Contributions
Abstract: P1197
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: From mid-1990s, interferon-β (IFN) are widely prescribed in patients with relapsing onset multiple sclerosis (MS). Studies about their long-term effect on disability showed contradictory results, probably due to methodological issues such as indication bias or immortal time bias.
Objective: Assess the long-term effect of IFN on disability progression in a large series of relapsing-remitting MS patients from the Rennes expert MS centre, France.
Methods: In this retrospective cohort study comparing IFN-treated group (N=1,172) and IFN-untreated group (N=1,279), inclusion was defined as the time of eligibility to IFN drugs in the period 1996-2015. We compared the time to reach an irreversible Expanded Disability Status Scale (EDSS) score of 6 between the two groups with an “intention to treat” (ITT) analysis, as recommended for efficacy studies. Treatment was studied as time-dependent covariate in a weighted Cox model using propensity score (PS). PS included gender, age, disease duration, number of relapses in the last 3 years and calendar year at inclusion.
Results: The mean±SD follow-up duration from inclusion was 9.6±5.8 years for IFN-treated and 6.9±5.3 for control groups. The number of patients reaching an irreversible EDSS score of 6 was higher in the IFN-treated group than in control group (155 (13%) vs 115 (9%), p=0.001). But IFN-treated patients and controls were different at inclusion regarding age (32.8±9.4 vs 35.1±10, p< 0.001) and MS duration (3.0±4.6 vs 4.3±5.6, p< 0.001). Use of PS makes the two groups comparable. The final Cox analysis gave a Hazard Ratio (HR) of 1.51 95%CI: 0.84 - 2.62. In a sensitivity analysis, patients with EDSS score of 4 or more at latest news but lost to follow-up for 5 years were assigned an irreversible EDSS score of 6, which led to a HR of 1.27 95%CI: 0.83 - 1.95.
Discussion: Our study did not permit to conclude to a significant benefit of IFN on disability progression. The inclusion at IFN eligibility combined with the use of PS allowed a high control of the indication bias. Moreover, considering treatment as time dependent variable, the exact treatment start was considered and the risk of immortal time bias was diminished. However, changes in treatment exposure (such as escalating therapy) cannot be taken into account with ITT analysis. Finally, our study may suffer from attrition bias and missed outcomes due to lack of regular follow-up in our expert centre.
Disclosure:
Lefort M. reports travel grants from Roche SAS. Her PhD, including the submitted work, is funded through donation from Roche SAS without any link with the scientific contents of this abstract and with only access to published work.
M. Goetz has no disclosure to report.
Pr. Edan reports personal fees from Sanofi, and personal fees and grants from Bayer, Merck Serono, Teva Pharma, Biogenidec, and Novartis, all outside the submitted work.
Dr Leray reports personal fees as speaker or consultant from Novartis and Sanofi Genzyme, outside the submitted work, and travel grants from Novartis and Roche SAS. Other sources of funding in the last year came from the French ARSEP Foundation, the French National Security Agency of Medicines and Health Products and the EDMUS Foundation
Abstract: P1197
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: From mid-1990s, interferon-β (IFN) are widely prescribed in patients with relapsing onset multiple sclerosis (MS). Studies about their long-term effect on disability showed contradictory results, probably due to methodological issues such as indication bias or immortal time bias.
Objective: Assess the long-term effect of IFN on disability progression in a large series of relapsing-remitting MS patients from the Rennes expert MS centre, France.
Methods: In this retrospective cohort study comparing IFN-treated group (N=1,172) and IFN-untreated group (N=1,279), inclusion was defined as the time of eligibility to IFN drugs in the period 1996-2015. We compared the time to reach an irreversible Expanded Disability Status Scale (EDSS) score of 6 between the two groups with an “intention to treat” (ITT) analysis, as recommended for efficacy studies. Treatment was studied as time-dependent covariate in a weighted Cox model using propensity score (PS). PS included gender, age, disease duration, number of relapses in the last 3 years and calendar year at inclusion.
Results: The mean±SD follow-up duration from inclusion was 9.6±5.8 years for IFN-treated and 6.9±5.3 for control groups. The number of patients reaching an irreversible EDSS score of 6 was higher in the IFN-treated group than in control group (155 (13%) vs 115 (9%), p=0.001). But IFN-treated patients and controls were different at inclusion regarding age (32.8±9.4 vs 35.1±10, p< 0.001) and MS duration (3.0±4.6 vs 4.3±5.6, p< 0.001). Use of PS makes the two groups comparable. The final Cox analysis gave a Hazard Ratio (HR) of 1.51 95%CI: 0.84 - 2.62. In a sensitivity analysis, patients with EDSS score of 4 or more at latest news but lost to follow-up for 5 years were assigned an irreversible EDSS score of 6, which led to a HR of 1.27 95%CI: 0.83 - 1.95.
Discussion: Our study did not permit to conclude to a significant benefit of IFN on disability progression. The inclusion at IFN eligibility combined with the use of PS allowed a high control of the indication bias. Moreover, considering treatment as time dependent variable, the exact treatment start was considered and the risk of immortal time bias was diminished. However, changes in treatment exposure (such as escalating therapy) cannot be taken into account with ITT analysis. Finally, our study may suffer from attrition bias and missed outcomes due to lack of regular follow-up in our expert centre.
Disclosure:
Lefort M. reports travel grants from Roche SAS. Her PhD, including the submitted work, is funded through donation from Roche SAS without any link with the scientific contents of this abstract and with only access to published work.
M. Goetz has no disclosure to report.
Pr. Edan reports personal fees from Sanofi, and personal fees and grants from Bayer, Merck Serono, Teva Pharma, Biogenidec, and Novartis, all outside the submitted work.
Dr Leray reports personal fees as speaker or consultant from Novartis and Sanofi Genzyme, outside the submitted work, and travel grants from Novartis and Roche SAS. Other sources of funding in the last year came from the French ARSEP Foundation, the French National Security Agency of Medicines and Health Products and the EDMUS Foundation