Different Responses to Ustekinumab of Two HLA-Cw6-positive Homozygous Twins with Psoriasis.

The immunopathogenesis of psoriasis has been extensively reviewed in recent literature. Human leukocyte antigen (HLA)-Cw6 has been identified as the major psoriasis susceptibility genetic polymorphism and identifies early-onset (type 1) psoriasis (1). Recently Tala-monti et al. (2) observed that the HLA-Cw6 allele is associated with a faster and better clinical response rate to ustekinumab. Ustekinumab is a human monoclonal antibody directed against interleukin 12 and interleu-kin 23; cytokines that regulate the immune system and immune-mediated inflammatory disorders. We describe here 2 HLA-Cw6-positive homozygous twins, both affected by psoriasis, who showed different responses to ustekinumab. CASE REPORTS The first of the homozygote twins, a 47-year-old obese man (160 kg, body mass index (BMI) 53.5) had had psoriasis since 1990. His medical history revealed that he had previously been treated with topical therapy (corticosteroid and calcipotriol) followed by cyclosporine, 3 mg/kg based on ideal weight, which was stopped after 6 months due to arterial hypertension. He then started metho-trexate, 15 mg/week, for approximately one year, experiencing only a partial response (Psoriasis Activity Severity Index (PASI) 50). When assessed at our unit, he had moderate psoriasis (PASI 17). Before starting biological therapy, general laboratory, physical examination and an X-ray were performed. Surprisingly no sign of metabolic disease was found. As the patient's weight was more than 100 kg, we decided to start ustekinumab, 90 mg, using the standard protocol (time 0, after 4 weeks, and every 12 weeks thereafter). After only 3 injections a significant improvement was noted (PASI 9). Due to this positive result, the patient's brother, his homozygous twin, who had had psoriasis since 1992 requested similar treatment. He had previously been treated with topical steroids and, when his psoriasis worsened (PASI 22), he started cyclosporine, 3 mg/kg, with a positive response after 6 months of therapy (PASI 5), but he had to stop the treatment due to severe epigastralgia. Methotrexate, 15 mg/week, was then introduced, but stopped after 3 months due to lack of improvement. Due to the patient's weight (140 kg, BMI 43.21), and thinking that uste-kinumab might also be efficient in the twin brother, we decided to start ustekinumab, 90 mg, following the standard protocol. After only 4 injections the PASI decreased from 22 to 7. All follow-up examinations for the 2 patients were within the normal ranges, but the clinical follow-up was different. After 2 years of treatment, the first twin showed progressive deterioration of the disease …