The purpose of this review is to (1) summarize Cal/BD foam efficacy and safety data for beyond-mild psoriasis, (2) summarize the cost-effectiveness of Cal/BD foam in comparison with systemic therapy, including biologic agents, and (3) provide practical recommendations for the use of Cal/BD foam in patients with beyond-mild psoriasis.
Definitions of Disease Severity
Body surface area (BSA), the PGA scale, and the Psoriasis Area and Severity Index (PASI) are commonly used assessments of psoriasis severity. They are continuous variables, reflecting a continuum of disease severity, that may be translated into distinct categories using predefined thresholds.1,21-23 In terms of BSA, both the National Psoriasis Foundation and the American Academy of Dermatology define mild, moderate, and severe psoriasis as <3%, 3-10%, and >10% BSA involvement, respectively,1 with 1% BSA estimated to equal the patient’s full handprint (including the palm and fingers).24 Regardless of the extent of BSA involvement, psoriasis that causes severe emotional consequences or that occurs on the scalp, face, hands, feet, or genitals may be classified as severe.1 The PGA is a 5- (or 6-) point scale that evaluates lesion induration, scaling, and erythema; it indicates scores of clear (PGA=0), almost clear (PGA=1), mild (PGA=2), moderate (PGA=3), and severe (PGA=4).25 The PASI is a composite score that evaluates BSA involvement, lesion sites, and lesion qualities.21 Although PASI is considered the gold standard for measuring severity in clinical trials,22,26 it is a complicated assessment that is timeconsuming and thus impractical to use in daily practice.27 PASI threshold scores of 7 and 12 have been proposed, whereby mild, moderate, and severe disease are defined as scores of <7, 7–12, and >12, respectively.22 As no single tool is optimal for assessing psoriasis, it has become standard practice to perform all three assessments PGA, BSA, and PASI in clinical trials.26
Psoriasis can have profound impacts on a patient’s psychosocial well-being, and none of the PGA, BSA, or PASI assessment methods account for QOL. Treatment adherence and outcomes may improve if management strategies are informed by patient perceptions, such as an individual's acceptance of potential lifealtering side effects, treatment costs, and incomplete resolution of symptoms.28,29 The patient-reported Dermatology Life Quality Index (DLQI) is often used in clinical studies to assess the impact of psoriasis and its treatment on patients’ QOL, particularly for agents seeking regulatory approval in Europe.30 It is incorporated in the Rule of Tens severity assessment tool where severe disease is defined as psoriasis with DLQI score >10, BSA involvement >10%, or PASI >10.24
The definitions of psoriasis severity discussed herein are not comprehensive. In 2019, the International Psoriasis Council proposed that, instead of severity categories, patients should be classified as candidates for either topical or systemic therapy, with systemic therapy candidates having BSA involvement >10%, disease involving special areas, or failed response to a topical therapy.31 While definitions may continue to evolve as our understanding of psoriasis improves, it is clear that PGA, BSA, PASI, and DLQI, either as stand-alone or as composite tools, serve important functions in current assessments of disease severity. In the next section, we review data supporting the effectiveness of Cal/BD foam in patients with beyond-mild psoriasis defined using various measures of severity.
Cal/BD Foam for Patients With Beyond-Mild Psoriasis
The efficacy of Cal/BD foam in plaque psoriasis of all severities has been demonstrated in several randomized clinical trials (RCTs).12-15 Across four RCTs, mean baseline BSA ranged from 6.7% to 8%, with overall baseline BSA ranging from 2% to 30%, and mean mPASI (modified PASI, excluding the head) scores ranged from 6.6 to 8.8. At baseline, >70% and <10% of patients had moderate and severe disease, respectively (Table 1).12-15 Thus, the majority of patients in these four RCTs had beyondmild psoriasis. Note that severity was defined according to the PGA; it is possible for patients with minimal or extensive BSA involvement (eg, <3% or >10%) to have been classified as moderate. Importantly, efficacy data from the overall population of more than 1300 patients showed consistent benefit with Cal/BD foam over Cal/BD topical suspension, Cal/BD ointment (mPASI75 and mPASI50, P=NS), Cal foam, BD foam, or foam vehicle (Table 2).12-15 Adverse events (AEs) reported with Cal/ BD foam have been mostly mild or moderate in severity, with similar incidence rates observed between groups.12-15
In patients with beyond-mild psoriasis, the efficacy of Cal/BD foam has been examined in several subgroup analyses and in a small, prospective study (Table 3).5,12,17,18 Higher treatment success rates were observed with Cal/BD foam in patients with moderate or severe disease at baseline (per PGA) than with either Cal/BD topical suspension (PSO-ABLE)12 or foam vehicle (PSO-FAST). Using data pooled from three Phase 2/3 RCTs, a post hoc analysis including 340 patients with 5-15% BSA and PGA=moderate/severe found statistically significant improvements in treatment success rates with Cal/BD foam vs foam vehicle as early as week 1, which continued to week 4 (Table 3).17 Improvements were also observed in mPASI and pruritus outcomes. In a subgroup analysis of the PSO-ABLE trial, where beyond-mild psoriasis was defined according to the Rule of Tens, patients achieved numerically or statistically significant improvements at week 4 with Cal/BD foam vs Cal/BD topical suspension in treatment success rate, BSA, mPASI75, mPASI90, and DLQI, and these improvements continued through week 12 (Table 3).5 Lastly, in 20 patients with moderate psoriasis involving the knees and elbows and 3-20% BSA at baseline, treatment with Cal/BD foam significantly improved PGA score, BSA involvement, and lesion qualities as early
Definitions of Disease Severity
Body surface area (BSA), the PGA scale, and the Psoriasis Area and Severity Index (PASI) are commonly used assessments of psoriasis severity. They are continuous variables, reflecting a continuum of disease severity, that may be translated into distinct categories using predefined thresholds.1,21-23 In terms of BSA, both the National Psoriasis Foundation and the American Academy of Dermatology define mild, moderate, and severe psoriasis as <3%, 3-10%, and >10% BSA involvement, respectively,1 with 1% BSA estimated to equal the patient’s full handprint (including the palm and fingers).24 Regardless of the extent of BSA involvement, psoriasis that causes severe emotional consequences or that occurs on the scalp, face, hands, feet, or genitals may be classified as severe.1 The PGA is a 5- (or 6-) point scale that evaluates lesion induration, scaling, and erythema; it indicates scores of clear (PGA=0), almost clear (PGA=1), mild (PGA=2), moderate (PGA=3), and severe (PGA=4).25 The PASI is a composite score that evaluates BSA involvement, lesion sites, and lesion qualities.21 Although PASI is considered the gold standard for measuring severity in clinical trials,22,26 it is a complicated assessment that is timeconsuming and thus impractical to use in daily practice.27 PASI threshold scores of 7 and 12 have been proposed, whereby mild, moderate, and severe disease are defined as scores of <7, 7–12, and >12, respectively.22 As no single tool is optimal for assessing psoriasis, it has become standard practice to perform all three assessments PGA, BSA, and PASI in clinical trials.26
Psoriasis can have profound impacts on a patient’s psychosocial well-being, and none of the PGA, BSA, or PASI assessment methods account for QOL. Treatment adherence and outcomes may improve if management strategies are informed by patient perceptions, such as an individual's acceptance of potential lifealtering side effects, treatment costs, and incomplete resolution of symptoms.28,29 The patient-reported Dermatology Life Quality Index (DLQI) is often used in clinical studies to assess the impact of psoriasis and its treatment on patients’ QOL, particularly for agents seeking regulatory approval in Europe.30 It is incorporated in the Rule of Tens severity assessment tool where severe disease is defined as psoriasis with DLQI score >10, BSA involvement >10%, or PASI >10.24
The definitions of psoriasis severity discussed herein are not comprehensive. In 2019, the International Psoriasis Council proposed that, instead of severity categories, patients should be classified as candidates for either topical or systemic therapy, with systemic therapy candidates having BSA involvement >10%, disease involving special areas, or failed response to a topical therapy.31 While definitions may continue to evolve as our understanding of psoriasis improves, it is clear that PGA, BSA, PASI, and DLQI, either as stand-alone or as composite tools, serve important functions in current assessments of disease severity. In the next section, we review data supporting the effectiveness of Cal/BD foam in patients with beyond-mild psoriasis defined using various measures of severity.
Cal/BD Foam for Patients With Beyond-Mild Psoriasis
The efficacy of Cal/BD foam in plaque psoriasis of all severities has been demonstrated in several randomized clinical trials (RCTs).12-15 Across four RCTs, mean baseline BSA ranged from 6.7% to 8%, with overall baseline BSA ranging from 2% to 30%, and mean mPASI (modified PASI, excluding the head) scores ranged from 6.6 to 8.8. At baseline, >70% and <10% of patients had moderate and severe disease, respectively (Table 1).12-15 Thus, the majority of patients in these four RCTs had beyondmild psoriasis. Note that severity was defined according to the PGA; it is possible for patients with minimal or extensive BSA involvement (eg, <3% or >10%) to have been classified as moderate. Importantly, efficacy data from the overall population of more than 1300 patients showed consistent benefit with Cal/BD foam over Cal/BD topical suspension, Cal/BD ointment (mPASI75 and mPASI50, P=NS), Cal foam, BD foam, or foam vehicle (Table 2).12-15 Adverse events (AEs) reported with Cal/ BD foam have been mostly mild or moderate in severity, with similar incidence rates observed between groups.12-15
In patients with beyond-mild psoriasis, the efficacy of Cal/BD foam has been examined in several subgroup analyses and in a small, prospective study (Table 3).5,12,17,18 Higher treatment success rates were observed with Cal/BD foam in patients with moderate or severe disease at baseline (per PGA) than with either Cal/BD topical suspension (PSO-ABLE)12 or foam vehicle (PSO-FAST). Using data pooled from three Phase 2/3 RCTs, a post hoc analysis including 340 patients with 5-15% BSA and PGA=moderate/severe found statistically significant improvements in treatment success rates with Cal/BD foam vs foam vehicle as early as week 1, which continued to week 4 (Table 3).17 Improvements were also observed in mPASI and pruritus outcomes. In a subgroup analysis of the PSO-ABLE trial, where beyond-mild psoriasis was defined according to the Rule of Tens, patients achieved numerically or statistically significant improvements at week 4 with Cal/BD foam vs Cal/BD topical suspension in treatment success rate, BSA, mPASI75, mPASI90, and DLQI, and these improvements continued through week 12 (Table 3).5 Lastly, in 20 patients with moderate psoriasis involving the knees and elbows and 3-20% BSA at baseline, treatment with Cal/BD foam significantly improved PGA score, BSA involvement, and lesion qualities as early
