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Area and Severity Index (PASI) scale, which was developed as part of a psoriasis clinical trial.1 Ideally, an outcome measure should be simple to understand, relevant to patients and clinicians, quick to perform and sensitive to change. By anchoring Patient-Oriented Eczema Measure (POEM) scores to five patient-assessed eczema severity bands, Charman et al.2 have further simplified the outcome measure to improve interpretation of scores. The authors asked 1000 patients with eczema to complete both a POEM score and two global anchor questions that summarized the severity of their eczema. High external validity was ensured by the inclusion of children and adults from both primary and secondary care, in both rural and urban settings. The results permitted conversion from the 28-point POEM numerical score to five bands ranging from clear/almost clear to very severe atopic eczema. It should be remembered that severity bands may not tell the whole story because a change from one band to another may be due to only a small change in score, for example from just below to just above a band cutoff. Fortunately, a minimal clinically important difference score of 3.4 has been established for the POEM3 and so the two parameters can be used together to permit a full interpretation of POEM score changes. Further development to improve the utility of the POEM is very helpful as part of the paradigm shift away from producing multiple disease severity scales that ultimately hamper advances in clinical care. Multiple scales used in different clinical trials prevent treatments being compared in meta-analyses.4 Multiple outcome measures used within one clinical trial can also be used to perform ‘data dredging’ of secondary outcomes to disguise treatment failure. The problem has been tackled by the Harmonising Outcomes Measures for Eczema initiative, which has developed consensus-based sets of core outcome domains for eczema.5,6 Improving the evidence base for outcome measures will not only improve clinical trials but may also have value for routine patient care. Dermatologists are increasingly using potentially toxic, expensive systemic medications to treat skin diseases. In this context there is a need to justify the use of these medications with formal documentation of disease severity. However, this may be lacking in the absence of a simple, quick outcome measure that can be used in a busy clinic and is easily understood by clinicians and patients. One partial solution may be greater use of validated quality-of-life scales. Looking to the future, an increase in computerized records combined with consensusbased disease severity scores might also permit routinely collected medical data to be used in clinical trials and other medical research.
Acknowledgments The author wishes to thank Professor Andrew Finlay of the Department of Dermatology & Wound Healing, Cardiff University, for comments on an earlier draft.
British Journal of Dermatology (2013) 169, pp1175–1179
Conflicts of interest None declared. Department of Dermatology & Wound Healing, Institute of Infection & Immunity, Cardiff University, Heath Park, Cardiff CF14 4XN, U.K. E-mail: [email protected]
J.R. INGRAM
References 1 Fredriksson T, Pettersson U. Severe psoriasis – oral therapy with a new retinoid. Dermatologica 1978; 157:238–44. 2 Charman CR, Venn AJ, Ravenscroft JC, Williams HC. Translating Patient-Oriented Eczema Measure (POEM) scores into clinical practice by suggesting severity strata derived using anchor-based methods. Br J Dermatol 2013; 169:1326–32. 3 Schram ME, Spuls PI, Leeflang MM et al. EASI, (objective) SCORAD and POEM for atopic eczema: responsiveness and minimal clinically important difference. Allergy 2012; 67:99–106. 4 Schmitt J, Langan S, Deckert S et al. Assessment of clinical signs of atopic dermatitis: a systematic review and recommendation. J Allergy Clin Immunol 2013. [Epub ahead of print]. 5 Schmitt J, Langan S, Stamm T, Williams HC. Harmonizing Outcome Measurements in Eczema (HOME) Delphi panel. J Invest Dermatol 2011; 131:623–30. 6 Schmitt J, Spuls P, Boers M et al. Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting. Allergy 2012; 67:1111–17.
Biologic therapy for psoriasis: early response implies future success DOI: 10.1111/bjd.12726 ORIGINAL ARTICLE, p 1337 Biologic therapies currently approved for the treatment of moderate-to-severe plaque psoriasis work well, and often work early. Clinical trials data demonstrate that 4 weeks after treatment initiation etanercept, adalimumab, infliximab and ustekinumab all reveal efficacy that significantly exceeds that of a placebo-receiving control group.1–5 But is the patient earmarked for success or failure early on during therapy, and thus confidently maintained, or switched after a brief exposure to the current drug? Using data from a phase II clinical study, Zhu et al.6 tackle these questions examining a very high-efficacy and currently unapproved interleukin-17 inhibitor, ixekizumab. Specifically, patients achieving a 40% improvement in their baseline Psoriasis Area and Severity Index score (PASI 40) within 4 weeks of starting ixekizumab had an approximately 90% chance of achieving a PASI 75 response within the following 8 weeks. Conversely, those patients not achieving PASI 40 at week 4 had a minimal chance of achieving PASI 75 within the next 8 weeks. This post
© 2013 British Association of Dermatologists
Commentaries 1179
hoc analysis provides the practitioner with an early benchmark upon which to base the rationale of continued therapy. If similar data were available for all treatments, then the expeditious cycling away from ineffective drugs would ultimately pair the patient with an effective medication. By inference, reduced time on ineffective modalities maximizes cost-effectiveness. It should be noted that biologic therapy for psoriasis has embarked on and will continue down a path of increasingly robust efficacy, with multiple drugs demonstrating the ability to achieve PASI 75 in at least 70% of treated patients.1,3–5,7,8 All of these drugs potentially reveal their efficacy by the 4–6-week follow-up visit. It is important to note that lower-efficacy modalities, such as methotrexate, may take longer to realize full efficacy. In fact, a similar assessment of methotrexate has already been performed.9 Therefore, different drugs would require separate analyses to determine a drug-specific optimal time point at which to render a ‘go or no–go’ decision. Importantly, other factors such as baseline disease severity and time of year of therapy may slow or hasten treatment response. Such analyses would also help to guide discussions with patients, clarifying the expectation of a good clinical response with each follow-up visit. Finally, these types of analyses may be a less costly and more accurate approach to prognosticating treatment success than using genetic predictors of response, where a patient’s genotype would guide treatment choice. Conflicts of interest B.S. has received speaking fees or consulting fees, or been an advisory board participant, for Amgen, Abbott, Janssen/J&J, Pfizer, UCB Pharma, Novartis, Lilly and Maruho. Department of Dermatology, University of Connecticut Health Center, 21 South Road, 2nd Floor, Farmington, CT 06032, U.S.A. E-mail: [email protected]
© 2013 British Association of Dermatologists
References 1 Leonardi CL, Kimball AB, Papp KA et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 2008; 371:1665–74. 2 Leonardi CL, Powers JL, Matheson MD et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med 2003; 349:2014– 22. 3 Menter A, Tyring SK, Gordon K et al. Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial. J Am Acad Dermatol 2008; 58:106–15. 4 Papp KA, Langley RG, Lebwohl M et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008; 371:1675–84. 5 Reich K, Nestle FO, Papp K et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 2005; 366:1367–74. 6 Zhu B, Edson-Heredia E, Cameron G et al. Early clinical response as a predictor of subsequent response to ixekizumab treatment: results from a phase II study of patients with moderate-to-severe plaque psoriasis. Br J Dermatol 2013; 169:1337–40. 7 Papp KA, Leonardi C, Menter A et al. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med 2012; 366:1181–9. 8 Papp KA, Langley RG, Sigurgeirsson B et al. Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study. Br J Dermatol 2013; 168:412–21. 9 Saurat JH, Langley RG, Reich K et al. Relationship between methotrexate dosing and clinical response in patients with moderate to severe psoriasis: subanalysis of the CHAMPION study. Br J Dermatol 2011; 165:399–406.
B. STROBER
British Journal of Dermatology (2013) 169, pp1175–1179
Area and Severity Index (PASI) scale, which was developed as part of a psoriasis clinical trial.1 Ideally, an outcome measure should be simple to understand, relevant to patients and clinicians, quick to perform and sensitive to change. By anchoring Patient-Oriented Eczema Measure (POEM) scores to five patient-assessed eczema severity bands, Charman et al.2 have further simplified the outcome measure to improve interpretation of scores. The authors asked 1000 patients with eczema to complete both a POEM score and two global anchor questions that summarized the severity of their eczema. High external validity was ensured by the inclusion of children and adults from both primary and secondary care, in both rural and urban settings. The results permitted conversion from the 28-point POEM numerical score to five bands ranging from clear/almost clear to very severe atopic eczema. It should be remembered that severity bands may not tell the whole story because a change from one band to another may be due to only a small change in score, for example from just below to just above a band cutoff. Fortunately, a minimal clinically important difference score of 3.4 has been established for the POEM3 and so the two parameters can be used together to permit a full interpretation of POEM score changes. Further development to improve the utility of the POEM is very helpful as part of the paradigm shift away from producing multiple disease severity scales that ultimately hamper advances in clinical care. Multiple scales used in different clinical trials prevent treatments being compared in meta-analyses.4 Multiple outcome measures used within one clinical trial can also be used to perform ‘data dredging’ of secondary outcomes to disguise treatment failure. The problem has been tackled by the Harmonising Outcomes Measures for Eczema initiative, which has developed consensus-based sets of core outcome domains for eczema.5,6 Improving the evidence base for outcome measures will not only improve clinical trials but may also have value for routine patient care. Dermatologists are increasingly using potentially toxic, expensive systemic medications to treat skin diseases. In this context there is a need to justify the use of these medications with formal documentation of disease severity. However, this may be lacking in the absence of a simple, quick outcome measure that can be used in a busy clinic and is easily understood by clinicians and patients. One partial solution may be greater use of validated quality-of-life scales. Looking to the future, an increase in computerized records combined with consensusbased disease severity scores might also permit routinely collected medical data to be used in clinical trials and other medical research.
Acknowledgments The author wishes to thank Professor Andrew Finlay of the Department of Dermatology & Wound Healing, Cardiff University, for comments on an earlier draft.
British Journal of Dermatology (2013) 169, pp1175–1179
Conflicts of interest None declared. Department of Dermatology & Wound Healing, Institute of Infection & Immunity, Cardiff University, Heath Park, Cardiff CF14 4XN, U.K. E-mail: [email protected]
J.R. INGRAM
References 1 Fredriksson T, Pettersson U. Severe psoriasis – oral therapy with a new retinoid. Dermatologica 1978; 157:238–44. 2 Charman CR, Venn AJ, Ravenscroft JC, Williams HC. Translating Patient-Oriented Eczema Measure (POEM) scores into clinical practice by suggesting severity strata derived using anchor-based methods. Br J Dermatol 2013; 169:1326–32. 3 Schram ME, Spuls PI, Leeflang MM et al. EASI, (objective) SCORAD and POEM for atopic eczema: responsiveness and minimal clinically important difference. Allergy 2012; 67:99–106. 4 Schmitt J, Langan S, Deckert S et al. Assessment of clinical signs of atopic dermatitis: a systematic review and recommendation. J Allergy Clin Immunol 2013. [Epub ahead of print]. 5 Schmitt J, Langan S, Stamm T, Williams HC. Harmonizing Outcome Measurements in Eczema (HOME) Delphi panel. J Invest Dermatol 2011; 131:623–30. 6 Schmitt J, Spuls P, Boers M et al. Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting. Allergy 2012; 67:1111–17.
Biologic therapy for psoriasis: early response implies future success DOI: 10.1111/bjd.12726 ORIGINAL ARTICLE, p 1337 Biologic therapies currently approved for the treatment of moderate-to-severe plaque psoriasis work well, and often work early. Clinical trials data demonstrate that 4 weeks after treatment initiation etanercept, adalimumab, infliximab and ustekinumab all reveal efficacy that significantly exceeds that of a placebo-receiving control group.1–5 But is the patient earmarked for success or failure early on during therapy, and thus confidently maintained, or switched after a brief exposure to the current drug? Using data from a phase II clinical study, Zhu et al.6 tackle these questions examining a very high-efficacy and currently unapproved interleukin-17 inhibitor, ixekizumab. Specifically, patients achieving a 40% improvement in their baseline Psoriasis Area and Severity Index score (PASI 40) within 4 weeks of starting ixekizumab had an approximately 90% chance of achieving a PASI 75 response within the following 8 weeks. Conversely, those patients not achieving PASI 40 at week 4 had a minimal chance of achieving PASI 75 within the next 8 weeks. This post
© 2013 British Association of Dermatologists
Commentaries 1179
hoc analysis provides the practitioner with an early benchmark upon which to base the rationale of continued therapy. If similar data were available for all treatments, then the expeditious cycling away from ineffective drugs would ultimately pair the patient with an effective medication. By inference, reduced time on ineffective modalities maximizes cost-effectiveness. It should be noted that biologic therapy for psoriasis has embarked on and will continue down a path of increasingly robust efficacy, with multiple drugs demonstrating the ability to achieve PASI 75 in at least 70% of treated patients.1,3–5,7,8 All of these drugs potentially reveal their efficacy by the 4–6-week follow-up visit. It is important to note that lower-efficacy modalities, such as methotrexate, may take longer to realize full efficacy. In fact, a similar assessment of methotrexate has already been performed.9 Therefore, different drugs would require separate analyses to determine a drug-specific optimal time point at which to render a ‘go or no–go’ decision. Importantly, other factors such as baseline disease severity and time of year of therapy may slow or hasten treatment response. Such analyses would also help to guide discussions with patients, clarifying the expectation of a good clinical response with each follow-up visit. Finally, these types of analyses may be a less costly and more accurate approach to prognosticating treatment success than using genetic predictors of response, where a patient’s genotype would guide treatment choice. Conflicts of interest B.S. has received speaking fees or consulting fees, or been an advisory board participant, for Amgen, Abbott, Janssen/J&J, Pfizer, UCB Pharma, Novartis, Lilly and Maruho. Department of Dermatology, University of Connecticut Health Center, 21 South Road, 2nd Floor, Farmington, CT 06032, U.S.A. E-mail: [email protected]
© 2013 British Association of Dermatologists
References 1 Leonardi CL, Kimball AB, Papp KA et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 2008; 371:1665–74. 2 Leonardi CL, Powers JL, Matheson MD et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med 2003; 349:2014– 22. 3 Menter A, Tyring SK, Gordon K et al. Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial. J Am Acad Dermatol 2008; 58:106–15. 4 Papp KA, Langley RG, Lebwohl M et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008; 371:1675–84. 5 Reich K, Nestle FO, Papp K et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 2005; 366:1367–74. 6 Zhu B, Edson-Heredia E, Cameron G et al. Early clinical response as a predictor of subsequent response to ixekizumab treatment: results from a phase II study of patients with moderate-to-severe plaque psoriasis. Br J Dermatol 2013; 169:1337–40. 7 Papp KA, Leonardi C, Menter A et al. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med 2012; 366:1181–9. 8 Papp KA, Langley RG, Sigurgeirsson B et al. Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study. Br J Dermatol 2013; 168:412–21. 9 Saurat JH, Langley RG, Reich K et al. Relationship between methotrexate dosing and clinical response in patients with moderate to severe psoriasis: subanalysis of the CHAMPION study. Br J Dermatol 2011; 165:399–406.
B. STROBER
British Journal of Dermatology (2013) 169, pp1175–1179
