The term “off-label” is described by the FDA as an unapproved use of an approved drug. Recently, a study conducted at Kaiser Permanente Colorado found that off-label uses of Rituximab, particularly to treat demyelinating neurologic diseases, now account for more than half of patients receiving rituximab. Originally approved in the United States in 1997 for treatment of non-Hodgkin lymphoma, the monoclonal antibody has multiple additional approvals for orphan and nonorphan indications.
The study included 1674 patients who received their first rituximab infusion between 2009 and 2017. Overall during that period, 1111 patients (66.4%) received rituximab for an approved indication and 563 (33.6%) received the drug for an off-label indication. However, off-label uses grew more common as the study went on, particularly in the latter half of the study period. By 2017, off-label indications were more common than approved indications; off-label use of rituximab rose from 1.2% of patients in 2009 to 55.6% by the end of the study in 2017. In contrast, use for approved orphan indications dropped from 92.8% of patients in 2009 to 38.8% in 2017.
A Myriad of Applications
Oncology indications comprised roughly three-fourths of the approved indications, most of which were non-Hodgkin lymphoma (66.4%), followed by autoimmune diseases, including both orphan-approved and orphan-designated indications, which accounted for 14.7%. The only approved nonorphan indication, rheumatoid arthritis, accounted for 11.3% of approved indications. Most off-label indications were neurologic diseases (72.7%), the vast majority of which were demyelinating diseases (91.4%), followed by hematologic diseases (7.3%).
The authors commented that the treatment of demyelinating neurologic conditions was “the primary driver of off-label use in our study,” and cited a recent Swedish study that found rituximab to be the disease-modifying therapy most commonly prescribed for patients with multiple sclerosis (MS). Furthermore, they noted that rituximab prescriptions in MS have risen following the publication of several small studies suggesting rituximab reduced inflammatory brain lesions in patients with MS.
New Biosimilars Enter a Huge and Growing Market
According to the authors, “Rituximab is considered a blockbuster specialty drug with nearly $4.2 billion in U.S. sales in 2017.” There are 2 FDA-approved rituximab biosimilars, Celltrion’s Truxima, which was approved in 2018, and Pfizer’s Ruxience, which was approved in 2019.
In light of non-Hodgkin lymphoma, an orphan indication, making up two-thirds of approved indications, the authors noted the expense of orphan drugs, writing “In 2017, the average cost per patient per year for an orphan drug was $147,308, compared with $30,708 for a nonorphan specialty drug.” They added that biosimilars could reduce these costs and stressed the importance of their findings for health plan policy makers, writing, “the launch of lower-cost rituximab biosimilars could lead to further increased use of the biosimilars for label and off-label indications.”
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