More tests, higher scores: Testing frequency and SDMT differences between natalizumab and rituximab
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Background The Symbol Digit Modalities Test (SDMT) measures information processing speed, and repeated testing can increase scores through practice effects. However, how differences in testing frequency bear on comparisons between disease-modifying therapies (DMTs) in real-world cohorts has not been fully explored. Objective To compare SDMT trajectories between natalizumab and rituximab users and quantify the association of the testing process with those trajectories. Methods Using the Swedish MS Registry, we studied adults with relapsing-remitting MS initiating natalizumab or rituximab (2010–2024) with ≥2 on-treatment SDMT assessments. Mixed-effects models with restricted cubic spline time were sequentially adjusted; log cumulative test number was the practice-effect adjustment. Results Among 2,458 individuals, natalizumab initiators were tested twice as often as rituximab initiators (1.6 vs. 0.8 tests/year). The predicted natalizumab-minus-rituximab SDMT difference at 3 years was 7.0 points (95% CI 5.7–8.3) unadjusted and 1.6 (0.7–2.6) after full adjustment including cumulative test number; at 1 year it fell from 4.4 (3.3–5.4) to −0.3 (−1.2 to 0.6). Conclusion Adjustment for cumulative test number substantially attenuated the SDMT difference between natalizumab and rituximab, leaving a small residual difference of uncertain clinical importance and underscoring the need to account for testing frequency in real-world comparisons.
Source: medRxiv
Institutions: Karolinska Institutet, Karolinska University Hospital
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Vetenskapsrådet
OpenAlex ID: W7223393498