colleagues' concern that there may be bias toward patients with more progressive disease in the control group compared with the treated group appears unlikely.
The 20% of patients in the control group who had discontinued immunomodulatory or immunosuppressive treatment in the first 3 to 6 weeks because of adverse events were not included in the treatment group intention-to-treat analysis because they were not receiving these therapies at the beginning of the follow-up. Moreover, the treatment group included only patients treated with interferon-β€ for at least 1 year. For potential imbalance between groups because of differences in patient attitude toward interferon-β€ treatment (eg, voluntary refusal of treatment), the expression "in ways not clearly measurable" given by Koch and colleagues appropriately stresses the importance of our sensitivity analysis.
Regarding the lack of blinding, we agree this might be of serious concern. Accordingly, this issue was addressed in the Discussion, 1 and it is a well-known, unavoidable bias in all observational studies.
We reported a global measure of patients' adherence to treatment, defined as the proportion of days covered by treatment (75.1%). The presence of differential loss to follow-up (ie, informative censoring) between the two arms was addressed 1 by assessing the consistency of the hazard ratios censoring the analysis to shorter time frames (from 6 to 3 years). Moreover, it is not appropriate to report absolute numbers of patients at risk for each year because this would be misleading when referring to an adjusted analysis. Finally, concerning the outcomes (secondary progression and Expanded Disability Status Scale scores of 4 and 6), we stated 1 that they were confirmed at 6 months, but also at the end of follow-up. However, we agree that it is better to say "confirmed" rather than "irreversible" disability.