{
  "abstract": "Background The ASCEND trial did not find benefit of natalizumab during secondary progressive multiple sclerosis compared to placebo, however its open label extension suggests this may be obscured by therapeutic lag.We aimed to compare the efficacy of natalizumab and interferon β-1a in slowing disease progression in secondary progressive multiple sclerosis after accounting for therapeutic lag.Methods We analysed pooled data from the ASCEND (natalizumab vs placebo) and SPECTRIMS (interferon β-1a vs placebo) trials. Cumulative hazards of six-month confirmed disability progression during secondary progressive multiple sclerosis were compared using Cox proportional hazards models adjusted for confounding variables. We accounted for therapeutic lag in each patient based on baseline EDSS, annualised relapse rate, and sex. Differences between SPECTRIMS and ASCEND placebo arms were used to adjust the differences between interferon β-1a and natalizumab arms.Results Baseline characteristics of 1156 patients were similar between SPECTRIMS and ASCEND cohorts, except for a higher proportion of older patients and lower relapse rates in the ASCEND trial. Natalizumab exhibited a lower cumulative hazard of disability progression compared to interferon β-1a (HR 0·15, 95% CI 0·08 – 0·29, p<0·0001). After adjusting for the difference in cumulative hazards between placebo groups (HR 0·36, 95% CI 0·20 – 0·63, p=0·0004), natalizumab remained associated with a lower hazard of disability progression compared to interferon β-1a (HR 0·42, 95% CI 0·22 – 0·77, p=0·0016).Conclusion After accounting for therapeutic lag and differences between ASCEND and SPECTRIMS trials, natalizumab, compared with interferon β-1a, reduces disability progression during secondary progressive multiple sclerosis.",
  "authors": [
    {
      "affiliations": [
        "Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia",
        "CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia"
      ],
      "name": "Winston Dzau"
    },
    {
      "affiliations": [
        "Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia",
        "CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia"
      ],
      "name": "Izanne Roos"
    },
    {
      "affiliations": [
        "Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia",
        "CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia"
      ],
      "name": "Tomas Kalincik"
    }
  ],
  "title": "3620 Efficacy of natalizumab in secondary progressive multiple sclerosis: analysis of two phase 3 trials",
  "uid": "59e62c50-cf8a-5024-bdfa-86669e148b83"
}