Musters Anne, Assaf Amira, Gerlag Danielle M, Tak Paul P, Tas Sander W
Amsterdam Rheumatology and immunology Center; Academic Medical Center, University of Amsterdam , Amsterdam , Netherlands.
Front Immunol. 2015 Dec 11;6:625. doi: 10.3389/fimmu.2015.00625. eCollection 2015.
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.
生物制剂彻底改变了临床免疫学领域，并已证明在类风湿性关节炎、炎症性肠病和各种血液系统疾病等常见免疫介导的炎症性疾病（IMIDs）中既有效又安全。然而，对于标准治疗无效的罕见、严重IMIDs患者，实际上不可能进行随机对照试验。因此，在这些通常病情严重的患者中，生物制剂通常是超说明书用药。不幸的是，在这些疾病中，超说明书用药有时会因缺乏报销而受阻，而报销往往基于假定的有效性证据不足。在本文中，我们将讨论生物制剂的超说明书用药可能是发现罕见病新疗法的一种好方法。这将通过多中心Castleman病（一种免疫介导的淋巴增殖性疾病）的病例来说明，在该病例中，超说明书使用托珠单抗（人源化抗IL-6受体阻断抗体）治疗带来了显著的临床改善。此外，我们将给出监测罕见IMIDs中生物治疗疗效和安全性的建议，包括使用登记系统。总之，我们提出，通过生物制剂的超说明书用药可以发现罕见IMIDs的创新疗法，前提是这基于合理的论证，包括对疾病病理生理学的了解。
