Clinical Policy Title: Phototherapy and photochemotherapy (PUVA) for skin conditions

Transcription

1 Clinical Policy Title: Phototherapy and photochemotherapy (PUVA) for skin conditions Clinical Policy Number: Effective Date: October 1, 2015 Initial Review Date: May 20, 2015 Most Recent Review Date: June 22, 2017 Next Review Date: June 2018 Policy contains: Phototherapy and photochemotherapy. Psoralen ultraviolet A (PUVA). Related policies: None. ABOUT THIS POLICY: Prestige Health Choice has developed clinical policies to assist with making coverage determinations. Prestige Health Choice s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peer-reviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by Prestige Health Choice when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. Prestige Health Choice s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. Prestige Health Choice s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, Prestige Health Choice will update its clinical policies as necessary. Prestige Health Choice s clinical policies are not guarantees of payment. Coverage policy Prestige Health Choice considers the use of phototherapy and photochemotherapy (PUVA) to be clinically proven and, therefore, medically necessary for the following skin conditions after conventional therapies have failed: Severe refractory atopic dermatitis/eczema. Eosinophilic folliculitis and other pruritic eruptions of HIV infection. Mycosis fungoides/sezary syndrome (cutaneous T-cell lymphoma). Severe lichen planus. Photodermatoses. Pityriasis lichenoides. Pityriasis rosea. Prurigo nodularis. Psoriasis. 1

2 Vitiligo. Prestige Health Choice considers the use of phototherapy at home to be investigational and, therefore, not medically necessary. Limitations: Coverage determinations are subject to benefit limitations and exclusions as delineated by the state Medicaid authority. The Florida Medicaid website may be accesses at PUVA treatments for the above conditions are limited to two to three times per week for 23 weeks and one treatment every one to three weeks thereafter if the patient s condition improves. If there is not adequate improvement after two months, the treatment is not considered medically necessary thereafter. All other uses of PUVA are not medically necessary, including, but not limited to: Keratosis follicularis. Lichen amyloidosis. Lichen myxedematosus. Melasma. Low skin tolerance for sunlight. Alternative covered services: Biologic systemic agents, nonbiologic systemic agents, and phototherapy including broadband (BB-UVB) and narrowband (NB-UVB). Background Ultraviolet (UV) light a cause of sunburns, wrinkles and skin cancer can be used in a medical setting as therapy for certain hard-to-treat skin problems and other medical conditions. The main forms of ultraviolet light are ultraviolet A (UVA) and ultraviolet B (UVB). Psoralen ultraviolet A (PUVA) is a topical treatment of disease by exposure to light at a specific portion of the solar spectrum 320 to 400 nanometers in wavelength. Psoralens are chemicals found in plants that can absorb UV light. PUVA treatment for various skin conditions typically involves administration of an oral drug (e.g., methoxypsoralen) followed by the UV portion 45 to 60 minutes later. Other forms of PUVA include: Topical PUVA, with subsequent PUVA exposure. Bath PUVA, which is not approved and rarely used in the United States. 2

3 Paint PUVA, used locally on palms and plantar surfaces of the feet with 8-methoxypsoralen ointment or lotion applied directly to lesions. Soak PUVA in which the area is immersed in a basin of water containing 8-methoxypsoralen. Originally PUVA was developed for psoriasis, a relatively common skin disorder. It is also used for conditions such as vitiligo and mycosis fungoides (the most common type of T-cell lymphoma). While mild psoriasis can often be controlled by topical medications, severe cases often require treatments involving UV light exposures. Before initiating PUVA therapy, other types of treatment should be discussed with the patient. The potential for PUVA to increase the risk of skin cancer, especially when treating psoriasis, should also be discussed. Persons at elevated risk for skin cancer from PUVA include children and persons with a genetic predisposition, a history of skin cancer or a history of at least 150 prior PUVA treatments. Toxicity to PUVA includes etythema, pruritus, xerosis, irregular pigmentation and gastrointestinal symptoms. Most toxicity can be avoided by altering or dividing the dose. There is an elevated (and dosedependent) risk of nonmelanoma skin cancer from PUVA. Whether PUVA raises the risk of melanoma is controversial. When administered to pregnant women, PUVA has been associated with a rise in lowweight births, but not congenital anomalies. An expert panel concluded that PUVA is contraindicated for patients with lupus erythematosus, porphyria or xeroderma pigmentation (Menter, 2010). Caution should be exercised for patients with skin types I and II who tend to burn easily; with a history of arsenic intake; with a likelihood of requiring cyclosporin or methotrexate with previous ionizing radiation therapy; or with a history of melanoma or nonmelanoma skin cancer. Searches Prestige Health Choice searched PubMed and the databases of: UK National Health Services Centre for Reviews and Dissemination. Agency for Healthcare Research and Quality s National Guideline Clearinghouse and other evidence-based practice centers. The Centers for Medicare & Medicaid Services (CMS). We conducted searches on April 24, Search terms were: Phototherapy" (MeSH), "Photochemotherapy" (MeSH), PUVA therapy, UVA, UV-B, and PUVA therapy home. We included: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. 3

4 Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. Findings PUVA-related guidelines are often specific to a patient s condition, e.g.: A 2014 practice guideline by the American Academy of Dermatology on dermatitis treatment recommended phototherapy as a second-line treatment if emollients, topical steroid, and calcineurin inhibitors have failed, and that phototherapy may be considered for home use if patients are unable to receive the treatment in an office setting (Sidbury, 2014). A 2012 guideline on psoriasis from the National Institute for Health and Clinical Excellence (NICE) suggests offering NB-UVB phototherapy to psoriasis patients whose condition cannot be controlled with topical treatments alone, but recommends not using any type of phototherapy as maintenance therapy (NICE, 2012). A 2016 review of guidelines for psoriasis concludes that NB-UVB is an effective treatment option for psoriasis (Mehta, 2016). A 2012 guideline on alopecia areata from the British Association of Dermatologists recommends against PUVA use due to potentially serious side-effects and inadequate evidence of efficacy (Messenger, 2012). A 2016 guideline on mycosis fungoindes and Sezary syndrome, for which ultraviolet light is often used, suggests a more refined guideline based on patient stage, centers, and in combination with other agents in practice and clinical trials (Olsen, 2016). Psoriasis is the condition most studied for phototherapy outcomes. A systematic review of 29 articles (n=675) of persons with palmoplantar pustular psoriasis found that phototherapy, ciclosporin, and topical corticosteroids each controlled the disease, with PUVA having greater efficacy than UVB therapy ( Sevrain, 2014). Another meta-analysis of psoriasis (23 studies, n=765) also found PUVA to be more efficacious than non-larger targeted UV-B phototherapy, although both treatments had positive outcomes (Almutawa, 2015). PUVA s superiority to NB-UVB was also upheld in a 2012 meta-analysis of 29 trials (n=773), and accomplished these results in fewer sessions (Archier, 2012). A 2013 Cochrane review of 13 trials (n=662) found the PUVA-UVB comparison to be hampered by heterogenous evidence, and could not make a definitive conclusion on which was more effective (Chen, 2013). Phototherapy is generally found to work better as part of combination treatments, rather than monotherapy, in psoriasis patients (Bailey, 2012). Another systematic review of 41 trials (n=2416) found that PUVA was more effective than NB-UVB as a monotherapy, and NB-UVB worked better than BB-UVB and bath PUVA in treating adults with moderate to severe psoriasis (Almutawa, 2013). A systematic review of 21 randomized controlled trials (RCTs) including 961 patients determined that NB-UVB and UV-A1 phototherapy in moderate to severe dermatitis were helpful, but data on PUVA use 4

5 and phototherapy in children are scarce (Perez-Ferriols, 2015). Another systematic review of 19 studies (n=905) found that UVA1 and NB-UVB were the most effective treatments for reducing signs and symptoms in dermatitis (Garritsen, 2014). Findings from 19 systematic reviews have determined that NB-UVB can be used for chronic atopic eczema, and UVA used for acute eczema (Williams, 2008). A recent meta-analysis of 38 studies of persons with vitiligo compared NB-UVB phototherapy (n=1201) to PUVA phototherapy (n=227). After six and 12 months of treatment, the UV-B group had more at least mild responses (74.2 and 75.0 percent) than did the PUVA group (51.4 and 61.6 percent). Marked responses were more common in the face and neck (44.2 percent) compared to the trunk (26.1) and the extremities (17.3) after six months of UV-B phototherapy (Bae, 2017). A literature review found that combination therapies for vitiligo, compared to monotherapy, was more effective, especially when phototherapy was included (Bacigalupi, 2012). A systematic review determined NB-UVB had fewer side effects and was marginally better than PUVA for vitiligo, and that (along with topical corticosteroids), offers the greatest benefits of any vitiligo treatment (Whitton, 2015). Mycosis fungoides is the most common cutaneous T-cell lymphoma, for which conventional therapy is not always effective. A review of 20 papers documents that photodynamic therapy is a promising and well-tolerated option for treating localized lesions, with excellent cosmetic outcomes (Xue, 2017). PUVA and NB-UVB monotherapy were found to be effective first-line interventions for mycosis fungoides; the effectiveness for PUVA either as maintenance therapy or combined with drugs as first-line therapy is uncertain, but may be beneficial for relapse and late-stage disease (Dogra, 2015). PUVA is usually administered in the outpatient setting, but this treatment is also available for home use. The costs of home therapy are considerably lower, in part because a home light box costs $3,000 to $7,000, compared to $15,000 or more for clinical units (Hayes, 2012). Yertzer (2009) reported that firstyear costs of PUVA to patients were $2,590 compared to $3,040 for office use; per-treatment costs to insurers were $5 for home use and $76 for office use. Research has yet to demonstrate the efficacy of home phototherapy, which was used for years despite lack of a consensus on efficacy (Koek, 2006). Raipara (2010) found home NB-UVB was as safe, effective, and cost-effective as outpatient treatment and was more convenient and generated higher satisfaction (Raipara, 2010). One study of home-based phototherapy found NB-UVB to be safer than PUVA (Lapolla, 2011). Regular skin examinations by a dermatologist should be performed as PUVA home treatments are conducted. But a Cochrane review failed to support or refute home-based phototherapy for nonhemolytic jaundice in infants over 37 weeks gestation (Malwade, 2014). The issue of whether home phototherapy use is safe and effective remains unresolved. A review of 60 publications on psoriasis treatments was not able to generate a comparable costeffectiveness analysis of various methods, including phototherapy (Gutknecht, 2016), as did another analysis from 2015 (Hamilton, 2015). 5

6 Policy updates: A total of six guidelines/other and 12 peer-reviewed references were added to this policy in Summary of clinical evidence: Citation Bae (2017) Content, Methods, Recommendations Key points: Comparison of phototherapy modes for vitiligo Meta-analysis of 35 studies (n=1428) comparing narrow band UV-B (n=1201) and UVA (n=227) phototherapy for vitiligo. At 6 and 12 months after therapy, UV-B had higher percent of patients with at least a mild response (74.2 and 75.0), compared to UVA (51.4 and 61.6). Percent of patients with marked responses was 44.2% in the face and neck, 26.1% on the trunk, and 17.3% on the extremeties. Almutawa (2015) PUVA, UVB and photodynamic therapy (PDT) for psoriasis Dogra (2015) Key points: Systematic review and meta-analysis of six RCTs and 17 case series. The primary outcome was 75% reduction in severity score from baseline. Overall quality: low with high risk of bias. Small sample size, study heterogeneity. PUVA had a statistically nonsignificant (P = 0.183) advantage over targeted UVB. The pooled effect estimate of topical PUVA, targeted UVB and PDT were 77%, 61% and 22%, respectively (15-case series). Topical PUVA and targeted UVB phototherapy are effective in treating localized psoriasis. PDT has low efficacy and high percentage of side effects. Key points: Phototherapy for mycosis fungoides (MF) Synthesis of 107 systematic reviews, meta-analyses, national guidelines, RCTs, prospective open label studies and retrospective case series. For early stage MF (stage IA, IB, and IIA): o PUVA is a safe, effective and well-tolerated first-line therapy (Level of evidence [LOE] 1+, grade of recommendation B). o NB-UVB is comparable to PUVA but less robust evidence (LOE 2++, Grade B). o PUVA with methotrexate, bexarotene or interferon-alpha-2b has unclear advantage over monotherapy. o NB-UVB preferred in patients with patches and thin plaques. o PUVA preferred for thick plaques and relapse after initial NB-UVB therapy. For inducing remission, three treatment sessions per week of either PUVA phototherapy or NB-UVB phototherapy until complete remission. In cases of relapse, PUVA monotherapy or PUVA combined with adjuvants like methotrexate and interferon (LOE 2+, Grade B). For late stage MF, above combination therapy may be first-line treatment (LOE 3, grade C). No consensus regarding maintenance therapy with phototherapy once in remission. Routine maintenance PUVA therapy not recommended; reserved for early relapse after initial 6

7 Citation Hamilton (2015) Economic evaluations of psoriasis treatment Lukacs (2015) Generalized granuloma annulare (GGA) Whitton (2015) Cochrane review Interventions for vitiligo Content, Methods, Recommendations course of phototherapy (LOE 2+, Grade B). Bath-water PUVA similar efficacy to oral PUVA and may be alternative in case PUVA cannot be administered (LOE 2-, Grade C). In pediatric MF and in hypopigmented MF, NB-UVB and PUVA may be tried (LOE 3, grade D). Key points: Systematic review of 37 studies reporting 71 comparisons: systemic treatment (45 studies), topical (22), phototherapies (14) and combination (four). Cost effectiveness of all therapies unclear due to variation in settings, perspective and design. Economic evaluations limited by: lack of high-quality short- and long-term head-to-head comparisons of the effectiveness, safety and adherence of different interventions; comparisons of interventions to placebo, with implicit comparisons of different therapies; absence of patient preferences; and barriers/facilitators to treatment. Primary and secondary integrated clinical and economic research is needed. Key points: Systematic review of individual case reports and small, uncontrolled series. No RCTs. Multiple treatment modalities for GGA were reported including topical and systemic steroids, PUVA and drug therapy. Insufficient evidence. Well-designed RCTs needed. Key points: Systematic review of 96 RCTs (4,512 total participants) of all interventions; three RCTs comparing NB-UVB with PUVA eligible for meta-analysis. Overall quality: Low with high risk of bias. NB-UVB has fewer side effects and is marginally better than PUVA. Proportion of participants achieving > 75% repigmentation favored NB-UVB compared to PUVA. NB-UVB group reported less nausea in three studies (N = 156) and erythema in two studies (N = 106), but not itching in two studies (N = 106). Very few studies only assessed children or included segmental vitiligo. There is a need for follow-up studies to assess permanence of repigmentation and high-quality RCTs using standardized measures that address quality of life. References Professional society guidelines/other: Ling TC, Clayton TH, Crawley J, et al. British Association of Dermatologists and British Photodermatology Group guidelines for the safe and effective use of psoralen-ultraviolet A therapy 2015 (Ling, 2016). Menter A, Korman NJ, 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 Audiol. January 2010; 62(1): Messenger AG, McKillop J, Farrant P, McDonagh AJ, Sladden M. British Association of Dermatologists 7

8 guidelines for the management of alopecia areata Br J Dermatol. 2012;166(5): Mehta D, Lim HW. Ultraviolet B phototherapy for psoriasis: review of practical guidelines. Am J Clin Dermatol. 2016;17(2): Morton C, Szeimies RM, Sidoroff A, et al. European Dermatology Forum Guidelines on topical photodynamic therapy. Eur J Dermatol. 2015;25(4): National Institute for Health and Clinical Excellence (NICE). Psoriasis: the assessment and management of psoriasis. October 2012; 61 p. (NICE clinical guideline; no. 153). Accessed April 24, Olsen EA, Hodak E, Anderson T, et al. Guidelines for phototherapy of mycosis fungoides and Sezary syndrome: a consensus statement of the United States Cutaneous Lymphoma Consortium. J Am Acad Dermatol. 2016;74(1): Sidbury R, Davis DM, Cohen DE, et al. guidelines of care for the management of atopic dermatitis. Section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014;71(2): Peer-reviewed references: 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. 2015; 31(1): Almutawa F, Alnomair N, Wang Y, Hamzavi I, Lim HW. Systematic review of UV-based therapy for psoriasis. Am J Clin Dermatol. 2013;14(2): Archier E, Devaux S, Castela E, et al. Efficacy of psoralen UV-A therapy vs. narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review. J Eur Acad Dermatol Venereol. 2012;26 Suppl 3: Bacigalupi RM, Postolova A, Davis RS. Evidence-based, non-surgical treatments for vitiligo: a review. Am J Clin Dermatol. 2012;13(4): Doi: / Bae JM, Jung HM, Hong BY, et al. Phototherapy for vitiligo: a systematic review and meta-analysis. JAMA Dermatol. March 29, 2017 [Epub ahead of print]. Doi: /jamadermatol Bailey EE, Ference EH, Alikhan A, Hession MT, Armstrong AW. Combination treatments for psoriasis: a systematic review and meta-analysis. Arch Dermatol. 2012; 148(4):

9 Chen X, Yang M, Cheng Y, Liu GJ, Zhang M. Narrow-band ultraviolet B phototherapy versus broad-band ultraviolet B or psoralen-ultraviolet A photochemotherapy for psoriasis. Cochrane Database Syst Rev. 2013; 10: CD Dogra S, Mahajan R. Phototherapy for mycosis fungoides. Indian J Dermatol Venereol Leprol. 2015; 81(2): Garritsen FM, Brouwer MW, Limpens J, Spuls PI. Photo(chemo) therapy in the management of atopic dermatitis: an updated systematic review with implications for practice and research. Br J Dermatol. 2014;170(3): Gutknecht M, Krensel M, Augustin M. Health economic analyses of psoriasis management: a systematic literature search. Arch Dermatol Res. 2016;308(9): Hamilton MP, Ntais D, Griffiths CE, Davies LM. Psoriasis treatment and management - a systematic review of full economic evaluations. Br J Dermatol. 2015; 172(3): Hayes Inc., Hayes Medical Technology Report. Phototherapy for early-stage mycosis fungoides.. Lansdale, Pa. Hayes Inc.; January 30, 2012, annual review. January 16, Koek MB, Buskens E, Bruijnzeel-Koomen CA, Sigurdsson V. Home ultraviolet B phototherapy for psoriasis: discrepancy between literature, guidelines, general opinions and actual use. Results of a literature review, a web search, and a questionnaire among dermatologists. Br J Dermatol. 2006;154(4): Lapolla W, Yentzer BA, Bagel J, Halvorson CR, Feldman SR. A review of phototherapy protocols for psoriasis treatment. J Am Acad Dermatol. 2011; 64(5): Lukacs J, Schliemann S, Elsner P. Treatment of generalized granuloma annulare - a systematic review. J Eur Acad Dermatol Venereol. 2015; 29(8): Malwade US, Jardine LA. Home- versus hospital-based phototherapy for the treatment of nonhaemolytic jaundice I infants at more than 37 weeks gestation. Cochrane Database Syst Rev. 2014;(6):CD Perez-Ferriols A, Aranegui B, Pujol-Montcusi JA, et al. Phototherapy in atopic dermatitis: a systematic review of the literature. Actas Dermosifiliogr. 2015;106(5): Rajpara AN, O'Neill JL, Nolan BV, Yentzer BA, Feldman SR. Review of home phototherapy. Dermatol Online J. 2010; 16(12): 2. 9

10 Sevrain M, Richard MA, Bametche T, et al. Treatment for palmoplantar pustular psoriasis: systematic literature review, evidence-based recommendations and expert opinion. J Eur Acad Dermatol Venereol. 2014;28 Suppl 5: Trott J, Gerber W, Hammes S, Ockenfels HM. The effectiveness of PUVA treatment in severe psoriasis is significantly increased by additional UV 308-nm excimer laser sessions. Eur J Dermatol. 2008; 18(1): Weberschock T, Strametz R, Lorenz M, et al. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2012; 9: Cd Whitton ME, Pinart M, Batchelor J, et al. Interventions for vitiligo. Cochrane Database Syst Rev. 2015; 2: Cd Williams HC, Grindlay DJ. What s new in atopic eczema? An analysis of the clinical significance of systematic reviews on atopic eczema published in 2006 and Clin Exp Dermatol. 2008;33(6): Xue J, Liu C, Liu Y. Photodynamic therapy as an alternative treatment for relapsed or refractory mycosis fungoides: a systemic review. Photodiagnosis Photodyn Ther. 2017;17: Yertzer BA, Yelverton CB, et al. Paradoxical effects of cost reduction measures in managed care systems for treatment of severe psoriasis. Dermatol Online J. April 15, 2009; 15(4):1. CMS National Coverage Determinations (NCDs): Treatment of Psoriasis. CMS website. Accessed April 21, Local Coverage Determinations (LCDs): L34966 Benign Skin Lesions. CMS website. Accessed April 21, L33918 Laser Treatment for Psoriasis. CMS website. Accessed April 21, Commonly submitted codes Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill accordingly. 10

11 CPT Code Description Comment Photodynamic therapy by external application of light to destroy premalignant and/or malignant lesions of the skin and adjacent mucosa (eg, lip) by activation of photosensitive drug(s), each phototherapy exposure session Photochemotherapy; psoralens and ultraviolet A (PUVA) Photochemotherapy (Goeckerman and/or PUVA) for severe photoresponsive dermatoses requiring at least 4-8 hours of care under direct supervision of the physician (includes application of medication and dressings) ICD-10 Code Description Comment L20.82 Flexural eczema L20.84 Intrinsic (allergic) eczema L28.0 Lichen simplex chronicus L28.1 Prurigo nodularis L40.0 Psoriasis vulgaris L40.1 Generalized pustular psoriasis L40.2 Acrodermatitis continua L40.3 Pustulosis palmaris et plantaris L40.4 Guttate psoriasis L40.8 Other psoriasis L40.9 Psoriasis, unspecified L41.0 Pityriasis lichenoides et varioliformis acuta L41.1 Pityriasis lichenoides chronica L41.3 Small plaque parapsoriasis L41.4 Large plaque parapsoriasis L41.5 Retiform parapsoriasis L41.8 Other parapsoriasis L41.9 Parapsoriasis, L42 Pityriasis rosea L43.0 Hypertrophic lichen planus L43.1 Bullous lichen planus L43.2 Lichenoid drug reaction L43.3 Subacute (active) lichen planus L43.8 Other lichen planus L43.9 Lichen planus, unspecified L57.8 Other skin L66.1 Lichen planopilaris L66.3 Perifolliculitis capitis abscedens L70.1 Acne vulgaris L70.2 Acne L70.3 Acne tropica L70.4 Infantile acne L70.5 Acne excoriee des jeunes L70.8 Other acne L70.9 Acne, unspecified L73.0 Acne, keloid L73.8 Other specified follicular disorders L80 Vitiligo 11

12 HCPCS Level II Code N/A Description Comment 12