Anti-inflammatory disease-modifying treatment and disability progression in primary progressive multiple sclerosis: a cohort study

J. Lorscheider, J. Kuhle, G. Izquierdo, A. Lugaresi, E. Havrdova, D. Horakova, R. Hupperts, P. Duquette, M. Girard, A. Prat, F. Grand'Maison, P. Grammond, P. Sola, D. Ferraro, M. Trojano, C. Ramo-Tello, J. Lechner-Scott, E. Pucci, C. Solaro, M. Slee & 7 others V. Van Pesch, J. L. Sanchez Menoyo, A. van der Walt, H. Butzkueven, L. Kappos, T. Kalincik, on behalf of the MSBase Study Group

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background and purpose: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti-inflammatory disease-modifying treatment on disability outcomes in PPMS. Methods: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease-modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses. Results: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on-study pairwise-censored follow-up was 3.4 years (quartiles 1.2–5.5). No difference in the hazard of experiencing 3-month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6–1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6–1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7–1.6, P = 0.69). Conclusion: Our pooled analysis of disease-modifying agents suggests that these therapies have no substantial effect on short- to medium-term disability outcomes in PPMS.

Original languageEnglish
Pages (from-to)363-370
Number of pages8
JournalEuropean Journal of Neurology
Volume26
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019

Keywords

  • clinical outcomes
  • immunomodulation
  • multiple sclerosis
  • observational study
  • primary progressive

Cite this

Lorscheider, J., Kuhle, J., Izquierdo, G., Lugaresi, A., Havrdova, E., Horakova, D., ... on behalf of the MSBase Study Group (2019). Anti-inflammatory disease-modifying treatment and disability progression in primary progressive multiple sclerosis: a cohort study. European Journal of Neurology, 26(2), 363-370. https://doi.org/10.1111/ene.13824
Lorscheider, J. ; Kuhle, J. ; Izquierdo, G. ; Lugaresi, A. ; Havrdova, E. ; Horakova, D. ; Hupperts, R. ; Duquette, P. ; Girard, M. ; Prat, A. ; Grand'Maison, F. ; Grammond, P. ; Sola, P. ; Ferraro, D. ; Trojano, M. ; Ramo-Tello, C. ; Lechner-Scott, J. ; Pucci, E. ; Solaro, C. ; Slee, M. ; Van Pesch, V. ; Sanchez Menoyo, J. L. ; van der Walt, A. ; Butzkueven, H. ; Kappos, L. ; Kalincik, T. ; on behalf of the MSBase Study Group. / Anti-inflammatory disease-modifying treatment and disability progression in primary progressive multiple sclerosis : a cohort study. In: European Journal of Neurology. 2019 ; Vol. 26, No. 2. pp. 363-370.
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abstract = "Background and purpose: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti-inflammatory disease-modifying treatment on disability outcomes in PPMS. Methods: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease-modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses. Results: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on-study pairwise-censored follow-up was 3.4 years (quartiles 1.2–5.5). No difference in the hazard of experiencing 3-month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95{\%} confidence interval (CI), 0.6–1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95{\%} CI, 0.6–1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95{\%} CI, 0.7–1.6, P = 0.69). Conclusion: Our pooled analysis of disease-modifying agents suggests that these therapies have no substantial effect on short- to medium-term disability outcomes in PPMS.",
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author = "J. Lorscheider and J. Kuhle and G. Izquierdo and A. Lugaresi and E. Havrdova and D. Horakova and R. Hupperts and P. Duquette and M. Girard and A. Prat and F. Grand'Maison and P. Grammond and P. Sola and D. Ferraro and M. Trojano and C. Ramo-Tello and J. Lechner-Scott and E. Pucci and C. Solaro and M. Slee and {Van Pesch}, V. and {Sanchez Menoyo}, {J. L.} and {van der Walt}, A. and H. Butzkueven and L. Kappos and T. Kalincik and {on behalf of the MSBase Study Group}",
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Lorscheider, J, Kuhle, J, Izquierdo, G, Lugaresi, A, Havrdova, E, Horakova, D, Hupperts, R, Duquette, P, Girard, M, Prat, A, Grand'Maison, F, Grammond, P, Sola, P, Ferraro, D, Trojano, M, Ramo-Tello, C, Lechner-Scott, J, Pucci, E, Solaro, C, Slee, M, Van Pesch, V, Sanchez Menoyo, JL, van der Walt, A, Butzkueven, H, Kappos, L, Kalincik, T & on behalf of the MSBase Study Group 2019, 'Anti-inflammatory disease-modifying treatment and disability progression in primary progressive multiple sclerosis: a cohort study' European Journal of Neurology, vol. 26, no. 2, pp. 363-370. https://doi.org/10.1111/ene.13824

Anti-inflammatory disease-modifying treatment and disability progression in primary progressive multiple sclerosis : a cohort study. / Lorscheider, J.; Kuhle, J.; Izquierdo, G.; Lugaresi, A.; Havrdova, E.; Horakova, D.; Hupperts, R.; Duquette, P.; Girard, M.; Prat, A.; Grand'Maison, F.; Grammond, P.; Sola, P.; Ferraro, D.; Trojano, M.; Ramo-Tello, C.; Lechner-Scott, J.; Pucci, E.; Solaro, C.; Slee, M.; Van Pesch, V.; Sanchez Menoyo, J. L.; van der Walt, A.; Butzkueven, H.; Kappos, L.; Kalincik, T.; on behalf of the MSBase Study Group.

In: European Journal of Neurology, Vol. 26, No. 2, 01.02.2019, p. 363-370.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Anti-inflammatory disease-modifying treatment and disability progression in primary progressive multiple sclerosis

T2 - a cohort study

AU - Lorscheider, J.

AU - Kuhle, J.

AU - Izquierdo, G.

AU - Lugaresi, A.

AU - Havrdova, E.

AU - Horakova, D.

AU - Hupperts, R.

AU - Duquette, P.

AU - Girard, M.

AU - Prat, A.

AU - Grand'Maison, F.

AU - Grammond, P.

AU - Sola, P.

AU - Ferraro, D.

AU - Trojano, M.

AU - Ramo-Tello, C.

AU - Lechner-Scott, J.

AU - Pucci, E.

AU - Solaro, C.

AU - Slee, M.

AU - Van Pesch, V.

AU - Sanchez Menoyo, J. L.

AU - van der Walt, A.

AU - Butzkueven, H.

AU - Kappos, L.

AU - Kalincik, T.

AU - on behalf of the MSBase Study Group

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Background and purpose: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti-inflammatory disease-modifying treatment on disability outcomes in PPMS. Methods: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease-modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses. Results: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on-study pairwise-censored follow-up was 3.4 years (quartiles 1.2–5.5). No difference in the hazard of experiencing 3-month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6–1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6–1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7–1.6, P = 0.69). Conclusion: Our pooled analysis of disease-modifying agents suggests that these therapies have no substantial effect on short- to medium-term disability outcomes in PPMS.

AB - Background and purpose: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti-inflammatory disease-modifying treatment on disability outcomes in PPMS. Methods: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease-modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses. Results: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on-study pairwise-censored follow-up was 3.4 years (quartiles 1.2–5.5). No difference in the hazard of experiencing 3-month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6–1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6–1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7–1.6, P = 0.69). Conclusion: Our pooled analysis of disease-modifying agents suggests that these therapies have no substantial effect on short- to medium-term disability outcomes in PPMS.

KW - clinical outcomes

KW - immunomodulation

KW - multiple sclerosis

KW - observational study

KW - primary progressive

UR - http://www.scopus.com/inward/record.url?scp=85055939122&partnerID=8YFLogxK

U2 - 10.1111/ene.13824

DO - 10.1111/ene.13824

M3 - Article

VL - 26

SP - 363

EP - 370

JO - European Journal of Neurology

JF - European Journal of Neurology

SN - 1351-5101

IS - 2

ER -