SummaryBackground Adherence to treatment is an indicator of treatment success. Long-term data on adherence to biologic treatment in psoriasis are lacking. Objectives To compare the tumour necrosis factor (TNF)-a inhibitors regarding drug survival rate and safety in patients with psoriasis. Methods This study is based on data from the Danish nationwide database DERM-BIO covering patients with psoriasis treated with a biologic agent. All patients who received anti-TNF-a treatment in academic referral centres were included. Baseline data, adverse events, time on treatment and reason for stopping treatment were recorded. Hazard ratios (HRs) for factors determining drug survival were calculated by logistic regression. Results In total, 882 treatment series with etanercept (n = 311), adalimumab (n = 427) or infliximab (n = 144) were administered to 747 patients. Significant predictors of drug survival were: sex, the anti-TNF-a agent and the previous response to an anti-TNF-a agent. In the group of anti-TNF-a-naïve patients the longest drug survival was observed for infliximab, followed by adalimumab [HR vs. infliximab 3AE70, 95% confidence interval (CI) 1AE99-6AE89] and etanercept (HR vs. infliximab 3AE18, 95% CI 1AE72-5AE86). The 4-year drug survival is in the range of 40% for etanercept or adalimumab vs. 70% for infliximab. There was no difference in number of adverse events. Conclusions The overall efficacy of anti-TNF-a drugs diminishes with time, as envisaged by the progressive loss of patient adherence to treatment. The major reasons for stopping treatment were loss of efficacy, followed by adverse events. Infliximab had the best patient retention ability, with 70% of patients still being on the drug after 4 years of treatment.
Ustekinumab was associated with the highest drug survival, and secukinumab with the lowest, although most patients on secukinumab were non-naïve. Switching from originator to biosimilar had no significant impact on drug survival, and the safety profiles were comparable. Adverse events occurred most frequently with secukinumab. Future studies are warranted to assess the long-term safety of novel biologics for psoriasis.
In this nationwide study of patients with severe psoriasis, systemic anti-inflammatory treatment with biological agents or methotrexate was associated with lower cardiovascular disease event rates compared to patients treated with other anti-psoriatic therapies.
Psoriasis is a chronic inflammatory disease of the skin characterized by epidermal hyperplasia, dermal angiogenesis, infiltration of activated T cells, and increased cytokine levels. One of these cytokines, IL-15, triggers inflammatory cell recruitment, angiogenesis, and production of other inflammatory cytokines, including IFN-γ, TNF-α, and IL-17, which are all upregulated in psoriatic lesions. To investigate the role of IL-15 in psoriasis, we generated mAb's using human immunoglobulin-transgenic mice. One of the IL-15-specific antibodies we generated, 146B7, did not compete with IL-15 for binding to its receptor but potently interfered with the assembly of the IL-15 receptor α, β, γ complex. This antibody effectively blocked IL-15-induced T cell proliferation and monocyte TNF-α release in vitro. In a human psoriasis xenograft model, antibody 146B7 reduced the severity of psoriasis, as measured by epidermal thickness, grade of parakeratosis, and numbers of inflammatory cells and cycling keratinocytes. These results obtained with this IL-15-specific mAb support an important role for IL-15 in the pathogenesis of psoriasis.
Our results suggest that the absence or reduced volume of the sebaceous gland may play a role in the pathogenesis of HS. The presence of fibrosis suggests that sebaceous glands are obliterated early in the pathogenesis of HS.
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