Patient 1 was a 37-year-old man weighing 90kg. He was a smoker (20 pack-years) and had no relevant past medical history. He had moderate to severe psoriasis that had begun 11 years earlier and for which he had received treatment with acitretin, ciclosporin, infliximab, and etanercept. This approach was partially successful. A new flare-up of psoriasis was treated with ustekinumab 45mg according to the standard regimen, and the initial response was excellent: his Psoriasis Area and Severity Index (PASI) fell from 10.2 to 1.2 (improvement of 90%), which was maintained until week 30, when he experienced a relapse (PASI, 9.8) (Fig. 1A), with no increase in body weight. At this point, phototherapy was combined with ustekinumab. After 17 sessions of narrowband UV-B phototherapy and a cumulative dose of 12.9J/cm2, his psoriasis improved considerably, and his PASI fell to 2.1 (improvement of 75%) (Fig. 1B). The patient remained stable and recurrence-free after 5 months of ustekinumab in monotherapy.

Figure 1.

A, Patient 1. Recurrence of psoriasis 30 weeks after initiation of ustekinumab (PASI, 9.8). B, Patient 1. PASI 75 after combining 17 sessions of narrowband UV-B therapy (12.9J/cm2) with ustekinumab (PASI, 2.1). PASI indicates Psoriasis Area and Severity Index.

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Patient 2 was a 57-year-old woman weighing 87kg with a previous history of arterial hypertension, positional vertigo, and anxiety. She was receiving treatment with betahistine, amiloride/hydrochlorothiazide, tetrazepam, and atenolol (indispensable for control of her arterial hypertension). She had a 15-year history of moderate to severe psoriasis and, during that time, she had received several treatments (methotrexate, infliximab, adalimumab, and etanercept), to which the response was poor or short-term. Her initial response to ustekinumab 45mg with the usual regimen was good (PASI 10.6 to PASI 4.2, improvement of 50%-75%), although at 64 weeks of treatment her condition worsened (PASI 7.8) (Fig. 2), with no change in body weight; therefore, ustekinumab was combined with narrowband UV-B phototherapy. After 16 sessions and a cumulative dose of 15J/cm2, her psoriasis improved considerably, and her PASI fell to 0.6 (improvement of 90%) (Fig. 3), which remained stable with ustekinumab in monotherapy after 3 months of follow-up.

Figure 2.

Patient 2. Worsening of psoriasis at 64 weeks after initiation of ustekinumab (Psoriasis Area and Severity Index, 7.8).

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Figure 3.

Patient 2. Psoriasis Area and Severity Index 90 response with the combination of ustekinumab and narrowband UV-B phototherapy (15J/cm2 in 16 sessions).

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Biologic agents constitute a major advance in the treatment of moderate to severe psoriasis. Although they are all efficacious in the short term, the response is lost over time in some cases.2

The PHOENIX 1 study showed that continuous therapy with ustekinumab maintained the clinical response in most patients over time.3 Overall, almost 80% continued to receive treatment until the third year, and the number of interruptions associated with efficacy was low (45mg [7.9%]; 90mg [4.2%]). Most patients had a lasting PASI 75 (45mg [62.7%]; 90mg [72.2%]), and 84% maintained a response that was equal to or greater than PASI 50.

Although it seems that there was no major decrease in response over time in the study population as a whole, it is important to identify this subgroup and prepare rescue strategies, such as reduction in the administration interval (eg, 12 to 8 weeks) or combination with other topical or systemic agents or phototherapy.

Several clinical studies have found that combination with narrowband UV-B phototherapy improves the efficacy of some tumor necrosis alfa (TNF-α) factor inhibitors such as etanercept4,5 and adalimumab.6,7 A recent study based on a small clinical series revealed similar findings in patients treated with ustekinumab,8 as in the 2 cases described above.

The clinical improvement in psoriasis treated with narrowband UV-B phototherapy is linked to suppression of the signaling pathways of type 17 helper T cells and types I and II interferons, which play a key role in pathogenesis.9 The modifying effects of phototherapy also have an effect on the antigen-presenting function and direct apoptosis of T lymphocytes.

Given that some experimental studies have shown how combination therapy with anti-TNF-α agents can increase the risk of photocarcinogenesis,10 the combination of biologic agents and phototherapy should be administered with caution and only in selected patients.

To conclude, narrowband UV-B phototherapy could be a good alternative for restoration of the response to ustekinumab in selected cases of moderate to severe psoriasis.