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What Do We Do Without Evidence in a World of Evidence-Based Medicine?

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I sit facing Ms. M in my exam room, looking at her while explaining the role of rituximab, a medication I use frequently for vasculitis and rheumatoid arthritis. Except Ms. M has Sjogrens disease and rituximab is used off-label for her condition. So I am explaining that it is possible her insurance may deny coverage of the medication at first, then we may have to request it from the drug company. I will use supporting case reports to justify using this medication for her refractory autoimmune condition, but this may not be enough.

Currently, there are no FDA-approved treatment options for Sjogrens disease, despite this being an autoimmune condition that affects millions of people in the U.S. As rheumatologists, we often use medications that are approved to treat rheumatoid arthritis and systemic lupus to also treat Sjogrens, but insurance companies typically only recognize FDA-approved medications for this particular diagnosis. In other words, we use medications that are based off limited case reports and sparse data that demonstrate their effectiveness. Then when you see the treatments work in patients, you begin to use them over and over in those populations. 

Talking to patients about their treatment plan is a ritual that is part habit and part creative experience. As a rheumatologist, many of the treatment options and combinations of medications I talk to my patients about every day have been developed by rigorous clinical trials and have years worth of data behind them to support the evidence of why those treatment options should be effective. We refer to this guideline-based practice as evidence-based medicine. 

In every field, this is what governs many of our decisions about how to select medication or treatment options. We are assured by the hundreds to potentially thousands of patients who have gone down this path before. The data supports our decision making. The data assures us that we can calculate risks and benefits of a drug and feel confident that we are practicing in alignment with what our peers would do, in the event of legal recourse. 

But what happens when we do not have specific guidelines to support medical decisions for certain diseases? Where do we turn for assurance that a medication or treatment plan is the recommended option? Do we hold back treating our patients when we know there is something available to use that has the potential to be effective? If you were the patient, would you want your physician to offer treatment based on case reports, even if that option was not widely accepted in the eyes of the FDA? 

This decision making is part of the art of medicine: the mentality that we can devise a plan together to try something that may not have a dedicated FDA-approved roadmap to follow. Eventually, through enough case reports and development of clinical trials, we tend to see these treatment options approved and as part of a dedicated arsenal that insurance companies then recognize. But this process may take decades and is largely dependent on the decision of the drug companies to conduct clinical trials with their product, or large-enough clinical trials funded by large academic centers to pique the interest from the drug manufacturer. Some fields move relatively quickly in this arena, like oncology, where chemotherapy regimens are manipulated based on a plethora of clinical trials. Rheumatology, however, is a slow-moving field and clinical trials are not as abundant nationwide. 

Treating gout is another great example of how long it can take for there to be an evidence-based approach to treatment. Throughout my career I have been using IL-1 inhibitors to treat gout flares. These medications are potent anti-inflammatory medications that are used in other conditions such as adult onset Still's disease and rheumatoid arthritis, and work spectacularly to treat gout flares. Yet, these products have been used off-label until the FDA approved use of one of these products this year. Despite there being “evidence” now that these medications work to treat gout, it will still take several more years for their use to be widely accepted by the medical community at large due to widespread hesitation about newly approved products on the market. 

Ultimately, Ms. M received her medication from the drug manufacturer based on compassionate use after her insurance company denied coverage of the infusion. I collected and presented several case reports and small studies highlighting the success of this treatment for her specific condition, and her insurance still determined the treatment not to be medically necessary, despite her continuing to decline with the other non-FDA approved oral medications that patients are required to try before moving on to biologic therapy. On her most recent visit, she was she was improving and now back to work. Together, we made a decision to go down a less-accepted path, but a path that I was confident would provide her some relief for a condition that is all too common but not commonly studied in medicine. Thankfully, there are several clinical trials being conducted for Sjogren’s disease and the future may not be as challenging to navigate for patients like her. But that will still take time, and when you are a patient struggling with a condition that does not have a clear evidence-based treatment algorithm to follow, time is not on your side. 

When have you had to make a “no evidence” treatment decision? Share in the comments.

Dr. Brittany Panico is a rheumatologist in Phoenix, AZ. She is a wife and mother of three awesome boys and enjoys hiking, being outdoors, traveling, and reading. She posts on @AZRheumDoc on Instagram and Brittany Panico, DO, on LinkedIn. Dr. Panico is a 2023–2024 Doximity Op-Med Fellow.

*Disclosure: This article is not intended to be used as support for off-label use of medications.

Image by Luciano Lozano / Getty

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