To the Editor: McHutchison et al. (Nov. 29 issue)1 report thateltrombopag (a thrombopoietin-receptor agonist) raises the plateletcount in patients with hepatitis C cirrhosis and thrombocytopenia.Its application in treating interferon-induced thrombocytopenia,however, necessitates that it improve the sustained virologicresponse. Even among patients with cirrhosis, thrombocytopenialeads to discontinuation of treatment in only 2% of patients.2Of interest, therefore, is the question of whether eltrombopagprevents the reduction in the dose of interferon that partiallyexplains the poor sustained virologic response in cirrhosis.3McHutchison et al. state that in their study, platelet countsremained higher than the level at which a reduction in the peginterferondose is recommended (<50,000 per cubic millimeter). The lowerend of the range for all eltrombopag groups was below this level,however, at the end of antiviral treatment. The authors' analysisof antiviral-treatment completion also includes five patientswhose baseline platelet levels were above the inclusion criterion.If two of these patients in the 30-mg group completed treatment,then their exclusion would have meant that there was no significantdifference from placebo at this dose.
Adam Lawson, B.M., B.S. University Hospital Nottingham Nottingham NG7 2UH, United Kingdom
References
McHutchison JG, Dusheiko G, Shiffman ML, et al. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med 2007;357:2227-2236. [Free Full Text]
Heathcote EJ, Shiffman ML, Cooksley WGE, et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N Engl J Med 2000;343:1673-1680. [Free Full Text]
McHutchison JG, Manns M, Patel K, et al. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology 2002;123:1061-1069. [CrossRef][Web of Science]
To the Editor: In the study of eltrombopag in the treatmentof idiopathic thrombocytopenic purpura (ITP), reported by Busselet al. (Nov. 29 issue),1 some patients received concomitantmedication for ITP, but the authors do not indicate which medication.In patients concomitantly treated with danazol, platelet countsmight have increased because of danazol, not eltrombopag.
Jacques Zimmer, M.D., Ph.D. François Hentges, M.D. CRP-Santé L-1526 Luxemburg City, Luxemburg jacques.zimmer{at}crp-sante.lu
Emmanuel Andrès, M.D. Hôpitaux Universitairesde Strasbourg F-67091 Strasburg, France
References
Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 2007;357:2237-2247. [Free Full Text]
Dr. McHutchison replies: Lawson cites the report by Heathcote et al., which indicates that only 2 to 4% of patients treatedwith peginterferon alfa-2a required a dose reduction for thrombocytopenia.1That study, however, excluded patients with baseline plateletcounts of less than 75,000 per cubic millimeter and hence doesnot represent the population studied in our trial or the populationtargeted in ongoing trials.
Of the five patients with baseline platelet counts that were70,000 or more per cubic millimeter (with the numbers accordingto study group listed correctly in Table 1 of our article butincorrectly in the legend for Fig. 1), three initiated and completedthe antiviral therapy phase (one in the 30-mg group and twoin the 75-mg group). Two patients did not enter the antiviraltherapy phase: one (in the 30-mg group) did not enter this phasebecause of an adverse event, and one (in the placebo group)had insufficient platelets for initiation of antiviral therapy.
John G. McHutchison, M.D. Duke Clinical Research Institute Durham, NC 27715 mchut001{at}mc.duke.edu
References
Heathcote EJ, Shiffman ML, Cooksley WGE, et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N Engl J Med 2000;343:1673-1680. [Free Full Text]
Dr. Bussel and colleagues reply: In our article, Figure 2D showsthat patients not receiving concomitant ITP medications hada good response to eltrombopag alone. When we compared patientswho received concomitant ITP medications with those who didnot, the response rates were as follows: placebo, 16.7% vs.9.5%; 30 mg, 44.4% vs. 20.0%; 50 mg, 72.7% vs. 68.8%; and 75mg, 60.0% vs. 93.8%. Of the patients receiving concomitant ITPmedications (6 in the placebo group [21%], 10 in the group receiving30 mg of eltrombopag [33%], 12 in the 50-mg group [40%], and10 in the 75-mg group [36%]), the majority were taking corticosteroids(21%, 33%, 37%, and 32%, respectively). Six patients were receivingdanazol (one in the placebo group and five in the group receiving50 mg of eltrombopag). In four of these five patients in the50-mg group (each of whom had taken danazol for at least 139days without a response), platelet counts of 171,000, 369,000,499,000, and 652,000 per cubic millimeter were achieved. Afterthe patients had discontinued eltrombopag (while they were continuingto receive danazol), the platelet counts decreased to 43,000,5000, 14,000, and 55,000 per cubic millimeter, respectively,indicating that eltrombopag, not danazol, was responsible forthese large increases in platelets.
James B. Bussel, M.D. Weill Cornell Medical College New York, NY 10065 jbussel{at}med.cornell.edu
Nicole L. Stone, Ph.D. Michael Arning, M.D., Ph.D. GlaxoSmithKline Collegeville, PA 19426-0989
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