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ARTICLES: S. D. Silberstein, L. K. Mannix, J. Goldstein, J. R. Couch, S. C. Byrd, M. H. Ames, S. A. McDonald, and S. E. Lener Multimechanistic (sumatriptan-naproxen) early intervention for the acute treatment of migraine Neurology 2008; 71: 114-121 [Abstract] [Full text] [PDF]

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Multimechanistic (sumatriptan-naproxen) early intervention for the acute treatment of migraine

Alan H. Lockwood   (22 January 2009)

Reply from the Authors

Stephen D. Silberstein, MD, L. K. Mannix (Cincinnati, OH), J. Goldstein (San Francisco, CA), J. R. Couch (Oklahoma City, OK), S. C. Byrd, M. H. Ames, S. A. McDonald, and S. E. Lener (Research Triangle Park, NC)   (22 January 2009)

Multimechanistic (sumatriptan-naproxen) early intervention for the acute treatment of migraine 22 January 2009
Alan H. Lockwood, Department of Neurology, University at Buffalo 100 High Street, Buffalo, NY, 14203 Send Correspondence to journal: Re: Multimechanistic (sumatriptan-naproxen) early intervention for the acute treatment of migraine ahl{at}buffalo.edu Alan H. Lockwood	The combination of sumatriptan 85 mg and naproxen sodium 500 mg is being heavily marketed by GlaxoSmithKline representatives as Treximet™ (sumptriptan/naproxen). The recent publication showing that this combination was superior to placebo for the relief of traditional and non-traditional migraine symptoms [1] is no surprise since the combination was shown to be superior to either of the two components or placebo in an earlier study, using traditional symptoms as endpoints. [2] A more appropriate question, posed under the rubric of the systems based practice core competency for resident training, is whether Treximet™ at about $22 dollars per dose is superior to 100 mg of generic sumatriptan taken simultaneously with 500 mg of naproxen at a cost of approximately $6.60. [3] In addition, the authors reported that the new formulation showed a "therapeutic advantage" over other formulations of sumatriptan at various end points in terms of the therapeutic gain, the therapeutic ratio, and the odds ratio. [1] However, these data were not presented nor was there a formal statistical analysis to buttress this claim. Now that this contention is published in Neurology, drug representatives are sure to emphasize this point. Finally, the acknowledgments state that Cynthia Toso assisted with the preparation of the manuscript. What was her role? In addition, why was the statistical analysis of the data performed by an employee of GlaxoSmithKline? References 1. Silberstein JD, Mannix LK, Goldstein MD et al. Multimechanistic (sumatriptan-naproxen) early intervention for the acute treatment of migraine. Neurology 2008;71:114-121. 2. Smith TR, Sunshine A, Stark SR. et al. Sumatriptan and naproxen sodium for the acute treatment of migraine. Headache 2005;45:983-991. 3. Available at: www.drugstore.com and www.shopping.com. Accessed on August 1, 2008. Disclosure: The author reports no disclosures.
Reply from the Authors 22 January 2009
Stephen D. Silberstein, MD, Jefferson Headache Center 111 South 11th Street, Suite 8130, Philadelphia, PA 19107, L. K. Mannix (Cincinnati, OH), J. Goldstein (San Francisco, CA), J. R. Couch (Oklahoma City, OK), S. C. Byrd, M. H. Ames, S. A. McDonald, and S. E. Lener (Research Triangle Park, NC) Send Correspondence to journal: Re: Reply from the Authors stephen.silberstein{at}jefferson.edu Stephen D. Silberstein, MD, et al.	Dr. Lockwood’s suggestion of a clinical trial comparing the benefits of sumatriptan-naproxen sodium with generic sumatriptan and naproxen sodium, while possible, has the following limitations: 1) the doses of the two marketed products are different than those in the combination tablet; 2) administration of two tablets requires patient compliance; and 3) the distinct pharmacokinetic profile of the fixed-dose single tablet cannot be guaranteed when co-administering two tablets. In addition, generic sumatriptan was not available at the time the studies were done and is still not available. While this trial may be clinically interesting, there is sufficient evidence to make prescribing decisions, balancing the benefits and risks to the patient, and the cost which is unknown. We intentionally did not include the presentation of new data (therapeutic gain, therapeutic ratio, and odds ratio) in the Discussion because the original citations were included in the article (Refs. 7,34-36). We have re-iterated them for the benefit of the readers. [4-7] Finally, all authors take full responsibility for the final content of this manuscript. Cynthia Toso assisted in early drafts of the manuscript. It is common practice in pharmaceutically-sponsored clinical trials for the company statistician, who has the expertise, to assist with the analysis of the data. References 4. Winner P, Landy S, Richardson M, Ames M. Early intervention in migraine with sumatriptan tablets 50 mg versus 100 mg: a pooled analysis of data from six clinical trials. Clin Ther 2005;27:1785–1794. 5. Fox AW, Keywood C, Sheftell FD, Spierings ELH, Winner P. Comparison of therapeutic gain with therapeutic ratio for the assessment of selective 5HT1B/1D agonist efficacy in migraine. Headache 2002;42:680–688. 6. Goadsby PJ, Ferrari MD, Lipton RB. Therapeutic gain or therapeutic ratio? Headache 2003;43:814–815; author reply 815–816. 7. McAlister FA, Laupacis A, Wells GA, Sackett DL. Users’guides to the medical literature: XIX: Applying clinical trial results B Guidelines for determining whether a drug is exerting (more than) a class effect. JAMA 1999;282:1371–1377. Disclosures: The study to which this corresondence refers was Sponsored by Pozen, Inc., and supported by GlaxoSmithKline, Research Triangle Park, NC. Dr. Silberstein is on the Advisory Panel or Speaker’s Bureau for Allergan, AstraZeneca, Endo Pharmaceuticals, GlaxoSmithKline, Medtronic, Merck, Ortho-McNeil, Pfizer, Pozen, and Valeant Pharmaceuticals. He receives research support from Abbott, Advanced Bionics, AGA, Advanced Neuro- Modulation Systems, Allergan, AstraZeneca, Endo Pharmaceuticals, Lilly, GlaxoSmithKline, Medtronic, Merck, OrthoMcNeil, Pfizer, Pozen, Pro- Ethic, Valeant Pharmaceuticals, and Vernalis. Dr. Mannix has served on the Advisory Board, Speaker’s Bureau, or as a consultant for Allergan, Endo Pharmaceuticals, GlaxoSmithKline, Merck, OMN, and Pfizer. She also receives research grants from Allergan, Endo Pharmaceuticals, GlaxoSmithKline, Merck, OMN, Pozen, and Alexza. Dr. Goldstein has served as a Consultant and/or served on Advisory Boards, Speaker Bureaus, conducted and/or received research support from Abbott Laboratories, Agouron Pharmaceuticals, Allergan Inc, Almirall, Alza Pharmaceuticals, Applied Analytical Industries, AstraZeneca, Bayer Corporation, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Bristol-Myers Products, Capnia Inc, Carnrick Laboratories, Cephalon Inc, Corcept Therapeutics, Daiichi Suntory Pharma, Eisai Inc, Elan Pharmaceuticals, Eli Lilly and Company, Forest Pharmaceuticals, Fujisawa Healthcare Inc, GlaxoSmithKline, Janssen/Johnson and Johnson, RWJohnson Pharmaceutical Research Institute, McNeil Consumer and Specialty Pharmaceuticals, Merck and Company, Mylan Pharmaceuticals, NPS Pharmaceutical, Neo Therapeutic, Novartis Pharmaceuticals, Ortho McNeil Pharmaceuticals, Parke-Davis, Pfizer Inc, Pharmacia, Pharmacia and Upjohn, Pozen, Proctor&Gamble, Renovis Inc, Roche Pharmaceuticals, Saegis Pharmaceuticals Inc, Sandoz Pharmaceuticals, Sanofi-Synthelabo Inc, Schwarz Bioscience, GD Searle, Syntex, UCB Pharma Inc, Vanguard Medica, Vernalis, Winston Laboratories, and Wyeth-Ayerst. Dr. James Couch has received research support from GlaxoSmithKline, Astra Zeneca, Merck, Pfizer, Ortho- McNeil, and Schwarz. He has also participated in Speakers Bureaus or Advisory Boards for GlaxoSmithKline, Astra Zeneca, Merck, Pfizer, and Ortho- McNeil. Susan Byrd, Michael Ames, Susan McDonald, and Shelly Lener are current employees of GlaxoSmithKline, and Michael Ames carried out the biostatistical analysis. Editors’ Note: After review by the Editors and further clarification by the authors, it was determined that Cynthia Toso played a role in drafting the original Silbertstein et al. manuscript. Ms. Toso was included in the Acknowledgments but should have been included in the byline as a co-author. Neurology’s policy effective December 15, 2006 states that “Manuscripts submitted for publication must list all authors, including the person who drafted the original manuscript. This includes paid or unpaid medical writers (“ghost writers”).” A Correction will be included a forthcoming print issue noting the error.