Biologics, acetaminophen and the multimillion-dollar lawsuit
Dr. Plaque, although practicing in a small town, is a renowned expert in psoriasis. He has practiced for 20 years, has been involved in numerous FDA trials for biologic agents used to treat psoriasis, and offers every known treatment for psoriasis. His expertise is clearly in the use of biologics. Such patients are often difficult to treat; some have a variety of other medical issues. He often treats those psoriatic patients who are eligible for phototherapy with biologics. He routinely does a variety of blood test and carefully follows his patients. Two years ago, one of these patients had acute onset liver failure with death in two months. It turned out the patient was using biologics to treat his psoriasis as well as taking daily acetaminophen.
The estate of this patient has now brought a multimillion-dollar lawsuit against Dr. Plaque, alleging that he should have warned his patient not to use these two drugs together. Is there any basis for such a lawsuit?
Biologic drugs have changed the face of psoriasis treatment but, with time, the warning labels have also expanded. A variety of issues are now linked to tumor necrosis factor-alpha (TNF-α) blocker use. Litigation has occurred with the use of a variety of biologics. These include adalimumab (Humira, Abbvie, Inc.), etanercept (Enbrel, Amgen) and infliximab (Remicade, Janssen), known as TNF-α inhibitors. The associated risks include cases of lupus, squamous cell cancer (SCC), histoplasmosis and coccidioidomycosis. While the biologic ustekinumab (Stelara, Janssen), an interleukin (IL) 12/IL23 inhibitor, has not engendered litigation, it seems logical to test for possible infections before starting patients on this biologic.
Indications and warnings
The package insert for biologics indicate that these drugs are for patients who are candidates for other systemic agents (eg, methotrexate) or phototherapy. Adalimumab is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. Adalmumab’s package insert states it should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician. Etanercept is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Infliximab is indicated for the treatment of adult patients with chronic severe (ie, extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. Infliximab should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician. Ustekinumab is indicated for the treatment of adult patients (18 years or older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.5
Black box warnings are included on the labeling for adalimumab, etanercept and infliximab. Ustekinumab does not have any black box warning but, from a physician’s medical legal perspective, this drug ought to be treated similarly. Most dermatologists and rheumatologists also routinely check both blood counts and liver function tests on their biologic patients. Similarly, the standard of care seems to be that patients not be placed on TNF-α inhibitors who have a family or personal history of lupus, lymphoma or multiple sclerosis.
What about the issue of liver failure? There are now over 150 reports of severe liver injury with infliximab use, including 10 cases of liver failure. Use of medications containing acetaminophen were linked to 139 cases of liver injury, but 69 cases of liver failure, making acetaminophen the most frequently cited cause of acute liver failure among medications monitored by the group.
There is no question that the use of acetaminophen in patients taking any biologic should be of concern to treating dermatologists. It would seem prudent to have such a conversation. If Dr. Plaque did not have such a discussion, an expert testifying against him might say that he deviated from the standard of care. Ultimately, if this case went to trail, a jury would need to decide if 1) not having a discussion about acetaminophen and the use of biologics represented a deviation in the standard of care and 2) is that breach actually was the cause of the death. If the jury agreed on both accounts, it is conceivable that Dr. Plaque could lose this multimillion-dollar lawsuit.