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Correspondence: When an article is eligible for submission of Correspondence, a link to the response form is available within the full-text article. You must be a current subscriber who has activated the online portion of your subscription in order to send a Correspondence. Any reader can read published Correspondence.
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Correspondence:Correspondence published:
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![[Read Correspondence]](/icons/misc/sectionDOWN.gif)
Reply to Benatar
- Jerry Mendell, et al (10 June 2001)
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Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating
- Michael Benatar (10 June 2001)
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Jerry Mendell, Professor and Chair of Neurology Ohio State University, Columbus, et al
Send Correspondence to journal:
mendell.1{at}osu.edu Jerry Mendell, et al.
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We appreciate the comments of Dr. Benatar regarding our treatment trial of IVIg in CIDP. Clinical equipoise is an important issue that all investigators must consider in the design of any study. Dr. Benatar’s concern that published reports of IVIg, steroids, and plasmapheresis precluded the need for our investigation of IVIg of previously untreated patients is flawed because the majority of CIDP patients in former studies were on maintenance therapy or had been treated and were drug-resistant. It is an erroneous assumption that the induction and maintenance response to treatment is the same in a chronic disorder or one altered by prior or ongoing therapy. (9-11) Our study was critical in order to test the hypothesis that IVIg is beneficial to the drug-naïve CIDP patient. It was gratifying to demonstrate a response as early as 10 days with continued improvement for the full length of the trial exceeding the number of estimated responders. (12) Considering the extensive side effect profile of prednisone, the impediments to ongoing plasmapheresis including limited availability, indwelling lines, and need for immunosupression to accompany ongoing treatment, and the occurrence of spontaneous improvement in some patients. The investigators and their respective institutional review boards believed that a genuine state of uncertainty regarding the merits of different therapies existed at the time of this study. We can now say with assurance that no patients should be refused IVIg as initial treatment if the patient’s physician considers it the appropriate approach. We are indebted to Dr. Benatar for the opportunity to further emphasize the importance of our paper. References 9. Fauci AS, Haynes BF, Katz P, et al. Wegener's granulomatosis: prospective and therapeutic experience with 85 patients for 21 years. Ann Intern Med 1983;98:76-85. 10. Gordon M, Luqmani RA, Adu D et al. Relapses in patients with a systemic vasculitis. Q J Med 1993;86:779-789. 11. Jayne D, Gaskin G. Randomized trial of cyclophosphamide versus azathioprine during remission in ANCA-associated vasculitis (CYCAZAREM). J Am Soc Nephrol 1999;10:105A. 12. Choudhary PP, Hughes RAC. Long-term treatment of chronic inflammatory demyelinating polyradiculoneuropathy with plasma exchange or intravenous immunoglobulin. QJM 1995;88:493-502. |
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Michael Benatar Beth Israel Deaconess Medical Center, Boston
Send Correspondence to journal:
mbenatar{at}bidmc.harvard.edu Michael Benatar
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Mendell et al report the results of a double-blind placebo-controlled randomized trial of intravenous immunoglobulin (IVIg) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) (1). I would question the need for such a trial given that prednisone (2) plasmapheresis (3,4) and IVIg (5,6) have each previously been shown in prospective randomized controlled trials, to be effective in the treatment of CIDP. The authors cite a variety of reasons to justify their study. First, many patients enrolled in the prior studies of IVIg had previously received or were receiving other forms of immunomodulatory therapy and so it had not been unequivocally established that IVIg is effective in untreated CIDP. A second related issue is the challenge from third-party carriers that the evidence does not support the use of IVIg as first-line therapy. Finally, they note that IVIg is not approved by the FDA for the treatment of CIDP. None of these factors mitigate the claim that there is general agreement amongst those who treat patients with CIDP that steroids, IVIg and plasmapheresis are all effective forms of therapy. It is widely acknowledged that clinical equipoise should serve as the moral underpinning of the randomized control trial (RCT) (7). Clinical equipoise reflects a collective professional uncertainty over the best treatment option. While there is good evidence that prednisone, IVIg and plasmapheresis may each benefit patients with CIDP, it could reasonably be argued that equipoise is present regarding which of these therapies is most effective. The need, therefore, is for a trial that will disturb the equipoise that exists. This would dictate that any further randomized control trial compare two (or more) of the known effective therapies, rather than an already proven therapy with placebo. References 1. Mendell JR, Barohn RJ, Freimer ML, et al. Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropaty. Neurology 2001 56:445-449. 2. Dyck PJ, O’Brien PC, Oviatt KF, et al. Prednisone improves chronic inflammatory demyelinating polyradiculneuropathy more than no treatment. Ann Neurol 1982 11:136-141 3. Dyck PJ, Daube J, O’Brien P, et al. Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy. New England Journal of Medicine 1986 314(8):461-465 4. Hahn AF, Bolton CF, Pillay N, et al. Plasma-exchange therapy in chronic inflammatory demyelinating polyneuropathy – a double-blind, sham- controlled, cross-over study. Brain 1996 119:1055-1066 5. Hahn AF, Bolton CF, Zochodne D and Feasby TE. Intravenous immunoglobulin treatment in chronic inflammatroy demyelinating polyneuropathy – a double-blind, placebo-controlled, cross-over study. Brain 1996 119:1067-1077 6. Dyck PJ, Litchy WJ, Kratz KM, et al. A plasma exchange versus immune globulin infusion trial in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol 1994 36:838-845 7. Freedman B. Equipoise and the ethics of clinical research. New England Journal of Medicine 1987 317(3):141-145 |
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