European Journal of Neurology 2014, 21: e84
doi:10.1111/ene.12480
LETTER TO THE EDITOR
Comment on the letter by Messori et al. (European Journal of Neurology 2013; 20: e131) M. P. Sormani Department of Health Sciences, University of Genoa, Genoa, Italy Correspondence: M. P. Sormani, Department of Health Sciences, University of Genoa, Genoa, Italy (tel.: +39-0103538473; fax: +39-010-3538441; e-mail: [email protected]).
Keywords: demyelinating diseases, multiple sclerosis, neurological disorders Received: 27 December 2013 Accepted: 13 March 2014 Dear Editor, I read with interest the letter by Messori et al. [1] which reports an analysis that could, in principle, have important clinical implications for patients with multiple sclerosis (MS). On the basis of their analysis, the authors report evidence of the inefficacy of intramuscular (im) IFNb-1a, a drug that has been approved for relapsing remitting (RR) MS based on its ability to reduce relapse rate and disability progression [2]. I must address at least two reasons, however, for considering the analysis of Messori et al. and their consequent conclusions inadequate, at best.
First, when the authors took the numbers reported in the recent Cochrane meta-analysis [3] to quantify the overall effect of im-IFNb-1a, they included two (out of three) trials relative to the progressive form of the disease. However, im-IFNb-1a was not approved as a treatment for the progressive form of the disease, since it was not able to reduce the disability accumulation as measured by the Expanded Disability Status Scale in progressive MS patients (as every single drug approved for the treatment of MS) [4]. For this reason, combining trials in RR and in progressive MS to assess the efficacy of a drug is, at least, a questionable approach. More importantly, Messori et al. analyzed just one endpoint that was, as they claim, relapses over 24 months. However, by checking the quoted reference [3], the numbers are clearly relative to the summary estimates related to disability progression. Thus, according to a more realistic evaluation of their analysis, their results should suggest that im-IFNb-1a is of proven inefficacy on disability progression in a mix of RR and progressive MS patients: a very different message in comparison with that suggested by the authors and stressed by a title that now appears more inappropriate than striking. It is surprising that experienced scientists, finding that a drug approved both in the USA and in Europe and used
by thousands of MS patients worldwide is of ‘proven inefficacy’ on relapses in MS, would not be puzzled by this unusual result, possibly confusing relapses with disability progression.
Disclosure of conflicts of interest MPS has received personal compensation for consulting services and for speaking activities from Teva, Novartis, Merck Serono and Biogen Idec. References 1. Messori A, Fadda V, Maratea D, et al. Intramuscular IFNb-1a in multiple sclerosis: ‘no proof of effectiveness’ or ‘proof of no effectiveness’? Eur J Neurol 2013; 20: e131. 2. Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 1996; 39: 285–294. 3. Filippini G, Del Giovane C, Vacchi L, et al. Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis. Cochrane Database Syst Rev 2013; 6: CD008933. 4. Cohen JA, Cutter GR, Fischer JS, et al. Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 2002; 59: 679–687.
© 2014 The Author(s) European Journal of Neurology © 2014 EFNS
doi:10.1111/ene.12480
LETTER TO THE EDITOR
Comment on the letter by Messori et al. (European Journal of Neurology 2013; 20: e131) M. P. Sormani Department of Health Sciences, University of Genoa, Genoa, Italy Correspondence: M. P. Sormani, Department of Health Sciences, University of Genoa, Genoa, Italy (tel.: +39-0103538473; fax: +39-010-3538441; e-mail: [email protected]).
Keywords: demyelinating diseases, multiple sclerosis, neurological disorders Received: 27 December 2013 Accepted: 13 March 2014 Dear Editor, I read with interest the letter by Messori et al. [1] which reports an analysis that could, in principle, have important clinical implications for patients with multiple sclerosis (MS). On the basis of their analysis, the authors report evidence of the inefficacy of intramuscular (im) IFNb-1a, a drug that has been approved for relapsing remitting (RR) MS based on its ability to reduce relapse rate and disability progression [2]. I must address at least two reasons, however, for considering the analysis of Messori et al. and their consequent conclusions inadequate, at best.
First, when the authors took the numbers reported in the recent Cochrane meta-analysis [3] to quantify the overall effect of im-IFNb-1a, they included two (out of three) trials relative to the progressive form of the disease. However, im-IFNb-1a was not approved as a treatment for the progressive form of the disease, since it was not able to reduce the disability accumulation as measured by the Expanded Disability Status Scale in progressive MS patients (as every single drug approved for the treatment of MS) [4]. For this reason, combining trials in RR and in progressive MS to assess the efficacy of a drug is, at least, a questionable approach. More importantly, Messori et al. analyzed just one endpoint that was, as they claim, relapses over 24 months. However, by checking the quoted reference [3], the numbers are clearly relative to the summary estimates related to disability progression. Thus, according to a more realistic evaluation of their analysis, their results should suggest that im-IFNb-1a is of proven inefficacy on disability progression in a mix of RR and progressive MS patients: a very different message in comparison with that suggested by the authors and stressed by a title that now appears more inappropriate than striking. It is surprising that experienced scientists, finding that a drug approved both in the USA and in Europe and used
by thousands of MS patients worldwide is of ‘proven inefficacy’ on relapses in MS, would not be puzzled by this unusual result, possibly confusing relapses with disability progression.
Disclosure of conflicts of interest MPS has received personal compensation for consulting services and for speaking activities from Teva, Novartis, Merck Serono and Biogen Idec. References 1. Messori A, Fadda V, Maratea D, et al. Intramuscular IFNb-1a in multiple sclerosis: ‘no proof of effectiveness’ or ‘proof of no effectiveness’? Eur J Neurol 2013; 20: e131. 2. Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 1996; 39: 285–294. 3. Filippini G, Del Giovane C, Vacchi L, et al. Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis. Cochrane Database Syst Rev 2013; 6: CD008933. 4. Cohen JA, Cutter GR, Fischer JS, et al. Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 2002; 59: 679–687.
© 2014 The Author(s) European Journal of Neurology © 2014 EFNS
