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Current Recommendations for the Treatment of Psoriasis
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Biological therapies are the latest addition to the treatment of moderate to severe psoriasis and have become increasingly utilized due to their high short- and long-term efficacy and good safety profile. Alefacept was the first biologic approved by the FDA for psoriasis treatment in 2003. It bound to CD2 on T cells, preventing its interaction with the LFA-3 on antigen-presenting cells, thereby preventing T-cell activation. Alefacept’s manufacturer discontinued production in 2011. Efalizumab, also approved by the FDA in 2003, targeted the CD11a subunit of LFA-1. It was voluntarily withdrawn from the market in 2009 due to reports of progressive multifocal leukoencephalopathy in patients undergoing long-term treatment. Currently available biologics exert their therapeutic effects through inhibition of TNF, IL-12 and IL-23, or IL-17A (Table 11.2). The downstream effects involve reduction of inflammatory cytokines and elimination of pathogenic T cells.
The history of psoriasis
Published in M. Alan Menter, Caitriona Ryan, Psoriasis, 2017
M. Alan Menter, Bobbak Mansouri
The first biologic injectable agent approved for psoriasis was Alefacept in January 2003. Alefacept inhibits the activation of CD4+ and CD8+ T cells by binding with CD2 on the T-cell membrane thereby blocking the costimulatory molecule lymphocyte function-associated antigen (LFA)-3/CD2 interaction and leading to apoptosis of memory-effector T lymphocytes.19 Alefacept had limited efficacy in the treatment of psoriasis, and production was discontinued in 2011. Subsequently, a second T-cell biologic agent, efalizumab, was introduced in 2005.20 Efalizumab binds to the CD11a subunit of lymphocyte function-associated antigen 1 to inhibit lymphocyte activation and cell migration out of blood vessels into tissues. Although efalizumab demonstrated efficacy in psoriasis, particularly in those with palmoplantar disease, it was removed from the market in 2009 due to three fatalities from progressive multifocal leukoencephalopathy (PML).21
Special Patient Populations
Published in John Y. M. Koo, Ethan C. Levin, Argentina Leon, Jashin J. Wu, Alice B. Gottlieb, Moderate to Severe Psoriasis, 2014
Daniel C. Butler, Faranak Kamangar, Ethan C. Levin, John Y. M. Koo, Anne L. S. Chang
Specific studies on alefacept, adalimumab, and etanercept detail their safe and effective use in elderly patients [23–25]. One study that examined etanercept in a cohort of more than 4000 patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis failed to find a higher incidence of serious adverse events (eg., infectious events or malignancies) in people over 65 years old compared with those under 65 years of age [26]. Conversely, a different cohort of more than 3000 patients from the British Biologics registry found an increased risk of serious infection for geriatric patients who are taking biologics [27]. Although a definitive answer on the absolute safety of biologics remains uncertain, biologics can be recommended to elderly patients as long as appropriate caution is taken regarding screening and follow-up.
Type 1 diabetes: key drug targets and how they could influence future therapeutics
Published in Expert Opinion on Therapeutic Targets, 2023
Yoon Kook Kim, Kashif M. Munir, Stephen N. Davis
Alefacept is a fusion protein of two leukocyte-function-associated antigen-3 molecules bound to IgG1. It binds CD2, expressed on CD4+ and CD8+ memory cells. These cells are thought to be primarily responsible for beta-cell destruction in T1DM. In a randomized, placebo-controlled, double-blind trial, 49 patients with recently diagnosed T1DM and confirmed the presence of DM-associated autoantibody were studied. Two 12-week courses of Alefacept (15 mg/week IM) showed improved preservation of C-peptide, lower insulin requirements (p = 0.002), and an approximately 50% reduction in severe hypoglycemic events (p = 0.001) compared with placebo. These benefits were seen 15 months after the last dose of alefacept, showing favorable sustained immunologic outcomes [22,23].
Biologic and small-molecule medications in the management of pyoderma gangrenosum
Published in Journal of Dermatological Treatment, 2019
Fatima McKenzie, Devin Cash, Angela Gupta, Laurel W. Cummings, Alex G. Ortega-Loayza
The goal of this review is to provide an update on the use of biologic and small-molecule medications for the treatment of PG. Information was gathered from a PubMed search with combinations of the terms ‘pyoderma gangrenosum’ and biologics’, ‘adalimumab’, ‘anakinra’, ‘apremilast’, ‘canakinumab’, ‘certolizumab’, ‘etanercept’, ‘gevokizumab’, ‘golimumab’, ‘guselkumab’, ‘infliximab’, ‘ruxolitinib’, ‘tildrakizumab’, ‘tocilizumab’, ‘tofacitinib’, ‘ustekinumab’, ‘vedolizumab’, and ‘visilizumab’; only English-language papers were included in this review. Alefacept and efalizumab are not discussed as they have been removed from the market by their manufacturers. A search of Clinicaltrials.gov with the term ‘pyoderma gangrenosum’ was also performed.
Tildrakizumab for the treatment of psoriasis
Published in Expert Review of Clinical Immunology, 2019
Rodney Sinclair, Vetrichevvel Thirthar Palanivelu
Biologicals are targeted therapies that can be used alone or in combination with the other systemic agents. Since the advent of alefacept, the first biological specifically designed and approved for psoriasis in the US in 2003 [4], evolving research into the immune regulation in the pathophysiology of psoriasis has led to continual advances in biologic therapy. Alefacept was succeeded first by TNF alfa inhibitors, then IL12-23 inhibitors and more recently IL 17 receptor antagonists.