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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Antivirals for management of herpes zoster including ophthalmicus: a systematic review of high-quality randomized controlled trials

EM McDonald, J De Kock, and FS Ram.

Review published: 2012.

Link to full article: [Journal publisher]

CRD summary

The authors concluded that valaciclovir and famciclovir showed greater reduction in pain compared to acyclovir in patients with shingles. Safety profiles were comparable. The authors’ conclusions reflect the evidence but should be considered tentative as there was some potential for bias in the review and the evidence base was small.

Authors' objectives

To assess the effectiveness of antivirals in the management of shingles (herpes zoster).

Searching

Eight databases, which included Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, and websites of relevant medical journals (not specified) were searched from inception up to May 2011. Search terms were not reported. No language restrictions were applied. Reference lists of retrieved articles, primary authors and pharmaceutical companies were contacted for further published, unpublished or ongoing studies.

Study selection

Eligible studies were randomised controlled trials (RCTs) that compared the efficacy of nucleoside analogues (acyclovir, valaciclovir, famciclovir and brivudin) in the management of immunocompetent patients (>18 years) with shingles. Patients had to be diagnosed within 72 hours of symptom onset and be treated for a minimum of seven days. The primary outcome was the proportion of patients with reduction in pain (as defined in the review). Secondary outcomes included rate of lesion healing and adverse effects. Studies were excluded if they included patients with acute retinal necrosis, progressive outer retinal necrosis or herpes simplex type I or II.

Included studies were conducted in America, France, Taiwan, China and multiple countries. Where reported, the mean age of patients ranged from 50 to 69 years. Acyclovir was administered as 200mg or 800mg five times per day for seven days. Valaciclovir was administered as 1,000mg three time a day for seven or 14 days. Famciclovir was given as 250mg, 500mg or 750mg three times per day for seven days. Brivudin was given as 125mg once a day for seven days. Pain was assessed using various questionnaires. Other outcomes were lesion healing, adverse effects, abnormal sensation and ocular complications. Outcomes were measured over one to 170 days.

Two reviewers independently screened studies for inclusion. Discrepancies were resolved through discussion or referred to a third reviewer.

Assessment of study quality

Trial quality was assessed according to the Jadad scale and Cochrane risk of bias tool (allocation concealment quality item). Trials scored zero to 5 on the Jadad scale (5 denoted higher quality) and were deemed adequate (A), unclear (B), inadequate (C) or unused (D) according to the Cochrane tool.

The authors did not state how many reviewers performed quality assessment.

Data extraction

Data were extracted on an intention-to-treat basis. Continuous data were extracted to calculate mean differences and 95% confidence intervals and dichotomous data were extracted to calculate relative risks and 95% confidence intervals. Primary authors were contacted where necessary.

The authors did not state how many reviewers extracted data.

Methods of synthesis

A fixed-effect model was used to combine relative risks (RRs) and combine mean differences to calculate weighted mean differences, each with the 95% confidence intervals (CIs). Where appropriate, the number needed to treat (NNT) to benefit one patient was calculated along with 95% CIs.

Statistical heterogeneity was assessed using the Χ² test.

Results of the review

Twelve RCTs (7,277 patients, range 55 to 2,027) were included in the review. Trials were considered good quality according to the Jadad scale (average score 3.58) and Cochrane allocation concealment item (six trials scored A and six scored B).

Pain was statistically significantly less with valaciclovir compared to acyclovir at time points between one and 112 days: one to 10 days (RR 0.92, 95% CI 0.88 to 0.97; three RCTs) and 61 to 112 days (RR 0.79, 95% CI 0.63 to 0.98; two RCTs). There was no evidence of statistical heterogeneity. NNT ranged from three to 17. The difference was not statistically significant between 113 and 170 days.

Pain was statistically significantly less in patients who received famciclovir compared to acyclovir at 28 to 30 days (RR 0.54, 95% CI 0.43 to 0.68; two RCTs; NNT=three). There was no evidence of statistical heterogeneity. There were no statistically significant differences between famciclovir and acyclovir in adverse events or lesion healing (three RCTs).

There were no statistically significant differences between valaciclovir or famciclovir versus acyclovir at any doses or time points in loss of vesicles, cessation of new lesions, full crusting or loss of crusts and adverse effects.

Results from dose response or single trials were reported in the review.

Authors' conclusions

Valaciclovir and famciclovir showed greater reduction in pain compared to acyclovir in patients with shingles. Safety profiles were comparable.

CRD commentary

The review question and inclusion criteria were stated clearly. There was a comprehensive search of the literature with no publication or language restrictions, which reduced potential for bias. Study selection was performed in duplicate; it was unclear whether this was also true for data extraction and quality assessment so reviewer error and bias could not be ruled out. Appropriate quality assessment scores were used and overall the quality was deemed to be good.

There was no evidence of statistical heterogeneity and studies were pooled using appropriate methods. Only a small number of studies were combined and these had small sample sizes. The magnitude of effect was small for some outcomes.

The authors’ conclusions reflect the evidence but should be considered tentative as there was some potential for bias in the review and the evidence base was small.

Implications of the review for practice and research

Practice: The authors stated that valaciclovir and famciclovir should be the treatments of choice in the management of shingles.

Research: The authors stated that further research was needed, particularly to assess the pharmacological differences between drugs and to identify the optimal dose of famciclovir. Further studies were needed to compare famciclovir versus acyclovir beyond 30 days, particularly in patients with ocular shingles.

Funding

None.

Bibliographic details

McDonald EM, De Kock J, Ram FS. Antivirals for management of herpes zoster including ophthalmicus: a systematic review of high-quality randomized controlled trials. Antiviral Therapy 2012; 17(2): 255-264. [PubMed: 22300753]

Indexing Status

Subject indexing assigned by NLM

MeSH

2-Aminopurine /administration & dosage /adverse effects /analogs & derivatives /therapeutic use; Acyclovir /administration & dosage /adverse effects /analogs & derivatives /therapeutic use; Antiviral Agents /administration & dosage /adverse effects /therapeutic use; Bromodeoxyuridine /administration & dosage /adverse effects /analogs & derivatives /therapeutic use; Herpes Zoster /drug therapy; Herpesvirus 3, Human /drug effects /pathogenicity; Humans; Pain Management /methods; Randomized Controlled Trials as Topic; Valine /administration & dosage /adverse effects /analogs & derivatives /therapeutic use

AccessionNumber

12012023525

Database entry date

30/11/2012

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 22300753

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