External validation and improvement of an algorithm that identifies multiple sclerosis relapses in the French national healthcare claims database

1. Mult Scler Relat Disord. 2026 Apr 24;111:107209. doi:
10.1016/j.msard.2026.107209. Online ahead of print.

External validation and improvement of an algorithm that identifies multiple
sclerosis relapses in the French national healthcare claims database.

Carcaillon-Bentata L(1), Abouelfath A(2), Lignot-Maleyran S(2), Lassalle R(2),
Jové J(2), Blin P(2), Berger E(3), Bourre B(4), Camdessanche JP(5), Casez O(6),
Ciron J(7), David T(8), De Seze J(9), Defer G(10), Doghri I(11), Santos AD(12),
Hankiewicz K(13), Heinzlef O(14), Labauge P(15), Page EL(16), Lebrun-Frenay
C(17), Leclancher A(18), Louapre C(19), Manchon E(20), Mathey G(21), Montcuquet
A(22), Papeix C(23), Pelletier J(24), Pottier C(25), Ruet A(26), Sarov-Riviere
M(27), Vukusic S(28), Magy L(29), Moulin M(30), Brochet B(31), Casey R(32),
Leray E(33); OFSEP Investigators.

Author information:
(1)Bordeaux PharmacoEpi, INSERM CIC-P1401, Univ. Bordeaux, Bordeaux, France.
Electronic address: .
(2)Bordeaux PharmacoEpi, INSERM CIC-P1401, Univ. Bordeaux, Bordeaux, France.
(3)CHU de Besançon, Service de Neurologie, Besançon, France.
(4)CHU de Rouen, Departement of Neurology, Rouen, France.
(5)CHU de Saint-Étienne, Hôpital Nord, Department of Neurology, Saint Etienne,
France.
(6)CHU Grenoble Alpes, Department of Neurology, Neurology MS Clinic Grenoble,
Grenoble Alpes university hospita, Grenoble, France; TIMC, T-RAIG (Translational
Research in Autoimmunity and Inflammation Group), Université Grenoble Alpes,
Grenoble, France.
(7)CHU de Toulouse, CRC-SEP, department of Neurology, Toulouse, France;
Université Toulouse III, Infinity, INSERM UMR1291 – CNRS UMR5051, Toulouse,
France.
(8)CHU de la Martinique, Department of Neurology, Fort-de-France, France.
(9)CHU de Strasbourg, Department of Neurology and Clinical Investigation Center,
CIC 1434, INSERM 1434, Strasbourg, France.
(10)CHU de Caen, MS expert centre, Department of Neurology, avenue de la
Côte-de-Nacre, Normandy University, Caen, France.
(11)CHU de Tours, Hôpital Bretonneau, CRC SEP and department of neurology,
Tours, France.
(12)CHU La Milétrie, Hôpital Jean Bernard, Department of neurology et Centre
d’Investigation Clinique, CIC INSERM 1402, Poitiers, France.
(13)Department of neurology, Hôpital Pierre Delafontaine, Centre Hospitalier de
Saint-Denis, Saint Denis, France.
(14)Hôpital de Poissy, Departement of Neurology, Poissy, France.
(15)CHU de Montpellier, MS Unit, F-34295 Montpellier Cedex 5, France; University
of Montpellier (MUSE), Montpellier, France.
(16)CHU Pontchaillou, CIC1414 INSERM, Rennes, France.
(17)Neurology, UR2CA_URRIS, Centre Hospitalier Universitaire Pasteur2,
Université Nice Côte d’Azur, Nice, France.
(18)GHH Du Havre, Department of Neurology, Le Havre, France.
(19)Sorbonne University, Department of Neurology, Pitié Salpêtrière Hospital,
APHP, CIC neurosciences, Paris Brain Institute, Paris, France.
(20)CH de Gonesse, Department of neurology, Gonesse, France.
(21)Université de Lorraine, CHRU-Nancy, Neurology, Nancy, France; Université de
Lorraine, Inserm, INSPIIRE, Nancy, France.
(22)CH Brive, Department of Neurology, Brive, France.
(23)Foundation Adolphe de Rothschild Hospital, Department of Neurology, Paris,
France.
(24)Aix Marseille Univ, APHM, Hôpital de la Timone, Pôle de Neurosciences
Cliniques, Service de Neurologie, Marseille, France.
(25)Hôpital NOVO, site Pontoise, Department of Neurology, Pontoise, France.
(26)Service de neurologie et maladies inflammatoires du système nerveux central,
CRC SEP, CHU de Bordeaux, Bordeaux, France; INSERM U1215, Neurocentre Magendie,
Université de Bordeaux, Bordeaux, France.
(27)APHP, Hôpital Kremlin Bicêtre, Deparement of Neurology, Le Kremlin Bicêtre,
France.
(28)Département Sclérose en plaques, pathologies de la myéline et
neuro-inflammation; Fondation Eugène Devic EDMUS sur la SEP; Hôpital
Neurologique Pierre Wertheimer – Hospices Civils de Lyon, Lyon, France;
Observatoire Français de la Sclérose en Plaques, Centre de Recherche en
Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292, Lyon, France.
(29)CHU de Limoges, Hôpital Dupuytren, Department of Neurology, Limoges, France.
(30)CHU de Reims, CRC-SEP, Department of neurology, Reims, France.
(31)U1215 INSERM, University of Bordeaux, Bordeaux, France.
(32)Univ Lyon, Université Claude Bernard Lyon 1, Hospices Civils de Lyon,
Fondation EDMUS, OFSEP, Centre de Recherche en Neurosciences de Lyon F-69000
Lyon, France; Hospices Civils de Lyon, Service de Neurologie, sclérose en
plaques, pathologies de la myéline et neuro-inflammation, F-69677 Bron, France;
Observatoire Français de la Sclérose en Plaques, Centre de Recherche en
Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292, F-69003 Lyon, France;
EUGENE DEVIC EDMUS Foundation against multiple sclerosis, state-approved
foundation, F-69677 Bron, France.
(33)Univ Rennes, EHESP, CNRS, Inserm, ARENES UMR 6051, RSMS U 1309, Rennes,
France.

BACKGROUND: Multiple sclerosis (MS) is a frequent neurological condition
affecting young adults with acute disabling neurological episodes (relapses). MS
relapses are not recorded in claims databases despite their importance for
(pharmaco)epidemiological studies. This study aimed to validate and improve an
algorithm identifying relapses in relapsing-remitting MS initiating
disease-modifying therapy (DMT) within the French nationwide claims database
(SNDS).
METHODS: Clinical data from the French MS registry (OFSEP) linked to the SNDS
were used. The cohort included MS patients with a first DMT claim between July
2015 and December 2017, naive to any MS treatment, followed until December 2018
(n=1,640). The initial relapse algorithm combined high-dose corticosteroid
prescriptions and hospitalization duration. Incidence of the first relapse
identified in the SNDS was compared with OFSEP confirmed relapses that have been
treated by corticosteroid or hospitalized (gold standard). Performances were
estimated using Sensitivity, Specificity, PPV, NPV. Algorithm were reevaluated
after revision of its criteria based on experts’ review of false positive and
negative cases’ claims, and finally after adding non-naive MS patients
(n=9,966).
RESULTS: The performances of the initial algorithm were Specificity 85.2%,
Sensitivity 74.0%, NPV 89.8%, PPV 65.3%. After revision of corticosteroid
dosages and hospitalization durations thresholds, performance slightly improved:
85.0%, 75.4%, 90.2%, 65.3%, respectively. When considering naive and non-naive
MS patients, Sensitivity and NPV stayed similar (75.1% and 91.6%) while
Specificity and PPV decreased (81.8% and 55.4%).
CONCLUSION: The final algorithm of treated/hospitalized relapses can be applied
accurately in naïve MS patients initiating a DMT, in the SNDS and likely in
other claims databases after adapting to each country’s reimbursement and care
practices.

Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.

DOI: 10.1016/j.msard.2026.107209
PMID: 42134166

Conflict of interest statement: Declaration of competing interest E. Berger:
honoraria and consulting fees from Novartis, Sanofi Aventis, Biogen, Genzyme,
Roche and Teva Pharma. B. Bourre served on scientific advisory board for
Alexion, BMS, Biogen, Sanofi, Janssen, Merck, Horizon, Novartis, Roche, Sandoz,
and received funding for travel and honoraria from Alexion, Merck, Novartis,
Sanofi, Roche and Janssen. JP Camdessanche: consulting and lecturing fees from
Akcea, Alexion, Alnylam, Argenx, Biogen, Bristol Myers Squibb, CSL-Behring,
Genzyme, Grifols, Laboratoire Français des Biotechnologies, Merck-Serono, Natus,
Novartis, Pfizer, Pharmalliance, UCB Pharma, Teva, SNF-Floerger; travel grants
from Akcea, Alexion, Alnylam, Argenx, Biogen, CSL-Behring, Genzyme, Grifols,
Laboratoire Français des Biotechnologies, Merck-Serono, Natus, Novartis, Pfizer,
Teva, SNF-Floerger. O. Casez: BIOGEN (personal fees), ROCHE (personal fees, non
financial support (travelling/congress), MERCK (personal fees, non financial
support (travelling/congress), NOVARTIS (personal fees, non financial support
(travelling/congress), JANSEN (personal fees), SANOFI (personal fees). J. Ciron:
consulting, serving on a scientific advisory board, speaking, or other
activities with Biogen, Novartis, Merck, Sanofi, Roche, Alexion and Horizon
Therapeutics-Amgen. J. De Seze: consulting and lecturing fees, travel grants and
unconditional research support from Biogen, Genzyme, Novartis, Roche, Sanofi
Aventis and Teva Pharma. G. Defer: consulting and lecturing fees for Biogen,
Novartis, Genzyme, Merck-Serono, Roche and Teva and funding for travel from
Merck Serono, Biogen, Sanofi-Genzyme, Novartis and Teva. Institution granted for
research supporting from Merck Serono, Biogen, Genzyme and Novartis. O Heinzlef:
consulting and lecturing fees from Bayer Schering, Merck, Teva, Genzyme,
Novartis, Almirall and BiogenIdec, travel grants from Novartis, Teva, Genzyme,
Merck Serono and Biogen Idec and research support from Roche, Merck and
Novartis. P. Labauge: fees and grants from Biogen, Sanofi Genzyme, Novartis,
Alexion, Merck. E. Le Page: consulting or lectures, and invitations for national
and international congresses from Biogen, Merck, Teva, Sanofi-Genzyme, Novartis
Alexion, research support from Teva and Biogen academic research grants from
PHRC and LFSEP, and travel grant from ARSEP Foundation. A. Leclancher: NOVARTIS
(participation in a board, hospitality for a congress); BIOPROJECT (conference
hospitality); UCB (hospitality for conferences and training) C. Louapre:
consulting or travel fees from Biogen, Merck, Novartis, Roche, Sanofi and
Oculis, and research grant from Biogen, none related to this study. E. Manchon:
consulting, serving on a scientific advisory board, speaking, or other
activities with Biogen, Novartis, Merck, Sanofi-Genzyme, Juvise and Roche. G.
Mathey: travel/accomodations/meeting expenses funded by BIOGEN, NOVARTIS,
SANOFI-GENZYME, MERCK, TEVA, and ROCHE. He had contracts for lectures or boards
with BIOGEN, SANOFI-GENZYME, ALEXION, ROCHE, MERCK and NOVARTIS without
compensation/honoraria. A. Ruet: personal fees or travel grants from Biogen,
Alexion, Novartis, Sanofi, Horizon therapeutics, Merck; her institution has
received research support from Biogen, BMS-Celgène, Sanofi, Roche, Merck. S.
Vucusik: consulting and lecture fees, travel grants and research support from
Biogen, Janssen, Merck, Novartis, Roche, Sandoz, Sanofi Genzyme and Teva Pharma.
All funding was paid to the Hospices Civils de Lyon or to a research
organization and did not result in any personal remuneration.B Brochet received
honoraria from Merck and Sanofi. E. Leray reports consulting and lecture fees or
travel grants from Alexion, Biogen, Genzyme, MedDay Pharmaceuticals, Merck,
Novartis, Roche; nothing related to the contents of the present work. All
remaining authors have declared no conflicts of interest.

Auteurs Bordeaux Neurocampus