title: Discovery of Innovative Therapies for Rare Immune-Mediated Inflammatory Diseases via Off-Label Prescription of Biologics: The Case of IL-6 Receptor Blockade in Castleman's Disease.
abstract: Biologics have revolutionized the field of clinical immunology and proven to be both effective and safe in common immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, inflammatory bowel diseases, and various hematological disorders. However, in patients with rare, severe IMIDs failing on standard therapies, it is virtually impossible to conduct randomized controlled trials. Therefore, biologics are usually prescribed off-label in these often severely ill patients. Unfortunately, off-label prescription is sometimes hampered in these diseases due to a lack of reimbursement that is often based on a presumed lack of evidence for effectiveness. In the present article, we will discuss that off-label prescription of biologics can be a good way to discover new treatments for rare diseases. This will be illustrated using a case of multicentric Castleman's disease, an immune-mediated lymphoproliferative disorder, in which off-label tocilizumab (humanized anti-IL-6 receptor blocking antibody) treatment resulted in remarkable clinical improvement. Furthermore, we will give recommendations for monitoring efficacy and safety of biologic treatment in rare IMIDs, including the use of registries. In conclusion, we put forward that innovative treatments for rare IMIDs can be discovered via off-label prescription of biologicals, provided that this is based on rational arguments including knowledge of the pathophysiology of the disease.
authors.affiliation: Amsterdam Rheumatology and immunology Center; Academic Medical Center, University of Amsterdam , Amsterdam , Netherlands.
authors.forename: Anne
authors.initials: A
authors.lastname: Musters
authors.affiliation: Amsterdam Rheumatology and immunology Center; Academic Medical Center, University of Amsterdam , Amsterdam , Netherlands.
authors.forename: Amira
authors.initials: A
authors.lastname: Assaf
authors.affiliation: Amsterdam Rheumatology and immunology Center; Academic Medical Center, University of Amsterdam , Amsterdam , Netherlands.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Gerlag
authors.affiliation: Amsterdam Rheumatology and immunology Center; Academic Medical Center, University of Amsterdam , Amsterdam , Netherlands.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.affiliation: Amsterdam Rheumatology and immunology Center; Academic Medical Center, University of Amsterdam , Amsterdam , Netherlands.
authors.forename: Sander W
authors.initials: SW
authors.lastname: Tas
keywords: biological products; giant lymph node hyperplasia; interleukin-6; multicentric Castleman’s disease; off-label use; registries; tocilizumab