Frequency of the off-label use of monoclonal antibodies in clinical practice: a systematic review of the literature.

Background: The monoclonal antibodies represent novel therapeutic options for many clinical entities. This study aimed to study the frequency of the off-label use to total use of different monoclonal antibodies in clinical practice.

Methods: This study systematically searched the PubMed and Scopus databases for relevant studies.

Results: Fifteen studies were considered eligible for inclusion in this review. Eight of the included studies referred to the off-label use of anti-neoplastic monoclonal antibodies, three referred to immunosuppressive ones, and four to other types of monoclonal antibodies. The most studied anti-neoplastic monoclonal antibody was rituximab; which was prescribed off-label at a frequency varying between 16-75%, mostly for an unapproved diagnosis. Bevacizumab was prescribed off-label for age-related macular degeneration more often than ranibizumab, the approved monoclonal antibody for this condition. Of the immunosuppressive monoclonal antibodies, infliximab was used off-label in an average of 15.4% (range=2.8-25%) and adalimumab in 10.5% (range=0-15.4% in different years).

Conclusion: The frequency of off-label use of different types of monoclonal antibodies varies, but appears to be considerably high for specific monoclonal antibodies or indications. In certain examples, this might reflect implementation into clinical practice of relevant scientific data, albeit not of the strength or quality that suffices for receipt of regulatory approval. In others, it might relate to the sub-optimal effectiveness and considerable toxicity of the conventional therapies. Still, the clinician should bear in mind the potential costs and toxicity that can be associated with off-label use of monoclonal antibodies.