[en] Pain typically accompanies acute herpes zoster and, in a proportion of patients, it persists well beyond rash healing. Pain must therefore be analyzed in trials of antiviral agents in herpes zoster, but different methods have been used to analyze pain in recent published trials. These reports are reviewed and their methodological strengths and weaknesses examined. Based on this review, recommendations for the design and analysis of future trials of antiviral agents in herpes zoster are proposed. The principal recommendation is that antiviral efficacy should be evaluated both by distinguishing post-herpetic neuralgia from acute pain and by considering pain as a continuum. The primary endpoint should address both the prevalence and duration of post-herpetic neuralgia and should be examined in those patients who have post-herpetic neuralgia. Adopting the proposed recommendations in design and analysis of future trials should facilitate comparison across trials of the efficacy of antiviral agents in the treatment of herpes zoster.
Disciplines :
Immunology & infectious disease
Author, co-author :
Dworkin, R. H.; Columbia Presbyterian Medical Center, New York, NY, USA
Carrington, D.; St George Hospital, London, UK
Cunningham, A.; Westmead Hospital, Westmead, Australia > Department of Virology
Kost, R.; National Institutes of Health, Bethesda, MD, USA
Levin, M.; University of Colorado Health Sciences Center, Denver, CO, USA
McKendrick, M. W.; Royal Hallamshire Hospital, Sheffield, UK
Oxman, M. N.; University of California, San Diego, CA, USA
Rentier, Bernard ; Université de Liège - ULiège > Département des Sciences de la Vie > Virologie fondamentale et Immunologie
Schmader, K.; Duke University Medical Center, Durham, NC, USA
Tappeiner, G.; Universitätsklinik für Dermatologie, Allgemeinses Krankenhaus der Stadt Wien, Vienna, Austria
Wassilew, S. W.; Dermatologische Klinik, Klinikum Krefeld, Germany
Whitley, R. J.; University of Alabama at Birmingham, Birmingham, AL, USA
Language :
English
Title :
Assessment of pain in herpes zoster: lessons learned from antiviral trials
Bennett, G.J. (1994) Hypotheses on the pathogenesis of herpes zoster-associated pain. Ann. Neurol. 35 Suppl., 38-41.
Beutner, K.R., Friedman, D.J., Forszpaniak, C., Andersen, P.L. and Wood, M.J. (1995) Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob. Agents Chemother. 39, 1546-1553.
Bhala, B.B., Ramamoorthy, C., Bowsher, D. and Yelnoorker, K.N. (1988) Shingles and postherpetic neuralgia. Clin. J. Pain 4, 169-174.
Boon, R.J. and Griffin, D.R.J. (1995) Efficacy of famciclovir in the treatment of herpes zoster: Reduction of pain associated with herpes zoster. Neurology 45 Suppl. 8, 76-77.
Boon, R.J. and Griffin, D.R.J. (1996) Famciclovir: efficacy in zoster and issues in the assessment of pain. In: J. Mills, P.A. Volberding and L. Corey (Eds.), Antiviral Chemotherapy 4: New Directions for Clinical Application and Research, pp. 17-31. Plenum Press, New York.
Bowsher, D. (1993) Sensory change in postherpetic neuralgia. In: C.P.N. Watson (Ed.), Herpes Zoster and Postherpetic Neuralgia, pp. 97-107. Elsevier, Amsterdam.
Brown, G.R. (1976) Herpes zoster: correlation of age, sex, distribution, neuralgia and associated disorders. South. Med. J. 69, 576-578.
Burgoon, C.F., Burgoon, J.S. and Baldridge, C.D. (1957) The natural history of herpes zoster. JAMA 164, 265-269.
Crooks, R.J., Jones, D.A. and Fiddian, A.P. (1991) Zoster-associated pain: an overview of clinical trials with acyclovir. Scand. J. Infect. Dis. Suppl. 80, 62-68.
Cunningham, A.L. (1995) Clinical success in treating patients with famciclovir: optimism for the future. Res. Clin. Forums 17, 45-53.
de Moragas, J.M. and Kierland, R.R. (1957) The outcome of patients with herpes zoster. AMA Arch. Dermatol. 75, 193-196.
Degreef, H. and the Famciclovir Herpes Zoster Clinical Study Group (1994) Famciclovir, a new oral antiherpes drug: results of the first controlled clinical study demonstrating its efficacy and safety in the treatment of uncomplicated herpes zoster in immunocompetent patients. Int. J. Antimicrob. Agents 4, 241-246.
Dworkin, R.H., Boon, R.J. and Griffin, D.R.J. (1995a) Famciclovir: effect on pain in herpes zoster. Antiviral Res. 26, 344.
Dworkin, R.H., Boon, R.J. and Griffin, D.R.G. (1995b) Covariates in herpes zoster and interpretation of clinical trial data. Antiviral Res. 26, 344.
Dworkin, R.H., Cooper, E.M., Walther, R.R. and Sweeney, E.W. (1996) Predicting the development of postherpetic neuralgia: a prospective study of herpes zoster patients. 8th World Congr. Pain, Vancouver, Canada, August 1996.
Dworkin, R.H. and Portenoy, R.K. (In press) Pain and its persistence in herpes zoster. Pain.
Eaglstein, W.H., Weinstein, G.D. and Brown, J.A. (1970) The effects of early corticosteroid therapy on the skin eruption and pain of herpes zoster. JAMA 101, 132-139.
Easterbrook, P. and Wood, M.J. (1995) Post-herpetic neuralgia: what do drugs really do? In: S.L. Sacks, S.E. Straus, R.S. Whitley and P.D. Griffiths (Eds.), Clinical Management of Herpes Viruses, pp. 211-235. IOS, Amsterdam.
Feigal, D.W. (1995) Summary basis of approval for NDA 20-487 (valaciclovir caplets). Department of Health and Human Services, Washington, D.C.
Friedman, L.M., Furberg, C.D. and DeMets, D.L. (1982) Fundamentals of Clinical Trials, p. 135. PSG, London.
Guess, H.A., Broughton, D.D., Melton, L.J. III and Kurland, L.T. (1985) Epidemiology of herpes zoster in children and adolescents: a population-based study. Pediatrics 76, 512-517.
Harding, S.P., Lipton, J.R. and Wells, J.C.D. (1987) Natural history of herpes zoster ophthalmicus: predictors of postherpetic neuralgia and ocular involvement. Br. J. Opthalmol. 71, 353-358.
Hope-Simpson, R.E. (1965) The nature of herpes zoster: a long-term study and a new hypothesis. Proc. R. Soc. Med. 58, 9-20.
Huff, J.C., Drucker, J.L., Clemmer, A., Laskin, O.L., Connor, J.D., Bryson, Y.J. and Balfour, H.H. Jr. (1993) Effect of oral acyclovir on pain resolution in herpes zoster: a reanalysis. J. Med. Virol. Suppl. 1, 93-96.
Lydick, E., Epstein, R.S., Himmelberger, D. and White, C.J. (1995) Herpes zoster and quality of life: a self limited disease with severe impact. Neurology 45 Suppl. 8, 52-53.
Max, M.B., Portenoy, R.K. and Laska, E.M. (1991) The Design of Analgesic Trials, pp. 729. Raven Press, New York.
McKendrick, M.W., Care, C.D., Ogan, P. and Wood, M.J. (1994) A retrospective study of the epidemiology of zoster with particular reference to factors pertinent to the development of chronic pain. 2nd Int. Conf. Varicella-Zoster Virus, Paris.
Melzack, R. (1975) The McGill Pain Questionnaire: major properties and scoring methods. Pain 1, 275-299.
Melzack, R. (1987) The short-form McGill Pain Questionnaire. Pain 30, 191-197.
Merskey, H. and Bogduk, N. (Eds.), (1994) Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms (2nd ed.). IASP Press, Seattle, WA.
Oxman, M.N., Levin, M., Johnson, G.R., Arbeit, R., Barry, P., Gershon, A.A., Schmader, K., Straus, S.E., White, C.J., Collins, D. and Colling, C.L. (1994) Trial of varicella vaccine for the prevention of herpes zoster and its complications (VA cooperative study no. 403): Vol. 1: protocol. Infectious Diseases Section, Veterans Affairs Medical Center, San Diego, CA.
Riopelle, J.M., Naraghi, M. and Grush, K.P. (1984) Chronic neuralgia incidence following local anesthetic therapy for herpes zoster. Arch. Dermatol. 120, 747-750.
Rogers, R.S. III and Tindall, J.P. (1971) Geriatric herpes zoster. J. Am. Geriatr. Soc. 19, 495-504.
Tyring, S., Barbarash, R.A., Nahlik, J.E., Cunningham, A., Marley, J., Heng, M., Jones, T., Rea, T., Boon, R., Saltzman, R. and the Collaborative Famciclovir Herpes Zoster Study Group (1995) Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Ann. Intern Med. 123, 89-96.
Watson, C.P.N. (1993) Herpes Zoster and Postherpetic Neuralgia, pp. 258. Elsevier, Amsterdam.
Watson, C.P.N. and Chipman, M. (1993) Suggestions for research and unanswered questions regarding postherpetic neuralgia. In: C.P.N. Watson (Ed.), Herpes Zoster and Postherpetic Neuralgia, pp. 239-253. Elsevier, Amsterdam.
Watson, C.P.N., Deck, J.H., Morshead, C., Van der Kooy, D. and Evans, R.J. (1991) Post-herpetic neuralgia: further post-mortem studies of cases with and without pain. Pain 44, 105-117.
Whitley, R.J., Weiss, H., Gnann, J.W. Jr., Tyring, S., Mertz, G.J., Pappas, P.G., Schluepner, C.J., Hayden, F., Wolf, J., Soong, S. and the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group (1996) Acyclovir with and without prednisone for the treatment of herpes zoster: a randomized, placebo-controlled trial. Ann. Intern. Med. 125, 376-383.
Wood, M.J., Ogan, P.K., McKendrick, M.W., Care, C.D., McGill, J.I. and Webb, E.M. (1988) Efficacy of oral acyclovir treatment of acute herpes zoster. Am. J. Med. 85 Suppl. 2A, 79-83.
Wood, M.J. and Easterbrook, P. (1995) Shingles, scourge of the elderly: the acute illness. In: S.L. Sacks, S.E. Straus, R.S. Whitley, and P.D. Griffiths (Eds.), Clinical Management of Herpes Viruses, pp. 193-210. IOS, Amsterdam.
Wood, M.J. and the Herpes Zoster Clinical Trial Consensus Group (1995) For debate: how should zoster trials be conducted? J. Antimicrob. Chemother. 36, 1089-1101.
Wood, M.J., Johnson, R.W., McKendrick, M.W., Taylor, J., Mandal, B.K. and Crooks, J. (1994) A randomized trial of acyclovir for 7 days or 21 days with and without prednisolone for treatment of acute herpes zoster. N. Engl. J. Med. 330, 896-900.
Wood, M.J., Kay, R., Dworkin, R.H., Soong, S.-J. and Whitley, R.J. (1996) Oral acyclovir therapy accelerates pain resolution in patients with herpes zoster: a meta-analysis of placebo-controlled trials. Clin. Infect. Dis., 22, 341-347.