Treating rheumatoid arthritis (RA) begins and ends with the goal of terminating synovitis. It should go without saying we must focus on disease activity and the many ways it is ascertained.
RA patients are homogeneous in that they are unified by seropositivity, chronicity and an additive synovitis over time. This pattern of expression makes RA a facile diagnosis.
But, every rheumatologist knows that each and every RA patient is different. Moreover, there’s a complexity to diagnosing, managing and treating RA.
Patients differ in their onset, progression, drug responses, lab profiles and their ability to take or tolerate medications. Each person is a unique challenge colored by age differences, comorbidities, medical histories, coping abilities, addictions, fears, intellect, family support, resources, money and an unquantifiable level of worry of the unknown. These make RA management a complex walk with each patient.
This past weekend I was fortunate to lecture at the Harvard Advances in Rheumatology Course, where I reviewed the safety issues surrounding the use of biologic therapies. In discussing infections, cancer, cardiovascular events, etc., it became very clear to me that these problems, while worrisome, are often escalated in their importance – all at the expense of what is most dangerous: RA itself.
- The short- and long-term hazards, pain, damage and disability are directly linked to disease activity; the same measures we use as goals in practice and trials are those that measure how low or how high disease activity is.
- Infection is more closely tied to disease activity and debility, making RA itself the prime risk factor for severe or serious infections. DMARDs pose a miniscule risk. Biologics have a small, often nonsignificant, risk that only becomes meaningful in patients with the most disease activity and complications and steroid use.
- Cancer risk, especially lymphoma, is closely linked to RA disease severity. The famed Baeckland study showed those with the highest disease activity had a greater than 70 fold increased risk of lymphoma. By comparison, most population based studies show that RA alone imparts a 2-6 fold increased risk of lymphoma. Again, inflammation and disease activity are the real bad guys when it comes to a grave safety concern like cancer.
- Cardiovascular risks in RA are also more likely to be linked with disease activity than a drug. Chronic use of methotrexate and TNF inhibitors (that control disease activity) have been shown to dramatically reduce the risk of CV events in RA patients.
- Most of the issues that worry patients and physicians most are 1 in 1000 rare events (cancer, lymphoma, TB, opportunistic infections, autoimmune phenomena, etc.).
The bottom line is that all discussions on safety have to begin first with an understanding that uncontrolled disease activity will cause most of the damage and disease, but it also increases the odds that a sick person will have more of the “adverse events” or toxicities that we all worry about.
In the movie, “28 Days”, one of the characters tries to support a recovering Sandra Bullock by hanging a sign about her neck that says:
It's the engine that kills ya’, not the caboose.
We need to focus and affix a primacy to disease activity in RA management. Safety managment becomes less complex once that is understood.