We thank Zara G for her interest in our paper on "Rituximab in
patients with chronic inflammatory demyelinating polyradiculoneuropathy
(CIDP): a report of 13 cases and review of the literature" (1). Most of
her comment reflect indeed what we reported and discussed in the
manuscript. We would like just to make a few comments to clarify some
aspects.
We were induced to perform this study by the few anecdotal reports (2-4)
on the efficacy of Rituximab in patients with chronic inflammatory
demyelinating polyradiculoneuropathy (CIDP). We therefore retrospectively
analysed the response to therapy in a series of patients with CIDP
unresponsive to conventional therapies treated independently in different
centres. In only few patients peripheral blood immunophenotype was
characterized before therapy and this is why we did not include the data
on the manuscript. From a diagnostic point of view all our patients had
indeed a chronic demyelinating polyneuropathy that fulfilled the
diagnostic criteria of CIDP proposed by European Federation of
Neurological Societies/Peripheral Nerve Society (5). According to these
criteria patients with IgM monoclonal gammopathy are excluded from the
diagnosis of CIDP if they have anti-MAG antibodies otherwise they are
included in the diagnosis of CIDP associated with other diseases. The
results of our study may indeed raise some concerns about including in
CIDP patients with IgM monoclonal gammopathy and no anti-MAG reactivity,
as they appear, at least from our retrospective study, to have a better
response to Rituximab than patients with idiopathic CIDP. It is not
possible however to know if a reduction of antibodies caused the
improvement since we did not find any reactivity with nerve in our
patients. Other factors, including the effect of Rituximab on
immunoregulatory T cell, may have also been implicated in the response to
therapy (6-8). In our study we also analysed a few additional
neurophysiologic parameters, besides motor conduction velocity (MCV),
including compound muscle action potential (CMAP) amplitudes, distal
latencies and F waves. We only included data on MCV as these showed the
higher improvement. These data are however only ancillary to our study
which mainly relies on clinical findings. This was also the case of the
recent randomized controlled trials on CIDP (MTX e IFN) where the results
of electrophysiologic studies were not included in the main study. In
conclusion our retrospective study confirms that Rituximab may have some
efficacy in patients with CIDP particularly when associated with
haematological diseases even if the data need to be confirmed in a
randomized controlled study. In the meantime, we think that Rituximab may
be considered as a possible option for patients with CIDP associated with
haematological diseases not responsive to conventional therapy.
References
1. Benedetti L, Briani C, Franciotta D, et al. Rituximab in patients
with CIDP: A report of 13 cases and review of the literature. J Neurol
Neurosurg Psychiatry 2010 Jul 16. [Epub ahead of print]
2. Knecht H, Baumberger M, Tobon A, et al. Sustained remission of CIDP
associated with Evans syndrome. Neurology 2004;63:730-2.
3. Briani C, Zara G, Zambello R, et al. Rituximab-responsive CIDP.
European Journal of Neurology 2004;11:788-791.
4. Benedetti L, Franciotta D, Beronio A, et al. Rituximab efficacy in CIDP
associated with idiopathic thrombocytopenic purpura. Muscle & Nerve
2008;38:1076-1077.
5. Hughes RA, Bouche P, Cornblath DR, et al. European Federation of
Neurological Societies/Peripheral Nerve Society guideline on management of
chronic inflammatory demyelinating polyradiculoneuropathy: report of a
joint task force of the European Federation of Neurological Societies and
the Peripheral Nerve Society. Eur J Neurol. 2006;13:326-332.
6. Dalakas MC, Rakocevic G, Salajegheh M, et al. A placebo-controlled
trial of rituximab in IgM anti-myelin-associated glycoprotein antibody
demyelinating neuropathy. Ann Neurol 2009;65:286-93.
7. Eisenberg R, Looney RJ. The therapeutic potential of anti-CD20 "what do
B-cells do?".Clin Immunol. 2005;117:207-13.
8. Stasi R. Rituximab in autoimmune hematologic diseases: not just a
matter of B cells. Semin Hematol. 2010;47:170-9.
Conflict of Interest:
None declared
We thank Zara G for her interest in our paper on "Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): a report of 13 cases and review of the literature" (1). Most of her comment reflect indeed what we reported and discussed in the manuscript. We would like just to make a few comments to clarify some aspects. We were induced to perform this study by the few anecdotal reports (2-4) on the efficacy of Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We therefore retrospectively analysed the response to therapy in a series of patients with CIDP unresponsive to conventional therapies treated independently in different centres. In only few patients peripheral blood immunophenotype was characterized before therapy and this is why we did not include the data on the manuscript. From a diagnostic point of view all our patients had indeed a chronic demyelinating polyneuropathy that fulfilled the diagnostic criteria of CIDP proposed by European Federation of Neurological Societies/Peripheral Nerve Society (5). According to these criteria patients with IgM monoclonal gammopathy are excluded from the diagnosis of CIDP if they have anti-MAG antibodies otherwise they are included in the diagnosis of CIDP associated with other diseases. The results of our study may indeed raise some concerns about including in CIDP patients with IgM monoclonal gammopathy and no anti-MAG reactivity, as they appear, at least from our retrospective study, to have a better response to Rituximab than patients with idiopathic CIDP. It is not possible however to know if a reduction of antibodies caused the improvement since we did not find any reactivity with nerve in our patients. Other factors, including the effect of Rituximab on immunoregulatory T cell, may have also been implicated in the response to therapy (6-8). In our study we also analysed a few additional neurophysiologic parameters, besides motor conduction velocity (MCV), including compound muscle action potential (CMAP) amplitudes, distal latencies and F waves. We only included data on MCV as these showed the higher improvement. These data are however only ancillary to our study which mainly relies on clinical findings. This was also the case of the recent randomized controlled trials on CIDP (MTX e IFN) where the results of electrophysiologic studies were not included in the main study. In conclusion our retrospective study confirms that Rituximab may have some efficacy in patients with CIDP particularly when associated with haematological diseases even if the data need to be confirmed in a randomized controlled study. In the meantime, we think that Rituximab may be considered as a possible option for patients with CIDP associated with haematological diseases not responsive to conventional therapy.
References
1. Benedetti L, Briani C, Franciotta D, et al. Rituximab in patients with CIDP: A report of 13 cases and review of the literature. J Neurol Neurosurg Psychiatry 2010 Jul 16. [Epub ahead of print]
2. Knecht H, Baumberger M, Tobon A, et al. Sustained remission of CIDP associated with Evans syndrome. Neurology 2004;63:730-2.
3. Briani C, Zara G, Zambello R, et al. Rituximab-responsive CIDP. European Journal of Neurology 2004;11:788-791.
4. Benedetti L, Franciotta D, Beronio A, et al. Rituximab efficacy in CIDP associated with idiopathic thrombocytopenic purpura. Muscle & Nerve 2008;38:1076-1077.
5. Hughes RA, Bouche P, Cornblath DR, et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. 2006;13:326-332.
6. Dalakas MC, Rakocevic G, Salajegheh M, et al. A placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein antibody demyelinating neuropathy. Ann Neurol 2009;65:286-93.
7. Eisenberg R, Looney RJ. The therapeutic potential of anti-CD20 "what do B-cells do?".Clin Immunol. 2005;117:207-13.
8. Stasi R. Rituximab in autoimmune hematologic diseases: not just a matter of B cells. Semin Hematol. 2010;47:170-9.
Conflict of Interest:
None declared