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Medical Policy

Policy Num:       02.001.045
Policy Name:    Light Therapy for Psoriasis
Policy ID:          [2.001.045][Ac B M+ P][2.01.47]

Last Review:      January 29, 2021
Next Review:      Policy Archived
Issue:                  January, 2021

Related Policies:

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2.01.44 Dematologic Applications of Photodynamic Therapy

2.01.86 Light Therapy for Vitiligo

Archived

Light Therapy for Psoriasis

Summary

Light therapy for psoriasis includes phototherapy with ultraviolet B (UVB) light boxes, targeted phototherapy, and photochemotherapy with psoralen plus ultraviolet A (PUVA). Targeted phototherapy describes the use of ultraviolet light focused on specific body areas or lesions. PUVA uses a psoralen derivative in conjunction with long-wavelength ultraviolet A light (sunlight or artificial) for photochemotherapy of skin conditions.

For individuals who have mild localized psoriasis who receive targeted phototherapy, there is little evidence. The relevant outcomes are symptoms, change in disease status, quality of life (QOL), and treatment-related morbidity. The evidence is lacking on the use of targeted phototherapy as the first-line treatment of mild psoriasis. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have mild psoriasis that is resistant to topical medications who receive targeted phototherapy, the evidence includes small within-subject studies. The relevant outcomes are symptoms, change in disease status, QOL, and treatment-related morbidity. The available pre-post studies have shown that targeted phototherapy can improve mild localized psoriasis (<10% body surface area) that has not responded to topical treatment. Targeted phototherapy is presumed to be safer or at least no riskier than whole body phototherapy, due to risks of exposing the entire skin to the carcinogenic effects of UVB light. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have moderate-to-severe localized psoriasis who receive targeted phototherapy, the evidence includes randomized controlled trials (RCTs) and systematic reviews of RCTs. The relevant outcomes are symptoms, change in disease status, QOL, and treatment-related morbidity. Systematic reviews of small RCTs and non-RCTs in patients with moderate-to-severe psoriasis have found that targeted phototherapy has efficacy similar to whole-body phototherapy and supports the use of targeted phototherapy for the treatment of moderate-to-severe psoriasis comprising less than 20% of body surface area for which narrowband UVB or phototherapy with PUVA are indicated. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have generalized psoriasis who receive PUVA, the evidence includes RCTs and systematic reviews. The relevant outcomes are symptoms, change in disease status, QOL, and treatment-related morbidity. RCTs and systematic reviews of RCTs have found that PUVA is more effective than narrowband UVB, topical steroids, or ultraviolet A without psoralens in patients with generalized psoriasis. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Objective

The objective of this evidence review is to evaluate whether the use of targeted phototherapy and psoralen plus ultraviolet A improves the net health outcome in patients with localized or generalized psoriasis.

Policy Statements

Psoralen plus ultraviolet A for the treatment of severe, disabling psoriasis, which is not responsive to other forms of conservative therapy (eg, topical corticosteroids, coal/tar preparations, ultraviolet light) may be considered medically necessary.

Targeted phototherapy may be considered medically necessary for the treatment of moderate-to-severe localized psoriasis (ie, comprising <20% body area) for which narrowband ultraviolet B or psoralen plus ultraviolet A are indicated.

Targeted phototherapy may be considered medically necessary for the treatment of mild-to-moderate localized psoriasis that is unresponsive to conservative treatment.

Targeted phototherapy is considered investigational for the first-line treatment of mild psoriasis.

Targeted phototherapy is considered investigational for the treatment of generalized psoriasis or psoriatic arthritis.

Policy Guidelines

Disease severity is minimally defined by body surface area (mild psoriasis affects <5% of body surface area, moderate psoriasis affects 5%-10%, and severe disease affects >10% body surface area). However, lesion characteristics (eg, location and severity of erythema, scaling, induration, pruritus) and impact on quality of life are also taken into account (see references 1-3). For example, while a handprint is equal to approximately 1% body surface area, lesions on the hands, feet, or genitalia that cause disability may be classified as moderate-to-severe. The Psoriasis Area and Severity Index may be used as an outcome measure in clinical research. Clinical assessment of disease severity is typically qualitative.

Established treatments for psoriasis include the use of topical ointments and ultraviolet light (“light lamp”) treatments. Lasers and targeted ultraviolet B lamps are considered equivalent devices; targeted ultraviolet devices are comparable with ultraviolet light panels for treatment purposes. First-line treatment of ultraviolet-sensitive lesions may involve around 6 to 10 office visits; treatment of recalcitrant lesions may involve around 24 to 30 office visits. Maintenance therapy or repeat courses of treatment may be required.

During psoralen plus ultraviolet A therapy, the patient needs to be assessed on a regular basis to determine the effectiveness of the therapy and the development of adverse effects. These evaluations are essential to ensure that the exposure dose of radiation is kept to the minimum compatible with adequate control of disease. Therefore, psoralen plus ultraviolet A is generally not recommended for home therapy.

See the Codes table for details.

Benefit Application

BlueCard/National Account Issues

State or federal mandates (eg, Federal Employee Program) may dictate that certain U.S. Food and Drug Administration-approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity.

Targeted phototherapy has not been shown to be superior to conventional phototherapy. Therefore, benefit or contract language describing the “least costly alternative” may be applied.

Specific contract language regarding definitions of cosmetic or reconstructive services may apply.

Background

Treatment of Psoriasis

Topical therapy (eg, corticosteroids, vitamin D analogues) is generally considered first-line treatments of psoriasis, especially for mild disease. Phototherapy and systemic therapy are treatment options for patients with more extensive and/or severe disease and those who fail conservative treatment with topical agents. Phototherapy is available in various forms including exposure to natural sunlight, use of broadband ultraviolet B devices, narrowband ultraviolet B (NB-UVB) devices, targeted phototherapy, and psoralen plus ultraviolet A (PUVA). NB-UVB is an established treatment for psoriasis, based on efficacy and safety. This evidence review addresses two alternative treatments: targeted phototherapy, which uses ultraviolet light that can be focused on specific body areas or lesions, and PUVA.

Targeted Phototherapy

Potential advantages of targeted phototherapy include the ability to use higher treatment doses and to limit exposure to surrounding tissue. Broadband ultraviolet B devices, which emit wavelengths from 290 to 320 nm, have been largely replaced by NB-UVB devices. NB-UVB devices eliminate wavelengths below 296 nm, which are considered erythemogenic and carcinogenic but not therapeutic. NB-UVB is more effective than broadband ultraviolet B and approaches PUVA in efficacy. Original NB-UVB devices consisted of a Phillips TL-01 fluorescent bulb with a maximum wavelength (lambda max) at 311 nm. Subsequently, an excimer (excited dimer) laser using xenon chloride (XeCl) and lamps were developed as targeted NB-UVB treatment devices; they generate monochromatic or very narrow band radiation with a lambda max of 308 nm. Targeted phototherapy devices are directed at specific lesions or affected areas, thus limiting exposure to the surrounding normal tissues. They may, therefore, allow higher dosages compared with a light box, which could result in fewer treatments to produce clearing. The original indication of the excimer laser was for patients with mild-to-moderate psoriasis, defined as involvement of less than 10% of the skin. Newer XeCl laser devices are faster and more powerful than the original models, which may allow the treatment of patients with more extensive skin involvement (10%-20% body surface area).

Psoralen Plus Ultraviolet A

PUVA uses a psoralen derivative in conjunction with long-wavelength ultraviolet A (UVA) light (sunlight or artificial) for photochemotherapy of skin conditions. Psoralens are tricyclic furocoumarins that occur in certain plants and can also be synthesized. They are available in oral and topical forms. Oral PUVA is generally given 1.5 hours before exposure to UVA radiation. Topical PUVA therapy refers to the direct application of the psoralen to the skin with subsequent exposure to UVA light. Bath PUVA is used in some European countries for generalized psoriasis, but the agent used (trimethylpsoralen) is not approved by the Food and Drug Administration (FDA). Paint PUVA and soak PUVA are other forms of topical application of psoralen and are often used for psoriasis localized to the palms and soles. In paint PUVA, 8-methoxypsoralen in ointment or lotion form is put directly on the lesions. With soak PUVA, the affected areas of the body are placed in a basin of water containing psoralen. With topical PUVA, UVA exposure is generally administered within 30 minutes of psoralen application.

PUVA has most commonly been used to treat severe psoriasis, for which there is no generally accepted first-line treatment. Each treatment option (eg, systemic therapies such as methotrexate, phototherapy, biologic therapies) has associated benefits and risks. Common minor toxicities associated with PUVA include erythema, pruritus, irregular pigmentation, and gastrointestinal tract symptoms; they generally can be managed by altering the dose of psoralen or ultraviolet light. Potential long-term effects include photoaging and skin cancer, particularly squamous cell carcinoma and possibly malignant melanoma. PUVA is generally considered more effective than targeted phototherapy for the treatment of psoriasis. However, the requirement of systemic exposure and the higher risk of adverse reactions (including a higher carcinogenic risk) have generally limited PUVA therapy to patients with more severe disease.

Regulatory Status

In 2001, XTRAC™ (PhotoMedex), a XeCl excimer laser, was cleared for marketing by the FDA through the 510(k) process for the treatment of mild-to-moderate psoriasis. The 510(k) clearance was subsequently obtained for a number of targeted UVB lamps and lasers, including newer versions of the XTRAC system (eg, XTRAC Ultra™), the VTRAC™ lamp (PhotoMedex), the BClear™ lamp (Lumenis), and the European manufactured Excilite™ and Excilite µ™ XeCl lamps. FDA product code: FTC.

In 2010, the Levia Personal Targeted Phototherapy® UVB device (Daavlin; previously manufactured by Lerner Medical Devices) was cleared for marketing by the FDA through the 510(k) process for home treatment of psoriasis.

The oral psoralen product, Oxsoralen-Ultra (methoxsalen soft gelatin capsules), has been approved by the FDA and is made by Bausch Health; a generic product is also available from various manufacturers Topical psoralen products ( Oxsoralen; Valeant Pharmaceuticals) and methoxsalen hard gelatin capsules have been discontinued. Injectable methoxsalen is available but not used for psoriasis.

Rationale

This evidence review was created in November 2001 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through  October 20, 2020.

Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life (QOL), and ability to function, including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, 2 domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent 1 or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings.The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Psoriasis is a common chronic immune-mediated disease characterized by skin lesions ranging from minor localized patches to complete body coverage. There are several types of psoriasis; most common is plaque psoriasis, which is associated with red and white scaly patches on the skin. In addition to being a skin disorder, psoriasis can negativelyimpact many organ systems and is associated with an increased risk of cardiovascular disease, some types of cancer,and autoimmune diseases (eg, celiac disease, Crohn disease). Although disease severity is minimally defined by body surface area (mild psoriasis affects < 3% of body surface area, moderate psoriasis affects 3% to 10%, and severe disease affects >10% of body surface area), lesion characteristics (eg, location and severity of erythema, scaling,induration, pruritus) and impact on QOL are also taken into account. The Psoriasis Area Severity Index (PASI) is a more specific means of quantifying the extent and severity of psoriasis and is utilized by both clinicians in practice and in clinical trials to monitor disease severity. The PASI takes into account the affected body surface area along with the intensity of redness, scaling, and plaque thickness. Severity scores generated using PASI range from 0 (no disease) to 72(maximal disease severity); a score >10 generally indicates moderate-to-severe disease. In clinical trials of patients with moderate-to-severe psoriasis, a 75% reduction in PASI (ie, PASI 75) is a common endpoint.^1,2,3,4,

Population Reference No. 1 Policy Statement

Targeted Phototherapy for Mild Localized Psoriasis

Clinical Context and Therapy Purpose

The purpose of targeted phototherapy is to provide a treatment option that is an alternative to or an improvement on existing therapies in patients with mild localized psoriasis.

The question addressed in this evidence review is: Does the use of targeted phototherapy improve the net health outcome in patients with localized or generalized psoriasis?

The following PICOs were used to select literature to inform this review.

Populations

The relevant population of interest is individuals with mild localized psoriasis (<3% body surface area and not affecting hands, feet, face, or genitals).

Interventions

The therapy being considered is targeted phototherapy, which is managed by dermatologists and primary care providers.

Comparators

The following therapy is currently being used to treat localized or generalized psoriasis: topical medication, which is managed by dermatologists and primary care providers.

Outcomes

The general outcomes of interest are symptoms, change in disease status, QOL, and treatment-related morbidity.

Though not completely standardized, follow-up for mild localized psoriasis symptoms would typically occur in the months to years after starting treatment.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

The original indication of the excimer laser was mild-to-moderate psoriasis, defined as involvement of less than 10% of the skin. Typically, this patient population has not been considered for light box therapy, because the risks of exposing the entire skin to the carcinogenic effects of ultraviolet B (UVB) light may outweigh the benefits of treating a small number of lesions. The American Academy of Dermatology does not recommend phototherapy for patients with mild localized psoriasis whose disease can be controlled with topical medications, including steroids, coal tar, vitamin D analogues (eg , calcipotriol, calcitriol), tazarotene, and anthralin.^5,

Section Summary: Mild Localized Psoriasis

For individuals who have mild localized psoriasis, the evidence is lacking on the use of targeted phototherapy. American Academy of Dermatology does not recommend phototherapy for patients with mild localized psoriasis whose disease can be controlled with topical medications. The evidence is insufficient to determine the effects of the technology on health outcomes.

Summary of Evidence

For individuals who have mild localized psoriasis, the evidence is lacking on the use of targeted phototherapy.Furthermore, the American Academy of Dermatology does not recommend phototherapy for patients with mild localized psoriasis whose disease can be controlled with topical medications. The evidence is insufficient to determine the effects of the technology on health outcomes.

Population Reference No. 2 Policy Statement

Targeted Phototherapy for Treatment-Resistant Mild Psoriasis

Clinical Context and Therapy Purpose

The purpose of targeted phototherapy is to provide a treatment option that is an alternative to or an improvement on existing therapies in patients with mild psoriasis that is resistant to topical medications.

The question addressed in this evidence review is: Does the use of targeted phototherapy improve the net health outcome in patients with localized or generalized psoriasis?

The following PICO was used to select literature to inform this review.

Populations

The relevant population of interest is individuals with mild psoriasis (<3% body surface area and not affecting hands, feet, face, or genitals) that is resistant to topical medications.

Interventions

The therapy being considered is targeted phototherapy, which is managed by dermatologists and primary care providers.

Comparators

The following therapy is currently being used to treat mild psoriasis resistant to topical medications: UVB light boxtherapy, which is managed by dermatologists and primary care providers.

Outcomes

The general outcomes of interest are symptoms, change in disease status, QOL, and treatment-related morbidity.

Though not completely standardized, follow-up for mild psoriasis that is resistant to topical medications symptoms would typically occur in the months to years after starting treatment.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

Several small within-subject studies have suggested that targeted phototherapy can be effective for treatment-resistant lesions. One 2003 patch comparison (N=14) reported effective clearing (pre-PASI score, 6.2; post-PASI score, 1.0) of treatment-resistant psoriatic lesions; 6 of the patients had previously received topical treatment, 5 had received conventional phototherapy, and 3 had received combined treatments including phototherapy.^6, In 2004, the same investigator group reported that 12 of 13 patients with “extensive and stubborn” scalp psoriasis (ie, unresponsive to class I topical steroids used in conjunction with tar and/or zinc pyrithione shampoos for at least 1 month) showed clearing following treatment with the 308-nm laser.^7, In a 2006 open trial from Europe, 44 (81%) of 54 patients with palmoplantar psoriasis resistant to combined phototherapy and systemic treatments were cleared of lesions with a single NB-UVB lamp treatment weekly for 8 weeks.^8,

Section Summary: Treatment-Resistant Mild Psoriasis

For individuals who have mild psoriasis that is resistant to topical medications who receive targeted phototherapy, the evidence includes small (N<60) within-subject studies. Studies have shown that targeted phototherapy can improve mild localized psoriasis that has not responded to topical treatment. Targeted phototherapy is presumed to be safer or at least riskier than whole body phototherapy, due to risks of exposing the entire skin to the carcinogenic effects of UVB light. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Summary of Evidence

For individuals who have mild psoriasis that is resistant to topical medications who receive targeted phototherapy, the evidence includes small (N<60) within-subject studies. Relevant outcomes are symptoms, change in disease status,QOL, and treatment-related morbidity. Studies have shown that targeted phototherapy can improve mild localized psoriasis that has not responded to topical treatment. Targeted phototherapy is presumed to be safer or at least no riskier than whole body phototherapy, due to risks of exposing the entire skin to the carcinogenic effects of UVB light. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 3 Policy Statement

Targeted Phototherapy for Moderate-to-Severe Localized Psoriasis

Clinical Context and Therapy Purpose

The purpose of targeted phototherapy is to provide a treatment option that is an alternative to or an improvement on existing therapies in patients with moderate-to-severe localized psoriasis.

The question addressed in this evidence review is: Does the use of targeted phototherapy improve the net health outcome in patients with localized or generalized psoriasis?

The following PICO was used to select literature to inform this review.

Populations

The relevant population of interest is individuals with moderate-to-severe localized psoriasis (3% to 10% body surface area or affecting hands, feet, face, or genitals).

Interventions

The therapy being considered is targeted phototherapy, which is managed by dermatologists and primary care providers.

Comparators

The following therapy is currently being used to treat moderate-to-severe localized psoriasis: UVB light box therapy, which is managed by dermatologists and primary care providers.

Outcomes

The general outcomes of interest are symptoms, change in disease status, QOL, and treatment-related morbidity.

Though not completely standardized, follow-up for moderate-to-severe localized psoriasis symptoms would typically occur in the months to years after starting treatment.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
• Studies with duplicative or overlapping populations were excluded.

Review of evidence

Systematic Reviews

There are several systematic reviews of the literature on targeted phototherapy. Reviews differed in the type of study selected and the comparison interventions. A systematic review by Almutawa et al (2015) considered only RCTs; PUVA was the comparison intervention.^8, Reviewers identified three RCTs comparing the efficacy of targeted UVB phototherapy with PUVA for the treatment of plaque psoriasis. Two of the 3 trials used an excimer laser (308 nm) as the source of targeted phototherapy, and the third used localized NB-UVB light. There was no statistically significant difference between the techniques in the proportion of patients with at least a 75% reduction in psoriasis. The pooled odds ratio was 3.48 (95% confidence interval, 0.56 to 22.84).

Mudigonda et al (2012) published a systematic review of controlled studies (RCTs and non-RCTs) on targeted vs nontargeted phototherapy for patients with localized psoriasis.^9, Reviewers identified 3 prospective nonrandomized studies comparing the 308-nm excimer laser with NB-UVB. Among these studies was a study by Goldinger et al (2006) that compared the excimer laser with full-body NB-UVB in 16 patients.^10, At the end of 20 treatments, PASI scores were equally reduced on the 2 sides, from a baseline of 11.8 to 6.3 for laser and from 11.8 to 6.9 for nontargeted NB-UVB. A study by Kollner et al (2005) included 15 patients with stable plaque psoriasis.^11, The study compared the 308-nm laser, the 308-nm excimer lamp, and standard TL-01 lamps. One psoriatic lesion per patient was treated with each therapy (ie, each patient received all three treatments). Investigators found no significant differences in the efficacy of the three treatments after ten weeks. The mean number of treatments to achieve clearance of lesions was 24.

Section Summary: Moderate-to-Severe Localized Psoriasis

For individuals who have moderate-to-severe localized psoriasis who receive targeted phototherapy, the evidence includes systematic reviews of small (N≤25) controlled trials (RCTs and non-RCTs). Systematic reviews of small controlled trials in patients with moderate-to-severe psoriasis have found that targeted phototherapy has efficacy similar to whole-body phototherapy. Targeted phototherapy is presumed to be safer or at least no riskier than whole body phototherapy, due to risks of exposing the entire skin to the carcinogenic effects of UVB light. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Summary of Evidence

For individuals who have moderate-to-severe localized psoriasis who receive targeted phototherapy, the evidence includes systematic reviews of small (N≤25) controlled trials (RCTs and non-RCTs). Relevant outcomes are symptoms, change in disease status, QOL, and treatment-related morbidity. Systematic reviews of small controlled trials in patients with moderate-to-severe psoriasis have found that targeted phototherapy has efficacy similar to whole-body phototherapy.Targeted phototherapy is presumed to be safer or at least no riskier than whole body phototherapy, due to risks of exposing the entire skin to the carcinogenic effects of UVB light. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 4 Policy Statement

Psoralen Plus Ultraviolet A for Generalized Psoriasis

Clinical Context and Therapy Purpose

The purpose of PUVA is to provide a treatment option that is an alternative to or an improvement on existing therapies in patients with generalized psoriasis.

The question addressed in this evidence review is: Does the use of PUVA improve the net health outcome in patients with localized or generalized psoriasis?

The following PICO was used to select literature to inform this review.

Populations

The relevant population of interest is individuals with generalized psoriasis (>10% body surface area).

Interventions

The therapy being considered is PUVA, which is managed by dermatologists and primary care providers.

Comparators

The following therapies are currently being used to treat generalized psoriasis: topical medications and UVB light box therapy, which is managed by dermatologists and primary care providers.

Outcomes

The general outcomes of interest are symptoms, change in disease status, QOL, and treatment-related morbidity.

Though not completely standardized, follow-up for generalized psoriasis symptoms would typically occur in the months to years after starting treatment.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
• Studies with duplicative or overlapping populations were excluded.

Review of evidence

Systematic Reviews and Randomized Controlled Trials

A number of RCTs and systematic reviews of RCTs have compared PUVA with other light therapies or with placebo. A Cochrane review by Chen et al (2013) assessed light therapy for psoriasis.^13, However, that review is less useful for this evidence evaluation because reviewers combined results of studies using PUVA and broadband UVB, rather than reporting outcomes separately for these treatment modalities.

Psoralens and Ultraviolet A versus Narrow Band-Ultraviolet B

An industry-sponsored systematic review by Archier et al (2012) focused on studies comparing PUVA with NB-UVB in patients who had chronic plaque psoriasis.^14, Pooled analysis of 3 RCTs found a significantly higher psoriasis clearance with PUVA than with NB-UVB (odds ratio=2.79; 95% confidence interval, 1.40 to 5.55). In addition, significantly more patients remained clear at 6 months with PUVA than with NB-UVB (odds ratio=2.73: 95% confidence interval, 1.18 to 6.27).

Psoralens and Ultraviolet A versus Topical Steroids

Amirnia et al (2012) published a trial in which 88 patients with moderate plaque psoriasis were randomized to PUVA or topical steroids.^15, Treatment was continued for four months or until clearance was achieved. Clearance was defined as the disappearance of at least 90% of baseline lesions. All patients in both groups achieved clearance within the four-month treatment period. Recurrence (defined as a resurgence of at least 50% of the baseline lesions) was reported significantly more often in the topical steroid group (9/44 [20.5%]) than in the PUVA group (3/44 [6.8%]; p=0.007) (Table 1).

Psoralens and Ultraviolet A versus Ultraviolet A Without Psoralens

El-Mofty et al (2014) published an RCT comparing PUVA with broadband-UVA in 61 patients who had psoriasis affecting at least 30% body surface area.^16, Clinical outcomes were significantly better in the PUVA group than in the broadband-UVA groups (see Table 1). For example, complete clearance was obtained by 23 (77%) of 30 patients in the PUVA group, 5 (31%) of 16 patients in the 10 J/cm² UVA group, and 5 (33%) of 15 patients in the 15 J/cm² UVA group (p=0.020).

Sivanesan et al (2009) published a double-blind RCT evaluating the efficacy of 8-methoxy psoralen PUVA treatment in patients with moderate-to-severe psoriasis affecting at least 10% body surface area.^17, The trial included 40 patients randomized to PUVA (n=30) and/or UVA plus placebo psoralens (n=10). Patients were treated 3 times weekly for 12 weeks. The primary outcome was a 75% or greater improvement in PASI 75 score. At 12 weeks, 19 (63%) of 30 patients in the PUVA group and 0 (0%) of 10 patients in the UVA plus placebo group achieved the primary outcome measure (p<0.001) (see Table 1). There were no serious adverse events.

Table 1. Summary of Individual RCTs of PUVA vs Other Light Treatments

PASI: Psoriasis Area Severity Index; PUVA: psoralen plus ultraviolet A; RCT: randomized controlled trials; UVA: ultraviolet A.Section Summary: Generalized Psoriasis

For individuals who have generalized psoriasis who receive PUVA, the evidence includes RCTs and systematic reviews of RCTs. Relevant outcomes are symptoms, change in disease status, QOL, and treatment-related morbidity. The available evidence demonstrates that PUVA is more effective than NB-UVB phototherapy, topical steroids, or ultraviolet A without psoralens in patients with generalized psoriasis. Due to side effects, PUVA is typically restricted to more severe cases. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Summary of Evidence

For individuals who have generalized psoriasis who receive PUVA, the evidence includes RCTs and systematic reviews of RCTs. Relevant outcomes are symptoms, change in disease status, QOL, and treatment-related morbidity. The available evidence demonstrates that PUVA is more effective than NB-UVB phototherapy, topical steroids, or ultraviolet A without psoralens in patients with generalized psoriasis. Due to side effects, PUVA is typically restricted to more severe cases. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Supplemental Information

Practice Guidelines and Position Statements

American Academy of Dermatology – National Psoriasis Foundation

In 2019, the American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) joint guidelines on the management and treatment of psoriasis with phototherapy give strong recommendations for the use of targeted ultraviolet B (UVB) (Table 2).^4,

Table 2. AAD-NPF Strength of Recommendations for Targeted UVB

Table adapted from Elmets et al (2019).4,

MED: minimal erythema dose; NB-UVB: narrowband ultraviolet B; UVB: ultraviolet B.

The guidelines state of home narrowband-UVB therapy that evidence shows similar results regarding efficacy, quality of life, and side effects between patients with mild-to-severe psoriasis who received home treatments and those who received treatments at hospitals. In addition, home treatment was found to significantly lessen the burden on patients who had to travel to a phototherapy center.

The AAD and NPF joint guidelines (2020) on the management and treatment of psoriasis in pediatric patients also provide recommendations for phototherapy (Table 3). ^18,
The evidence for phototherapy in the pediatric population is limited and generally of low quality.

Table 3. AAD-NPF Strength of Recommendations for Phototherapy/Photochemotherapy

Table adapted from Menter et al 2020. 18,

NB-UVB: narrowband ultraviolet B; PUVA: psoralens and ultraviolet A.

American Academy of Dermatology

In 2010, the American Academy of Dermatology guidelines on the management of psoriasis recommended that patients with psoriasis who are compliant could, under dermatologist supervision, be considered appropriate candidates for home UVB therapy.^5, Targeted phototherapy was recommended for patients with mild, moderate, or severe psoriasis with less than 10% involvement of the body surface area. Systemic psoralen plus ultraviolet A was indicated in adults with generalized psoriasis resistant to topical therapy.

National Psoriasis Foundation

In 2017, the National Psoriasis Foundation published consensus guidance based on a task force review of the literature on the treatment for psoriasis involving skinfolds (inverse or intertriginous) psoriasis.^19, The treatment guidance for intertriginous or genital psoriasis stated: "....there is anecdotal evidence demonstrating the strong clinical efficacy of
biologic treatment; with limited knowledge on the effects of biologics on intertriginous or genital psoriasis." The guidance on inverse psoriasis is provided in Table 4.

Table 4. Recommendations on Treatment of Inverse Psoriasis

The National Psoriasis Foundation (2017) also published recommendations based on a review of the literature on the treatment for psoriasis in solid organ transplant patients.^20, Because organ transplant patients are excluded from randomized controlled trials, there are limited data. The recommendations were based on case series (see Table 5).

Table 5. Recommendations on Treatment of Psoriasis for Solid Organ Transplant Patients

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials
There are currently no ongoing trials that might influence this review.

Medicare National Coverage

Ultraviolet light treatment is covered; targeted phototherapy is not specifically mentioned. There is no national coverage determination on psoralen plus ultraviolet A.

References

1.
Callen JP, Krueger GG, Lebwohl M, et al. AAD consensus statement on psoriasis therapies. J Am Acad Dermatol.Nov 2003; 49(5): 897-9. PMID 14576671
2.
Finlay AY. Current severe psoriasis and the rule of tens. Br J Dermatol. May 2005; 152(5): 861-7. PMID 15888138
3.
Legwohl MD, van de Kerkhof P. Psoriasis. In Treatment of Skin Disease: Comprehensive Therapeutic Strategies.London: Mosby; 2005.
4.
Elmets CA, Lim HW, Stoff B, et al. Joint American Academy of Dermatology-National Psoriasis Foundationguidelines of care for the management and treatment of psoriasis with phototherapy. J Am Acad Dermatol. Sep2019; 81(3): 775-804. PMID 31351884
5.
Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis:Section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am AcadDermatol. Jan 2010; 62(1): 114-35. PMID 19811850
6.
Taneja A, Trehan M, Taylor CR. 308-nm excimer laser for the treatment of psoriasis: induration-based dosimetry.Arch Dermatol. Jun 2003; 139(6): 759-64. PMID 12810507
7.
Taylor CR, Racette AL. A 308-nm excimer laser for the treatment of scalp psoriasis. Lasers Surg Med. 2004; 34(2):136-40. PMID 15004825
8.
Nistico SP, Saraceno R, Stefanescu S, et al. A 308-nm monochromatic excimer light in the treatment ofpalmoplantar psoriasis. J Eur Acad Dermatol Venereol. May 2006; 20(5): 523-6. PMID 16684278
9.
Almutawa F, Thalib L, Hekman D, et al. Efficacy of localized phototherapy and photodynamic therapy for psoriasis:a systematic review and meta-analysis. Photodermatol Photoimmunol Photomed. Jan 2015; 31(1): 5-14. PMID24283358
10.
Mudigonda T, Dabade TS, West CE, et al. Therapeutic modalities for localized psoriasis: 308-nm UVB excimerlaser versus nontargeted phototherapy. Cutis. Sep 2012; 90(3): 149-54. PMID 23094316
11.
Goldinger SM, Dummer R, Schmid P, et al. Excimer laser versus narrow-band UVB (311 nm) in the treatment ofpsoriasis vulgaris. Dermatology. 2006; 213(2): 134-9. PMID 16902290
12.
Kollner K, Wimmershoff MB, Hintz C, et al. Comparison of the 308-nm excimer laser and a 308-nm excimer lampwith 311-nm narrowband ultraviolet B in the treatment of psoriasis. Br J Dermatol. Apr 2005; 152(4): 750-4. PMID15840108
13.
Chen X, Yang M, Cheng Y, et al. Narrow-band ultraviolet B phototherapy versus broad-band ultraviolet B orpsoralen-ultraviolet A photochemotherapy for psoriasis. Cochrane Database Syst Rev. Oct 23 2013; (10):CD009481. PMID 24151011
14.
Archier E, Devaux S, Castela E, et al. Efficacy of psoralen UV-A therapy vs. narrowband UV-B therapy in chronicplaque psoriasis: a systematic literature review. J Eur Acad Dermatol Venereol. May 2012; 26 Suppl 3: 11-21.PMID 22512676
15.
Amirnia M, Khodaeiani E, Fouladi RF, et al. Topical steroids versus PUVA therapy in moderate plaque psoriasis: aclinical trial along with cost analysis. J Dermatolog Treat. Apr 2012; 23(2): 109-11. PMID 21254854
16.
El-Mofty M, Mostafa WZ, Yousef R, et al. Broadband ultraviolet A in the treatment of psoriasis vulgaris: arandomized controlled trial. Int J Dermatol. Sep 2014; 53(9): 1157-64. PMID 24697586
17.
Sivanesan SP, Gattu S, Hong J, et al. Randomized, double-blind, placebo-controlled evaluation of the efficacy oforal psoralen plus ultraviolet A for the treatment of plaque-type psoriasis using the Psoriasis Area Severity Indexscore (improvement of 75% or greater) at 12 weeks. J Am Acad Dermatol. Nov 2009; 61(5): 793-8. PMID19766350
18.
Menter A, Cordoro KM, Davis DMR, et al. Joint American Academy of Dermatology-National Psoriasis Foundationguidelines of care for the management and treatment of psoriasis in pediatric patients. J Am Acad Dermatol. Jan2020; 82(1): 161-201. PMID 31703821
19.
Khosravi H, Siegel MP, Van Voorhees AS, et al. Treatment of Inverse/Intertriginous Psoriasis: Updated Guidelinesfrom the Medical Board of the National Psoriasis Foundation. J Drugs Dermatol. Aug 01 2017; 16(8): 760-766.PMID 28809991
20.
Prussick R, Wu JJ, Armstrong AW, et al. Psoriasis in solid organ transplant patients: best practicerecommendations from The Medical Board of the National Psoriasis Foundation. J Dermatolog Treat. Jun 2018;29(4): 329-333. PMID 28884635

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