Journal of Dermatological Treatment
ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage: http://www.tandfonline.com/loi/ijdt20
Topical treatment for scalp psoriasis: Comparison of patient preference, quality of life and efficacy for non-alcoholic mometasone emulsion versus calcipotriol/betamethasone gel in daily clinical practice Adrià Gual, Ignasi Pau-Charles & Sonja Molin To cite this article: Adrià Gual, Ignasi Pau-Charles & Sonja Molin (2016) Topical treatment for scalp psoriasis: Comparison of patient preference, quality of life and efficacy for non-alcoholic mometasone emulsion versus calcipotriol/betamethasone gel in daily clinical practice, Journal of Dermatological Treatment, 27:3, 228-234, DOI: 10.3109/09546634.2015.1093590 To link to this article: http://dx.doi.org/10.3109/09546634.2015.1093590
Published online: 27 Oct 2015.
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Date: 28 September 2017, At: 05:34
http://tandfonline.com/ijdt ISSN: 0954-6634 (print), 1471-1753 (electronic) J Dermatolog Treat, 2016; 27(3): 228–234 ! 2015 Taylor & Francis. DOI: 10.3109/09546634.2015.1093590
ORIGINAL ARTICLE
Topical treatment for scalp psoriasis: Comparison of patient preference, quality of life and efficacy for non-alcoholic mometasone emulsion versus calcipotriol/betamethasone gel in daily clinical practice Adria` Gual1, Ignasi Pau-Charles1, and Sonja Molin2
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1
Department of Dermatology, Universitat de Barcelona, Hospital Clı´nic, Barcelona, Spain and 2Department of Dermatology and Allergy, Ludwig Maximilian University, Munich, Germany Abstract
Keywords
Objective: To evaluate patients’ assessment of therapy, efficacy, quality of life and treatment adherence in patients with scalp psoriasis treated with non-alcoholic mometasone emulsion or calcipotriol/betamethasone gel. Methods: Prospective, open-label, multicentre, noninterventional study. Patients with non-severe scalp psoriasis were treated with mometasone emulsion or calcipotriol/betamethasone gel. Evaluations included patient’s global assessment of treatment, physician’s global assessment of disease severity, quality of life (Dermatology Life Quality Index), physician’s subjective evaluation of therapy, treatment adherence and adverse events. Results: Ninety-five patients treated with mometasone emulsion and 88 treated with calcipotriol/betamethasone gel were included in the intention-to-treat analysis. Patients’ global assessment of treatment favoured mometasone emulsion over calcipotriol/betamethasone gel (p ¼ 0.008), with treatment rated as good/very good by 91% versus 82.5%. Patients were less likely to report irritation of fingers’ skin with mometasone than with calcipotriol/ betamethasone (p ¼ 0.0015). Severity of scalp psoriasis and quality of life improved in both groups. Adherence to treatment was similar in both groups. Physicians’ perception of efficacy, tolerability and compliance was better for mometasone emulsion. Conclusion: Non-alcoholic mometasone emulsion achieved greater acceptability to patients and physicians than calcipotriol/betamethasone gel for the treatment of scalp psoriasis. Both topical treatments were similarly effective in terms of disease severity and quality of life.
Calcipotriol/betamethasone gel, mometasone emulsion, scalp psoriasis, topical treatments
Introduction Psoriasis is a common disease, affecting 1–3% of the population in western countries (1). The course of this chronic, inflammatory skin disorder is unpredictable, and its extent and severity vary between patients and over time (2,3). The condition has a substantial impact on patients’ quality of life, not only adversely affecting their daily activities, social and professional life but also leading to stigmatization and social exclusion (4–6). The scalp is affected in 50–80% of patients with psoriasis (7,8). Scalp involvement has a strong effect on patients’ quality of life because of its visibility (3,9). In addition, scalp psoriasis is often difficult to treat due to the peculiarities of the anatomical area. It is usually treated with topical therapy, but hair makes it difficult to apply preparations and some drugs need to be kept away from the face because the skin in this area is more prone to develop adverse effects (10). Furthermore, many patients are reluctant to use topical treatments on visible areas if they are cosmetically unappealing (10). The effectiveness of a therapy in a real-life setting depends not only on its intrinsic efficacy and safety, but also on patients’
Correspondence: Dr Adria` Gual, Department of Dermatology, Hospital Clı´nic, Universitat de Barcelona, Villarroel St, 170, 08036 Barcelona, Spain. Tel: +34 932275400. E-mail: [email protected]
History Received 20 July 2015 Accepted 5 September 2015 Published online 13 October 2015
adherence to it (11). Poor adherence to topical treatment of psoriasis is a common problem (12), and creates a barrier to achieving optimal outcomes (13). It has been reported that in a clinical setting only 50–60% of the expected number of topical treatment applications is performed (14). Common reasons for non-adherence include poor cosmetic characteristics, messiness of the formulation, lack of efficacy, inconvenient regimens and adverse effects (15). Widely used topical therapies for psoriasis include corticosteroids, which are available as ointments, creams, lotions, gels, shampoos and foams, and vitamin D analogues, which are available as ointments or solutions (10,16). Patients have different preferences regarding the various topical formulations. For instance, some patients may find ointments unacceptable for scalp application because they are greasy and difficult to remove (10,17), while others experience scalp irritation with many gels and solutions due to their alcohol content (10,16). Improved formulations and dosing regimens that are more acceptable to patients may therefore help to improve adherence to treatment, thus leading to greater effectiveness. A non-alcoholic corticosteroid emulsion formulation of mometasone furoate, with a galenic formulation optimized for scalp skin (Almirall S.A., Barcelona, Spain) (18) has recently been approved. The aim of this study was to examine patient acceptability and efficacy of the mometasone emulsion among patients with scalp psoriasis in a daily clinical practice setting
DOI: 10.3109/09546634.2015.1093590
compared with the widely used combination of calcipotriol plus betamethasone gel. The primary objective was to evaluate the patients’ assessment of their medication. Secondary objectives included the evaluation of treatment efficacy, quality of life and adherence to therapy.
Materials and methods
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Study design This prospective, multicentre, open-label, non-interventional study was performed at 17 dermatology centres in southern Germany between February and September 2014. Patients with non-severe scalp psoriasis treated with either mometasone emulsion or a combination gel product containing calcipotriol plus betamethasone were eligible to participate. Decisions about the treatment of individual patients were made by dermatologists in the course of their routine clinical practice, and were based exclusively on their assessment of the need for treatment and the most suitable agent to use. Patients were evaluated at the beginning of treatment and at the planned end of treatment. The study was conducted in accordance with the German Medicinal Products Act (AMG) section 4(23) sentence 3, and was approved by the ethics committee of the University of Munich and the Freiburg international ethics committee. All the patients provided written informed consent. Patients To be eligible for enrolment into the study, patients had to be adults with non-severe scalp psoriasis (defined as the involvement of no more than 50% of the scalp, no cicatricial alopecia or facial lesions, and without moderate/severe erythema, infiltration or pruritus). Participants had not received treatment with either mometasone or calcipotriol/betamethasone gel within the previous 3 months, and were not receiving any topical treatment for scalp psoriasis when they were enrolled. In addition, patients must not have received systemic treatment with retinoids, methotrexate, cyclosporine or phototherapy for body psoriasis during 4 weeks prior or with biologics during 6 months prior to enrolment. Other exclusion criteria were the presence of contraindications to the study medications, hypersensitivity to any of the ingredients or to other corticosteroids, and patients who were aiming to become pregnant or who were breast-feeding. Treatment The attending physicians chose treatment for each patient according to their usual therapeutic decision process. Mometasone emulsion (mometasone furoate 0.1% w/w) and calcipotriol/ betamethasone gel (calcipotriol monohydrate 0.05 mg/g plus betamethasone dipropionate 0.5 mg/g) were both administered in accordance with the relevant summary of product characteristics, which recommend that the treatment should be administered for a maximum of 3 weeks for mometasone emulsion or 4 weeks for calcipotriol/betamethasone gel. The final decision on the duration of therapy was made by the physicians. Assessments and outcome measures After patients had been prescribed treatment, they were considered for enrolment into the study. At visit 1 (baseline), physicians recorded information on inclusion/exclusion criteria, demographics, diagnosis, treatment history, concurrent diseases and concomitant medications, baseline disease severity by means of Physician’s Global Assessment (PGA), and whether patients had been prescribed mometasone emulsion or calcipotriol/ betamethasone gel. In addition, patients completed a baseline
Mometasone emulsion versus calcipotriol/betamethasone gel
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Table 1. Patients’ treatment assessment questionnaire. Patient’s global assessment of treatment In response to the question ‘‘How do you assess the treatment with the scalp medication?’’ patients rated the treatment as: very good, good, moderate, poor or very poor. Assessment of specific aspects of treatment Patients rated the correctness of the following statements as: very good, good, moderate, hardly or not at all. 1. Easy to use 2. Must be washed out 3. Is difficult to remove 4. Glued to the hair 5. Absorbs quickly into the scalp 6. Could be applied in the morning as well 7. Leaves residue on hair or clothing 8. Is better than other preparations 9. Smells pleasant 10. Discolours hair 11. Does not change my appearance 12. Has irritated the skin of my fingers 13. Worked quickly 14. Is in a bottle which can be easily opened 15. Can be portioned easily from the bottle 16. Relieves itching quickly
Dermatology Life Quality Index (DLQI) questionnaire, and were given a diary (a calendar-based form with tick boxes to indicate the days the treatment was applied) to take home and complete during the treatment period. At visit 2 (final examination), patients handed in their adherence diary, and completed a second DLQI questionnaire and a questionnaire on their overall assessment of the treatment (Table 1). The outcome of treatment was assessed, including efficacy (evaluated by PGA and DLQI), patient’s global assessment of treatment, patient compliance and physician’s subjective evaluation of efficacy, tolerability and compliance. Adherence to treatment was calculated as the number of days the medication was applied divided by the total number of days from the first to the last application. The primary endpoint was patient’s assessment of treatment. Secondary endpoints included quality of life, efficacy and treatment adherence. Statistical analysis Descriptive analyses were performed. Mean, SD, quartiles, and maximum and minimum values were calculated. Absolute, relative and adjusted relative frequencies (with the latter excluding patients with missing data) were assessed. Multiple entries per patient (e.g. multiple drugs) were counted, meaning that relative frequencies, which referred to the number of cases, could exceed 100%. Cross tables were prepared, including variables versus expression/quality of the variable, and shifts in variables between two time points. Statistical significance was evaluated for key parameters, using two-tailed p values with an alpha level of 0.05. ‘‘Tendency’’ was defined as p50.10. However, no statistical hypotheses were formulated in advance and therefore tests of significance were considered exploratory only. No correction of alpha for multiple comparisons was performed. Tests included the Jonckheere– Terpstra non-parametric test for ordered difference among classes; the Wilcoxon two-sample test, a non-parametric test of the null hypothesis versus an alternative hypothesis; and the Cochran–Mantel–Haenszel statistic for the analysis of stratified categorical data. Analyses were performed on two populations. The intentionto-treat (ITT) population comprised all the patients treated with one of the two study treatments at least once, excluding patients
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J Dermatolog Treat, 2016; 27(3): 228–234
Figure 1. Disposition of patients.
Enrolled into study (n=185) Withdrew consent (n=1) Did not start treatment (n=1)
Mometasone emulsion (n=95)
Calcipotriol/betamethasone gel (n=88)
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Discontinued treatment (n=11)* -Recovery/remission (n=7) -Patient missed visit (n=3) -Adverse event (n=2) -Patient’s request (n=1) -Inpatient treatment for widespread psoriasis (n=1)
Discontinued treatment (n=16)* Recovery/remission (n=6) -Lack of compliance (n=5) -Patient’s request (n=3) -Patient missed visit (n=2) -Lack of efficacy (n=1)
Completed planned treatment (n=84) -Stopped treatment at study end (n=46) -Continued beyond study end (n=37) -Not known if continued or not (n=1)
Completed planned treatment (n=72) -Stopped treatment at study end (n=43) -Continued beyond study end (n=29)
ITT analysis set (n=95) PP analysis set (n=93). Exclusions: -Calcipotriol/betamethasone received until 5 weeks prior to study (n=1) -Mometasone received until 10 weeks prior to study (n=1)
ITT analysis set (n=88) PP analysis set (n=85). Exclusions: -Concomitant betamethasone (n=1) -Concomitant mometasone (n=1) -Mometasone received until 10 weeks prior to study (n=1)
* Some patients had more than one reason.
who revoked their consent. The per-protocol (PP) population comprised all patients from the ITT population who met the inclusion criteria, did not meet any exclusion criteria, and had data recorded at baseline. A sample size of 200 patients (100 per group) was considered feasible in a routine clinical practice setting, and sufficient to provide a representative group of patients with non-severe scalp psoriasis.
Results A total of 185 patients were enrolled into the study between February and September 2014, 183 of whom were included in the ITT population: 95 patients were treated with mometasone emulsion and 88 were treated with calcipotriol/betamethasone gel (Figure 1). Two patients were excluded from the ITT population (one who revoked their consent and one who did not commence treatment). The PP population comprised 93 recipients of mometasone emulsion and 85 recipients of calcipotriol/ betamethasone gel. An analysis of the PP population showed no significant differences from the ITT analysis. The results presented below are for the ITT population. Baseline characteristics were similar between the treatment groups (Table 2). There were more female than male patients in both groups. The mean and median duration of scalp psoriasis was somewhat longer in the calcipotriol/betamethasone group than in the mometasone group (131.6 versus 120.3 months and 96.2 versus 45.9 months, respectively), but there were no significant differences in the severity of scalp psoriasis (p ¼ 0.171), with most patients having disease of moderate severity. In both groups, the most common form of treatment received for scalp psoriasis prior to the study was potent or very potent corticosteroids.
Treatments administered Mometasone emulsion was prescribed for most patients as one application per day (95.8% of patients). Similarly, once daily applications was prescribed for 96.6% of the calcipotriol/ betamethasone group. Physicians most commonly prescribed mometasone emulsion and calcipotriol/betamethasone gel for a period of 22–28 days (52.6% and 69.3%, respectively) or 15–21 days (31.6% and 14.8%). Most patients used the treatment for 22– 28 days (mometasone 37.2%; calcipotriol/betamethasone 40.2%) or even longer (29–35 days; mometasone 26.6%; calcipotriol/ betamethasone 29.9%). Treatment ended as initially planned by the treating physician in 48.4% of mometasone recipients and 48.9% of calcipotriol/ betamethasone recipients, while it was continued beyond the prescribed period in 39.0% patients of the mometasone group and in 33.0% patients of the calcipotriol/betamethasone group (for a mean of 26 and 24 days, respectively). Overall, 11.6% of the mometasone group and 18.2% of the calcipotriol/betamethasone gel group discontinued treatment earlier than planned (Figure 1). The most common reason for premature discontinuation in both groups was recovery/remission of scalp psoriasis (mometasone 7.4% versus calcipotriol/betamethasone 6.8%). The second most common reason in the calcipotriol/betamethasone group was a lack of compliance (5.7%). No patient in the mometasone group withdrew for this reason. Patients’ assessment of treatment Analysis of patients’ global assessment of treatment showed a statistically significant difference between the groups in favour of mometasone emulsion (p ¼ 0.008; Figure 2). Overall, 91% of
Mometasone emulsion versus calcipotriol/betamethasone gel
DOI: 10.3109/09546634.2015.1093590
Table 2. Patient demographics and baseline characteristics.
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Parameter
Mometasone emulsion (n ¼ 95)
Calcipotriol/ betamethasone gel (n ¼ 88)
Sex, n (%) Male/female 40 (42.1)/55 (57.9) 31 (35.2)/57 (64.8) Age distribution (%) 18–30 years 17.9 11.4 31–40 years 11.6 9.1 41–50 years 8.4 20.5 51–60 years 21.1 18.2 61–70 years 20.0 21.6 71–80 years 15.8 15.9 480 years 5.3 3.4 Duration of scalp psoriasis (months) Mean 120.3 131.6 Median 45.9 96.2 Distribution (%) 56 months 17.9 14.9 6–11 months 20.0 12.6 12–23 months 5.3 4.6 24–59 months 14.7 14.9 60–119 months 8.4 8.1 120–239 months 20.0 25.3 240 months 13.7 19.5 Severity of scalp psoriasisa, n (%) Almost without findings 0 1 (1.1) Mild 32 (33.7) 37 (42.1) Moderate 63 (66.3) 50 (56.8) Previous therapy, n (%) 33 (34.7) 18 (20.5) Most common, n (%) Clobetasol 14 (42.4) 6 (33.3) Betamethasone 8 (24.2) 5 (27.8) Calcipotriol combinations 3 (9.1) 2 (11.1) Mometasone 3 (9.1) 2 (11.1) Most common concurrent disorders (body system), n (%) Vascular 16 (16.8) 16 (18.2) Metabolism/nutrition 11 (11.6) 9 (10.2) Skin/subcutaneous 6 (6.3) Endocrine 8 (9.1) a
Almost without findings: a small area of scalp affected. Mild: 550% of the scalp affected plus 1 of the following present – mild erythema, mild scaling, minimal thickness (barely any/no infiltration) and mild pruritus. Moderate:550% of the scalp affected plus 1 of the following present – moderate erythema, moderate scaling, moderate thickness (some infiltration), mild to moderate pruritus.
patients treated with mometasone emulsion rated their treatment as very good or good compared with 82.5% of calcipotriol/ betamethasone gel recipients. In terms of individual items associated with treatment, mometasone emulsion was significantly less likely than calcipotriol/betamethasone gel to cause irritation of the skin of the fingers (p ¼ 0.0015), with 77.5% of mometasone recipients reporting no irritation versus 56.6% of the calcipotriol/betamethasone gel group. Statistical analysis also showed a tendency favouring mometasone emulsion regarding three other items: being in an easy-to-open bottle (p ¼ 0.057), pleasant smell (p ¼ 0.068) and quick absorption into the scalp (p ¼ 0.089). Severity of scalp psoriasis At baseline, the distribution of psoriasis severity was similar in the two groups. In both groups it decreased during the study compared to baseline, based on PGA. The proportion of patients with moderate psoriasis decreased from 66.0% to 4.3% at the final assessment in the mometasone group, and from 56.3% to 5.8% in the calcipotriol/betamethasone group. The proportion of patients clear or almost clear of psoriasis increased from 0% to 73.4% in the mometasone group, and from 1.1% to 68.9% in the calcipotriol/betamethasone group. There was no statistically significant difference between the two groups in terms of the
231
distribution of psoriasis severity at the final assessment, either overall (Figure 3; p ¼ 0.195) or when the subgroups with mild (p ¼ 0.424) or moderate (p ¼ 0.179) psoriasis at baseline were analyzed. Quality of life In both groups, the mean DLQI score at baseline (mometasone 8.07 points; calcipotriol/betamethasone 8.83 points) showed that patients felt that their scalp psoriasis had a moderate effect on their quality of life. At the final assessment, the mean score had decreased in both groups, which indicated that scalp psoriasis then only had a small effect on their quality of life. The improvement in DLQI scores did not differ significantly between the two groups (Figure 4). Treatment adherence Treatment adherence in the two groups, based on patients’ diaries, is summarized in Figure 5. There were no statistically significant differences between groups (p ¼ 0.685). Most patients had high or very high compliance rates according to their diary record. Tolerability Three patients in the mometasone group reported a total of six adverse events during the study, including application site pain, application site pustules, pruritus, burning skin sensation and lack of improvement. All the adverse events potentially related to mometasone emulsion were mild in severity. Lack of improvement was reported in one patient due to aggravation of psoriasis on the trunk and extremities and was not considered to be related to study medication. Physician’s subjective evaluation of therapy At the final assessment, the physicians assessed mometasone with higher scores than calcipotriol/betamethasone gel in terms of general efficacy, general tolerability and compliance with treatment (Table 3).
Discussion Psoriasis is a highly visible disease that impacts the quality of life and well-being of sufferers. Topical medications are a mainstay of treatment, and the formulation of the product and the acceptability to the patient are important characteristics that influence adherence to therapy and overall clinical efficacy. The results of the current study in a daily clinical practice setting showed that non-alcoholic mometasone emulsion is an appropriate alternative first-line therapeutic option for the treatment of patients with non-severe scalp psoriasis, exhibiting similar efficacy with greater acceptance by patients compared to calcipotriol/ betamethasone gel. Topical corticosteroids and combination therapy with calcipotriol/betamethasone are known to be efficacious for the treatment of psoriasis and are recommended as first-line therapies for scalp lesions (10). The calcipotriol/betamethasone combination gel formulation has previously been shown to be generally well accepted by patients (19), who judged it as being more convenient and less time-consuming than their previous therapy (20). It was also associated with a greater improvement of quality of life compared to monotherapy with calcipotriol solution (21). Moreover, the gel formulation has been described as being more advantageous than an ointment formulation containing the same active ingredients (22). In the present study, mometasone emulsion improved scalp psoriasis and quality of life of patients to a similar level as
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J Dermatolog Treat, 2016; 27(3): 228–234
Figure 2. Patients’ global assessment of treatment.
70% 62.5%
Non-alcoholic mometasone emulsion (n=88) Calcipotriol/betamethasone gel (n=80)
60% 53.4%
p=0.0082** (Jonckheere-Terpstra Test)
50% 40%
37.5%
30% 20.0% 16.3%
20% 6.8%
10%
2.3%
0.0%
0.0% 1.3%
0% Very good
Good
Moderate
Poor
Very poor
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−10%
Figure 3. Scalp psoriasis severity at final assessment.
60%
Non-alcoholic mometasone emulsion (n=94) Calcipotriol/betamethasone gel (n=87)
50% 42.5% 40%
36.2%
30%
p=0.1954 (Jonckheere-Terpstra Test)
37.2%
26.4% 22.3%
24.1%
20%
10% 4.3%
5.8% 0.0% 1.2%
0% Without findings
10 9
8.83
Non-alcoholic mometasone emulsion (n=90) Calcipotriol/betamethasone gel (n=86)
8 7
8.07
p=0.3368 (Wilcoxon rank-sum Test)
6 5 4
3.22
3 2 2.02
1 0 Baseline
Final examinaon
Higher DLQI scores indicate greater impairment in quality life. Total possible score 0 to 30.
Figure 4. Dermatology Life Quality Index (DLQI) scores at baseline and at final assessment.
calcipotriol/betamethasone gel. In addition, mometasone emulsion achieved better ratings by patients and physicians for overall acceptability. The real-life effectiveness of topical therapy is a balance between efficacy, safety and compliance with treatment (11).
Almost without findings
Mild
Moderate
Severe
Adherence is a complex multidimensional concept, which in the case of psoriasis involves not only the treatment vehicle, but also patient motivation and preference, and the patient–physician relationship (13). Adherence to topical treatments for psoriasis generally tends to be poor, and although there are multiple reasons for this, one important factor is the patients’ willingness to use the available treatments (13). In this study, both treatments produced good adherence results, and no significant differences between the two groups were observed. The evaluation of adherence by indirect measures such as patient diaries is simple and therefore the most practical method in the real-world clinical setting, but the results can easily be distorted if patients do not complete the diaries accurately (23,24). This, together with the multidimensional attribute of adherence may have limited the ability of the study to fully assess differences between treatments. Nonetheless, the subjective assessment of adherence by physicians did favour mometasone emulsion. The study has several strengths. Firstly, the non-interventional design enabled assessment in a setting close to daily clinical practice conditions of treatment. Secondly, the study evaluated patients’ acceptance of topical treatment, focusing on galenic characteristics. This is relevant because of the important role that treatment acceptance and preference play in determining adherence to topical treatments. Thirdly, the study did not only evaluate
Mometasone emulsion versus calcipotriol/betamethasone gel
DOI: 10.3109/09546634.2015.1093590
Figure 5. Adherence to treatment.
233
80% Non-alcoholic mometasone emulsion (n=92)
68.7%
70%
65.2%
Calcipotriol/betamethasone gel (n=83) 60% 50%
p=0.6851 (Jonckheere-Terpstra test)
40% 30% 20.7% 20%
16.9% 8.7% 9.6%
10%
5.4% 4.8% 0%
0%
0% Very poor (
ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage: http://www.tandfonline.com/loi/ijdt20
Topical treatment for scalp psoriasis: Comparison of patient preference, quality of life and efficacy for non-alcoholic mometasone emulsion versus calcipotriol/betamethasone gel in daily clinical practice Adrià Gual, Ignasi Pau-Charles & Sonja Molin To cite this article: Adrià Gual, Ignasi Pau-Charles & Sonja Molin (2016) Topical treatment for scalp psoriasis: Comparison of patient preference, quality of life and efficacy for non-alcoholic mometasone emulsion versus calcipotriol/betamethasone gel in daily clinical practice, Journal of Dermatological Treatment, 27:3, 228-234, DOI: 10.3109/09546634.2015.1093590 To link to this article: http://dx.doi.org/10.3109/09546634.2015.1093590
Published online: 27 Oct 2015.
Submit your article to this journal
Article views: 276
View related articles
View Crossmark data
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijdt20 Download by: [Australian Catholic University]
Date: 28 September 2017, At: 05:34
http://tandfonline.com/ijdt ISSN: 0954-6634 (print), 1471-1753 (electronic) J Dermatolog Treat, 2016; 27(3): 228–234 ! 2015 Taylor & Francis. DOI: 10.3109/09546634.2015.1093590
ORIGINAL ARTICLE
Topical treatment for scalp psoriasis: Comparison of patient preference, quality of life and efficacy for non-alcoholic mometasone emulsion versus calcipotriol/betamethasone gel in daily clinical practice Adria` Gual1, Ignasi Pau-Charles1, and Sonja Molin2
Downloaded by [Australian Catholic University] at 05:34 28 September 2017
1
Department of Dermatology, Universitat de Barcelona, Hospital Clı´nic, Barcelona, Spain and 2Department of Dermatology and Allergy, Ludwig Maximilian University, Munich, Germany Abstract
Keywords
Objective: To evaluate patients’ assessment of therapy, efficacy, quality of life and treatment adherence in patients with scalp psoriasis treated with non-alcoholic mometasone emulsion or calcipotriol/betamethasone gel. Methods: Prospective, open-label, multicentre, noninterventional study. Patients with non-severe scalp psoriasis were treated with mometasone emulsion or calcipotriol/betamethasone gel. Evaluations included patient’s global assessment of treatment, physician’s global assessment of disease severity, quality of life (Dermatology Life Quality Index), physician’s subjective evaluation of therapy, treatment adherence and adverse events. Results: Ninety-five patients treated with mometasone emulsion and 88 treated with calcipotriol/betamethasone gel were included in the intention-to-treat analysis. Patients’ global assessment of treatment favoured mometasone emulsion over calcipotriol/betamethasone gel (p ¼ 0.008), with treatment rated as good/very good by 91% versus 82.5%. Patients were less likely to report irritation of fingers’ skin with mometasone than with calcipotriol/ betamethasone (p ¼ 0.0015). Severity of scalp psoriasis and quality of life improved in both groups. Adherence to treatment was similar in both groups. Physicians’ perception of efficacy, tolerability and compliance was better for mometasone emulsion. Conclusion: Non-alcoholic mometasone emulsion achieved greater acceptability to patients and physicians than calcipotriol/betamethasone gel for the treatment of scalp psoriasis. Both topical treatments were similarly effective in terms of disease severity and quality of life.
Calcipotriol/betamethasone gel, mometasone emulsion, scalp psoriasis, topical treatments
Introduction Psoriasis is a common disease, affecting 1–3% of the population in western countries (1). The course of this chronic, inflammatory skin disorder is unpredictable, and its extent and severity vary between patients and over time (2,3). The condition has a substantial impact on patients’ quality of life, not only adversely affecting their daily activities, social and professional life but also leading to stigmatization and social exclusion (4–6). The scalp is affected in 50–80% of patients with psoriasis (7,8). Scalp involvement has a strong effect on patients’ quality of life because of its visibility (3,9). In addition, scalp psoriasis is often difficult to treat due to the peculiarities of the anatomical area. It is usually treated with topical therapy, but hair makes it difficult to apply preparations and some drugs need to be kept away from the face because the skin in this area is more prone to develop adverse effects (10). Furthermore, many patients are reluctant to use topical treatments on visible areas if they are cosmetically unappealing (10). The effectiveness of a therapy in a real-life setting depends not only on its intrinsic efficacy and safety, but also on patients’
Correspondence: Dr Adria` Gual, Department of Dermatology, Hospital Clı´nic, Universitat de Barcelona, Villarroel St, 170, 08036 Barcelona, Spain. Tel: +34 932275400. E-mail: [email protected]
History Received 20 July 2015 Accepted 5 September 2015 Published online 13 October 2015
adherence to it (11). Poor adherence to topical treatment of psoriasis is a common problem (12), and creates a barrier to achieving optimal outcomes (13). It has been reported that in a clinical setting only 50–60% of the expected number of topical treatment applications is performed (14). Common reasons for non-adherence include poor cosmetic characteristics, messiness of the formulation, lack of efficacy, inconvenient regimens and adverse effects (15). Widely used topical therapies for psoriasis include corticosteroids, which are available as ointments, creams, lotions, gels, shampoos and foams, and vitamin D analogues, which are available as ointments or solutions (10,16). Patients have different preferences regarding the various topical formulations. For instance, some patients may find ointments unacceptable for scalp application because they are greasy and difficult to remove (10,17), while others experience scalp irritation with many gels and solutions due to their alcohol content (10,16). Improved formulations and dosing regimens that are more acceptable to patients may therefore help to improve adherence to treatment, thus leading to greater effectiveness. A non-alcoholic corticosteroid emulsion formulation of mometasone furoate, with a galenic formulation optimized for scalp skin (Almirall S.A., Barcelona, Spain) (18) has recently been approved. The aim of this study was to examine patient acceptability and efficacy of the mometasone emulsion among patients with scalp psoriasis in a daily clinical practice setting
DOI: 10.3109/09546634.2015.1093590
compared with the widely used combination of calcipotriol plus betamethasone gel. The primary objective was to evaluate the patients’ assessment of their medication. Secondary objectives included the evaluation of treatment efficacy, quality of life and adherence to therapy.
Materials and methods
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Study design This prospective, multicentre, open-label, non-interventional study was performed at 17 dermatology centres in southern Germany between February and September 2014. Patients with non-severe scalp psoriasis treated with either mometasone emulsion or a combination gel product containing calcipotriol plus betamethasone were eligible to participate. Decisions about the treatment of individual patients were made by dermatologists in the course of their routine clinical practice, and were based exclusively on their assessment of the need for treatment and the most suitable agent to use. Patients were evaluated at the beginning of treatment and at the planned end of treatment. The study was conducted in accordance with the German Medicinal Products Act (AMG) section 4(23) sentence 3, and was approved by the ethics committee of the University of Munich and the Freiburg international ethics committee. All the patients provided written informed consent. Patients To be eligible for enrolment into the study, patients had to be adults with non-severe scalp psoriasis (defined as the involvement of no more than 50% of the scalp, no cicatricial alopecia or facial lesions, and without moderate/severe erythema, infiltration or pruritus). Participants had not received treatment with either mometasone or calcipotriol/betamethasone gel within the previous 3 months, and were not receiving any topical treatment for scalp psoriasis when they were enrolled. In addition, patients must not have received systemic treatment with retinoids, methotrexate, cyclosporine or phototherapy for body psoriasis during 4 weeks prior or with biologics during 6 months prior to enrolment. Other exclusion criteria were the presence of contraindications to the study medications, hypersensitivity to any of the ingredients or to other corticosteroids, and patients who were aiming to become pregnant or who were breast-feeding. Treatment The attending physicians chose treatment for each patient according to their usual therapeutic decision process. Mometasone emulsion (mometasone furoate 0.1% w/w) and calcipotriol/ betamethasone gel (calcipotriol monohydrate 0.05 mg/g plus betamethasone dipropionate 0.5 mg/g) were both administered in accordance with the relevant summary of product characteristics, which recommend that the treatment should be administered for a maximum of 3 weeks for mometasone emulsion or 4 weeks for calcipotriol/betamethasone gel. The final decision on the duration of therapy was made by the physicians. Assessments and outcome measures After patients had been prescribed treatment, they were considered for enrolment into the study. At visit 1 (baseline), physicians recorded information on inclusion/exclusion criteria, demographics, diagnosis, treatment history, concurrent diseases and concomitant medications, baseline disease severity by means of Physician’s Global Assessment (PGA), and whether patients had been prescribed mometasone emulsion or calcipotriol/ betamethasone gel. In addition, patients completed a baseline
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Table 1. Patients’ treatment assessment questionnaire. Patient’s global assessment of treatment In response to the question ‘‘How do you assess the treatment with the scalp medication?’’ patients rated the treatment as: very good, good, moderate, poor or very poor. Assessment of specific aspects of treatment Patients rated the correctness of the following statements as: very good, good, moderate, hardly or not at all. 1. Easy to use 2. Must be washed out 3. Is difficult to remove 4. Glued to the hair 5. Absorbs quickly into the scalp 6. Could be applied in the morning as well 7. Leaves residue on hair or clothing 8. Is better than other preparations 9. Smells pleasant 10. Discolours hair 11. Does not change my appearance 12. Has irritated the skin of my fingers 13. Worked quickly 14. Is in a bottle which can be easily opened 15. Can be portioned easily from the bottle 16. Relieves itching quickly
Dermatology Life Quality Index (DLQI) questionnaire, and were given a diary (a calendar-based form with tick boxes to indicate the days the treatment was applied) to take home and complete during the treatment period. At visit 2 (final examination), patients handed in their adherence diary, and completed a second DLQI questionnaire and a questionnaire on their overall assessment of the treatment (Table 1). The outcome of treatment was assessed, including efficacy (evaluated by PGA and DLQI), patient’s global assessment of treatment, patient compliance and physician’s subjective evaluation of efficacy, tolerability and compliance. Adherence to treatment was calculated as the number of days the medication was applied divided by the total number of days from the first to the last application. The primary endpoint was patient’s assessment of treatment. Secondary endpoints included quality of life, efficacy and treatment adherence. Statistical analysis Descriptive analyses were performed. Mean, SD, quartiles, and maximum and minimum values were calculated. Absolute, relative and adjusted relative frequencies (with the latter excluding patients with missing data) were assessed. Multiple entries per patient (e.g. multiple drugs) were counted, meaning that relative frequencies, which referred to the number of cases, could exceed 100%. Cross tables were prepared, including variables versus expression/quality of the variable, and shifts in variables between two time points. Statistical significance was evaluated for key parameters, using two-tailed p values with an alpha level of 0.05. ‘‘Tendency’’ was defined as p50.10. However, no statistical hypotheses were formulated in advance and therefore tests of significance were considered exploratory only. No correction of alpha for multiple comparisons was performed. Tests included the Jonckheere– Terpstra non-parametric test for ordered difference among classes; the Wilcoxon two-sample test, a non-parametric test of the null hypothesis versus an alternative hypothesis; and the Cochran–Mantel–Haenszel statistic for the analysis of stratified categorical data. Analyses were performed on two populations. The intentionto-treat (ITT) population comprised all the patients treated with one of the two study treatments at least once, excluding patients
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Figure 1. Disposition of patients.
Enrolled into study (n=185) Withdrew consent (n=1) Did not start treatment (n=1)
Mometasone emulsion (n=95)
Calcipotriol/betamethasone gel (n=88)
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Discontinued treatment (n=11)* -Recovery/remission (n=7) -Patient missed visit (n=3) -Adverse event (n=2) -Patient’s request (n=1) -Inpatient treatment for widespread psoriasis (n=1)
Discontinued treatment (n=16)* Recovery/remission (n=6) -Lack of compliance (n=5) -Patient’s request (n=3) -Patient missed visit (n=2) -Lack of efficacy (n=1)
Completed planned treatment (n=84) -Stopped treatment at study end (n=46) -Continued beyond study end (n=37) -Not known if continued or not (n=1)
Completed planned treatment (n=72) -Stopped treatment at study end (n=43) -Continued beyond study end (n=29)
ITT analysis set (n=95) PP analysis set (n=93). Exclusions: -Calcipotriol/betamethasone received until 5 weeks prior to study (n=1) -Mometasone received until 10 weeks prior to study (n=1)
ITT analysis set (n=88) PP analysis set (n=85). Exclusions: -Concomitant betamethasone (n=1) -Concomitant mometasone (n=1) -Mometasone received until 10 weeks prior to study (n=1)
* Some patients had more than one reason.
who revoked their consent. The per-protocol (PP) population comprised all patients from the ITT population who met the inclusion criteria, did not meet any exclusion criteria, and had data recorded at baseline. A sample size of 200 patients (100 per group) was considered feasible in a routine clinical practice setting, and sufficient to provide a representative group of patients with non-severe scalp psoriasis.
Results A total of 185 patients were enrolled into the study between February and September 2014, 183 of whom were included in the ITT population: 95 patients were treated with mometasone emulsion and 88 were treated with calcipotriol/betamethasone gel (Figure 1). Two patients were excluded from the ITT population (one who revoked their consent and one who did not commence treatment). The PP population comprised 93 recipients of mometasone emulsion and 85 recipients of calcipotriol/ betamethasone gel. An analysis of the PP population showed no significant differences from the ITT analysis. The results presented below are for the ITT population. Baseline characteristics were similar between the treatment groups (Table 2). There were more female than male patients in both groups. The mean and median duration of scalp psoriasis was somewhat longer in the calcipotriol/betamethasone group than in the mometasone group (131.6 versus 120.3 months and 96.2 versus 45.9 months, respectively), but there were no significant differences in the severity of scalp psoriasis (p ¼ 0.171), with most patients having disease of moderate severity. In both groups, the most common form of treatment received for scalp psoriasis prior to the study was potent or very potent corticosteroids.
Treatments administered Mometasone emulsion was prescribed for most patients as one application per day (95.8% of patients). Similarly, once daily applications was prescribed for 96.6% of the calcipotriol/ betamethasone group. Physicians most commonly prescribed mometasone emulsion and calcipotriol/betamethasone gel for a period of 22–28 days (52.6% and 69.3%, respectively) or 15–21 days (31.6% and 14.8%). Most patients used the treatment for 22– 28 days (mometasone 37.2%; calcipotriol/betamethasone 40.2%) or even longer (29–35 days; mometasone 26.6%; calcipotriol/ betamethasone 29.9%). Treatment ended as initially planned by the treating physician in 48.4% of mometasone recipients and 48.9% of calcipotriol/ betamethasone recipients, while it was continued beyond the prescribed period in 39.0% patients of the mometasone group and in 33.0% patients of the calcipotriol/betamethasone group (for a mean of 26 and 24 days, respectively). Overall, 11.6% of the mometasone group and 18.2% of the calcipotriol/betamethasone gel group discontinued treatment earlier than planned (Figure 1). The most common reason for premature discontinuation in both groups was recovery/remission of scalp psoriasis (mometasone 7.4% versus calcipotriol/betamethasone 6.8%). The second most common reason in the calcipotriol/betamethasone group was a lack of compliance (5.7%). No patient in the mometasone group withdrew for this reason. Patients’ assessment of treatment Analysis of patients’ global assessment of treatment showed a statistically significant difference between the groups in favour of mometasone emulsion (p ¼ 0.008; Figure 2). Overall, 91% of
Mometasone emulsion versus calcipotriol/betamethasone gel
DOI: 10.3109/09546634.2015.1093590
Table 2. Patient demographics and baseline characteristics.
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Parameter
Mometasone emulsion (n ¼ 95)
Calcipotriol/ betamethasone gel (n ¼ 88)
Sex, n (%) Male/female 40 (42.1)/55 (57.9) 31 (35.2)/57 (64.8) Age distribution (%) 18–30 years 17.9 11.4 31–40 years 11.6 9.1 41–50 years 8.4 20.5 51–60 years 21.1 18.2 61–70 years 20.0 21.6 71–80 years 15.8 15.9 480 years 5.3 3.4 Duration of scalp psoriasis (months) Mean 120.3 131.6 Median 45.9 96.2 Distribution (%) 56 months 17.9 14.9 6–11 months 20.0 12.6 12–23 months 5.3 4.6 24–59 months 14.7 14.9 60–119 months 8.4 8.1 120–239 months 20.0 25.3 240 months 13.7 19.5 Severity of scalp psoriasisa, n (%) Almost without findings 0 1 (1.1) Mild 32 (33.7) 37 (42.1) Moderate 63 (66.3) 50 (56.8) Previous therapy, n (%) 33 (34.7) 18 (20.5) Most common, n (%) Clobetasol 14 (42.4) 6 (33.3) Betamethasone 8 (24.2) 5 (27.8) Calcipotriol combinations 3 (9.1) 2 (11.1) Mometasone 3 (9.1) 2 (11.1) Most common concurrent disorders (body system), n (%) Vascular 16 (16.8) 16 (18.2) Metabolism/nutrition 11 (11.6) 9 (10.2) Skin/subcutaneous 6 (6.3) Endocrine 8 (9.1) a
Almost without findings: a small area of scalp affected. Mild: 550% of the scalp affected plus 1 of the following present – mild erythema, mild scaling, minimal thickness (barely any/no infiltration) and mild pruritus. Moderate:550% of the scalp affected plus 1 of the following present – moderate erythema, moderate scaling, moderate thickness (some infiltration), mild to moderate pruritus.
patients treated with mometasone emulsion rated their treatment as very good or good compared with 82.5% of calcipotriol/ betamethasone gel recipients. In terms of individual items associated with treatment, mometasone emulsion was significantly less likely than calcipotriol/betamethasone gel to cause irritation of the skin of the fingers (p ¼ 0.0015), with 77.5% of mometasone recipients reporting no irritation versus 56.6% of the calcipotriol/betamethasone gel group. Statistical analysis also showed a tendency favouring mometasone emulsion regarding three other items: being in an easy-to-open bottle (p ¼ 0.057), pleasant smell (p ¼ 0.068) and quick absorption into the scalp (p ¼ 0.089). Severity of scalp psoriasis At baseline, the distribution of psoriasis severity was similar in the two groups. In both groups it decreased during the study compared to baseline, based on PGA. The proportion of patients with moderate psoriasis decreased from 66.0% to 4.3% at the final assessment in the mometasone group, and from 56.3% to 5.8% in the calcipotriol/betamethasone group. The proportion of patients clear or almost clear of psoriasis increased from 0% to 73.4% in the mometasone group, and from 1.1% to 68.9% in the calcipotriol/betamethasone group. There was no statistically significant difference between the two groups in terms of the
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distribution of psoriasis severity at the final assessment, either overall (Figure 3; p ¼ 0.195) or when the subgroups with mild (p ¼ 0.424) or moderate (p ¼ 0.179) psoriasis at baseline were analyzed. Quality of life In both groups, the mean DLQI score at baseline (mometasone 8.07 points; calcipotriol/betamethasone 8.83 points) showed that patients felt that their scalp psoriasis had a moderate effect on their quality of life. At the final assessment, the mean score had decreased in both groups, which indicated that scalp psoriasis then only had a small effect on their quality of life. The improvement in DLQI scores did not differ significantly between the two groups (Figure 4). Treatment adherence Treatment adherence in the two groups, based on patients’ diaries, is summarized in Figure 5. There were no statistically significant differences between groups (p ¼ 0.685). Most patients had high or very high compliance rates according to their diary record. Tolerability Three patients in the mometasone group reported a total of six adverse events during the study, including application site pain, application site pustules, pruritus, burning skin sensation and lack of improvement. All the adverse events potentially related to mometasone emulsion were mild in severity. Lack of improvement was reported in one patient due to aggravation of psoriasis on the trunk and extremities and was not considered to be related to study medication. Physician’s subjective evaluation of therapy At the final assessment, the physicians assessed mometasone with higher scores than calcipotriol/betamethasone gel in terms of general efficacy, general tolerability and compliance with treatment (Table 3).
Discussion Psoriasis is a highly visible disease that impacts the quality of life and well-being of sufferers. Topical medications are a mainstay of treatment, and the formulation of the product and the acceptability to the patient are important characteristics that influence adherence to therapy and overall clinical efficacy. The results of the current study in a daily clinical practice setting showed that non-alcoholic mometasone emulsion is an appropriate alternative first-line therapeutic option for the treatment of patients with non-severe scalp psoriasis, exhibiting similar efficacy with greater acceptance by patients compared to calcipotriol/ betamethasone gel. Topical corticosteroids and combination therapy with calcipotriol/betamethasone are known to be efficacious for the treatment of psoriasis and are recommended as first-line therapies for scalp lesions (10). The calcipotriol/betamethasone combination gel formulation has previously been shown to be generally well accepted by patients (19), who judged it as being more convenient and less time-consuming than their previous therapy (20). It was also associated with a greater improvement of quality of life compared to monotherapy with calcipotriol solution (21). Moreover, the gel formulation has been described as being more advantageous than an ointment formulation containing the same active ingredients (22). In the present study, mometasone emulsion improved scalp psoriasis and quality of life of patients to a similar level as
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Figure 2. Patients’ global assessment of treatment.
70% 62.5%
Non-alcoholic mometasone emulsion (n=88) Calcipotriol/betamethasone gel (n=80)
60% 53.4%
p=0.0082** (Jonckheere-Terpstra Test)
50% 40%
37.5%
30% 20.0% 16.3%
20% 6.8%
10%
2.3%
0.0%
0.0% 1.3%
0% Very good
Good
Moderate
Poor
Very poor
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−10%
Figure 3. Scalp psoriasis severity at final assessment.
60%
Non-alcoholic mometasone emulsion (n=94) Calcipotriol/betamethasone gel (n=87)
50% 42.5% 40%
36.2%
30%
p=0.1954 (Jonckheere-Terpstra Test)
37.2%
26.4% 22.3%
24.1%
20%
10% 4.3%
5.8% 0.0% 1.2%
0% Without findings
10 9
8.83
Non-alcoholic mometasone emulsion (n=90) Calcipotriol/betamethasone gel (n=86)
8 7
8.07
p=0.3368 (Wilcoxon rank-sum Test)
6 5 4
3.22
3 2 2.02
1 0 Baseline
Final examinaon
Higher DLQI scores indicate greater impairment in quality life. Total possible score 0 to 30.
Figure 4. Dermatology Life Quality Index (DLQI) scores at baseline and at final assessment.
calcipotriol/betamethasone gel. In addition, mometasone emulsion achieved better ratings by patients and physicians for overall acceptability. The real-life effectiveness of topical therapy is a balance between efficacy, safety and compliance with treatment (11).
Almost without findings
Mild
Moderate
Severe
Adherence is a complex multidimensional concept, which in the case of psoriasis involves not only the treatment vehicle, but also patient motivation and preference, and the patient–physician relationship (13). Adherence to topical treatments for psoriasis generally tends to be poor, and although there are multiple reasons for this, one important factor is the patients’ willingness to use the available treatments (13). In this study, both treatments produced good adherence results, and no significant differences between the two groups were observed. The evaluation of adherence by indirect measures such as patient diaries is simple and therefore the most practical method in the real-world clinical setting, but the results can easily be distorted if patients do not complete the diaries accurately (23,24). This, together with the multidimensional attribute of adherence may have limited the ability of the study to fully assess differences between treatments. Nonetheless, the subjective assessment of adherence by physicians did favour mometasone emulsion. The study has several strengths. Firstly, the non-interventional design enabled assessment in a setting close to daily clinical practice conditions of treatment. Secondly, the study evaluated patients’ acceptance of topical treatment, focusing on galenic characteristics. This is relevant because of the important role that treatment acceptance and preference play in determining adherence to topical treatments. Thirdly, the study did not only evaluate
Mometasone emulsion versus calcipotriol/betamethasone gel
DOI: 10.3109/09546634.2015.1093590
Figure 5. Adherence to treatment.
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80% Non-alcoholic mometasone emulsion (n=92)
68.7%
70%
65.2%
Calcipotriol/betamethasone gel (n=83) 60% 50%
p=0.6851 (Jonckheere-Terpstra test)
40% 30% 20.7% 20%
16.9% 8.7% 9.6%
10%
5.4% 4.8% 0%
0%
0% Very poor (
