icon-folder.gif   Conference Reports for NATAP  
  American Association for the Study of Liver Diseases 2003 Conference
Boston, MA
Oct 24-28, 2003
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Rofecoxib (Vioxx) Prevents Reduction in Platelets During Pegasys Therapy for HCV: short term pilot study
  Reported by Jules Levin
David H Van Thiel and researchers at University Medical Center, Maywood, IL reported at AASLD (Oct 2003) on seeing increase of platelets during treatment for HCV with Pegasys. In order to improve tolerability for HCV IFN/RBV therapy non-steroidal ant-inflammatory medications are often used, such as Motrin, Tylenol, Advil, etc. Vioxx is an anti-arthritis drug sometimes often used by doctors for the same purpose, to reduce the body aches, arthralgia and myalgia, associated with IFN/RBV therapy. This pilot study reports for the first time that Vioxx may also improve platelet count reductions associated with IFN/RBV therapy, called thrombocytopenia.
Thrombocytopenia (reduced platelet count) is a major limiting factor in the treatment of chronic hepatitis C with interferon preparations. This is particularly true for individuals with advanced disease because of a combination of factors that include: 1) reduced thrombopoietin production by the diseased liver, 2) hypersplenism and 3) actions of interferon per se:
The use of a Cox II inhibitor like rofecoxib (Vioxx) is known to inhibit the inflammatory and vasoconstriction actions of prostacyclin but has little or no effect on prostaglandin production and any adverse effect on iNOS and the production of NO, actions that are inhibited by nonselective NSAIDS.
The aim of the present short-term pilot study was to define the effect of rofecoxib combined with Pegasys as compared to Pegasys therapy alone for chronic hepatitis C on platelet numbers and the expected decline in platelet numbers associated with Pegasys therapy.
18 subjects with chronic hepatitis C documented by positivity for anti-HCV, HCV-RNA and abnormal liver injury tests and a liver biopsy consistent with chronic hepatitis C were treated with Pegasys 180ug SQ weekly plus daily oral rofecoxib (12.5mg/day) (n = 9) or Pegasys alone (n = 9) for 8 weeks.
The changes in Hgb, WBC, platelet count, serum ALT, AST, BUN, creatinine and viral load were assessed weekly in both groups.
No differences in the levels of Hgb or WBC counts were evident between the two groups treated with Pegasys. Similarly, no change in the serum ALT, AST, BUN and creatinine levels were observed between the 2 groups.
In contrast, the platelet count declined from a mean baseline value of 193±13 in the group treated with Pegasys and rofecoxib such that at 8 weeks, the value was 162±12, a 16% decline. The decline in platelet count in the group not using rofecoxib was 41% with a reduction in platelets from 166 ±18 to a value of 89±11. (All comparisons p<0.005).
These data demonstrate that rofecoxib, when used in combination with Pegasys to treat advanced chronic hepatitis C, results in a highly significant reduction in the decline in platelet numbers associated with Pegasys therapy. Importantly, this platelet sparing effect of rofecoxib is not associated with an alteration in the values for Hgb, WBC, BUN or creatinine.
This suggests that patients with advanced disease (stage 3 or 4), who have baseline thrombocytopenia, should be treated with rofecoxib as well as Pegasys in an effort to avoid high-grade thrombocytopenia that might limit the dose or duration of Pegasys therapy when used alone to treat chronic hepatitis C.