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MP 2.01.07

Psoralens with Ultraviolet A (PUVA)


Medical Policy    
Section
Medicine
 
Original Policy Date
12/1/95
Last Review Status/Date
Reviewed by consensus/1:2011
Issue
1:2011
  Return to Medical Policy Index

Disclaimer

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically. 


Description

Psoralens with ultraviolet A (PUVA) has been used to treat a variety of skin conditions including psoriasis and vitiligo. Use of PUVA involves balancing the potential benefits of clearing the skin conditions with short-term and possibly long-term adverse effects.

PUVA (psoralens with ultraviolet A) 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 by 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 directly applying 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 an 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.

A PUVA regimen has four components: the dose of psoralen, the starting dose of UVA, the incremental increases in UVA dose and the treatment frequency. Dosage often takes skin type into consideration. Skin type is categorized according to the Fitzpatrick scale, as follows:

Type I: Very fair; freckles; always burns, never tans:
Type II: White; fair; usually burns, tans with difficulty
Type III: Beige; sometimes mild burn, gradually tans
Type IV: Beige with a brown tint; rarely burns, tans with ease
Type V: Dark brown; very rarely burns, tans very easily
Type VI Black; never burns, tans very easily.

PUVA has most commonly been used to treat moderate to severe psoriasis, for which there is no generally accepted first-line treatment. Each treatment option (e.g., systemic therapies such as methotrexate, phototherapy, biologic therapies, etc.) has associated benefits and risks. Common minor toxicities associated with PUVA include erythema, pruritis, irregular pigmentation and gastrointestinal symptoms; these generally can be managed by altering the dose of psoralen or UV light. Potential long-term effects include photoaging and skin cancer, particularly squamous cell carcinoma (SCC) and possibly malignant melanoma. The risk of skin cancer has been found to be related to the lifetime cumulative exposure to oral PUVA and may be higher in people with lighter skin types. For example, one study found that patients treated with at least 337 PUVA treatments had at least a 100-fold increase in risk of SCC compared to general population incidence rates. In addition, the risk of malignancy was nearly 3 times higher in individuals with Fitzpatrick skin types I and II, compared to those with types III and IV. (1) Thus, an attempt is made to reduce the total exposure, especially in lighter skin types, such as limiting the number of treatments and/or avoiding maintenance treatment. There is also a concern from animal studies about a potential risk of cataract development and eye protection is recommended.

Note: This policy only addresses PUVA for the treatment of psoriasis.

Regulatory Status
The oral psoralen products Oxsoralen-Ultra (methoxsalen soft gelatin capsules) and 8-MOP (methoxsalen hard gelatin capsules) have been approved by the FDA; both are made by Valeant Pharmaceuticals. Topical psoralen products have also received FDA approval e.g., Oxsoralen (Valeant Pharmaceuticals).


Policy

PUVA for the treatment of vitiligo or severe, disabling psoriasis, which is not responsive to other forms of conservative therapy (e.g., topical corticosteroids, coal/tar preparations, and ultraviolet light), may be considered medically necessary.


Policy Guidelines

During a course of PUVA therapy, the patient needs to be assessed on a regular basis to determine the effectiveness of the therapy and the development of side 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, PUVA is generally not recommended for home therapy.


Benefit Application
BlueCard/National Account Issues

Coverage eligibility of PUVA, particularly as a treatment of vitiligo, may be subject to contractual exclusions regarding cosmetic services. Please refer to Policy No. 10.01.09 for discussion of interpretation of contractual language.


Rationale

This policy was created in 1998 with a search of the MEDLINE database through June 1998. It was subsequently updated by consensus without additional literature reviews. An updated search of the MEDLINE database was performed for the period November 2010 through November 2011. Following is a summary of the key literature to date:

 

One systematic review of the literature was identified, a Health Technology Assessment (HTA) from the U.K, published in 2000, on treatments for severe psoriasis. The review identified 5 randomized trials that compared psoralens with ultraviolet A (PUVA) to placebo and/or forms of phototherapy; studies were published in the 1980s or 1990s. (2) The authors of the systematic review were able to calculate differences in success rates between the treatment and control groups in only 2 of the trials; the others did not report data in such a way that these data were extractable. In a trial published in 1994 by Pai and colleagues with 24 participants, topical PUVA (applied to a bathing suit) 3 times a week resulted in a significantly greater benefit of PUVA versus placebo PUVA (risk difference [RD]: 0.67, 95% confidence interval [CI]: 0.38 to 0.96). The other trial, published by de Berker and colleagues in 1997, did not find a significant difference in success rates when PUVA twice a week was compared to psoralens plus ultraviolet B (UVB) twice a week (RD: -0.12, 95% CI: -0.28 to 0.04). The authors were not able to pool the findings of any of the studies on PUVA.

More recent randomized controlled trials (RCTs) evaluating PUVA for treating psoriasis are described below:

In 2011, Amirnia and colleagues published a study from Iran in which 88 patients with moderate plaque psoriasis were randomized to receive PUVA or topical steroids. (3) Treatment was continued for 4 months or until clearance was achieved. Clearance was defined as disappearance of at least 90% of baseline lesions. All patients in both groups achieved clearance within the 4-month treatment period. Recurrence (defined as a resurgence of at least 50% of the baseline lesions) occurred significantly more often in the topical steroid group (9 of 44, 20.5%) than in the PUVA group (3 of 44, 6.8%), (p=0.007).

In 2009, Sivanesan and colleagues published a double-blind RCT evaluating the efficacy of 8-MOP PUVA treatment in patients 18 years and older with moderate to severe psoriasis affecting at least 10% of their body surface area. (4) Individuals with a history of serious side effects from oral PUVA, phototoxic reactions, or cancer; including skin cancer; were excluded. The study included 40 patients, 30 randomly assigned to receive PUVA and 10 to receive UVA plus placebo psoralens. After a washout period of 2 weeks for topical psoriasis medications and 4 weeks for phototherapy and systemic therapies, patients were treated 3 times a week for 12 weeks. A total of 28 patients completed the study, 21 in the PUVA group and 7 in the UVA plus placebo group. The primary outcome was at least a 75% improvement in the Psoriasis Area and Severity Index (PASI) score (PASI 75). In an intention-to-treat (ITT) analysis with the last observation carried forward to analysis at 12 weeks, 19 of 30 (63%) in the PUVA group and 0 of 10 (0%) in the UVA with placebo group achieved at least a 75% improvement in the PASI 7 score (p<0.001). In the per protocol analysis, 18 of 21 (86%) in the PUVA group and 0 of 7 (0%) in the placebo group achieved PASI 75. There were no serious adverse effects. The study found a dramatic treatment benefit with PUVA compared to UVA plus placebo; however, there was substantial drop-out and no long-term follow-up.

Two recent RCTs from India compared outcomes after treatment with oral methoxsalen PUVA or narrow-band UVB (NB-UVB). In 2011, Chauhan and colleagues included 51 patients with plaque psoriasis involving greater than 20% of their body surface area. (5) Patients received treatment with NB-UVB or PUVA 3 times a week. Treatment continued until greater than 75% clearance was attained or for a maximum of 16 weeks. A total of 43 of 51 (84%) patients completed the study. Marked improvement (>75% clearance) was seen in 17 of 21 (90.9%) study completers in the NB-UVB group and 18 of 22 (81.8%) in the PUVA group; p>0.05. The mean time to achieve results was also similar in the 2 groups; a mean of 9.9 weeks with each treatment. A 2010 study by Dayal and colleagues randomly assigned 60 patients with chronic plaque psoriasis to receive twice weekly PUVA (n=30) or twice weekly NB-UVB phototherapy (n=30). (6) After the 3-month treatment period, all patients in both groups had at least 75% clearance of psoriasis or complete clearance. The PASI score did not differ significantly between groups (mean of 1.39 in the PUVA group and 1.61 in the NB-UVB group). The mean number of treatments to achieve clearance, however, was significantly higher in the NB-UVB group than the PUVA group, 16.4 and 12.7, respectively.

No studies were identified that compared home-based PUVA to office-based PUVA. A 2010 review of various types of home phototherapies for psoriasis did not discuss any studies on PUVA delivered at home. (7)

Summary

Multiple RCTs have evaluated psoralens with ultraviolet A (PUVA) for treating severe psoriasis. Among recent trials (2009 or later), one study found significantly greater benefit with PUVA compared to UVA; this study was limited by a high drop-out rate. Two recent RCTs from India found similar benefit of PUVA and NB-UVB. In addition, PUVA for severe treatment-resistant psoriasis is well-accepted and is recommended by the American Academy of Dermatology. One 2011 RCT from Iran focusing on patients with moderate psoriasis showed similar benefits with PUVA and topical steroids and a lower rate of recurrence in the PUVA group; this study is insufficient to draw definitive conclusions about the efficacy of PUVA in this patient population. There is a lack of evidence that home-based PUVA for treating psoriasis is as safe or effective as office-based treatment.

Practice Guidelines and Position Statements

The American Academy of Dermatology sponsored a series of guidelines on the treatment of psoriasis. Recommendations on PUVA from the guideline on use of phototherapy and photochemotherapy, published in 2009, are as follows (8):

  • Systemic PUVA with ultraviolet A is indicated in adults with generalized psoriasis who are resistant to topical therapy.
  • There are no studies in children; systemic PUVA may be used with caution in individuals less than 18 years.
  • Systemic PUVA is contraindicated in patients with known lupus erythematosus, porphyria or xeroderma pigmentosum.
  • Caution is recommended for several groups of patients including those with skin types I and II, and pregnant and nursing women.

Medicare National Coverage

No national coverage determination.

References:

 

  1. Patel RV, Clark LN, Lebwohl M et al. Treatments for psoriasis and the risk of malignancy. J Am Acad Dermatol 2009; 60(6):1001-17.
  2. Griffiths CE, Clark CM, Chalmers RJ et al. A systematic review of treatments for severe psoriasis. Health Technol Assess 2000; 4(40):1-125.
  3. Amirnia M, Khodaeiani E, Fouladi RF et al. Topical steroids in moderate plaque psoriasis: A clinical trial with cost analysis. J Dermatolog Treat 2011 [Epub ahead of print].
  4. Sivanesan SP, Gattu S, Hong J et al. Randomized, double-blind, placebo-controlled evaluation of the efficacy of oral psoralen plus ultraviolet A for the treatment of plaque-type psoriasis using the Psoriasis Area Severity Index score (improvement of 75% or greater) at 12 weeks. J Am Acad Dermatol 2009; 61(5):793-8.
  5. Chauhan PS, Kaur I, Dogra S et al. Narrowband ultraviolet B versus psoralen plus ultraviolet A therapy for severe plaque psoriasis: an Indian perspective. Clin Exp Dermatol 36(2):169-73.
  6. Dayal S, Mayanka, Jain VK. Comparative evaluation of NBUVB phototherapy and PUVA photochemotherapy in chronic plaque psoriasis. Indian J Dermatol Venereol Leprol 2010; 76(5):533-7.
  7. Nolan BV, Yentzer BA, Feldman SR. A review of home phototherapy for psoriasis. Dermatol Online J 2010; 16(2):1.
  8. 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 Acad Dermatol 2010; 62(1):114-35.

Codes

Number

Description

CPT  96912  Photochemotherapy; psoralens, and ultraviolet A (PUVA) 
ICD-9 Procedure  99.83  Other phototherapy (includes photochemotherapy) 
ICD-9 Diagnosis  696.1 Other psoriasis, any type except arthropathy 
HCPCS  J8999  Prescription drug, oral, chemotherapeutic, not otherwise specified 
ICD-10-CM (effective 10/1/13)  L40.0 - L40.9 Psoriasis code range
ICD-10-PCS (effective 10/1/13)   ICD-10-PCS codes are only used for inpatient services. There is no specific ICD-10-PCS code for the initiation of this therapy.
  6A600ZZ; 6A601ZZ Extracorporeal therapies, physiological systems, phototherapy skin, codes for single and multiple
Type of Service  DME 
Place of Service  Inpatient 
Outpatient
 
Physician’s Office
 


Index

Psoralens with Ultraviolet A (PUVA)
Psoriasis, PUVA Treatment
PUVA (Psoralens with Ultraviolet A)


Policy History

Date Action Reason

12/01/95

Add to Medicine section

New Policy

11/01/98

Replace Policy

Policy reviewed, policy statement revised

04/15/02

Replace Policy

Policy reviewed without literature review; new review date only.

04/29/03

Replace Policy

Policy reviewed without literature review; new review date only.

1/13/11 Replace policy Policy returned to active review. Policy updated with literature search through May 2010; references 1-9 added. Policy changed to reflect correct wording of medically necessary statements.
01/12/12 Replace policy Policy updated with literature search. References 3 and 5 added; other references renumbered or removed. Vitiligo removed from policy statement and title changed to indicate the policy is specific to psoriasis.