ABSTRACT
The phosphodiesterase 4 inhibitor apremilast is used for the treatment of psoriasis. We investigated the effects of apremilast on endothelial glycocalyx, vascular and left ventricular (LV) myocardial function in psoriasis. One hundred and fifty psoriatic patients were randomized to apremilast (n = 50), anti-tumor necrosis factor-α (etanercept; n = 50), or cyclosporine (n = 50). At baseline and 4 months post-treatment, we measured: (1) Perfused boundary region (PBR), a marker of glycocalyx integrity, in sublingual microvessels with diameter 5-25 µm using a Sidestream Dark Field camera (GlycoCheck). Increased PBR indicates damaged glycocalyx. Functional microvascular density, an index of microvascular perfusion, was also measured. (2) Pulse wave velocity (PWV-Complior) and (3) LV global longitudinal strain (GLS) using speckle-tracking echocardiography. Compared with baseline, PBR5-25 µm decreased only after apremilast (-12% at 4 months, p < 0.05) whereas no significant changes in PBR5-25 µm were observed after etanercept or cyclosporine treatment. Compared with etanercept and cyclosporine, apremilast resulted in a greater increase of functional microvascular density (+14% versus +1% versus -1%) and in a higher reduction of PWV. Apremilast showed a greater increase of GLS (+13.5% versus +7% versus +2%) than etanercept and cyclosporine (p < 0.05). In conclusion, apremilast restores glycocalyx integrity and confers a greater improvement of vascular and myocardial function compared with etanercept or cyclosporine after 4 months.
ABSTRACT
BACKGROUND: Pemphigus is a group of autoimmune blistering diseases, potentially life-threatening. Rituximab received FDA approval in June 2018 for the treatment of moderate to severe pemphigus vulgaris. OBJECTIVES: To evaluate the efficacy and safety of rituximab in patients with pemphigus, resistant to previous therapies or unable to receive classic immunosuppressive treatment due to serious adverse events or comorbidities. MATERIALS AND METHODS: Twenty-five patients (9 men, 16 women), mean age 49.4 ± 15.9 years (range 21-74 years), mean disease duration 4 ± 2.7 years (range 0.25-10 years) were included in the study: 19 patients with pemphigus vulgaris and 6 with pemphigus foliaceous. The efficacy of rituximab was evaluated according to the control of disease, retention of remission, disease severity, previous treatments and adverse reactions. During COVID-19 pandemic patients are monitored closely through tele-dermatology. RESULTS: Twenty-three out of 25 patients had great improvement, 2 out of 25 ceased therapy due to adverse events (arthralgias and dyspnea). Sixteen out of 23 received additional course after 8 months (range 5-60 months). More aged patients presented more frequently adverse events and underwent additional courses (p = 0.002). Rituximab was found superior to classic immunosuppressive treatment in terms of efficacy and safety, with larger periods of remission and lower doses of corticosteroids and immunosuppressants. No major adverse events were noticed. CONCLUSIONS: Rituximab is a very effective treatment of pemphigus and, remarkably, superior to classic immunosuppressive treatment.