A Randomized Controlled Trial with a Medical Device Containing Sodium Hyaluronate and Nicotinic Acid to Increase the Efficacy of Ultraviolet Phototherapy in Psoriasis

Psoriasis is a chronic autoimmune disorder, with a prevalence in adults that varies from 0.91% (USA) to 8.5% (Norway) [1], that considerably decreases the health-related quality of life. Although chronic plaque psoriasis, which is the most common type of psoriasis, can be diagnosed without major difficulties, the disease may still be underdiagnosed and undertreated [2‐4]. Several treatment options are available for psoriasis. Topical therapy is typically chosen in mild to moderate manifestations, with corticosteroids [5], vitamin D3 analogues [6] and the combination thereof [7] shown to be effective. In more severe cases, systemic therapy is indicated, most commonly with immunosuppressants (e.g., methotrexate, cyclosporine), immune modulators (e.g., leflunomide), and biological agents [8‐10]. In addition to these different pharmacological approaches, phototherapy is also considered to be a safe and effective method for the treatment of psoriasis. Many types of phototherapy use ultraviolet B (UVB) light [11], with the most effective wavelengths of the UVB spectrum being between 310 and 320 nm. Wavelengths of 280–300 nm have a reduced therapeutic effect and cause severe and unnecessary skin inflammation [12‐14]. The efficacy of phototherapy is influenced by the reflection of UV light from the skin surface, with dry, scaly skin reflecting more UV light than healthy skin; accordingly, a lower proportion of the radiation penetrates the psoriatic lesions, thereby decreasing the therapeutic effect. Thus, the efficacy of phototherapy might be improved by optimizing skin transmittance and irradiating at a wavelength of 310–320 nm. Different topicals have been tested with this goal (e.g., petrolatum, basis cream, glycerine, olive oil, aqueous cream, Eucerin skin products, Kamillosan ointment, paraffin ointment, mineral oil [15‐17]); however, some preparations had unfavorable cosmetic properties or absorbed light in the UV spectrum, requiring higher UVB doses to be effective.

The aims of this study was to test a novel medical device containing polyethylene glycol 4000, nicotinic acid, and sodium hyaluronate (UV Fotogel®) for the enhancement of phototherapy in psoriatic patients and to monitor its efficacy and tolerability. The investigation was performed in two parts. In Part I, the preparation was applied before the patient received narrow-band UVB therapy (NB-UVB), and in Part II, UV Fotogel was used by the patients prior to going sunbathing.

In Part I, one patient left the study due to progression of the disease (systemic therapy was required). Cessation of desquamation was observed in three patients by the fourth visit. The study was terminated for an additional nine patients at visit 4, 18 patients at visit 5, and eight patients at visit 6 as these patients had L-PSI scores < 4. With the exception of one patient, the improvement leading to termination of the study was detected on the UV Fotogel-treated side (Fig. 2).

In Part II, one patient decided to terminate his enrollment after visit 2. Another patient quit due to an adverse effect of the treatment (burning sensation) but attended the final visit. Desquamation had ceased in 40 patients by visit 3 and in the remaining four patients by visit 4 (Fig. 2).

The treatment of psoriasis depends on the severity of the disease. In mild to moderate psoriasis, topical therapy is indicated alone or in combination with UV phototherapy.

NB-UVB is currently the first-line phototherapy for stable plaque psoriasis. Compared to broadband UVB phototherapy, NB-UVB results in a faster reduction of lesions, with longer remissions expected [10]. Nevertheless, careful design of the therapy is necessary, as UV light might lead to cataracts, photodermatitis, and photoaging. Carcinogenesis is also a potential risk [18]. However, the efficacy of UVB therapy can potentially be increased by combining it with different topical and systemic agents. Historically, UVB phototherapy was combined with coal tar; however, this preparation smells, stains skin, has irritative and carcinogenic properties, and may block UVB rays. Dithranol has also applied to the skin to improve the efficacy of UVB therapy, but this preparation is associated with an increased risk of irritation [19]. Other topical treatments used just before UV irradiation (e.g., different emollients, ichthyol, and calcipotriol) block the penetration of UV light, thereby decreasing the therapeutical efficacy of the phototherapy [20‐22]. In the present study, we combined NB-UVB with a preparation which, when used alone, does not have a therapeutic effect, but which may enhance the efficacy of phototherapy.

The optical properties of the psoriatic skin differ from those of normal skin [17, 23]. The multiple air–keratin interfaces in psoriatic scales allow reflection and refraction of incident radiation, and the lesions, thereby, act as a partial optic barrier. Successful treatment of psoriasis with UV-light requires adequate penetration of the radiation to at least the level of viable epidermal cells.

Compared to other combination therapies, there appear to be fewer possibilities to modify the transmission of UVB. A saltwater shower and application of lipophilic compounds may be beneficial [19, 24]. These latter compounds reduce the fraction of incident radiation which is then backscattered or re-emitted from the skin. It has been confirmed in vivo that the application of non-photosensitizing oily lubricants to the skin increases the transmission of light through psoriatic plaques, resulting in increased effectivity of the phototherapy [15, 17, 23]. Mineral oil (e.g., liquid paraffin) can penetrate and fill the air–stratum corneum interfaces, thereby facilitating the transmission of radiation. It is currently the only Medicare-approved treatment to increase the efficacy of UVB phototherapy in the USA. However, the majority of psoriasis treating centers have reported that they do not routinely use emollients before UV irradiation [16].

The lack of randomized controlled studies on the benefit of using emollients concomitantly with UVB is a further difficulty. The only clinical investigation performed to date was conducted with paraffin oil in children. This study reported a significantly greater improvement in scaling, induration, and area of involvement after application of mineral oil while no adverse effects were observed [16]. Nevertheless, mineral oil is considered to be cosmetically unfavorable.

Although mineral oil stains clothes and patients encounter difficulties in dressing after the treatment, UVB with mineral oil is the most frequently used phototherapy for psoriasis in the USA according to an analysis of Healthcare Common Procedure Coding System (HCPCS) codes. In 2015, approximately 400,000 UVB therapy treatments with mineral oil (HCPCS code 96910) were performed in the USA, and the corresponding USD 21.7 million cost accounted for 48% of the total Medicare budget for phototherapy [25]. Other emollient preparations (e.g., tar, salicylic acid, thickly applied petrolatum) are cosmetically more favorable, but have the disadvantages of absorbing UV light, increasing MED, and slowing the clearance of psoriasis [15, 26, 27].

The components of the UV Fotogel were selected solely on their optical properties, as the aim was to develop a medical device that decreases the reflection of UVB light while at the same time blocks the shorter wavelengths. The absorption spectra of different compounds and the UV transmittance through the gel were measured in vitro [28]. Based on the results of our previous in vitro examination, the components of UV Fotogel facilitate the penetration of UVB wavelengths in the 310- to 320-nm range into the skin and block wavelengths in the range of 280–300 nm [28]. Thus, the preparation facilitates penetration of the therapeutically useful fraction and blocks the range which may evoke an inflammatory reaction (Fig. 4). Moreover, topical use of the listed components can be considered safe [29‐31]. The findings of the present study confirm the beneficial effect of the preparation. After exposure to NB-UVB, L-PSI values were found to be significantly lower in UV Fotogel-treated lesions than in skin not treated with UV Fotogel. Moreover, each parameter of the L-PSI (erythema, infiltration, and desquamation) showed a considerable improvement with the application of UV Fotogel compared to the control skin. In addition to the beneficial therapeutic effect, the preparation was well tolerated, and the cosmetic acceptability was good.

Further interesting results were provided by Part II, in which UV Fotogel was used by patients prior to sunbathing. Although sunbathing is not considered to be a first-line therapy in psoriasis [10], UV radiation from the sun is an effective and natural treatment for the disease [32]. The results from this part of the study confirm that the preparation is cosmetically favorable and free of considerable adverse reactions under the circumstances of home application.

The limitations of our study include the relatively low number of enrolled patients in Part I and the lack of dosimetry in Part II.

Regarding the applicability of the results in the general population, worldwide approximately 200 million patients have only mild psoriasis that is frequently treated by natural sunlight. However, no approved medical device is as yet available to increase the transmittance of UVB light by reducing the reflectance of the sunlight. Since UV Fotogel allows and enhances the penetration of therapeutically useful wavelengths (310–320 nm) and blocks the most erythematogenic part of the UVB spectrum below 300 nm, this medical device may improve the therapeutic effects of natural sunlight in millions of affected individuals.

Although the preparation has been primarily designed for the treatment of psoriasis, the treatment of other diseases that are responsive to UV therapy (e.g., atopic dermatitis, early-stage cutaneous T-cell lymphoma) might possibly also be enhanced with UV Fotogel. However, further investigation is necessary to determine this.

In conclusion, application of a novel preparation containing sodium hyaluronate and nicotinic acid prior to NB-UVB phototherapy led to a greater reduction of psoriatic lesions than NB-UVB phototherapy alone. Furthermore, the cosmetic acceptability of the preparation was good, and there were no reports of considerable side effects. The preparation was also well tolerated by patients who used it prior to sunbathing. The results suggest that UV Fotogel might be a useful device for the enhancement of phototherapy in psoriasis.