Disease Background

Plaque psoriasis is a chronic, inflammatory skin disease caused in part by dysregulation of the immune system. It is a T cell-mediated disease primarily driven by pathogenic T cells that produce high levels of interleukin (IL)-17 and tumour necrosis factor alpha (TNF-alpha) in response to IL-23.² The estimated number of Canadians living with psoriasis is approximately one million.⁵ The sponsor submitted an estimation of 2.49% for the prevalence of psoriasis in Canada based on two real-world database studies. Plaque psoriasis is the most common form and represents approximately 90% of cases.^4,5 Approximately 35% of patients with psoriasis have moderate-to-severe disease.¹⁵

Psoriasis is characterized by the presence of erythematous inflammatory plaques that may be itchy or painful and are usually covered by silver, flaking scales.^2,3 In addition to the overt dermatological symptoms, plaque psoriasis is often associated with psychosocial symptoms including poor self-esteem and may affect various aspects of social functioning including interpersonal relationships and performance at school or work.³ According to patient input received for this review, participants also reported loss of sleep, negative effects on self-confidence, and problems with intimacy. Psoriasis is associated with several comorbid conditions including depressive symptoms, conditions associated with an increased risk of cardiovascular disease (such as type 2 diabetes, metabolic syndrome, and obesity), psoriatic arthritis, inflammatory bowel disease, and kidney disease.^4,16–22

The severity of psoriasis may be classified as either mild, moderate, or severe using criteria such as BSA or scores on the PASI and DLQI. The Canadian Guidelines for the Management of Plaque Psoriasis provides two definitions for each measure of disease severity: definitions used in clinical trials and definitions for clinical practice.⁴ These definitions have been summarized in Figure 1; however, the guidelines highlight that despite the literature available, there is a lack of consensus regarding how disease severity should be defined. This was affirmed by the clinical expert consulted by CADTH for this review.

Figure 1

Terms Used in Evaluating Plaque Psoriasis. BSA = body surface area; DLQI = Dermatology Life Quality Index; PASI = Psoriasis Area Severity Index; QoL = quality of life.

Standards of Therapy

Plaque psoriasis requires lifelong treatment. Measures of treatment success in clinical practice may include clearance (absence of signs of disease), control (satisfactory response to therapy as defined by the patient and/or physician), and remission (suppression of signs and symptoms over time).⁴ Clearance and symptom control have been identified as treatment outcomes that are important to patients.

In patients with plaque psoriasis, topical agents (such as corticosteroids, vitamin D analogues, and retinoids) are the most widely used treatments for the mild form of the disease. Of the available topical agents, corticosteroids are the most widely used treatment with higher potency agents being the most efficacious, but also having increased potential for AEs.⁴ Anthralin and tars may also be used, but their use has declined as there are other treatments that are more acceptable to patients that have become available. In an effort to reduce side effects with long-term use of corticosteroids, the topical agents may be used intermittently by either reducing the dose or taking a drug holiday for a period of time.⁷ Combination therapy may also be considered, which is typically more efficacious than monotherapy.⁴ For example, calcipotriol/betamethasone is more effective than either of the components alone; however AEs may be of concern.

The Canadian guidelines for management of plaque psoriasis define moderate-to-severe psoriasis by the inability to be controlled by topical therapy, as previously described; however, it also states that topical agents used to treat mild psoriasis may still be used as adjunct therapy to systemic therapies or phototherapy for this population. Calcipotriol/betamethasone ointment is noted as an exception as it has demonstrated efficacy in patients with relatively severe disease (average baseline PASI score of 22.6).⁴ According to the clinical expert consulted for this review, if it is clear that the patient presenting to a dermatologist with moderate-to-severe plaque psoriasis has not received appropriate topical therapy, nor an adequate trial of phototherapy, a trial of topical therapy alone or topical therapy combined with phototherapy may be offered. The clinical expert also noted that frequently a combination of topical agents, including corticosteroids, calcipotriol, and retinoids, is prescribed and if adequate improvement cannot be achieved with topical therapy and/or phototherapy, systemic therapies will be considered.^4,6

Traditional systemic agents include cyclosporine and methotrexate, but long-term use may be limited by toxicity.⁴ In Canada, there are several biologic agents approved for the treatment of psoriasis. The first biologic agents licensed to treat plaque psoriasis were TNF-alpha inhibitors (i.e., etanercept, infliximab, certolizumab, and adalimumab). While effective and associated with rapid disease control, these TNF-alpha inhibitors are associated with a number of safety concerns including serious infections (e.g., sepsis, reactivated tuberculosis, and viral infections), autoimmune conditions (e.g., lupus and demyelinating disorders), and malignancies such as lymphoma.^4,6 Newer biologic agents include the IL-23 inhibitors risankizumab and guselkumab, the IL-12/23 inhibitor ustekinumab, and the IL-17 inhibitors secukinumab, ixekizumab, and brodalumab. These agents have been associated with serious infections, potential activation of inflammatory bowel disease with IL-17 inhibitors, and suicidal ideation in the case of brodalumab. The clinical expert consulted for this review noted that assuming an effective biologic agent is chosen, treatment must be continued indefinitely for efficacy to continue. The clinical expert also noted that the majority of patients who are treated with biologics or non-biologic systemic agents will require ongoing topical therapy to treat disease that the systemic drug has not cleared.

Despite the variety of treatments available for patients across the spectrum of plaque psoriasis, an overarching theme presented throughout the literature, which was aligned with the opinion of the clinical expert on this review, is that an effective treatment for plaque psoriasis is also one that a patient is willing to work with.^4,7,8 Adherence is a significant issue associated with treating these patients, particularly those using topical therapies; therefore, finding a therapy that a patient is likely to use consistently and long-term is critical. An ideal therapy would produce remission without the need for continuous long-term administration or could be administered intermittently as needed as per feedback from the clinical expert consulted for this review. Lastly, the approach to treating plaque psoriasis is heavily patient-centred where the goals of therapy may differ from patient to patient. This was confirmed by the clinical expert who also noted that what the patient hopes to achieve, which can range from eliminating symptoms such as pruritus to total clearance, will have a significant influence on the clinical decisions regarding appropriate therapies.

Drug

HP/TAZ lotion (Duobrii) is a combination product composed of a topical corticosteroid, 0.01% w/w HP, and a retinoid product, 0.045% w/w TAZ.

HP is a superpotent corticosteroid²³ with anti-inflammatory, anti-pruritic, and vasoconstrictive actions.⁹ The mechanism of action is unclear, but it has been suggested that it induces proteins that inhibit phospholipase A2. Phospholipase A2 is responsible for releasing arachidonic acid, which is a precursor to prostaglandins and leukotrienes and consequently leads to anti-inflammatory effects.^9,24 TAZ is a prodrug that is converted to tazarotenic acid, which regulates gene expression of retinoic acid receptors. There is uncertainty around the mechanism of action in psoriasis, although in vivo studies have shown TAZ to have a role in reducing cell proliferation and hyperplasia, suppressing inflammatory markers, and inhibiting the formation of elements of psoriatic scale. It also reduces markers related to epidermal hyperplasia and abnormal differentiation.⁹

In Canada, HP/TAZ is indicated for improving the signs and symptoms of plaque psoriasis in adult patients with moderate-to-severe plaque psoriasis.⁹ It is recommended that HP/TAZ is applied in a thin layer to the affected area once a day, and the total dosage should not exceed 50 g per week. Treatment with HP/TAZ should be discontinued once control has been achieved, although it may be reinitiated intermittently as necessary. If no improvement is seen within 12 weeks of treatment, reassessment of the diagnosis may be necessary. Efficacy and safety of HP/TAZ has not been established in patients with more than 12% BSA affected by plaque psoriasis.⁹

The sponsor is requesting that HP/TAZ is reimbursed as per the indication reviewed by CADTH.

Table 3

Key Characteristics of HP/TAZ and Other Relevant Topical Therapies for the Treatment of Plaque Psoriasis.