Chronic Vulvovaginal Candidiasis
http://www.100md.com
《新英格兰医药杂志》
To the Editor: The results of the study of maintenance fluconazole therapy for recurrent vulvovaginal candidiasis by Sobel et al. (Aug. 26 issue)1 are misleading. A better assessment of the effect of weekly maintenance fluconazole therapy would be obtained by comparing the proportions of women who were free of disease at a given time after the most recent dose of fluconazole. This study shows that women who receive weekly therapy with fluconazole for six months have a 57 percent chance of a recurrence within six months after the last dose of fluconazole, whereas women who receive one dose of fluconazole have a 64 percent chance of a recurrence within six months after the last dose of fluconazole. This small difference hardly seems worth the expense or risk of weekly fluconazole therapy.
Christopher T. Kuebrich, M.D.
2120 Driftwood Blvd.
Kenner, LA 70065
kuebrich@cox.net
References
Sobel JD, Wiesenfeld HC, Martens M, et al. Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis. N Engl J Med 2004;351:876-883.
To the Editor: The report by Sobel et al. mentions briefly the effectiveness of intravaginal antimycotic agents, which were previously found to be effective but are now deemed "inconvenient and expensive." A comparison at a local pharmacy revealed that the course of fluconazole advocated in the report costs $457.89, versus $30.82 for a similar regimen of intravaginal clotrimazole. Of concern is Dr. Eschenbach's conclusion, in his Perspective article accompanying the report,1 that "managed care groups need to start authorizing payment for prolonged suppressive therapy with fluconazole or intravaginal azoles."
Daniel R. Retzer, M.D.
Swedish American Primary Care Group
Byron, IL 61010
sk8indr@aol.com
References
Eschenbach DA. Chronic vulvovaginal candidiasis. N Engl J Med 2004;351:851-852.
Dr. Sobel replies: Dr. Kuebrich asserts that the results that my colleagues and I report in our article are misleading; he maintains that we should have compared disease-free activity in the two groups at the same time after the most recent dose of fluconazole. This would entail comparing the cure rate at 6 months of follow-up in the placebo group (35.9 percent) with that in the fluconazole group at the 12-month follow-up (42.9 percent). In fact, the difference in the cure rate at the same point in time (12 months) between the groups was found to be significant (P<0.001). Comparing the two groups at different times points is not valid, although Dr. Kuebrich's underlying premise is entirely reasonable. The fundamental goal of the study was not to show that maintenance fluconazole therapy is curative but to show that as long as once-weekly fluconazole was administered, women previously incapacitated by frequent recurrent episodes of symptomatic vaginitis had more than a 90 percent likelihood of protection from clinical recurrence. Unfortunately, few women were actually cured by taking fluconazole (approximately 21 percent) when one compares the fluconazole and placebo groups at the same end-of-study point (42.9 percent vs. 21.9 percent, P<0.001).
The maintenance dose therefore does not result in a cure in the majority of women, and the low dose used may be part of the explanation. We emphasize the lack of a long-term cure in the report. The relief from frequent relapses is anything but trivial, and, as we show, the associated risk is minimal.
Cost remains an issue. Dr. Retzer correctly emphasizes the cost of weekly fluconazole; however, since the generic brand became available in early August 2004, the cost of weekly fluconazole has declined by approximately 75 percent. The monthly cost now approaches $20, and although generic suppositories of clotrimazole are even cheaper, the 500-mg suppository is no longer available in the United States. The 100-mg suppositories would have to be given daily, not weekly, and 200-mg suppositories would need to be inserted three to four times per week. Accordingly, cost is no longer a major issue, and the convenience of once-weekly oral therapy is substantial. We have found that the women who have a relapse after discontinuing suppressive prophylaxis with fluconazole uniformly request its immediate reinstitution.
Jack D. Sobel, M.D.
Wayne State University School of Medicine
Detroit, MI 48201
jsobel@med.wayne.edu
Dr. Eschenbach replies: Dr. Retzer asks if alternative therapies are less expensive. A two-week regimen to induce candida remission and six additional months of candida suppressive therapy as in the study by Sobel et al. would cost about $457 for 27 fluconazole capsules and $56 to $80 for multiple doses of intravaginal clotrimazole or miconazole, as have been used in other studies.1,2 The clotrimazole alternative, while cheaper, could lead to less compliance, and as a result, added cost for patient visits to care for treatment failure. Few patients have chronic, recurrent vulvovaginal candidiasis, and the development of symptomatic infection every one to two months is very debilitating. The report by Sobel et al. attests to the effectiveness of fluconazole. Perhaps Dr. Retzer is suggesting that the next battle is who pays to reduce this debilitation — the insurers for fluconazole or the patient for over-the-counter clotrimazole. Clearly, stop orders by insurers after one or two doses of fluconazole are not helpful to patients with this condition.
As Dr. Kuebrich indicates, fluconazole provided relief to women when they were on the drug but recurrent candidiasis started immediately after the drug was withdrawn. Physicians who treat such conditions agree with patients that the relief was well worth the effort. However, longer therapy, additional approaches, or both are required to produce a more lasting cure.
David A. Eschenbach, M.D.
University of Washington Medical Center
Seattle, WA 98195
References
Roth AC, Milsom I, Forssman L, Wahlen P. Intermittent prophylactic treatment of recurrent vaginal candidiasis by postmenstrual application of a 500 mg clotrimazole vaginal tablet. Genitourin Med 1990;66:357-360.
Balsdon MJ, Tobin JM. Recurrent vaginal candidosis: prospective study of effectiveness of maintenance miconazole treatment. Genitourin Med 1988;64:124-127.
Christopher T. Kuebrich, M.D.
2120 Driftwood Blvd.
Kenner, LA 70065
kuebrich@cox.net
References
Sobel JD, Wiesenfeld HC, Martens M, et al. Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis. N Engl J Med 2004;351:876-883.
To the Editor: The report by Sobel et al. mentions briefly the effectiveness of intravaginal antimycotic agents, which were previously found to be effective but are now deemed "inconvenient and expensive." A comparison at a local pharmacy revealed that the course of fluconazole advocated in the report costs $457.89, versus $30.82 for a similar regimen of intravaginal clotrimazole. Of concern is Dr. Eschenbach's conclusion, in his Perspective article accompanying the report,1 that "managed care groups need to start authorizing payment for prolonged suppressive therapy with fluconazole or intravaginal azoles."
Daniel R. Retzer, M.D.
Swedish American Primary Care Group
Byron, IL 61010
sk8indr@aol.com
References
Eschenbach DA. Chronic vulvovaginal candidiasis. N Engl J Med 2004;351:851-852.
Dr. Sobel replies: Dr. Kuebrich asserts that the results that my colleagues and I report in our article are misleading; he maintains that we should have compared disease-free activity in the two groups at the same time after the most recent dose of fluconazole. This would entail comparing the cure rate at 6 months of follow-up in the placebo group (35.9 percent) with that in the fluconazole group at the 12-month follow-up (42.9 percent). In fact, the difference in the cure rate at the same point in time (12 months) between the groups was found to be significant (P<0.001). Comparing the two groups at different times points is not valid, although Dr. Kuebrich's underlying premise is entirely reasonable. The fundamental goal of the study was not to show that maintenance fluconazole therapy is curative but to show that as long as once-weekly fluconazole was administered, women previously incapacitated by frequent recurrent episodes of symptomatic vaginitis had more than a 90 percent likelihood of protection from clinical recurrence. Unfortunately, few women were actually cured by taking fluconazole (approximately 21 percent) when one compares the fluconazole and placebo groups at the same end-of-study point (42.9 percent vs. 21.9 percent, P<0.001).
The maintenance dose therefore does not result in a cure in the majority of women, and the low dose used may be part of the explanation. We emphasize the lack of a long-term cure in the report. The relief from frequent relapses is anything but trivial, and, as we show, the associated risk is minimal.
Cost remains an issue. Dr. Retzer correctly emphasizes the cost of weekly fluconazole; however, since the generic brand became available in early August 2004, the cost of weekly fluconazole has declined by approximately 75 percent. The monthly cost now approaches $20, and although generic suppositories of clotrimazole are even cheaper, the 500-mg suppository is no longer available in the United States. The 100-mg suppositories would have to be given daily, not weekly, and 200-mg suppositories would need to be inserted three to four times per week. Accordingly, cost is no longer a major issue, and the convenience of once-weekly oral therapy is substantial. We have found that the women who have a relapse after discontinuing suppressive prophylaxis with fluconazole uniformly request its immediate reinstitution.
Jack D. Sobel, M.D.
Wayne State University School of Medicine
Detroit, MI 48201
jsobel@med.wayne.edu
Dr. Eschenbach replies: Dr. Retzer asks if alternative therapies are less expensive. A two-week regimen to induce candida remission and six additional months of candida suppressive therapy as in the study by Sobel et al. would cost about $457 for 27 fluconazole capsules and $56 to $80 for multiple doses of intravaginal clotrimazole or miconazole, as have been used in other studies.1,2 The clotrimazole alternative, while cheaper, could lead to less compliance, and as a result, added cost for patient visits to care for treatment failure. Few patients have chronic, recurrent vulvovaginal candidiasis, and the development of symptomatic infection every one to two months is very debilitating. The report by Sobel et al. attests to the effectiveness of fluconazole. Perhaps Dr. Retzer is suggesting that the next battle is who pays to reduce this debilitation — the insurers for fluconazole or the patient for over-the-counter clotrimazole. Clearly, stop orders by insurers after one or two doses of fluconazole are not helpful to patients with this condition.
As Dr. Kuebrich indicates, fluconazole provided relief to women when they were on the drug but recurrent candidiasis started immediately after the drug was withdrawn. Physicians who treat such conditions agree with patients that the relief was well worth the effort. However, longer therapy, additional approaches, or both are required to produce a more lasting cure.
David A. Eschenbach, M.D.
University of Washington Medical Center
Seattle, WA 98195
References
Roth AC, Milsom I, Forssman L, Wahlen P. Intermittent prophylactic treatment of recurrent vaginal candidiasis by postmenstrual application of a 500 mg clotrimazole vaginal tablet. Genitourin Med 1990;66:357-360.
Balsdon MJ, Tobin JM. Recurrent vaginal candidosis: prospective study of effectiveness of maintenance miconazole treatment. Genitourin Med 1988;64:124-127.