January 19, 2017
4 min read

Comorbidities in Rheumatoid Arthritis: More Work or Part of Job?

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Caring for patients with rheumatoid arthritis today is a joy compared to the challenge posed merely a generation ago. However, this transformation has come with costs in terms of our efforts. When we had little to offer in terms of treating the underlying disease, the primary challenges were to stop progressive bone destruction and attendant incapacity, as well as focus on the ravages of complications, such as nodulosis, vasculitis and cytopenia.

By the 1980s, numerous investigators, such as James F. Fries, MD, and Theodore Pincus, MD, and others began to clearly demonstrate the increased mortality of rheumatoid arthritis (RA) from manifestations previously less well appreciated such as accelerated ischemic heart disease. Over time, with the standardization of the use of drugs such as methotrexate and then the introduction of biologics in the late 1990s, came the hope the end of our struggles to manage both the articular and extra-articular manifestations of the disease was near.

Leonard H. Calabrese

As with so many forms of progress, we have been both blessed and cursed by our success. Indeed, patients are now better controlled than ever and the wheelchairs, assistive devices and, for that matter, rheumatoid nodules are all rare in the present climate of aggressive, treat-to-target therapy. Even the extremes of mortality from rapidly progressive ischemic heart disease have regressed but have far from disappeared. We now have a more granular view of associated comorbidities, including ischemic heart disease, congestive failure, metabolic bone disease and infections, which occupy our worry and time.

In the Cover Story of this issue of Healio Rheumatology, we are fortunate to have commentary by numerous key opinion leaders in the field of comorbid complications and are appreciative of their insights.

Prevention of Infections

I would like to focus on one area of comorbidity of interest to me and that is serious infections and their prevention. Serious infections are part of the fabric of the treatment of RA and have not gone away despite advances in therapy. We know that, aside from biologic therapies, glucocorticoids still hold sway as a dominant risk factor for serious infections in the RA population. While in theory the need for glucocorticoids has diminished with the advent of new and potent combination disease-modifying anti-rheumatic drugs (DMARDs) and biological DMARDs, unfortunately their use is still too frequent as evidenced by data describing cohorts of patients entering clinical trials for DMARDs (ie, generally near 50%). In addition, we are in an era where we are confronted with new and emerging pathogens, such as hepatitis C and hepatitis B, as well as the infrequent occurrence of potentially devastating opportunistic infections from biologic therapy not envisioned 20 years ago. As a result, practice patterns have changed as dictated by guidelines that we are now screening (successfully I might add) for tuberculosis and chronic viral hepatitis as part of standard of care.

In addition to these screening biomarkers, we have recommendations of prevention through vaccinations which, a generation ago, were not on the rheumatology radar screen. I am afraid to say that evidence has suggested that routine vaccination has not been seamlessly incorporated into our practice settings. The reasons are complex but are useful to consider. In the past, vaccinations were considered the domain of the family physician but as we all know, many primary care physicians are intimidated by patients on complex immunosuppressive regimens and are under-immunizing by default. On the other hand, many patients who are on biological DMARDs are inadvertently given live vaccines, such as zoster vaccine, which is by labeling contraindicated. Both practices leave patients with less than a robust standard of care.


What is a rheumatologist supposed to do? For us to take on the task of vaccinating patients with RA takes time, effort and money, as few offices can afford to stock some of the costlier vaccines. There is a perpetual competition for the few minutes we have with patients to accomplish important tasks. Depending on the primary care physicians has not worked well either.


The Infectious Disease Society of America in their 2013 recommendations on immunizations in compromised hosts state up front: “Specialists who care for immunocompromised patients share responsibility with the primary care provider for ensuring that appropriate vaccinations are administered to immunocompromised patients.”

Even accepting this tenant, however, we are then on our own to get the job done. On the positive side, it has been clearly demonstrated that to improve the uptake of vaccines in patient populations with rheumatic disease the answer is to change the system.

I would like to note a recent publication and a recent presentation asserting that changing the system is the way to go. First in an excellent review of barriers to immunizations Elizabeth Kirchner, MSN, CNP, and Victoria Ruffing, RN-BC, CCRP, from Cleveland Clinic and Johns Hopkins, have provided an excellent and practical review of the problems, standards and possible strategies to improve vaccine rates. In addition, Laure Gossec, MD, PhD, and colleagues reported on a multicenter 3-year intervention that demonstrated when advanced practitioners lead the initiative things happen.

Let us all examine our internal systems to improve our prevention efforts from infectious comorbidities. Consider doing the little things first and the more complex things later. Simplify, simplify.

Follow me on Twitter @LCalabrese DO.

Disclosure: Calabrese reports he is a consultant for Genentech, Pfizer, Bristol-Myers Squibb, GlaxoSmithKline, Sanofi, Jansen and AbbVie; and is on the speakers bureau for Genentech, AbbVie and Bristol-Myers Squibb and Crescendo Bioscience.