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Switching first-line disease-modifying therapy after failure: impact on the course of relapsing–remitting multiple sclerosis

Multiple Sclerosis Center, Department of Neurology, University of California, San Francisco, California, USA; Department of Neurological and Vision Sciences, University of Verona, Verona, Italy

P Bacchetti

Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA

B Grimes

Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA

A High

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA

E Waubant

Multiple Sclerosis Center, Department of Neurology, University of California, San Francisco, California, USA emmanuelle.waubant{at}ucsf.edu

Background

Options for non-responders to relapsing–remitting multiple sclerosis (RRMS) first-line disease-modifying therapies (DMT) are limited. We explored whether switching first-line DMT is effective.

Methods

Patients with RRMS who first received interferon-beta (IFNB) or glatiramer acetate (GA) were classified in three categories: DMT change because of suboptimal response, DMT change because of other reasons, and no DMT change during follow-up. Outcomes included annualized relapse rate (ARR) and relapse-free proportions.

Results

We identified 597 patients who initiated first-line DMT. For patients who did not change DMT (n = 240), pre-DMT and on-DMT median ARR were 0.50 and 0 (P < 0.0001). At 24 months, 76% (95%CI = 69–81%) of patients who did not change DMT were relapse-free. Of the 155 who switched because of suboptimal response, 101 switched to another first-line DMT. Median ARR pre-DMT, on first DMT and second DMT were: 0.50, 0.55, and 0.25 for switchers from IFNB to GA (IFNB/GA, n = 12) (pre-DMT versus first DMT: P = 0.92; first versus second DMT: P = 0.31); 0.90, 0.50, and 0 for switchers from GA to IFNB (GA/IFNB, n = 18; P = 0.19; P = 0.01); 0.50, 0.68, and 0 for switchers from an IFNB to another IFNB (IFNB/IFNB’, n = 71; P = 0.34; P = 0.02). Estimated relapse-free proportion after 24 months of treatment was 42% (95%CI=15–66%) during the period on IFNB versus 53% (95%CI = 17–80%) on GA for IFNB/GA (P = 0.21); 12% (95%CI = 0–40%) on GA versus 87% (95%CI = 59–97%) on IFNB for GA/IFNB (P = 0.001); and 41% (95%CI = 29–52%) on initial IFNB versus 67% (95%CI = 53–79%) on subsequent IFNB for IFNB/IFNB’ (P = 0.0001).

Conclusions

Switching first-line DMT in patients with RRMS failing initial therapy may be effective in many cases.

Key Words: disease-modifying therapy • multiple sclerosis • therapy switch • treatment failure

This version was published on January 1, 2009

Multiple Sclerosis, Vol. 15, No. 1, 50-58 (2009)
DOI: 10.1177/1352458508096687


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