Genes and structure of selected cytokines involved in pathogenesis of psoriasis.

Psoriasis is a common skin disease involving 1-4% of human population worldwide, of strong genetic background. The following cytokines are directly involved in psoriasis: TNF, IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-18, IL-19, IL-20, IL-23 whereas IL-4, IL-10, IL-12 as well as IL-11, IL-17 and IFN-gamma are rather indirectly engaged. This work is a review of some genetic factors and structure of selected cytokines and receptors and their genes location

Psoriasis vulgaris and digestive system disorders: is there a linkage?

Psoriasis is well-known immune-mediated skin disease often associated with co-morbidities, including dyslipidaemia and obesity. Few reports imply that the disease might be also related to pathology of mucosal surfaces, especially that of the digestive system. The authors present a case of psoriasis and concurrent digestive system abnormalities, and review the literature regarding the topic. A 40-year-old man suffered from an exacerbation of exudative psoriasis for about 6 months. Topical antipsoriatics proved ineffective and the disease gradually progressed to a severe disseminated form. Subsequent detailed examinations revealed persistent gastroduodenitis due to H. pylori infection, pancreatic dysfunction and fatty change of the liver, although the patient denied any gastrointestinal symptoms. As a result appropriate treatment of the diagnosed digestive system disorders was added to topical antipsoriatic therapy. Within 2 weeks of treatment clinical symptoms and laboratory signs showed a marked trend to normalisation. The presented medical history seems to suggest that there may be some kind of interplay between psoriasis and digestive system disorders

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known

Genes and structure of selected cytokines involved in pathogenesis of psoriasis.

Psoriasis is a common skin disease involving 1-4% of human population worldwide, of strong genetic background. The following cytokines are directly involved in psoriasis: TNF, IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-18, IL-19, IL-20, IL-23 whereas IL-4, IL-10, IL-12 as well as IL-11, IL-17 and IFN-gamma are rather indirectly engaged. This work is a review of some genetic factors and structure of selected cytokines and receptors and their genes location

Psoriasis vulgaris and digestive system disorders: is there a linkage?

Psoriasis is well-known immune-mediated skin disease often associated with co-morbidities, including dyslipidaemia and obesity. Few reports imply that the disease might be also related to pathology of mucosal surfaces, especially that of the digestive system. The authors present a case of psoriasis and concurrent digestive system abnormalities, and review the literature regarding the topic. A 40-year-old man suffered from an exacerbation of exudative psoriasis for about 6 months. Topical antipsoriatics proved ineffective and the disease gradually progressed to a severe disseminated form. Subsequent detailed examinations revealed persistent gastroduodenitis due to H. pylori infection, pancreatic dysfunction and fatty change of the liver, although the patient denied any gastrointestinal symptoms. As a result appropriate treatment of the diagnosed digestive system disorders was added to topical antipsoriatic therapy. Within 2 weeks of treatment clinical symptoms and laboratory signs showed a marked trend to normalisation. The presented medical history seems to suggest that there may be some kind of interplay between psoriasis and digestive system disorders