score was 6,8 (SD± 5,5). 6,1% of the InRIMS study population had an IR score ≥17, which was indicative for an increased susceptibility to infections according to results of the population-based AWIS study. Discussion: The InRIMS study assesses risk factors for infections in the real world-setting of a well-defined MS cohort. In the first study phase, most participants enrolled before onset of the SARSCOV2 pandemic in Switzerland - enabling prospective infectious risk assessment. We envisage that the results of the InRIMS study will help to inform counselling of MS patients in clinical practice and support personalized treatment choices as well as preventive measures.