Off-Label Use of Biological Agents in Rheumatological Diseases
Rheumatological diseases are particularly difficult to diagnose; and in their more severe forms, even more challenging to treat. Case managers should use the guidelines in this article to determine the medical necessity of off-label use of biological agents for rheumatological diseases.
Approved rheumatological drugs
The U.S. Food and Drug Administration has approved three drugs for the treatments of rheumatoid arthritis, juvenile idiopathic arthritis and psoriatic arthritis. They are Remicade, Enbrel and Humira. The FDA approved Orencia and Rituxan for rheumatoid arthritis only. Some of these drugs are very costly, with prices rising up to $20,000 a year. Appropriately, they are reserved for specific rheumatological diseases based on the most thorough supporting medical evidence. In addition, due to the unique side effects of these drugs, the prescribing physician must monitor the patient meticulously.
Off-label use
Doctors treating rheumatological diseases commonly use rheumatological medications off-label. Many rheumatological diseases share a common pathophysiological pathway and, consequently, conclusions emerging from treatments of one disease can be applied to other, less-common situations. In many ways, rheumatological diseases can be regarded as “orphan diseases.” Because of the unusual nature of these diseases, and the small populations involved, large-scale studies are unachievable. For example, observed findings regarding treatment of lupus vasculitis with Cytoxan are applied successfully to unusual diseases such as ANCA associated vasculitis.
Why guidelines?
Guidelines assist case managers in determining whether a requested medication is appropriate. The reviewer should examine the medical record for supporting clinical evidence detailing the rheumatological disease, and for documentation regarding failure of prior conventional treatments. In some cases, the case manager may conduct a search for peer-reviewed literature detailing favorable outcomes and acceptable risks regarding the off-label use of the requested medication.
These suggestions are particularly true of rheumatological diseases in which the patient may be very ill and refractory to otherwise acceptable treatments. In many cases, the physician moves quickly and takes extraordinary steps to prevent patients from loosing their limbs – or lives.
Wegener's disease, with acute ocular involvement, is one example. Wegener's disease is rare. A patient who is refractory to Cytoxan or steroids may require an extraordinary and expeditious intervention with an off-label use of medication, such as Remicade or Rituxan. A literature review regarding the disease discloses that biological drugs such as Enbrel may not be as efficacious as Remicade or Rituxan. In both instances, the use of either of these drugs is obviously off-label. However, the patient is critically ill and is refractory to other, more conventional, notwithstanding, toxic medication. In such a scenario, selection of a biological agent may be necessary.
Questions to Consider
Two types of questions must be asked when reviewing the medical records:
First, is the disease for which the medication is requested well documented in the medical record? A corollary concern is whether the patient is refractory to more conventional modalities.
Second, is the requested medication FDA-approved for the disease? If not, do peer-reviewed studies support the off-label use of these medications? Do these studies involve a series of patients or case studies? Do these studies indicate a promising and salutary benefit while maintaining a reasonable safety profile? Is there favorable data within a study that can be extrapolated out and applied to circumstances that are not the specific study outcome?
What to look for
In conclusion, the case reviewer needs to find the following documented in the patient’s file:
- supporting clinical evidence detailing the disease in question
- documentation regarding failure of prior conventional modalities
- peer-reviewed literature detailing favorable outcomes and acceptable risks regarding the off-label use of the requested medication
If all three are not present, then it is reasonable to deny the request for off-label use of the rheumatological drugs. If this is not the case, then a trial basis can be approved – especially if it follows guidelines and the physician closely monitors the outcome.
Failing to properly treat the more serious manifestations of these diseases potentially places the patient in dire circumstances that could lead to the loss of a limb, or life.
