494 Commentaries
cytotoxic chemotherapy. Secondly, it demonstrates that the skills of hair biologists and clinicians in measuring hair growth, which have become de riguer in assessing treatments for other hair-loss disorders, have a place in the development of treatments aimed at the prevention of chemotherapy alopecia. In the search for more effective treatments we need precise measurements – subjective assessments of hair status are not sufficient. Thirdly, and perhaps more importantly from a biological standpoint, this study questions the role of oestrogens in regulating human hair growth. The results are not conclusive but they nevertheless cast doubt on the common assumption that oestrogens have a stimulatory effect on scalp hair growth. This has relevance, for example, to our understanding of the age-related decline in hair density in women, which is often ascribed to postmenopausal oestrogen deficiency. Devising studies that provide a more definitive answer should not be too difficult. Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, U.K. E-mail: [email protected]
A.G. MESSENGER
References 1 Kanti V, Nuwayhid R, Lindner J et al. Analysis of quantitative changes in hair growth during treatment with chemotherapy or tamoxifen in patients with breast cancer: a cohort study. Br J Dermatol 2014; 170:643–650. 2 Eckert J, Church RE, Ebling FJ. The pathogenesis of alopecia areata. Br J Dermatol 1968; 80:203–10. 3 Thornton MJ, Taylor AH, Mulligan K et al. Oestrogen receptor beta is the predominant oestrogen receptor in human scalp skin. Exp Dermatol 2003; 12:181–90. 4 Saggar V, Wu S, Dickler MN, Lacouture ME. Alopecia with endocrine therapies in patients with cancer. Oncologist 2013; 18:1126–34.
Do we need a patient satisfaction score? DOI: 10.1111/bjd.12867 ORIGINAL ARTICLE, p 672 At lectures on psoriasis you can see eyes glaze over; BlackBerry addicts turn on their cell phones, and workaholics open their laptops when a speaker mentions quality of life or patient satisfaction. Quality-of-life and patient satisfaction surveys are met with groans by investigators for whom this just means more work. But the impact of patient satisfaction on patients’ current and future quality of life is critical, and the impact on their family, friends, coworkers, employers and customers is tangible. Moreover, satisfaction with therapy affects adherence to that therapy, and poor adherence is known to be an enormous problem in dermatology. In a study performed at an outpatient clinic, one-third of prescriptions were never even filled.1 In another small study, 95% of patients were found to British Journal of Dermatology (2014) 170, pp490–495
underdose topical therapies,2 and adherence to a 5-day treatment course of a topical steroid among patients with atopic dermatitis was only 40%.3 As shown in the study by Callis Duffin et al.,4 in this issue of BJD, it is not surprising that patient satisfaction is lower for topical therapies than for all other therapies. Nor is it surprising that these scores are also lower for narrowband ultraviolet (UV)B, which requires office visits up to three times per week, and for infliximab, which requires in-office infusions at least every 8 weeks. More than ever before, patient-reported outcomes are being used by the government and by insurers to justify treatments. And in an era when adherence is coming under closer scrutiny, treatments associated with greater patient satisfaction are likely to lead to greater adherence. Clinical scores such as the Psoriasis Activity and Severity Index are helpful, even if imperfect. Those scores generally correlate well with quality-of-life scores and patient satisfaction scores. However, looking only at clinical scores, it is easy for physicians to overlook the side-effects of treatments that work – but these emerge much more clearly in patient satisfaction scores. Methotrexate, for example, requires more laboratory monitoring and is often associated with nausea, oral ulcers and a sense of malaise, not to mention the symptoms associated with megaloblastic anaemia. Yet, all of us have heard the methotrexate enthusiast who says: ‘I’ve never had a patient with side-effects from methotrexate and it works for everyone.’ It’s amazing how many of our colleagues don’t realize their patients are doing well only because they’ve gone to other dermatologists who prescribed more satisfying treatments. By now, we all should realize that the justifiable enthusiasm for methotrexate should be related to its price, as it has been shown to be less effective and have more side-effects than at least one of our biological therapies for which a headto-head comparison has been performed.5 The challenge is to come up with an easy quality-of-life or patient satisfaction measure that takes little time on the part of investigators and clinicians. The Treatment Satisfaction Questionnaire for Medication version II (TSQM) consists of 11 items concerning key points: effectiveness, adverse effects, convenience of therapies and satisfaction with those therapies.6 Using that simple questionnaire, Callis Duffin et al. have shown that patients receiving methotrexate monotherapy had significantly lower patient-reported effectiveness scores than those receiving subcutaneously administered biologics (adalimumab, etanercept, ustekinumab), narrowband UVB phototherapy or adalimumab with methotrexate. Conversely, methotrexate monotherapy was significantly more convenient than topical therapies, infliximab or narrowband UVB phototherapy. Because we are all under pressure by insurers to see more patients in less time, and because clinical evaluations of psoriasis correlate with patient satisfaction and quality of life, it is unlikely that surveys like the TSQM will be performed in clinical practice. But in a study setting, the TSQM provides valuable information that can be used to influence regulatory agencies and insurers. © 2014 British Association of Dermatologists
Commentaries
Conflicts of interest Dr Lebwohl has been an investigator for Inbios, Coronado Biosciences; he has been a consultant forAbbvie,Valeant, Taro, Pfizer, UCB pharma, Forward pharma, Dermipsor,Galderma; and he has been a consultant andan investigator for Ranbaxy, Novartis, Dermira, Merz, Merck, Leo pharma,Janssen-biotech, Glaxo SmithKline,Elililly,Celgene,Can-Fitebiopharma,Anacor,andAmgen. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A. E-mail: [email protected]
M. LEBWOHL
References 1 Storm A, Andersen SE, Benfeldt E, Serup J. One in 3 prescriptions are never redeemed: primary nonadherence in an outpatient clinic. J Am Acad Dermatol 2008; 59:27–33. 2 Storm A, Benfeldt E, Andersen SE, Serup J. A prospective study of patient adherence to topical treatments: 95% of patients underdose. J Am Acad Dermatol 2008; 59:975–80. 3 Hix E, Gustafson CJ, O’Neill JL et al. Adherence to a five day treatment course of topical fluocinonide 0.1% cream in atopic dermatitis. Dermatol Online J 2013; 19:20029. 4 Callis Duffin K, Yeung H, Takeshita J et al. Patient satisfaction with treatments for moderate-to-severe plaque psoriasis in clinical practice. Br J Dermatol 2014; 170:672–80. 5 Saurat JH, Stingl G, Dubertret L et al. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol 2008; 158:558–66. 6 Atkinson MJ, Kumar R, Cappelleri JC, Hass SL. Hierarchical construct validity of the treatment satisfaction questionnaire for medication (TSQM version II) among outpatient pharmacy consumers. Value Health 2005; 8(Suppl. 1):S9–24.
overall safety evaluation of this important agent for the treatment of this disease. Even though the data reported in the first study showed no evidence of systemic absorption, which may in the long term contribute to toxic side-effects, there is no doubt that local cytotoxic efficacy is associated with local absorption and should always be taken into consideration when used in early disease and young patients. This needs to be considered for a number of reasons. (i) In a significant number of patients the disease has a very protracted course, so that overall survival may not be affected; thus in younger patients long-term extended use may eventually be associated with unexpected side-effects and should be monitored carefully. (ii) In the study by Lindahl et al., even though the data are very suggestive of a very low long-term side-effect profile, some additional information needs to be gathered and analysed to generate even more conclusive evidence. In their study the authors did not include as an additional control a cohort without mycosis fungoides for comparison. Furthermore, which may prove to be very important, they did not evaluate within the mycosis fungoides groups those patients who did versus those who did not receive any carcinogenic therapies including psoralen–ultraviolet A (PUVA). A statistical evaluation of these therapies in a more detailed form may provide important information in this respect and should be attempted. In this case for the skin, one can most likely conclude only that this therapy may not be more carcinogenic than PUVA. In addition, a critical question that this study does not explore, and which remains to be answered, is the effect that this therapy may have on caregivers who may be involved for years in the assistance and close delivery of this substance to patients in either the clinical or home setting. It may not be possible to answer this latter question, but by understanding the mechanisms by which this undoubtedly useful drug works, one can recommend users always to follow appropriate safety precautions in both its therapeutic use and disposal.
Nitrogen mustard revisited
Conflicts of interest
DOI: 10.1111/bjd.12890
None declared.
ORIGINAL ARTICLE, p 699
Medical University of Vienna, W€ahringerg€urtel 18-20, 1090 Vienna, Austria E-mail: [email protected]
Mechlorethamine [methyl-bis(2-chloroethyl)amine] hydrochloride, also known as nitrogen mustard, is a chemotherapeutic agent that has been used for over six decades in the treatment of cutaneous T-cell lymphoma.1,2 It has recently gained renewed attention due to the approval by the US Food and Drug Administration for the use of a gel formulation in the local treatment of mycosis fungoides stages IA and IB. This was based on the additional information provided by a recent randomized, controlled, multicentre trial on 260 patients testing the efficacy of a 002% gel in mycosis fungoides.3 The timely publication by Lindahl et al.4 on a 30-year population-based follow-up study evaluating the possible long-term side-effect profile of the use of nitrogen mustard in the treatment of mycosis fungoides is an important contribution to the © 2014 British Association of Dermatologists
495
R. KNOBLER
References 1 Bunn PA Jr, Hoffmann SJ, Norris D et al. Systemic therapy of cutaneous T-cell lymphomas (mycosis fungoides and the Sezary syndrome). Ann Intern Med 1994; 121:592–602. 2 Ramsay DL, Meller JA, Zackheim HS. Topical treatment of early cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 1995; 9:1031–56. 3 Lessin SR, Duvic M, Guitart J et al. Topical chemotherapy in cutaneous T-cell lymphoma. JAMA Dermatol 2013; 149:25–32. 4 Lindahl LM, Fenger-Grøn M, Iversen L. Secondary cancers, comorbidities and mortality associated with nitrogen mustard therapy in patients with mycosis fungoides: a 30-year population-based cohort study. Br J Dermatol 2014; 170:699–704. British Journal of Dermatology (2014) 170, pp490–495
cytotoxic chemotherapy. Secondly, it demonstrates that the skills of hair biologists and clinicians in measuring hair growth, which have become de riguer in assessing treatments for other hair-loss disorders, have a place in the development of treatments aimed at the prevention of chemotherapy alopecia. In the search for more effective treatments we need precise measurements – subjective assessments of hair status are not sufficient. Thirdly, and perhaps more importantly from a biological standpoint, this study questions the role of oestrogens in regulating human hair growth. The results are not conclusive but they nevertheless cast doubt on the common assumption that oestrogens have a stimulatory effect on scalp hair growth. This has relevance, for example, to our understanding of the age-related decline in hair density in women, which is often ascribed to postmenopausal oestrogen deficiency. Devising studies that provide a more definitive answer should not be too difficult. Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, U.K. E-mail: [email protected]
A.G. MESSENGER
References 1 Kanti V, Nuwayhid R, Lindner J et al. Analysis of quantitative changes in hair growth during treatment with chemotherapy or tamoxifen in patients with breast cancer: a cohort study. Br J Dermatol 2014; 170:643–650. 2 Eckert J, Church RE, Ebling FJ. The pathogenesis of alopecia areata. Br J Dermatol 1968; 80:203–10. 3 Thornton MJ, Taylor AH, Mulligan K et al. Oestrogen receptor beta is the predominant oestrogen receptor in human scalp skin. Exp Dermatol 2003; 12:181–90. 4 Saggar V, Wu S, Dickler MN, Lacouture ME. Alopecia with endocrine therapies in patients with cancer. Oncologist 2013; 18:1126–34.
Do we need a patient satisfaction score? DOI: 10.1111/bjd.12867 ORIGINAL ARTICLE, p 672 At lectures on psoriasis you can see eyes glaze over; BlackBerry addicts turn on their cell phones, and workaholics open their laptops when a speaker mentions quality of life or patient satisfaction. Quality-of-life and patient satisfaction surveys are met with groans by investigators for whom this just means more work. But the impact of patient satisfaction on patients’ current and future quality of life is critical, and the impact on their family, friends, coworkers, employers and customers is tangible. Moreover, satisfaction with therapy affects adherence to that therapy, and poor adherence is known to be an enormous problem in dermatology. In a study performed at an outpatient clinic, one-third of prescriptions were never even filled.1 In another small study, 95% of patients were found to British Journal of Dermatology (2014) 170, pp490–495
underdose topical therapies,2 and adherence to a 5-day treatment course of a topical steroid among patients with atopic dermatitis was only 40%.3 As shown in the study by Callis Duffin et al.,4 in this issue of BJD, it is not surprising that patient satisfaction is lower for topical therapies than for all other therapies. Nor is it surprising that these scores are also lower for narrowband ultraviolet (UV)B, which requires office visits up to three times per week, and for infliximab, which requires in-office infusions at least every 8 weeks. More than ever before, patient-reported outcomes are being used by the government and by insurers to justify treatments. And in an era when adherence is coming under closer scrutiny, treatments associated with greater patient satisfaction are likely to lead to greater adherence. Clinical scores such as the Psoriasis Activity and Severity Index are helpful, even if imperfect. Those scores generally correlate well with quality-of-life scores and patient satisfaction scores. However, looking only at clinical scores, it is easy for physicians to overlook the side-effects of treatments that work – but these emerge much more clearly in patient satisfaction scores. Methotrexate, for example, requires more laboratory monitoring and is often associated with nausea, oral ulcers and a sense of malaise, not to mention the symptoms associated with megaloblastic anaemia. Yet, all of us have heard the methotrexate enthusiast who says: ‘I’ve never had a patient with side-effects from methotrexate and it works for everyone.’ It’s amazing how many of our colleagues don’t realize their patients are doing well only because they’ve gone to other dermatologists who prescribed more satisfying treatments. By now, we all should realize that the justifiable enthusiasm for methotrexate should be related to its price, as it has been shown to be less effective and have more side-effects than at least one of our biological therapies for which a headto-head comparison has been performed.5 The challenge is to come up with an easy quality-of-life or patient satisfaction measure that takes little time on the part of investigators and clinicians. The Treatment Satisfaction Questionnaire for Medication version II (TSQM) consists of 11 items concerning key points: effectiveness, adverse effects, convenience of therapies and satisfaction with those therapies.6 Using that simple questionnaire, Callis Duffin et al. have shown that patients receiving methotrexate monotherapy had significantly lower patient-reported effectiveness scores than those receiving subcutaneously administered biologics (adalimumab, etanercept, ustekinumab), narrowband UVB phototherapy or adalimumab with methotrexate. Conversely, methotrexate monotherapy was significantly more convenient than topical therapies, infliximab or narrowband UVB phototherapy. Because we are all under pressure by insurers to see more patients in less time, and because clinical evaluations of psoriasis correlate with patient satisfaction and quality of life, it is unlikely that surveys like the TSQM will be performed in clinical practice. But in a study setting, the TSQM provides valuable information that can be used to influence regulatory agencies and insurers. © 2014 British Association of Dermatologists
Commentaries
Conflicts of interest Dr Lebwohl has been an investigator for Inbios, Coronado Biosciences; he has been a consultant forAbbvie,Valeant, Taro, Pfizer, UCB pharma, Forward pharma, Dermipsor,Galderma; and he has been a consultant andan investigator for Ranbaxy, Novartis, Dermira, Merz, Merck, Leo pharma,Janssen-biotech, Glaxo SmithKline,Elililly,Celgene,Can-Fitebiopharma,Anacor,andAmgen. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A. E-mail: [email protected]
M. LEBWOHL
References 1 Storm A, Andersen SE, Benfeldt E, Serup J. One in 3 prescriptions are never redeemed: primary nonadherence in an outpatient clinic. J Am Acad Dermatol 2008; 59:27–33. 2 Storm A, Benfeldt E, Andersen SE, Serup J. A prospective study of patient adherence to topical treatments: 95% of patients underdose. J Am Acad Dermatol 2008; 59:975–80. 3 Hix E, Gustafson CJ, O’Neill JL et al. Adherence to a five day treatment course of topical fluocinonide 0.1% cream in atopic dermatitis. Dermatol Online J 2013; 19:20029. 4 Callis Duffin K, Yeung H, Takeshita J et al. Patient satisfaction with treatments for moderate-to-severe plaque psoriasis in clinical practice. Br J Dermatol 2014; 170:672–80. 5 Saurat JH, Stingl G, Dubertret L et al. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol 2008; 158:558–66. 6 Atkinson MJ, Kumar R, Cappelleri JC, Hass SL. Hierarchical construct validity of the treatment satisfaction questionnaire for medication (TSQM version II) among outpatient pharmacy consumers. Value Health 2005; 8(Suppl. 1):S9–24.
overall safety evaluation of this important agent for the treatment of this disease. Even though the data reported in the first study showed no evidence of systemic absorption, which may in the long term contribute to toxic side-effects, there is no doubt that local cytotoxic efficacy is associated with local absorption and should always be taken into consideration when used in early disease and young patients. This needs to be considered for a number of reasons. (i) In a significant number of patients the disease has a very protracted course, so that overall survival may not be affected; thus in younger patients long-term extended use may eventually be associated with unexpected side-effects and should be monitored carefully. (ii) In the study by Lindahl et al., even though the data are very suggestive of a very low long-term side-effect profile, some additional information needs to be gathered and analysed to generate even more conclusive evidence. In their study the authors did not include as an additional control a cohort without mycosis fungoides for comparison. Furthermore, which may prove to be very important, they did not evaluate within the mycosis fungoides groups those patients who did versus those who did not receive any carcinogenic therapies including psoralen–ultraviolet A (PUVA). A statistical evaluation of these therapies in a more detailed form may provide important information in this respect and should be attempted. In this case for the skin, one can most likely conclude only that this therapy may not be more carcinogenic than PUVA. In addition, a critical question that this study does not explore, and which remains to be answered, is the effect that this therapy may have on caregivers who may be involved for years in the assistance and close delivery of this substance to patients in either the clinical or home setting. It may not be possible to answer this latter question, but by understanding the mechanisms by which this undoubtedly useful drug works, one can recommend users always to follow appropriate safety precautions in both its therapeutic use and disposal.
Nitrogen mustard revisited
Conflicts of interest
DOI: 10.1111/bjd.12890
None declared.
ORIGINAL ARTICLE, p 699
Medical University of Vienna, W€ahringerg€urtel 18-20, 1090 Vienna, Austria E-mail: [email protected]
Mechlorethamine [methyl-bis(2-chloroethyl)amine] hydrochloride, also known as nitrogen mustard, is a chemotherapeutic agent that has been used for over six decades in the treatment of cutaneous T-cell lymphoma.1,2 It has recently gained renewed attention due to the approval by the US Food and Drug Administration for the use of a gel formulation in the local treatment of mycosis fungoides stages IA and IB. This was based on the additional information provided by a recent randomized, controlled, multicentre trial on 260 patients testing the efficacy of a 002% gel in mycosis fungoides.3 The timely publication by Lindahl et al.4 on a 30-year population-based follow-up study evaluating the possible long-term side-effect profile of the use of nitrogen mustard in the treatment of mycosis fungoides is an important contribution to the © 2014 British Association of Dermatologists
495
R. KNOBLER
References 1 Bunn PA Jr, Hoffmann SJ, Norris D et al. Systemic therapy of cutaneous T-cell lymphomas (mycosis fungoides and the Sezary syndrome). Ann Intern Med 1994; 121:592–602. 2 Ramsay DL, Meller JA, Zackheim HS. Topical treatment of early cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 1995; 9:1031–56. 3 Lessin SR, Duvic M, Guitart J et al. Topical chemotherapy in cutaneous T-cell lymphoma. JAMA Dermatol 2013; 149:25–32. 4 Lindahl LM, Fenger-Grøn M, Iversen L. Secondary cancers, comorbidities and mortality associated with nitrogen mustard therapy in patients with mycosis fungoides: a 30-year population-based cohort study. Br J Dermatol 2014; 170:699–704. British Journal of Dermatology (2014) 170, pp490–495
