Assessment of efficacy and safety of UV-based therapy for psoriasis: a network meta-analysis of randomized controlled trials.

BACKGROUND: Previous studies have proven that ultraviolet (UV)-based phototherapy, including UVB or psoralen UVA (PUVA), and their combination therapies, is effective for psoriasis treatment. OBJECTIVE: To compare the clinical efficacy and adverse events (AEs) of different UV-based phototherapy in psoriasis. METHODS: PubMed, Cochrane Library, Scopus and Embase were systematically searched. A random-effect model network meta-analysis with frequentist framework was performed, and results were reported as risk ratios (RRs) with 95% CI. The main variable for assessing effectiveness and safety are PASI 75 response and withdrawal due to AEs. Ranking effects were calculated by surface under the cumulative ranking analysis (SUCRA). RESULTS: Thirty-two studies involving a total of 2120 psoriasis patients were included in this network meta-analysis. Overall, no significant difference was reported with respect to withdrawal due to AEs or incidence of erythema. The relatively safest strategy was combined adjuvant therapy with PUVA (cPUVA), especially PUVA combined with calcium/vitamin D derivatives (RR 0.98, 95% CI [0.30-3.17], SUCRA = 80.8%). Both cPUVA (RR 1.39, 95% CI [1.00- 1.94]) and combined adjuvant therapy with UVB (cUVB) (RR 1.27, 95% CI [1.03-1.57]) showed a superior effect than the monotherapy of UVA or UVB, respectively. PUVA combined with vitamin D and its derivatives (PAVD) ranked highest concerning clinical effect and safety (clusterank value = 7393.2). CONCLUSIONS: The efficacy of all the combination therapy regimens was significantly superior to that of UV monotherapy, without significant differences in tolerability and safety. cUVB and cPUVA, and particularly the combination of UVA with calcium/vitamin D derivatives, was ranked as the overall safest and most effective phototherapy method.

Differences in phototherapy among skin diseases and genders in real-life conditions-A retrospective analysis of the cumulative doses, numbers of sessions, side effects and costs in 561 patients.

BACKGROUND: Phototherapy has been a mainstay therapy for dermatological diseases since more than a century. Although phototherapy is still extensively used and some recommendations exist, only scarce data are available addressing disease-specific differences in cumulative doses, treatment durations and costs. Knowledge of such differences could help to avoid over-/undertreatment, predict treatment duration and costs. Therefore, we sought to determine differences in cumulative doses, numbers of sessions, side effects and costs among different skin diseases and genders in real-life conditions. METHODS: In this single-centre, retrospective study, patients treated with phototherapy between March 2014 and April 2019 were classified into seven diagnostic groups and analysed according to the study goals. RESULTS: Out of 561 patients (age 53.9 ± 20.3 yrs; 52.9% females), 83.7% percent were treated with cabin NB-UVB (mean cumulative dose 17.79 ± 17.11 J/cm2 ). Patients with vitiligo and psoriasis were treated with significantly higher cumulative NB-UVB doses (cabin, local) in comparison with the five other diagnostic groups as were males in comparison with females. Consequently, significantly higher UV-related costs resulted in patients with vitiligo, psoriasis and males. Patients with atopic dermatitis and pruritus were treated with significantly higher cumulative UVA1 doses compared to patients with non-atopic eczema. The complication rate (pooled from all UV modalities) in our population was 3.8% (erythema 3.4%, aggravated itch 0.4% and worsening of symptoms 0.2%). CONCLUSIONS: Our results demonstrate that cumulative doses and phototherapy-related costs vary strongly among skin diseases-a fact not adequately considered in recommendations. A more disease-specific stratification of phototherapy could not only help to optimize outcomes, but also to facilitate comparability of clinical trials using phototherapy.

Home-based narrowband UVB, topical corticosteroid or combination for children and adults with vitiligo: HI-Light Vitiligo three-arm RCT.

BACKGROUND: Systematic reviews suggest that narrowband ultraviolet B light combined with treatments such as topical corticosteroids may be more effective than monotherapy for vitiligo. OBJECTIVE: To explore the clinical effectiveness and cost-effectiveness of topical corticosteroid monotherapy compared with (1) hand-held narrowband ultraviolet B light monotherapy and (2) hand-held narrowband ultraviolet B light/topical corticosteroid combination treatment for localised vitiligo. DESIGN: Pragmatic, three-arm, randomised controlled trial with 9 months of treatment and a 12-month follow-up. SETTING: Sixteen UK hospitals - participants were recruited from primary and secondary care and the community. PARTICIPANTS: Adults and children (aged ≥ 5 years) with active non-segmental vitiligo affecting ≤ 10% of their body area. INTERVENTIONS: Topical corticosteroids [mometasone furoate 0.1% (Elocon®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) plus dummy narrowband ultraviolet B light]; narrowband ultraviolet B light (narrowband ultraviolet B light plus placebo topical corticosteroids); or combination (topical corticosteroids plus narrowband ultraviolet B light). Topical corticosteroids were applied once daily on alternate weeks and narrowband ultraviolet B light was administered every other day in escalating doses, with a dose adjustment for erythema. All treatments were home based. MAIN OUTCOME MEASURES: The primary outcome was self-assessed treatment success for a chosen target patch after 9 months of treatment ('a lot less noticeable' or 'no longer noticeable' on the Vitiligo Noticeability Scale). Secondary outcomes included blinded assessment of primary outcome and percentage repigmentation, onset and maintenance of treatment response, quality of life, side effects, treatment burden and cost-effectiveness (cost per additional successful treatment). RESULTS: In total, 517 participants were randomised (adults, n = 398; and children, n = 119; 52% male; 57% paler skin types I-III, 43% darker skin types IV-VI). At the end of 9 months of treatment, 370 (72%) participants provided primary outcome data. The median percentage of narrowband ultraviolet B light treatment-days (actual/allocated) was 81% for topical corticosteroids, 77% for narrowband ultraviolet B light and 74% for combination groups; and for ointment was 79% for topical corticosteroids, 83% for narrowband ultraviolet B light and 77% for combination. Target patch location was head and neck (31%), hands and feet (32%), and rest of the body (37%). Target patch treatment 'success' was 20 out of 119 (17%) for topical corticosteroids, 27 out of 123 (22%) for narrowband ultraviolet B light and 34 out of 128 (27%) for combination. Combination treatment was superior to topical corticosteroids (adjusted risk difference 10.9%, 95% confidence interval 1.0% to 20.9%; p = 0.032; number needed to treat = 10). Narrowband ultraviolet B light was not superior to topical corticosteroids (adjusted risk difference 5.2%, 95% confidence interval -4.4% to 14.9%; p = 0.290; number needed to treat = 19). The secondary outcomes supported the primary analysis. Quality of life did not differ between the groups. Participants who adhered to the interventions for > 75% of the expected treatment protocol were more likely to achieve treatment success. Over 40% of participants had lost treatment response after 1 year with no treatment. Grade 3 or 4 erythema was experienced by 62 participants (12%) (three of whom were using the dummy) and transient skin thinning by 13 participants (2.5%) (two of whom were using the placebo). We observed no serious adverse treatment effects. For combination treatment compared with topical corticosteroids, the unadjusted incremental cost-effectiveness ratio was £2328.56 (adjusted £1932) per additional successful treatment (from an NHS perspective). LIMITATIONS: Relatively high loss to follow-up limits the interpretation of the trial findings, especially during the post-intervention follow-up phase. CONCLUSION: Hand-held narrowband ultraviolet B light plus topical corticosteroid combination treatment is superior to topical corticosteroids alone for treatment of localised vitiligo. Combination treatment was relatively safe and well tolerated, but was effective in around one-quarter of participants only. Whether or not combination treatment is cost-effective depends on how much decision-makers are willing to pay for the benefits observed. FUTURE WORK: Development and testing of new vitiligo treatments with a greater treatment response and longer-lasting effects are needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN17160087. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 64. See the NIHR Journals Library website for further project information.

The Home Interventions and Light therapy for the treatment of vitiligo (HI-Light Vitiligo) trial aimed to find out whether or not treating vitiligo at home with a narrowband ultraviolet B light, either by itself or with a steroid ointment, is better than treatment using a steroid ointment only. We enrolled 517 children (aged ≥ 5 years) and adults who had small, active (i.e. recently changing) patches of vitiligo into the study. Participants received one of three possible treatment options: steroid ointment (plus dummy light), hand-held narrowband ultraviolet B light therapy (plus placebo ointment) or both treatments used together. We asked participants to judge how noticeable their target vitiligo patch was after 9 months of treatment. We considered the treatment to be successful if the participants' responses were either 'a lot less noticeable' or 'no longer noticeable'. The results showed that using both treatments together was better than using a steroid ointment on its own. Around one-quarter of participants (27%) who used both treatments together said that their vitiligo was either 'no longer noticeable' or 'a lot less noticeable' after 9 months of treatment. This was compared with 17% of those using steroid ointment on its own and 22% of those using narrowband ultraviolet B light on its own. All treatments were able to stop the vitiligo from spreading. Patches on the hands and feet were less likely to respond to treatment than patches on other parts of the body. The trial found that the vitiligo tended to return once treatments were stopped, so ongoing intermittent treatment may be needed to maintain the treatment response. The treatments were found to be relatively safe and easy to use, but light treatment required a considerable time commitment (approximately 20 minutes per session, two or three times per week). This trial showed that using steroid ointment and narrowband ultraviolet B light together is likely to be better than steroid ointment alone for people with small patches of vitiligo. Steroid ointment alone can still be effective for some people and remains a useful treatment that is able to stop vitiligo from spreading. The challenge is to make hand-held narrowband ultraviolet B light treatment available as normal care in the NHS for people with vitiligo.

Efficacy assessment of UVA1 and narrowband UVB for treatment of scalp psoriasis.

To compare the efficacy and safety of UVA1 and narrowband UVB (NB-UVB) therapy in the treatment of scalp psoriasis. Patients with scalp psoriasis were randomly assigned to either UVA1 or NB-UVB therapy. Both treatments were performed three times weekly for 6 weeks. Clinical efficacy was evaluated by using Psoriasis Scalp Severity Index (PSSI), and patient-reported quality of life (QoL) was assessed by Dermatology Life Quality Index (DLQI). Totally 68 patients completed the study. Both UVA1 and NB-UVB phototherapy achieved a statistically significant reduction of PSSI and DLQI scores at the end of the treatment period. Compared with the NB-UVB group, the significantly greater improvements occurred in UVA1 treatment group at week 3, although differences declined thereafter through week 10. Both UVA1 and NB-UVB therapy were well-tolerated in this study, and the occurrence of adverse events (AEs) was uncommon. Both UVA1 and NB-UVB phototherapy could offer relief of scalp symptoms in patients with scalp involvement. Furthermore, UVA1 treatment could improve the clinical manifestations and QoL more quickly than NB-UVB therapy.

Malignancy rates in a large cohort of patients with systemically treated psoriasis in a managed care population.

BACKGROUND: Moderate to severe psoriasis often requires treatment with systemic agents, many of which have immunosuppressive properties and could increase cancer risk, including nonmelanoma skin cancer (NMSC). OBJECTIVE: We sought to estimate the overall malignancy rate (excluding NMSC) and NMSC rate among 5889 patients with systemically treated psoriasis. METHODS: We identified a cohort of adult Kaiser Permanente Northern California health plan members with psoriasis diagnosed from 1998 to 2011 and treated with at least 1 systemic antipsoriatic agent and categorized them into ever-biologic or nonbiologic users. Malignancy rates were calculated per 1000 person-years of follow-up with 95% confidence intervals (CI). Crude and confounder-adjusted hazard ratios (aHRs) were calculated using Cox regression. RESULTS: Most biologic-exposed members were treated with TNF-alfa inhibitors (n = 2214, 97%). Overall incident cancer rates were comparable between ever-biologic as compared to nonbiologic users (aHR 0.86, 95% CI 0.66-1.13). NMSC rates were 42% higher among individuals ever exposed to a biologic (aHR 1.42, 95% CI 1.12-1.80), largely driven by increased cutaneous squamous cell carcinoma risk (aHR 1.81, 95% CI 1.23-2.67). LIMITATIONS: No information was available on disease severity. CONCLUSION: We found increased incidence of cutaneous squamous cell carcinoma among patients with systemically treated psoriasis who were ever exposed to biologics, the majority of which were TNF-alfa inhibitors. Increased skin cancer surveillance in this population may be warranted.

Phototherapy and photochemotherapy for psoriasis.

Phototherapy is a first-line option for the treatment of moderate to severe psoriasis. Systematic reviews indicate near comparable efficacy of the different forms of phototherapy. Localized phototherapy can be an adjunctive treatment of recalcitrant plaques during systemic treatment of psoriasis. More than 200 psoralen-UV-A therapy treatment sessions is associated with an increased risk of keratinocytic cancers, whereas no increased risk has been demonstrated for narrow-band UV-B therapy. The mechanism of action of phototherapy in psoriasis is via inhibition of keratinocyte proliferation; induction of apoptosis in keratinocytes, dendritic, and T cells; and inhibition of Th1 and Th17 pathways, but activation of Th2.

Summary of the Dutch S3-guidelines on the treatment of psoriasis 2011. Dutch Society of Dermatology and Venereology.

This document provides a summary of the Dutch S3-guidelines on the treatment of psoriasis. These guidelines were finalized in December 2011 and contain unique chapters on the treatment of psoriasis of the face and flexures, childhood psoriasis as well as the patient's perspective on treatment. They also cover the topical treatment of psoriasis, photo(chemo)therapy, conventional systemic therapy and biological therapy.

[Psoriasis and cardiovascular risk factors].

Psoriasis is a common inflammatory skin disease which may dramatically affect patients' lives. This chronic disease is characterized by a protracted course of alternating remissions and relapses. In recent years, the attention of researchers has focused on the association between psoriasis and cardiovascular disease risk factors. This review summarizes the literature on this topic with an emphasis on research conducted in Israel.

Efficacy and safety assessment of a novel ultraviolet C device for treating corneal bacterial infections.

BACKGROUND: A prototype solid-state Ultraviolet-C (UVC) LED device may be useful in the treatment of corneal microbial infections, as UVC is commonly used for eradicating bacteria, fungi and viruses in other settings. This study assessed the efficacy of 265 nm UVC from this LED, on four different bacterial strains, and investigated the consequences of corresponding exposures on human corneal epithelial cells in vitro. METHODS: Agar plate lawns of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Streptococcus pyogenes were exposed to a 4.5 mm diameter 265 nm UVC beam at a fixed intensity and distance, for 30, 5, 4, 2 and 1 seconds. Growth inhibition was assessed with a BioRad Gel imager, and the diameter of lucent areas of bacterial inhibition recorded. Human corneal epithelial cells cultured on glass cover-slips were exposed to corresponding doses of UVC from the same device. Live/dead staining was performed and the results quantified. RESULTS: There was 100% inhibition of growth for all bacteria tested, at all exposure times. A 30-second exposure of human corneal epithelium to UVC gave no statistically significant decrease (P = 0.877) in the ratio of live to dead cells when compared to control cultures. CONCLUSION: The results confirmed that a 1 second exposure to germicidal UVC from this LED source was sufficient to inhibit microbial proliferation in the four bacterial strains tested in vitro. The literature suggests UVC at this dose could potentially be beneficial in treating corneal surface infections, without causing significant adverse effects, supported by our findings in human corneal epithelium exposed to UVC.

What impact would effective solarium regulation have in Australia?

1) Leading international health organisations are concerned about high use of artificial tanning services and the associated risk of skin cancer. Similar concerns exist about the growing Australian solarium industry. 2) Pre-teens appear to be ignoring sun safety messages in their desire to tan and use solaria. 3) A significantly elevated risk of melanoma exists among people exposed to artificial ultraviolet radiation; the risk is higher for those younger than 35 years at first solarium use. For all users, the risk of squamous cell carcinoma is more than doubled compared with non-users. 4) We estimated the numbers of new melanoma cases and melanoma-related deaths attributable to solarium use by younger people in the five most populous Australian states and indirectly quantified potential costs to the health system that could be saved by effective regulation of the solarium industry. 5) Annually, 281 new melanoma cases, 43 melanoma-related deaths and 2572 new cases of squamous cell carcinoma were estimated to be attributable to solarium use. 6) The annual cost to the health system--predominantly Medicare Australia--for these avoidable skin cancer cases and deaths is about $3 million. 7) By successfully enforcing solarium regulations that ban use by people younger than 18 years or with fair skin, favourable health and cost benefits could be expected.

Patients with moderate-to-severe plaque psoriasis preferred oral therapies to phototherapies: a preference assessment based on clinical scenarios with trade-off questions.

OBJECTIVE: The importance of validly identifying and incorporating patients' views for improving health care is generally acknowledged. Common approaches to assess patients' preferences are based on the quality adjusted life year (QALY) framework, but this ignores a number of aspects that may be relevant. As an alternative, we assessed patients' treatment preferences and trade-offs for five common systemic therapies for psoriasis. STUDY DESIGN AND SETTING: Twenty-nine patients with moderate-to-severe psoriasis expressed treatment preferences for five oral and phototherapies and indicated the relative importance of various treatment attributes, such as adverse effects, discomforts, and safety measures. In a structured interview, they were presented with clinical scenarios that contained descriptions of process and outcome characteristics and illustrations of the anticipated treatment benefit. RESULTS: Over all paired comparisons, methotrexate (33%), cyclosporin (30%), acitretin (15%), UV-B (14%), and PUVA (8%) were preferred to the other treatment. Patients were willing to trade-off their initial preference for more improvement of psoriasis. CONCLUSIONS: Psoriasis patients generally prefer oral to phototherapies and consider most adverse effects and several discomforts important for selecting treatment. Our scenario-based structured interview approach to treatment preferences allowed us to incorporate a broad spectrum of potentially relevant decision components in a clinically meaningful way.

Traditional therapies in the management of moderate to severe chronic plaque psoriasis: an assessment of the benefits and risks.

Psoriasis is a chronic, recurrent disease that affects between 1% and 3% of the population. Patients with moderate to severe disease generally require phototherapy (e.g. narrowband ultraviolet B radiation), photochemotherapy (oral psoralen plus ultraviolet A radiation) or systemic agents (e.g. ciclosporin, methotrexate, oral retinoids, fumaric acid esters) to control their disease adequately. In general, these therapeutic modalities have proven to be highly effective in the treatment of psoriasis. However, potentially serious toxicities can limit their long-term use. Given that there is no standard therapeutic approach for patients with moderate to severe psoriasis, the benefits and risks of phototherapy, photochemotherapy and systemic therapy must be weighed carefully for each patient, and treatment individualized accordingly. This review summarizes the benefits and risks of traditional, nonbiological therapies for moderate to severe chronic plaque psoriasis.

Taking treatment to the patient: development of a home TL-01 ultraviolet B phototherapy service.

BACKGROUND: While most patients requiring phototherapy can attend for hospital-based out-patient ultraviolet (UV) B therapy, a significant number cannot attend because of geographical, work, economic and other reasons. OBJECTIVES: To determine whether there was a need for home phototherapy in the Tayside area and, if so, to establish protocols and then to assess if such a service would be workable. METHODS: Patients referred from dermatology out-patient clinics in Tayside for narrow-band UVB (TL-01) phototherapy completed a pilot questionnaire that was followed by a two-phase project. In phase 1, patients with psoriasis were trained to use the home phototherapy equipment (HoPE) within the hospital department under nursing supervision while a teaching package and protocols were developed. In phase 2, home phototherapy was made available for patient use in the community, supported by a specialist home phototherapy nurse. Waldmann UV100 home therapy units were used, with accurate dosimetry. Detailed treatment records were kept and questionnaires were used to assess acceptability and costs of therapy. RESULTS: Fifty-two pilot questionnaires were completed. Forty-two per cent of respondents found hospital phototherapy inconvenient and 75% felt phototherapy at home would be helpful. In phase 1, seven of 10 patients trained to use the HoPE completed therapy with the HoPE unit alone, reaching minimal residual activity (MRA) or clearance in a median of 18 exposures (median dose 10.38 J cm-2). In phase 2, 32 courses of home phototherapy were given to 30 patients. Of 23 with psoriasis, 18 reached clearance or MRA in a median of 22.5 exposures (median dose 9.84 J cm-2). Although self-reported erythema rates appeared higher than expected, all post-treatment questionnaire respondents would choose home phototherapy over hospital therapy if required in the future. CONCLUSIONS: UVB (TL-01) home phototherapy is a useful practical development that has fulfilled a need in our catchment area. Where appropriate training and support teams are available it appears to be similar in effectiveness to hospital therapy, to be safe and to be cost-effective for patients.

[The UV record. Document for quality control, therapy planning and risk assessment in dermatologic photo- and photochemotherapy]. / Der UV-Pass. Instrument der Qualitätskontrolle, Therapieplanung und Risikoabschätzung bei dermatologischer Photo- und Photochemotherapie.

Ultraviolet (UV-) radiation therapy as a mono- or combination therapy (UV-A, UV-A1, UV-B, SUP, UV-B311) or as photochemotherapy with photosensitization (systemic PUVA-, bath PUVA-, topical PUVA-therapy) are successfully used for the treatment of several dermatological disorders. Long-term side effects of natural UV (sun light) include photoaging and induction of skin tumors. At present, the relevance of in-vitro findings of potential tumor induction in animals through therapeutic levels of UV radiation is a matter of debate. To assess these risks, information on treated location, kind of UV radiation and cumulative UV doses are required. Practically this information is barely accessible. This makes decisions on possible therapies difficult. To solve this problem we propose to use an "UV pass". At the end of each UV radiation cycle, the body location, the type of radiation and the cumulative dose are documented and this pass is given to the patient. This will improve the information transfer if the doctor is changed, as well as facilitating decisions about certain therapies and calculation of long-term risks of UV radiation. Finally it will improve the quality of UV photo- and photochemotherapy.

An assessment of potential problems of home phototherapy treatment of psoriasis.

Very little has been reported about how patients use home ultraviolet B (UVB) phototherapy. A survey of thirty-one patients who were prescribed a home UVB phototherapy unit to treat psoriasis was performed as a pilot study of home UVB phototherapy usage; twenty-two patients responded. Generally, respondents reported home UVB phototherapy to be very helpful for their psoriasis. We conclude that home UVB is an effective and appropriate treatment for many patients with psoriasis, but screening and education of candidates for home UVB phototherapy is important to ensure compliance with the treatment program.

Ultraviolet radiation for treatment of cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) often begins as limited patches and plaques on the skin that can be effectively treated with ultraviolet radiation. Many long-term remissions and cures have been well documented with the use of ultraviolet radiation alone for stage I CTCL. The side effects of this treatment are minimal.