Ustekinumab treats psoriasis refractory to seven conventional and biologic therapies
- Author(s): Rallis, Efstathios;
- Verros, Constantinos D
- et al.
Published Web Locationhttps://doi.org/10.5070/D337d5g41t
Ustekinumab treats psoriasis refractory to seven conventional and biologic therapies1. Veterans Administration Hospital (NIMTS), Athens, Greece
Efstathios Rallis1 MD PhD, Constantinos D Verros2 MD
Dermatology Online Journal 17 (4): 14
2. Private Practice, Tripolis, Greece
|Figure 1||Figure 2|
|Figure 1. Psoriasis of the palms. The patient was receiving cyclosporine 25 mg and topical calcipotriol/betamethasone at that
Figure 2. Complete clearance was achieved after the fifth treatment with ustekinumab.
Psoriasis is a common, chronic, inflammatory and disabling skin disease with an estimated prevalence of 2-3 percent of the world’s population . Despite the numerous, systemic therapeutic agents that have been used for the treatment of this disease, there is still a number of psoriatic patients unable to respond to any treatment.
Ustekinumab is a human immunoglobulin G1 kappa monoclonal antibody that binds with high specificity and affinity to the p40 subunit of the cytokines interleukin 12 (IL-12) and interleukin 23 (IL-23) and has been licensed for the treatment of moderate-to-severe plaque psoriasis. Based on preliminary observations ustekinumab seems to provide an interesting therapeutic choice in patients with ‘difficult-to-treat’ psoriasis .
A 68-year-old female with body weight: 69 Kg, was referred to our department with refractory plaque type proriasis of 9-year duration. According to her past medical history, she had been treated unsuccessfully with topical therapies including topical corticosteroids, calsipotriol, calcitriol, tacrolimus, pimecrolimus, and all systemic treatments available in Greece. She had been unresponsive to administration of methotrexate, etanercept and adalimumab, showed partial response to cyclosporine but switched to infliximab because of exacerbation of psoriasis during withdrawal of cyclosporine and developed significant side effects during administration of acitrecin, efalizumab, and infliximab (Table 1).
She was adviced to receive ustekinumab. At that time, she was tapering cyclosporine receiving 25 mg daily and was also under topical treatment with calcipotriol/betamethasone, once daily, with poor results (Figure 1). Her parameters before commencement of therapy were as follows: mean psoriasis area and severity index (PASI): 32 (range 16–36) and physician’s global assessment (PGA): 4.
She discontinued cyclosporine and after week, initiated ustekinumab. She was treated with ustekinumab at a dose of 45 mg at weeks 0 and 4 and achieved PASI 50 at week 6. She continued treatment with ustekinumab every 12 weeks, her psoriasis remained stable for 6 months and she eventually achieved PASI 90 and PGA: 0 after the fifth treatment (Figure 2).
Ustekinumab has demonstrated a high efficacy, relatively rapid onset of action, favorable safety profile and convenient dosing profile in adult patients with chronic moderate-to-severe plaque-type psoriasis, achieving at least 75 percent reduction of their lesions and significant improvement of their health-related quality of life. The high level of efficacy is generally maintained with dosing every 12 weeks. However, a subpopulation achieves only partial response either because in these patients psoriasis is mediated by immune pathways distinct from those mediated by IL-12 and IL-23 or this subgroup requires greater exposure to this drug  and the latent is probably occurred in our patient.
Agents targeting IL-12 and IL-23 seem to provide highly selectivity and effectiveness for the treatment of plaque psoriasis. On the other hand, immunosuppressive agents such as methotrexate and cyclosporine target the underlying inflammation whereas TNF-α blockers have broader anti-inflammatory effects compared with ustekinumab.
Patients with refractory psoriasis that have inadequate response, intolerance, or contraindication to other systemic and/or biologic agents seem to potentially benefit more from ustekinumab administration [2, 4]. However, temporary blockade of IL-12 and IL-23 does not reverse the underlying causal mechanism of psoriasis and patients recur after discontinuation of ustekinumab implying an existing gap in the understanding of pathogenesis and therapy of psoriasis.
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3. Papp KA, Langley RG, Lebwohl M et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008;371; 1675-84. [PubMed]
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