The purpose of this evidence based analysis was to determine the effectiveness and safety of ultraviolet phototherapy for moderate-to-severe plaque psoriasis.
The specific research questions for the evidence review were as follows:
What is the safety of ultraviolet phototherapy for moderate-to-severe plaque psoriasis?
What is the effectiveness of ultraviolet phototherapy for moderate-to-severe plaque psoriasis?
Clinical Need: Target Population and Condition
Psoriasis is a common chronic, systemic inflammatory disease affecting the skin, nails and occasionally the joints and has a lifelong waning and waxing course. It has a worldwide occurrence with a prevalence of at least 2% of the general population, making it one of the most common systemic inflammatory diseases. The immune-mediated disease has several clinical presentations with the most common (85% - 90%) being plaque psoriasis.
Characteristic features of psoriasis include scaling, redness, and elevation of the skin. Patients with psoriasis may also present with a range of disabling symptoms such as pruritus (itching), pain, bleeding, or burning associated with plaque lesions and up to 30% are classified as having moderate-to-severe disease. Further, some psoriasis patients can be complex medical cases in which diabetes, inflammatory bowel disease, and hypertension are more likely to be present than in control populations and 10% also suffer from arthritis (psoriatic arthritis). The etiology of psoriasis is unknown but is thought to result from complex interactions between the environment and predisposing genes.
Management of psoriasis is related to the extent of the skin involvement, although its presence on the hands, feet, face or genitalia can present challenges. Moderate-to-severe psoriasis is managed by phototherapy and a range of systemic agents including traditional immunosuppressants such as methotrexate and cyclospsorin. Treatment with modern immunosuppressant agents known as biologicals, which more specifically target the immune defects of the disease, is usually reserved for patients with contraindications and those failing or unresponsive to treatments with traditional immunosuppressants or phototherapy.
Treatment plans are based on a long-term approach to managing the disease, patient’s expectations, individual responses and risk of complications. The treatment goals are several fold but primarily to:
1) improve physical signs and secondary psychological effects,
2) reduce inflammation and control skin shedding,
3) control physical signs as long as possible, and to
4) avoid factors that can aggravate the condition.
Approaches are generally individualized because of the variable presentation, quality of life implications, co-existent medical conditions, and triggering factors (e.g. stress, infections and medications). Individual responses and commitments to therapy also present possible limitations.
Ultraviolet phototherapy units have been licensed since February 1993 as a class 2 device in Canada. Units are available as hand held devices, hand and foot devices, full-body panel, and booth styles for institutional and home use. Units are also available with a range of ultraviolet A, broad and narrow band ultraviolet B (BB-UVB and NB-UVB) lamps. After establishing appropriate ultraviolet doses, three-times weekly treatment schedules for 20 to 25 treatments are generally needed to control symptoms.
Evidence-Based Analysis Methods
The literature search strategy employed keywords and subject headings to capture the concepts of 1) phototherapy and 2) psoriasis. The search involved runs in the following databases: Ovid MEDLINE (1996 to March Week 3 2009), OVID MEDLINE In-Process and Other Non-Indexed Citations, EMBASE (1980 to 2009 Week 13), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination/International Agency for Health Technology Assessment. Parallel search strategies were developed for the remaining databases. Search results were limited to human and English-language published between January 1999 and March 31, 2009. Search alerts were generated and reviewed for relevant literature up until May 31, 2009.
English language reports and human studies
Ultraviolet phototherapy interventions for plaque-type psoriasis
Reports involving efficacy and/or safety outcome studies
Original reports with defined study methodology
Standardized measurements on outcome events such as technical success, safety, effectiveness, durability, quality of life or patient satisfaction
Non-systematic reviews, letters, comments and editorials
Randomized trials involving side-to-side or half body comparisons
Randomized trials not involving ultraviolet phototherapy intervention for plaque-type psoriasis
Trials involving dosing studies, pilot feasibility studies or lacking control groups
Summary of Findings
A 2000 health technology evidence report on the overall management of psoriasis by The National Institute Health Research (NIHR) Health Technology Assessment Program of the UK was identified in the MAS evidence-based review. The report included 109 RCT studies published between 1966 and June 1999 involving four major treatment approaches – 51 on phototherapy, 32 on oral retinoids, 18 on cyclosporin and five on fumarates.. The absence of RCTs on methotrexate was noted as original studies with this agent had been performed prior to 1966.
Of the 51 RCT studies involving phototherapy, 22 involved UVA, 21 involved UVB, five involved both UVA and UVB and three involved natural light as a source of UV. The RCT studies included comparisons of treatment schedules, ultraviolet source, addition of adjuvant therapies, and comparisons between phototherapy and topical treatment schedules. Because of heterogeneity, no synthesis or meta-analysis could be performed. Overall, the reviewers concluded that the efficacy of only five therapies could be supported from the RCT-based evidence review: photochemotherapy or phototherapy, cyclosporin, systemic retinoids, combination topical vitamin D3 analogues (calcipotriol) and corticosteroids in combination with phototherapy and fumarates. Although there was no RCT evidence supporting methotrexate, it’s efficacy for psoriasis is well known and it continues to be a treatment mainstay.
The conclusion of the NIHR evidence review was that both photochemotherapy and phototherapy were effective treatments for clearing psoriasis, although their comparative effectiveness was unknown. Despite the conclusions on efficacy, a number of issues were identified in the evidence review and several areas for future research were discussed to address these limitations. Trials focusing on comparative effectiveness, either between ultraviolet sources or between classes of treatment such as methotrexate versus phototherapy, were recommended to refine treatment algorithms. The need for better assessment of cost-effectiveness of therapies to consider systemic drug costs and costs of surveillance, as well as drug efficacy, were also noted. Overall, the authors concluded that phototherapy and photochemotherapy had important roles in psoriasis management and were standard therapeutic options for psoriasis offered in dermatology practices.
The MAS evidence-based review focusing on the RCT trial evidence for ultraviolet phototherapy management of moderate-to-severe plaque psoriasis was performed as an update to the NIHR 2000 systemic review on treatments for severe psoriasis. In this review, an additional 26 RCT reports examining phototherapy or photochemotherapy for psoriasis were identified. Among the studies were two RCTs comparing ultraviolet wavelength sources, five RCTs comparing different forms of phototherapy, four RCTs combining phototherapy with prior spa saline bathing, nine RCTs combining phototherapy with topical agents, two RCTs combining phototherapy with the systemic immunosuppressive agents methotrexate or alefacept, one RCT comparing phototherapy with an additional light source (the excimer laser), and one comparing a combination therapy with phototherapy and psychological intervention involving simultaneous audiotape sessions on mindfulness and stress reduction. Two trials also examined the effect of treatment setting on effectiveness of phototherapy, one on inpatient versus outpatient therapy and one on outpatient clinic versus home-based phototherapy.
The conclusions of the MAS evidence-based review are outlined in Table ES1. In summary, phototherapy provides good control of clinical symptoms in the short term for patients with moderate-to-severe plaque-type psoriasis that have failed or are unresponsive to management with topical agents. However, many of the evidence gaps identified in the NIHR 2000 evidence review on psoriasis management persisted. In particular, the lack of evidence on the comparative effectiveness and/or cost-effectiveness between the major treatment options for moderate-to-severe psoriasis remained. The evidence on effectiveness and safety of longer term strategies for disease management has also not been addressed. Evidence for the safety, effectiveness, or cost-effectiveness of phototherapy delivered in various settings is emerging but is limited. In addition, because all available treatments for psoriasis – a disease with a high prevalence, chronicity, and cost – are palliative rather than curative, strategies for disease control and improvements in self-efficacy employed in other chronic disease management strategies should be investigated.
RCT Evidence for Ultraviolet Phototherapy Treatment of Moderate-To-Severe Plaque Psoriasis
Phototherapy is an effective treatment for moderate-to-severe plaque psoriasis
Narrow band PT is more effective than broad band PT for moderate-to-severe plaque psoriasis
Oral-PUVA has a greater clinical response, requires less treatments and has a greater cumulative UV irradiation dose than UVB to achieve treatment effects for moderate-to-severe plaque psoriasis
Spa salt water baths prior to phototherapy did increase short term clinical response of moderate-to-severe plaque psoriasis but did not decrease cumulative UV irradiation dose
Addition of topical agents (vitamin D3 calcipotriol) to NB-UVB did not increase mean clinical response or decrease treatments or cumulative UV irradiation dose
Methotrexate prior to NB-UVB in high need psoriasis patients did significantly increase clinical response, decrease number of treatment sessions and decrease cumulative UV irradiation dose
Phototherapy following alefacept did increase early clinical response in moderate-to-severe plaque psoriasis
Effectiveness and safety of home NB-UVB phototherapy was not inferior to NB-UVB phototherapy provided in a clinic to patients with psoriasis referred for phototherapy. Treatment burden was lower and patient satisfaction was higher with home therapy and patients in both groups preferred future phototherapy treatments at home
Ontario Health System Considerations
A 2006 survey of ultraviolet phototherapy services in Canada identified 26 phototherapy clinics in Ontario for a population of over 12 million. At that time, there were 177 dermatologists and 50 geographic regions in which 28% (14/50) provided phototherapy services. The majority of the phototherapy services were reported to be located in densely populated areas; relatively few patients living in rural communities had access to these services. The inconvenience of multiple weekly visits for optimal phototherapy treatment effects poses additional burdens to those with travel difficulties related to health, job, or family-related responsibilities.
Physician OHIP billing for phototherapy services totaled 117,216 billings in 2007, representing approximately 1,800 patients in the province treated in private clinics. The number of patients treated in hospitals is difficult to estimate as physician costs are not billed directly to OHIP in this setting. Instead, phototherapy units and services provided in hospitals are funded by hospitals’ global budgets. Some hospitals in the province, however, have divested their phototherapy services, so the number of phototherapy clinics and their total capacity is currently unknown.
Technological advances have enabled changes in phototherapy treatment regimens from lengthy hospital inpatient stays to outpatient clinic visits and, more recently, to an at-home basis. When combined with a telemedicine follow-up, home phototherapy may provide an alternative strategy for improved access to service and follow-up care, particularly for those with geographic or mobility barriers. Safety and effectiveness have, however, so far been evaluated for only one phototherapy home-based delivery model. Alternate care models and settings could potentially increase service options and access, but the broader consequences of the varying cost structures and incentives that either increase or decrease phototherapy services are unknown.
The focus of the current economic analysis was to characterize the costs associated with the provision of NB-UVB phototherapy for plaque-type, moderate-to-severe psoriasis in different clinical settings, including home therapy. A literature review was conducted and no cost-effectiveness (cost-utility) economic analyses were published in this area.
Hospital, Clinic, and Home Costs of Phototherapy
Costs for NB-UVB phototherapy were based on consultations with equipment manufacturers and dermatologists. Device costs applicable to the provision of NB-UVB phototherapy in hospitals, private clinics and at a patient’s home were estimated. These costs included capital costs of purchasing NB-UVB devices (amortized over 15-20 years), maintenance costs of replacing equipment bulbs, physician costs of phototherapy treatment in private clinics ($7.85 per phototherapy treatment), and medication and laboratory costs associated with treatment of moderate-to-severe psoriasis.
NB-UVB phototherapy services provided in a hospital setting were paid for by hospitals directly. Phototherapy services in private clinic and home settings were paid for by the clinic and patient, respectively, except for physician services covered by OHIP. Indirect funding was provided to hospitals as part of global budgeting and resource allocation. Home therapy services for NB-UVB phototherapy were not covered by the MOHLTC. Coverage for home-based phototherapy however, was in some cases provided by third party insurers.
Device costs for NB-UVB phototherapy were estimated for two types of phototherapy units: a “booth unit” consisting of 48 bulbs used in hospitals and clinics, and a “panel unit” consisting of 10 bulbs for home use. The device costs of the booth and panel units were estimated at approximately $18,600 and $2,900, respectively; simple amortization over 15 and 20 years implied yearly costs of approximately $2,500 and $150, respectively. Replacement cost for individual bulbs was about $120 resulting in total annual cost of maintenance of about $8,640 and $120 for booth and panel units, respectively.
Estimated Total Costs for Ontario
Average annual cost per patient for NB-UVB phototherapy provided in the hospital, private clinic or at home was estimated to be $292, $810 and $365 respectively. For comparison purposes, treatment of moderate-to-severe psoriasis with methotrexate and cyclosporin amounted to $712 and $3,407 annually per patient respectively; yearly costs for biological drugs were estimated to be $18,700 for alefacept and $20,300 for etanercept-based treatments.
Total annual costs of NB-UVB phototherapy were estimated by applying average costs to an estimated proportion of the population (age 18 or older) eligible for phototherapy treatment. The prevalence of psoriasis was estimated to be approximately 2% of the population, of which about 85% was of plaque-type psoriasis and approximately 20% to 30% was considered moderate-to-severe in disease severity. An estimate of 25% for moderate-to-severe psoriasis cases was used in the current economic analysis resulting in a range of 29,400 to 44,200 cases. Approximately 21% of these patients were estimated to be using NB-UVB phototherapy for treatment resulting in a number of cases in the range between 6,200 and 9,300 cases. The average (7,700) number of cases was used to calculate associated costs for Ontario by treatment setting.
Total annual costs were as follows: $2.3 million in a hospital setting, $6.3 million in a private clinic setting, and $2.8 million for home phototherapy. Costs for phototherapy services provided in private clinics were greater ($810 per patient annually; total of $6.3 million annually) and differed from the same services provided in the hospital setting only in terms of additional physician costs associated with phototherapy OHIP fees.
Psoriasis, ultraviolet radiation, phototherapy, photochemotherapy, NB-UVB, BB-UVB PUVA