Patient satisfaction with calcipotriol/betamethasone dipropionate cutaneous foam for the treatment of plaque psoriasis: The LION real‐life multicenter prospective observational cohort study

Abstract Topical treatment is the mainstay for mild or moderate psoriasis, but patients are generally little satisfied. Calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam has shown to improve signs and symptoms in plaque psoriasis patients. This study assessed patient's satisfaction with Cal/BD foam in a real‐life Italian dermatological clinical practice. A multicenter, 4‐week observational prospective cohort study enrolled, in 17 Italian dermatology clinics, adult patients with plaque psoriasis on the body and/or scalp. Treatment satisfaction was assessed by 9‐item Treatment Satisfaction Questionnaire for Medication (TSQM‐9), preference over previous treatments by Patient Preference Questionnaire (PPQ), and change in disease state by Psoriasis Area Severity Index (PASI). Overall 256 patients were eligible, with a mean (SD) age of 55.6 (15.4) years, 59.4% were males. Psoriasis severity was mild in 52.0% of patients, moderate in 43.3%, and severe in 4.7%. Scalp involvement was present in 36.7% of patients. Previous antipsoriatic treatments had been received by 80.5% of patients. TSQM‐9 median (25th–75th percentile) scores were 83.3 (66.7–88.9) for effectiveness, 77.8 (66.7–88.9) for convenience, and 78.6 (64.3–92.9) for global satisfaction. Mean (SD) PASI value decreased from 7.3 (4.8) to 2.1 (2.7) after 4 weeks. More than 90% of patients previously treated for psoriasis evaluated the Cal/BD foam more effective, easier to use and better tolerated compared to previous topical treatments at PPQ. This observational study provides real‐life evidence of a high level of satisfaction with effectiveness and convenience of the Cal/BD foam in a cohort of plaque psoriasis patients, with an objective improvement in PASI.

dermatology clinics, adult patients with plaque psoriasis on the body and/or scalp. Treatment satisfaction was assessed by 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9), preference over previous treatments by Patient Preference Questionnaire (PPQ), and change in disease state by Psoriasis Area Severity Index (PASI). Overall 256 patients were eligible, with a mean (SD) age of 55.6 (15.4) years, 59.4% were males. Psoriasis severity was mild in 52.0% of patients, moderate in 43.3%, and severe in 4.7%. Scalp involvement was present in 36.7% of patients. Previous antipsoriatic treatments had been received by 80.5% of patients. TSQM-9 median (25th-75th percentile) scores were 83.3 (66.7-88.9) for effectiveness, 77.8 (66.7-88.9) for convenience, and 78.6 (64.3-92.9) for global satisfaction. Mean (SD) PASI value decreased from 7.3 (4.8) to 2.1 (2.7) after 4 weeks. More than 90% of patients previously treated for psoriasis evaluated the Cal/BD foam more effective, easier to use and better tolerated compared to previous topical treatments at PPQ. This observational study provides real-life evidence of a high level of satisfaction with effectiveness and convenience of the Cal/BD foam in a cohort of plaque psoriasis patients, with an objective improvement in PASI.

K E Y W O R D S
psoriasis, therapy-topical

| INTRODUCTION
Psoriasis is a common chronic inflammatory multisystem disease with a strong genetic predisposition and an immune pathogenetic component. [1][2][3] Approximately 90% of patients affected with psoriasis have plaque psoriasis. 4 Psoriasis is recognized to severely impact patients' quality of life (QoL) largely due the appearance of skin lesions and the troublesome itch. 5,6 Topical treatment is the mainstay for mild or moderate psoriasis, also in addition to phototherapy, systemic conventional or biologic therapy. 7 In general, psoriasis patients are not very satisfied with their treatment and significantly least those receiving topical treatment, especially when affected with moderate disease. 8,9 A topical once-daily, fixed-dose combination (FDC) of 50 μg/g of calcipotriol (Cal)-a synthetic vitamin D3 analog-with 0.5 mg/g of the synthetic corticosteroid betamethasone dipropionate (BD) in a cutaneous foam formulation (LEO Pharma) has been introduced in the treatment armamentarium for plaque psoriasis in adults. In phase II-III studies, Cal/BD foam obtained significantly greater improvements in Psoriasis Area Severity Index (PASI), Dermatology Life-Quality Index (DLQI), and total clinical scores than placebo, BD topical comparators, or a gel and ointment Cal/BD formulation, with a favorable safety profile. [10][11][12][13] In the foam aerosol, the active ingredients are dissolved in volatile propellants that evaporate when the product is applied to the skin, creating a foam layer containing a supersaturation of the actives that enables a greater penetration of the drug through the epidermis. This is believed to account for the higher efficacy shown by the cutaneous foam compared to the gel and ointment Cal/BD formulation. 12 Confirmation of a drug effectiveness in the real-life setting is becoming increasingly relevant. 14 Factors such as patient preference and satisfaction with the prescribed therapy-which have a major impact on adherence to treatment-are paramount in how treatments perform in everyday clinical practice. Measurement of these parameters is becoming increasingly valuable because it can provide data on how satisfaction improves adherence and influences treatment choice.
The LION study was aimed at providing real-life evidence of the satisfaction of plaque psoriasis patients with Cal/BD cutaneous foam treatment in the Italian dermatological clinical practice.

| PATIENTS AND METHODS
The LION study was an Italian multicenter observational prospective cohort study conducted in 17 dermatology clinics across different Italian regions. The observational period was framed between the enrolment visit, performed prior to the initiation of Cal/BD foam treatment, and the follow-up visit, performed as per clinical practice 4 ± 1 weeks after treatment initiation or at patient's exit from study, whichever occurred first. Data sources for primary data collection included medical records and patient-reported outcome (PRO) questionnaires.

| Patients
Patients aged ≥18 years with plaque psoriasis on the body and/or scalp, providing written informed consent before the data collection and assigned to treatment with Cal/BD foam as per ordinary clinical practice were enrolled in the study. Cal/BD foam was prescribed according to the summary of product characteristics (SmPC) clinical information according to the observational nature of the study. Patients did not undergo any additional diagnostic or monitoring procedures. Patients treated with systemic conventional or biologic agents within 16 weeks before enrolment, or under treatment with other therapies for psoriasis in an interventional clinical trial were excluded, as were pregnant or breastfeeding women and patients unable to understand and fill in the study questionnaires.
The use of concurrent phototherapy or topical corticosteroid did not represent an exclusion criterion.

| Study objectives
The primary objective of the LION study was to describe the patients' satisfaction with Cal/BD cutaneous foam treatment after 4 weeks of therapy in the clinical practice setting, by means of the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9). 15,16 Secondary objectives of the study were to describe (I) factors potentially associated to the satisfaction with Cal/BD foam treatment, such as age, gender, and duration and severity of psoriasis, (II) patients' treatment preference using the Patient Preference Questionnaire (PPQ), 17 and (III) the change in the PASI score 18 following treatment.

| Sample size
According to feasibility considerations, assuming the inclusion of 250 psoriatic patients (20% of whom possibly not evaluable for the primary analysis due to non-available data, dropout, or failure in meeting the eligibility criteria), we estimated the achievable precision of the primary endpoint on 200 patients.

| Statistical analysis
No formal statistical hypotheses were set. Only descriptive analyses were performed. Continuous variables were reported as mean (SD) and median (25th-75th percentile), while categorical variables were reported as number and percentage of cases and distribution of frequencies.
PRO questionnaires scores were calculated according to the instructions obtained from copyright holders. The three TSQM-9 domain scores (effectiveness, convenience, and global satisfaction), ranging from 0 to 100 with higher scores representing higher satisfaction, were calculated as primary analysis. 15,16,19 In addition, a sensitivity analysis was performed for the primary objective providing treatment satisfaction among patients not previously treated with other antipsoriatic therapies (treatment-naïve patients). Wilcoxon's test was used to compare TSQM-9 domain scores between subgroups of patients having experienced previous antipsoriatic treatments at the time of treatment initiation with Cal/BD foam and treatmentnaïve patients. In order to describe predefined factors potentially associated to treatment satisfaction, the Spearman's correlation matrix and the Kruskal-Wallis test were used for continuous variables (i.e., age at Cal/BD foam treatment initiation; duration of plaque psoriasis since first diagnosis) and categorical variables (i.e., gender; plaque psoriasis severity at enrolment), respectively. Regarding PPQ, higher single-item scores reflect the presence of favorable adherence, influencing patient preference factors. 17 Table 1.

| Treatments
Previous antipsoriatic treatments had been received by 80.5% of patients (n/N = 206/256), as detailed in Table 2 Descriptive statistics for all three TSQM-9 domains obtained at the 4-week final visit in overall patients and in patients treated on scalps with available data are shown in Table 3.

| Secondary objectives
As reported in Figure 2  In patients who had been treated for psoriasis prior to the Cal/BD foam, the reasons for preferring the Cal/BD foam over previous therapies were assessed by PPQ. Regardless of the treatment previously received, most patients 'agreed' or 'strongly agreed' that Cal/BD foam was more effective, easier to use and associated with fewer side effects and better tolerability than previous treatments (Table 4).

| DISCUSSION
First-line management of mild or moderate plaque psoriasis consists of topical treatments 20 ; however, they are associated with lower adherence rates than systemic treatments, which represents a major issue for treatment effectiveness. 21 Probably consistent with this, patients with plaque psoriasis are generally not very satisfied with their treatment. 8,9,22 A successful topical treatment option should be able to achieve higher patient acceptability and adherence in order to improve signs and symptoms.
TSQM-9 median values of global satisfaction and satisfaction for the effectiveness of Cal/BD foam after 4 weeks of therapy were extremely high and identical in both treatment-naïve and previously treated patients, and did not differ according to patient's demographics or main psoriasis disease characteristics. Satisfaction for the convenience of the treatment was slightly lower but overall high, and was significantly higher among patients that had been previously treated for psoriasis. This suggests that experience with previous types of therapies increased the patients' satisfaction using Cal/BD foam regarding to convenience. The first study addressing patients' treatment satisfaction with the Cal/BD foam registered a proportion of overall satisfied patients (84%) comparable to that of our study. 23 The ease of use of the Cal/BD foam had been previously reported in one Spanish study and a few other trials before. 12,24 It is well known that dissatisfaction with treatments results in poor adherence, which in turn impacts treatment effectiveness. 25,26 Conversely, in several different disease settings it has been reported that treatment satisfaction is associated with greater adherence, in particular, the global satisfaction and the convenience domains. [27][28][29][30] Importantly, adherence to treatment in our study was remarkably high and the majority of patients remained on Cal/BD foam after study completion. The patients who discontinued treatment permanently did so by medical decision linked to the therapeutic strategy in place, and not due to adverse events.
The favorable results in terms of treatment satisfaction are consistent with those obtained at the PPQ, a tool that specifically assesses the patient's preference for the current treatment over previous ones. More than 97% of non-naïve patients highly preferred Cal/BD foam over previously received topical treatments and between 92 and 96% of patients considered it more effective, better tolerated, and easier to use compared to previous topicals. Slightly less than 94% of patients also reported a perception of fewer side effects. These percentages are even higher than those obtained in the PSO-ABLE clinical trial. 12 However, it must be taken into account that these data are obtained in a patient population selected based on a need for treatment change (e.g., due to insufficient response or sideeffects with previous treatment). Therefore, these results cannot be generalized or attributable exclusively to the Cal/BD foam treatment.
As an objective measure of change in disease state, by psoriasis signs and symptoms, we collected absolute PASI scores and PASI response rates, although only as a secondary objective. Unfortunately, T A B L E 3 Patients' treatment satisfaction according to the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) domains (primary objective) Patients treated on scalp with available TSQM-9 data   [Correction added on May 24, 2022, after first online publication: CRUI funding statement has been added.]

AUTHOR CONTRIBUTIONS
All authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) and were fully responsible for all aspects of manuscript development. All authors together with the study group have made substantial contribution to investigation and acquisition of data.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.