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Sir, Dr Greenberg misinterprets several important aspects of our study, including the scope and applied methodology. Below we have addressed the points raised in his correspondence.
This was a proof-of principle molecular clinicopathological study designed to investigate the effect of alemtuzumab on endomysial T cells and disease progression; it was not primarily a trial of clinical efficacy. As stated, alemtuzumab did not significantly improve patients’ strength and function but only induced short-term stability based on the difference between two time periods. Contrary to Dr Greenberg's comments, outcome was not based on any predetermined percentages that were subsequently amended. The percentages mentioned by Dr Greenberg were used only to power the sample size. As our results show, these percentages do not relate to the outcome or conclusions of the study because, regardless of whether a 10%, 13% or 15% difference is used, there is no significant improvement in the patients’ strength (as he correctly points out, only 4 of 13 patients improved, by only 4%–19%, while the mean strength for all patients declined by 1.9%).
Our data and the interpretation of results have now been ratified in an independent review by the National Institutes of Health. The main finding was a significant reduction of relevant molecules seen in repeated muscle biopsies, combined with short-term clinical stability; this is encouraging and, as we stressed, warrants a controlled study. One should not read more than that from these results. The study was arguably small and uncontrolled but taught us a lot about the pathogenesis of inclusion body myositis; it was not designed to demonstrate clinical efficacy and we do not recommend alemtuzumab as a treatment for inclusion body myositis.
Regarding Dr Greenberg's specific points (and necessarily restating some of our general responses already outlined), our comments are as follows:
We are enthusiastic about exploring further the use of alemtuzumab based on the significant short-term stability that we describe. Since publication, the National Institute of Neurological Disorders and Stroke requested an independent review of our paper and we are happy to confirm that the results have been independently verified; and our main message, that ‘the rate of strength decline 6 months after alemtuzumab was significantly reduced compared with the 12 month natural history period’ was ratified.
The significant modulation of relevant molecules in the repeated muscle biopsies, along with the noted strength gains in some patients, has been informative with respect to the pathogenesis of inclusion body myositis. We are pleased to have completed a difficult clinicopathological study, one of the few of its kind, and grateful to all our patients for contributing to the study.