SciCombinator

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Concept: Ustekinumab

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Palmoplantar pustulosis is characterized by sterile pustules with hyperkeratosis, erythema, scaling, and fissuring on the palms and soles.(1) It has been reported to be more frequent in middle-aged women, smokers, and diabetic patients(2) , and it is increasingly reported as a paradoxical reaction to antitumor necrosis factor alpha (anti-TNF) biological agents.(3, 4.) It can present itself alone (PPP), or in association with psoriasis vulgaris (palmoplantar pustular psoriasis, PPPP).

Concepts: Ultraviolet, Tumor necrosis factor-alpha, Psoriatic arthritis, Psoriasis, Etanercept, Pustulosis palmaris et plantaris, Ustekinumab, Adalimumab

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The development of several highly effective biologic drugs in the past decade has revolutionized the treatment of moderate-to-severe plaque psoriasis. With increased understanding of the immunopathogenesis of psoriasis, the emphasis has turned toward more specific targets for psoriasis drugs. Although the complex immunological pathway of psoriasis is not yet completely understood, current models emphasize the significant importance of interleukin (IL)-23 and IL-17. Several biologic drugs targeting these cytokines are now in various stages of drug development. Drugs targeting IL-23 include BI-655066, briakinumab, guselkumab, tildrakizumab, and ustekinumab. Drugs targeting IL-17 include brodalumab, ixekizumab, and secukinumab. While many of these have shown safety and good efficacy in clinical trials of moderate-to-severe plaque psoriasis, long-term safety is still to be established.

Concepts: Pharmacology, Clinical trial, Cytokine, Effectiveness, Interleukin 17, Interleukin, Psoriasis, Ustekinumab

4

Background Interleukin-23 is thought to be critical to the pathogenesis of psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically targeting the p19 subunit and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, in patients with moderate-to-severe plaque psoriasis. Methods We randomly assigned a total of 166 patients to receive subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to body weight, at weeks 0, 4, and 16). The primary end point was a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12. Results At week 12, the percentage of patients with a 90% or greater reduction in the PASI score was 77% (64 of 83 patients) for risankizumab (90-mg and 180-mg groups, pooled), as compared with 40% (16 of 40 patients) for ustekinumab (P<0.001); the percentage of patients with a 100% reduction in the PASI score was 45% in the pooled 90-mg and 180-mg risankizumab groups, as compared with 18% in the ustekinumab group. Efficacy was generally maintained up to 20 weeks after the final dose of 90 or 180 mg of risankizumab. In the 18-mg and 90-mg risankizumab groups and the ustekinumab group, 5 patients (12%), 6 patients (15%), and 3 patients (8%), respectively, had serious adverse events, including two basal-cell carcinomas and one major cardiovascular adverse event; there were no serious adverse events in the 180-mg risankizumab group. Conclusions In this phase 2 trial, selective blockade of interleukin-23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab. This trial was not large enough or of long enough duration to draw conclusions about safety. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT02054481 ).

Concepts: Immune system, Clinical trial, Monoclonal antibodies, Psoriasis, Serious adverse event, Psoriasis Area Severity Index, Ustekinumab, Boehringer Ingelheim

4

Secukinumab demonstrated superior efficacy to ustekinumab at week 4 and week 16 of the CLEAR study, with comparable safety, in subjects with moderate-to-severe plaque psoriasis.

Concepts: Psoriasis, Clear, Ustekinumab, Tetrahydrogestrinone, Clearing

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The aim of this study was to identify clinical factors associated with dose reduction and dose escalation in the treatment with ustekinumab in patients with moderate to severe plaque psoriasis.

Concepts: Psoriasis, Ustekinumab

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Brodalumab (Kyntheum®) is a human anti-interleukin-17 receptor A (IL-17RA) monoclonal antibody available for use in patients with moderate to severe plaque psoriasis. In the phase III AMAGINE trials in this patient population, 12 weeks of induction therapy with subcutaneous brodalumab was superior to placebo in terms of the proportion of patients with ≥ 75% improvement in the Psoriasis Area and Severity Index score (PASI 75) and the proportion of patients with a static Physician Global Assessment score of 0 or 1. Brodalumab was also superior to ustekinumab for PASI 100 (i.e. complete skin clearance) at week 12. Health-related quality of life (HR-QOL) outcomes improved to a significantly greater extent with brodalumab than with placebo. Moreover, brodalumab was more effective than placebo in patients with difficult-to-treat nail or scalp psoriasis. Brodalumab was generally well tolerated, with low rates of immunogenicity. Efficacy was sustained and brodalumab remained well tolerated during up to 52 weeks of maintenance therapy. Thus, subcutaneous brodalumab is a useful addition to the treatment options currently available for patients with moderate to severe plaque psoriasis.

Concepts: Clinical trial, Patient, Monoclonal antibodies, Physician, Infliximab, Psoriasis, Ustekinumab, Dandruff

0

Biologics used increasingly used for treating moderate-to-severe psoriasis. Efficacy may differ in patients with previous biologics exposure.

Concepts: Psoriasis, Ustekinumab

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We report the case of a 9-year-old girl with severe plaque psoriasis refractory to multiple topical and systemic therapies. Physical examination revealed extensive, erythematous plaques with overlying thick scales that covered more than 80% of her body surface area, which included the face, scalp, trunk, and limbs. Because of the severity of the disease and lack of treatment response to other systemic therapies, she was treated with ustekinumab. Three weeks after ustekinumab was initiated, her psoriatic lesions fully cleared.

Concepts: Ultraviolet, Immunosuppressive drug, Psoriatic arthritis, Psoriasis, Ustekinumab, Dandruff