Causal Effects of Multiple Sclerosis Therapies in Left-Truncated Registry Data

Causal Effects of Multiple Sclerosis Therapies in Left-Truncated Registry Data Publisher Pubmed

Summary: Can delayed registry entry distort MS treatment estimates? A simulation found left-truncation biased relapse effects; statistical adjustments reduced the distortion. #MultipleSclerosis #Epidemiology

Diouf I ; Ozakbas S ; Horakova D ; Havrdova E K ; Patti F ; Eichau S ; Alroughani R ; Prat A ; Girard M ; Terzi M ; Yamout B ; Khoury S J ; Grammond P ; Blanco Y Show All Authors

Diouf I
Ozakbas S
Horakova D
Havrdova E K
Patti F
Eichau S
Alroughani R
Prat A
Girard M
Terzi M
Yamout B
Khoury S J
Grammond P
Blanco Y
Shaygannejad V
Foschi M
Surcinelli A
Neri S
Weinstock Guttman B
Prevost J
Barnett M
Van Der Walt A
Butzkueven H
Van Pesch V
Soysal A
Spitaleri D
Cartechini E
Maimone D
Ampapa R
Laureys G
Ramo Tello C
Di Gregorio M
Lapointe E
Slee M
Karabudak R
Garber J
Altintas A
Sanchez Menoyo J L
Castillo Trivino T
Habek M
Al Asmi A
Al Harbi T
Csepany T
Taylor B
Shalaby N
Moore F
Massey J
Hardy T A
Gray O
Decoo D
Simu M
Rozsa C
Stuart E A
Sharmin S
Roos I
Kalincik T

Source: Multiple Sclerosis Journal Published:2026

Abstract

Background: Left-truncation is an unrecorded interval between multiple sclerosis (MS) onset and initial data in observational studies. This delay may bias estimates of disease-modifying therapy (DMT) effectiveness, especially when determined by patient or disease characteristics. Objectives: To examine whether causal effect estimates of DMTs over the full disease course can be reliably derived from left-truncated registry data. Methods: We analysed data from MSBase (144 centres, 41 countries) to assess the impact of left-truncation on causal treatment effect estimates. Cox marginal structural models (MSMs) estimated hazard ratios (HRs) for relapses, disability worsening and improvement, considering left-truncation at random and not-at-random. Fixed-time truncation and multivariable adjustment were applied to remediate bias. Results: The study included 5588 patients tracked from true MS onset. The null model, without left-truncation, estimated the DMT effect on relapse risk (HR = 0.64; 95% confidence interval (CI) = 0.54–0.77). Left-truncation inflated this estimate. Shorter random truncation (1 year) produced greater bias (HR = 0.34), decreasing with longer durations (3-year HR = 0.48). Truncation not-at-random biased relapse estimates (HR = 0.37). Disability outcomes were less sensitive. Conclusion: MSMs can reliably estimate DMT effectiveness in left-truncated MS registry data, although accuracy depends on truncation mechanism and duration. Both random and not-at-random truncation impact relapse estimates. Disability outcomes appear less sensitive. Fixed-time truncation and covariate adjustment mitigated bias. © The Author(s), 2026. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

2. Preserving Neurological Function in People at High and Low Risk of Aggressive Multiple Sclerosis: An Observational Cohort Study, CNS Drugs (2026)

Experts (# of related papers)

Vahid Shaygannejad (2)

Causal Effects of Multiple Sclerosis Therapies in Left-Truncated Registry Data

Style	Citing Format
MLA	Diouf I, et al.. "Causal Effects of Multiple Sclerosis Therapies in Left-Truncated Registry Data." Multiple Sclerosis Journal, vol. 32, no. 10, 2026, pp. 1052-1068.
APA	Diouf I, Ozakbas S, Horakova D, Havrdova E K, Patti F, Eichau S, Alroughani R, Prat A, Girard M, Terzi M, Yamout B, Khoury S J, Grammond P, Blanco Y, Shaygannejad V, Foschi M, Surcinelli A, Neri S, Weinstock Guttman B, ... Kalincik T (2026). Causal Effects of Multiple Sclerosis Therapies in Left-Truncated Registry Data. Multiple Sclerosis Journal, 32(10), 1052-1068.
Chicago	Diouf I, Ozakbas S, Horakova D, Havrdova E K, Patti F, Eichau S, Alroughani R, et al.. "Causal Effects of Multiple Sclerosis Therapies in Left-Truncated Registry Data." Multiple Sclerosis Journal 32, no. 10 (2026): 1052-1068.
Harvard	Diouf I et al. (2026) 'Causal Effects of Multiple Sclerosis Therapies in Left-Truncated Registry Data', Multiple Sclerosis Journal, 32(10), pp. 1052-1068.
Vancouver	Diouf I, Ozakbas S, Horakova D, Havrdova E K, Patti F, Eichau S, et al.. Causal Effects of Multiple Sclerosis Therapies in Left-Truncated Registry Data. Multiple Sclerosis Journal. 2026;32(10):1052-1068.
BibTex	@article{ author = {Diouf I and Ozakbas S and Horakova D and Havrdova E K and Patti F and Eichau S and Alroughani R and Prat A and Girard M and Terzi M and Yamout B and Khoury S J and Grammond P and Blanco Y and Shaygannejad V and Foschi M and Surcinelli A and Neri S and Weinstock Guttman B and Prevost J and Barnett M and Van Der Walt A and Butzkueven H and Van Pesch V and Soysal A and Spitaleri D and Cartechini E and Maimone D and Ampapa R and Laureys G and Ramo Tello C and Di Gregorio M and Lapointe E and Slee M and Karabudak R and Garber J and Altintas A and Sanchez Menoyo J L and Castillo Trivino T and Habek M and Al Asmi A and Al Harbi T and Csepany T and Taylor B and Shalaby N and Moore F and Massey J and Hardy T A and Gray O and Decoo D and Simu M and Rozsa C and Stuart E A and Sharmin S and Roos I and Kalincik T}, title = {Causal Effects of Multiple Sclerosis Therapies in Left-Truncated Registry Data}, journal = {Multiple Sclerosis Journal}, volume = {32}, number = {10}, pages = {1052-1068}, year = {2026} }
RIS	TY - JOUR AU - Diouf I AU - Ozakbas S AU - Horakova D AU - Havrdova E K AU - Patti F AU - Eichau S AU - Alroughani R AU - Prat A AU - Girard M AU - Terzi M AU - Yamout B AU - Khoury S J AU - Grammond P AU - Blanco Y AU - Shaygannejad V AU - Foschi M AU - Surcinelli A AU - Neri S AU - Weinstock Guttman B AU - Prevost J AU - Barnett M AU - Van Der Walt A AU - Butzkueven H AU - Van Pesch V AU - Soysal A AU - Spitaleri D AU - Cartechini E AU - Maimone D AU - Ampapa R AU - Laureys G AU - Ramo Tello C AU - Di Gregorio M AU - Lapointe E AU - Slee M AU - Karabudak R AU - Garber J AU - Altintas A AU - Sanchez Menoyo J L AU - Castillo Trivino T AU - Habek M AU - Al Asmi A AU - Al Harbi T AU - Csepany T AU - Taylor B AU - Shalaby N AU - Moore F AU - Massey J AU - Hardy T A AU - Gray O AU - Decoo D AU - Simu M AU - Rozsa C AU - Stuart E A AU - Sharmin S AU - Roos I AU - Kalincik T TI - Causal Effects of Multiple Sclerosis Therapies in Left-Truncated Registry Data JO - Multiple Sclerosis Journal VL - 32 IS - 10 SP - 1052 EP - 1068 PY - 2026 ER -

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