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Case

A 32-year-old male with a 10-year history of chronic plaque psoriasis presents for follow up. He has been taking etanercept 50 mg weekly for the past 3 years. It was initially working well and his skin was almost clear for the first 2 years. However, in the past year, his psoriasis has worsened slowly. He has been using clobetasol ointment twice daily to the affected areas without much additional improvement. He complains of itching and discomfort, as well as dissatisfaction with the current treatment. On examination, he is noted to have well-demarcated, erythematous, indurated plaques with silver scale on the elbows and knees. He also has similar but smaller plaques scattered on the chest, abdomen, and trunk. The patient is tolerating etanercept with no side effects. He asks what more can be done for his psoriasis. The patient denies personal history of melanoma or non-melanoma skin cancers.

The decision is made for the patient to add NB-UVB treatments at a frequency of 3 times per week. He is treated as per protocol. He returns to your clinic 3 months later with marked improvement of the psoriasis on his trunk and extremities. At this time, you conduct a thorough full body skin check and ascertain no new suspicious skin lesions and only a few psoriasis plaques. Given the positive outcome, the patient is able to decrease the frequency of phototherapy down to twice weekly, followed by once weekly a few months later with maintenance of near clear skin. He continues to take etanercept once weekly and applies topical corticosteroids as needed.

Discussion

Although several biologic agents showing excellent efficacy for the treatment of moderate to severe psoriasis have been developed in the last decade, phototherapy appears to play an important role in a subset of patients with severe, recalcitrant psoriasis despite treatment with a biologic agent. Several studies have demonstrated the efficacy of using etanercept and NB-UVB in combination [1–6]. These studies evaluated this combination therapy in patients who had not previously received treatment, patients who had an inadequate response with etanercept alone (50 mg once-weekly or 50 mg twice-weekly dosing), or patients who had an inadequate response to NB-UVB alone. Overall, combination therapy was superior and time to clearance was reduced. A study by Lynde et al. also demonstrated the importance of high adherence to the NB-UVB regimen in order to achieve significant clinical improvement [4]. High adherence to the NB-UVB regimen was defined as missing not more than 2 treatments in any 4-week period.

One study to date has failed to establish efficacy of combination therapy of etanercept and NB-UVB. This head-to-head pilot study by Park et al., who examined combination treatment with NB-UVB and etanercept 50 mg twice weekly compared with etanercept monotherapy, did not demonstrate significantly enhanced improvement with combination therapy [7]. However, this study was limited by a small sample size of 13 patients. Furthermore, the patients all had a body mass index (BMI) of greater than 30, and studies have reported a suboptimal response to etanercept in psoriasis patients with a BMI of greater than 30 [8, 9].

Adalimumab or ustekinumab in combination with NB-UVB has also been investigated in a limited number of studies. A study by Bagel et al. evaluated the combination of adalimumab and NB-UVB [10], and another study, by Wolf et al., evaluated adalimumab and the excimer laser [11]. Both studies demonstrated that phototherapy significantly accelerates therapeutic response and improves the clearance of psoriatic lesions in patients who received adalimumab treatment. One study to date has evaluated the combination of ustekinumab with the excimer laser [12]. This was an intra-individual, half-body comparison study in which PASI-75 was achieved significantly more often on the UV-irradiated half than on the non-irradiated half at week 6 in patients on ustekinumab.

In general, combination therapy involving a biologic agent with NB-UVB phototherapy is very well tolerated with the most common side effects being mild burning and erythema. Patients with recalcitrant disease despite being on a biologic, such as in this case in which the patient has active, symptomatic psoriasis causing dissatisfaction, may benefit from this combination therapy. In this case, the patient is a candidate for the addition of traditional phototherapy, rather than excimer laser, as he has many small, scattered psoriatic lesions on the trunk that would be difficult to treat with a targeted modality such as the excimer laser. Although increased risk of skin cancers have not been reported throughout the duration of the above-mentioned trials, long-term studies do not currently exist. Therefore, patients being treated with phototherapy while on a biologic agent should be monitored periodically for any new lesions suspicious for skin cancer.