Therapeutics
Review: Oral antiviral drugs reduce clinical recurrence in recurrent genital herpes Clinical impact ratings:
多多多多多多夞
Le Cleach L, Trinquart L, Do G, et al. Oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients. Cochrane Database Syst Rev. 2014;8: CD009036.
多多多多多夞夞
Question
Main results
In patients with recurrent genital herpes, do oral antiviral drugs reduce recurrence?
Meta-analysis of parallel-group RCTs showed that acyclovir, famciclovir, and valacyclovir each reduced risk for clinical recurrence more than placebo (Table). 1 RCT showed that valacyclovir was not as effective as acyclovir for reducing clinical recurrence, and 1 RCT showed that valacyclovir did not differ from famciclovir (Table). Network meta-analysis did not find evidence of differences between drugs.
Review scope Included studies compared suppressive treatment with oral acyclovir, famciclovir, or valacyclovir (continuous treatment for several months with the goal of preventing recurrence) with each other or placebo in patients with ≥ 4 genital herpes outbreaks per year due to herpes simplex virus (HSV). Studies of patients with HIV or pregnant women were excluded. Outcomes included the proportion of patients with ≥ 1 clinical genital herpes recurrence during treatment.
Review methods MEDLINE; EMBASE/Excerpta Medica; Cochrane Central Register of Controlled Trials; specialized registers of the Cochrane Infectious Diseases Group, Cochrane Skin Group, and Cochrane Sexually Transmitted Infections Group; LILACS; World Health Organization International Clinical Trials Registry Platform; US Food and Drug Administration drug registration Web site; clinical trials results databases of pharmaceutical companies that produce relevant antiretroviral agents; and reference lists were searched to Feb 2014 for randomized controlled trials (RCTs). Authors in the field were contacted, and proceedings of relevant conferences were searched. 26 RCTs (n = 6950, mean age 35 y, 54% women) met the selection criteria. 13 RCTs were determined to be at high risk for bias, and 13 were at unclear risk based on the Cochrane Collaboration risk-of-bias tool.
Effect of suppressive oral antiviral treatments on risk for ≥ 1 clinical recurrence in recurrent genital herpes* Comparisons†
Number of trials (n)
Weighted event rates
RRR (95% CI)
NNT (CI)
Acyclovir vs placebo
9 (2049)
43% vs 96% 52% (42 to 61)‡
2 (2 to 3)
Valacyclovir vs placebo
4 (1788)
39% vs 79% 59% (31 to 76)‡
3 (2 to 5)
Famciclovir vs placebo
2 (832)
43% vs 73% 43% (36 to 50)
4 (3 to 8)
Valacyclovir vs acyclovir
1 (1345)
53% vs 46% 16% (1 to 34)
Famciclovir vs valacyclovir
1 (320)
34% vs 29% 18% (⫺14 to 63)
RRI (CI)
NNH (CI) 15 (8 to 100) Not significant
Conclusion In patients with recurrent genital herpes, oral antiviral drugs reduce risk for ≥ 1 clinical recurrence compared with placebo. Sources of funding: Association Recommandations en Dermatologie (aRED) and Programme Hospitalier de Recherche Clinique, French Ministry of Health. For correspondence: Dr. L. Le Cleach, Hoˆpital Henri Mondor, Cre´teil, France. E-mail [email protected].
Commentary HSV, primarily HSV-2, is the most common cause of genital ulcers worldwide. This virus is associated with significant morbidity during primary infection, painful lesions during recurrences, childbirth infection, and neonatal herpes encephalitis. Genital HSV is also a relevant public health issue as it affects transmission of other sexually transmitted diseases, including HIV. Le Cleach and colleagues did a comprehensive systematic review and meta-analysis of antiviral agents to prevent outbreaks of genital herpes. The mean number of recurrences was 11 per year, and duration of prophylaxis ranged from 2 to 12 months. Results of direct comparisons showed that acyclovir, valacyclovir, and famciclovir were all superior to placebo for reducing the relative number of clinical recurrences by about 50% to 60%; indirect comparisons suggested that no drug is superior to another. Risk for bias was high for half of the trials and unclear for the other half. Substantial publication bias and exaggerated benefits seen among clinical trials with small sample sizes precluded more definitive conclusions about which drug would be most efficacious. The results of the meta-analysis by Le Cleach and colleagues strongly suggest that further placebo-controlled trials would be unethical given the proven efficacy of these 3 antiviral drugs, any of which are appropriate for preventing recurrent genital herpes in clinical practice. Nonetheless, real-life studies assessing comparative effectiveness are needed to evaluate the effects of each of these drugs on patient quality of life and cost-effectiveness. Andre C. Kalil, MD, MPH Uriel S. Sandkovsky, MD, MS University of Nebraska Medical Center Omaha, Nebraska, USA
*Abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from data in article using a random-effects model. †Includes only parallel-group RCTs (not crossover RCTs). ‡Statistically significant heterogeneity of treatment effect was present.
17 February 2015 Annals of Internal Medicine ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/27/2015
JC7
姝 2015 American College of Physicians
Review: Oral antiviral drugs reduce clinical recurrence in recurrent genital herpes Clinical impact ratings:
多多多多多多夞
Le Cleach L, Trinquart L, Do G, et al. Oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients. Cochrane Database Syst Rev. 2014;8: CD009036.
多多多多多夞夞
Question
Main results
In patients with recurrent genital herpes, do oral antiviral drugs reduce recurrence?
Meta-analysis of parallel-group RCTs showed that acyclovir, famciclovir, and valacyclovir each reduced risk for clinical recurrence more than placebo (Table). 1 RCT showed that valacyclovir was not as effective as acyclovir for reducing clinical recurrence, and 1 RCT showed that valacyclovir did not differ from famciclovir (Table). Network meta-analysis did not find evidence of differences between drugs.
Review scope Included studies compared suppressive treatment with oral acyclovir, famciclovir, or valacyclovir (continuous treatment for several months with the goal of preventing recurrence) with each other or placebo in patients with ≥ 4 genital herpes outbreaks per year due to herpes simplex virus (HSV). Studies of patients with HIV or pregnant women were excluded. Outcomes included the proportion of patients with ≥ 1 clinical genital herpes recurrence during treatment.
Review methods MEDLINE; EMBASE/Excerpta Medica; Cochrane Central Register of Controlled Trials; specialized registers of the Cochrane Infectious Diseases Group, Cochrane Skin Group, and Cochrane Sexually Transmitted Infections Group; LILACS; World Health Organization International Clinical Trials Registry Platform; US Food and Drug Administration drug registration Web site; clinical trials results databases of pharmaceutical companies that produce relevant antiretroviral agents; and reference lists were searched to Feb 2014 for randomized controlled trials (RCTs). Authors in the field were contacted, and proceedings of relevant conferences were searched. 26 RCTs (n = 6950, mean age 35 y, 54% women) met the selection criteria. 13 RCTs were determined to be at high risk for bias, and 13 were at unclear risk based on the Cochrane Collaboration risk-of-bias tool.
Effect of suppressive oral antiviral treatments on risk for ≥ 1 clinical recurrence in recurrent genital herpes* Comparisons†
Number of trials (n)
Weighted event rates
RRR (95% CI)
NNT (CI)
Acyclovir vs placebo
9 (2049)
43% vs 96% 52% (42 to 61)‡
2 (2 to 3)
Valacyclovir vs placebo
4 (1788)
39% vs 79% 59% (31 to 76)‡
3 (2 to 5)
Famciclovir vs placebo
2 (832)
43% vs 73% 43% (36 to 50)
4 (3 to 8)
Valacyclovir vs acyclovir
1 (1345)
53% vs 46% 16% (1 to 34)
Famciclovir vs valacyclovir
1 (320)
34% vs 29% 18% (⫺14 to 63)
RRI (CI)
NNH (CI) 15 (8 to 100) Not significant
Conclusion In patients with recurrent genital herpes, oral antiviral drugs reduce risk for ≥ 1 clinical recurrence compared with placebo. Sources of funding: Association Recommandations en Dermatologie (aRED) and Programme Hospitalier de Recherche Clinique, French Ministry of Health. For correspondence: Dr. L. Le Cleach, Hoˆpital Henri Mondor, Cre´teil, France. E-mail [email protected].
Commentary HSV, primarily HSV-2, is the most common cause of genital ulcers worldwide. This virus is associated with significant morbidity during primary infection, painful lesions during recurrences, childbirth infection, and neonatal herpes encephalitis. Genital HSV is also a relevant public health issue as it affects transmission of other sexually transmitted diseases, including HIV. Le Cleach and colleagues did a comprehensive systematic review and meta-analysis of antiviral agents to prevent outbreaks of genital herpes. The mean number of recurrences was 11 per year, and duration of prophylaxis ranged from 2 to 12 months. Results of direct comparisons showed that acyclovir, valacyclovir, and famciclovir were all superior to placebo for reducing the relative number of clinical recurrences by about 50% to 60%; indirect comparisons suggested that no drug is superior to another. Risk for bias was high for half of the trials and unclear for the other half. Substantial publication bias and exaggerated benefits seen among clinical trials with small sample sizes precluded more definitive conclusions about which drug would be most efficacious. The results of the meta-analysis by Le Cleach and colleagues strongly suggest that further placebo-controlled trials would be unethical given the proven efficacy of these 3 antiviral drugs, any of which are appropriate for preventing recurrent genital herpes in clinical practice. Nonetheless, real-life studies assessing comparative effectiveness are needed to evaluate the effects of each of these drugs on patient quality of life and cost-effectiveness. Andre C. Kalil, MD, MPH Uriel S. Sandkovsky, MD, MS University of Nebraska Medical Center Omaha, Nebraska, USA
*Abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from data in article using a random-effects model. †Includes only parallel-group RCTs (not crossover RCTs). ‡Statistically significant heterogeneity of treatment effect was present.
17 February 2015 Annals of Internal Medicine ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/27/2015
JC7
姝 2015 American College of Physicians
