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.