Rheumatology

Rheumatoid Arthritis

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Partnering With Primary Care on Cardiovascular Health, Vaccinations, and More

expert roundtables by Jonathan Kay, MD; Leonard H. Calabrese, DO; Vibeke Strand, MD, MACR, FACP

Overview

Patients with rheumatoid arthritis (RA) have benefited from a reduction in cardiovascular morbidity in recent decades, but their cardiovascular risk is still increased relative to the general population, and cardiovascular disease progression often occurs at an accelerated rate. Thus, identifying and reducing cardiovascular risk is particularly important, as are other preventive strategies, such as vaccination.

Q:

What is the rheumatologist’s role in preventive strategies such as cardiovascular risk factor reduction and vaccination?

Leonard H. Calabrese, DO

Professor of Medicine
RJ Fasenmyer Chair of Clinical Immunology
Director, RJ Fasenmyer Center for Clinical Immunology
Vice Chair, Department of Rheumatic and Immunologic Diseases
Cleveland Clinic Foundation
Cleveland, OH

“We should be enthusiastic and fully committed when talking to our patients about vaccination. We should also counsel patients about the importance of family members being vaccinated.”

Leonard H. Calabrese, DO

RA is an accelerator of cardiovascular risk, so cardiovascular risk reduction is highly relevant. Although our patients with RA have benefited from reduced cardiovascular morbidity over the years, they still have increased risk relative to the general population. We rightly focus on the use of biologics to lower inflammation, but we should also, at the very least, be nominal partners in seeing that our patients have aggressive cardiovascular risk reduction. In our preventive cardiology clinic, the low-density lipoprotein target is 70 mg/dL or lower.

Vaccines are important at the individual level and the societal level. Even with vaccines that might not be highly effective for an individual (eg, the seasonal influenza vaccine), public health is improved if a sufficient percentage of the population is vaccinated. The Infectious Diseases Society of America endorses shared responsibility between primary care physicians and subspecialists in vaccinating patients with altered immunocompetence. We should be enthusiastic and fully committed when talking to our patients about preventive strategies such as vaccination. We should also counsel patients about the importance of family members being vaccinated. For instance, we need to support seasonal influenza vaccination; there are very few contraindications to the inactivated influenza vaccine, and we advise that methotrexate (MTX) be held for 2 weeks following the administration of the influenza vaccine to increase the immune response. Patients with immune-mediated rheumatic disease also need pneumococcal vaccination and herpes zoster vaccination. Systematic adaptations, such as electronic flags on the electronic medical record (EMR), standing orders, and posters in your office asking patients to remind you to talk to them about vaccines, have been shown to be among the most effective adjuncts for increasing vaccine uptake.

Vibeke Strand, MD, MACR, FACP

Adjunct Clinical Professor, Division of Immunology/Rheumatology
Stanford University School of Medicine
Biopharmaceutical Consultant
Palo Alto, CA

“Although rheumatologists are not in a position to manage all aspects of cardiovascular risk, we can target the inflammation that drives both RA and cardiovascular disease progression.”

Vibeke Strand, MD, MACR, FACP

Although rheumatologists are not in a position to manage all aspects of cardiovascular risk, we can target the inflammation that drives both RA and cardiovascular disease progression. The multi-biomarker disease activity score can be used as a helpful tool for recognizing cardiovascular risk, but more work must be done to tease out cardiovascular risk in patients with RA. Patients with an elevated multi-biomarker disease activity score need better control of the inflammation that is driving both RA disease activity and cardiovascular disease. Interestingly, Karpouzas et al reported on the effects of biologic disease-modifying antirheumatic drugs (DMARDs) on coronary plaque formation or progression in patients with RA. They followed 150 patients using coronary computed tomographic angiography for approximately 7 years (756.8 patient-years), and through multivariable analysis found that biologic DMARD use was linked to reduced cardiovascular disease risk and a lower likelihood of new plaque formation, independent of time-varying statin use and C-reactive protein levels. This was a small study, but sufficiently powerful to demonstrate that biologic DMARDs are cardioprotective in patients with RA.

We have instituted a program to increase vaccinations and compliance with vaccine recommendations. One of the important issues brought to light is that simple recommendations for vaccination are not sufficient. Insurance companies have different requirements regarding where the patient can be vaccinated (eg, pharmacy vs clinic). If you do it the wrong way, the vaccine is not covered. Even if you integrate the vaccine recommendations in the EMR, which also has the patient’s insurance information, you still need to make sure that the patient actually gets vaccinated appropriately; so, there are many barriers that can make things genuinely challenging.

Jonathan Kay, MD

Professor of Medicine and Population and Quantitative Health Sciences
Timothy S. and Elaine L. Peterson Chair in Rheumatology
Director of Clinical Research, Rheumatology
University of Massachusetts Medical School
Worcester, MA

High RA disease activity contributes to increased cardiovascular risk. Rheumatologists should have a low threshold for referring patients with cardiac symptoms for cardiovascular evaluation.”

Jonathan Kay, MD

During a visit with a patient with RA, the rheumatologist must deal with issues related to disease activity and drug therapy. This may leave little time to address the prevention and management of comorbidities. High RA disease activity contributes to increased cardiovascular risk. When a patient with RA experiences dyspnea on exertion or left arm discomfort, we should consider that cardiovascular disease might be the cause. Rheumatologists should have a low threshold for referring patients with such symptoms for cardiovascular evaluation. Also, since some of the medications that we prescribe increase lipid levels, we should monitor and address those lipid abnormalities, either by initiating lipid-lowering therapy or by referring our patients to preventive cardiologists for evaluation and appropriate treatment.

Vaccination is an important issue that must be attended to, and EMRs can prompt us to ensure that this happens. Influenza vaccination is of particular importance, since this infection may result in significant cardiopulmonary morbidity and mortality, especially in patients receiving immunosuppressive medications. We advise patients who are treated with MTX to hold their MTX dose for 2 weeks after getting their flu shot, since this has been shown by Park and colleagues to increase substantially the proportion of patients who achieve a satisfactory immune response (75.5% of those who held MTX vs 54.5% of those who continued MTX). Despite its importance, not all patients are compliant with vaccination. For example, giving a patient a prescription for the herpes zoster vaccine does not guarantee that they will be vaccinated. An often-overlooked opportunity for vaccination is among patients who have had hepatitis B serologies performed before initiating treatment with MTX or a biologic DMARD. We routinely check these serologies, which often reveal that patients are not immune to hepatitis B, but do not necessarily follow up by immunizing them with the hepatitis B vaccine. 

References

Bartels CM, Roberts TJ, Hansen KE, et al. Rheumatologist and primary care management of cardiovascular disease risk in rheumatoid arthritis: patient and provider perspectives. Arthritis Care Res (Hoboken). 2016;68(4):415-423. doi:10.1002/acr.22689

Dell’ Era L, Esposito S, Corona F, Principi N. Vaccination of children and adolescents with rheumatic diseases. Rheumatology (Oxford). 2011;50(8):1358-1365. doi:10.1093/rheumatology/ker102

Furer V, Rondaan C, Heijstek MW, et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020;79(1):39-52. doi:10.1136/annrheumdis-2019-215882

Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Biologics may prevent cardiovascular events in rheumatoid arthritis by inhibiting coronary plaque formation and stabilizing high-risk lesions. Arthritis Rheumatol. 2020 Apr 21. doi:10.1002/art.41293

Karpouzas G, Ormseth S, Hernandez E, et al. Biologics prevent cardiovascular events in rheumatoid arthritis by inhibiting non-calcified coronary plaque progression and stabilizing vulnerable plaques [abstract 1895]. Abstract presented at: 2019 American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting; November 9-13, 2019; Atlanta, GA.

Navarro-Milán I, Cornelius-Schecter A, O'Beirne RJ, et al. Views of primary care physicians and rheumatologists regarding screening and treatment of hyperlipidemia among patients with rheumatoid arthritis. BMC Rheumatol. 2020;4:14. doi:10.1186/s41927-020-0112-5

Park JK, Lee YJ, Shin K, et al. Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis. 2018;77(6):898-904. doi:10.1136/annrheumdis-2018-213222

Rondaan C, Furer V, Heijstek MW, et al. Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases: a systematic literature review for the 2019 update of EULAR recommendations. RMD Open. 2019;5(2):e001035. doi:10.1136/rmdopen-2019-001035

Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1):1-26. doi:10.1002/art.39480

Westra J, Rondaan C, van Assen S, Bijl M. Vaccination of patients with autoimmune inflammatory rheumatic diseases. Nat Rev Rheumatol. 2015;11(3):135-145. doi:10.1038/nrrheum.2014.206

Jonathan Kay, MD

Professor of Medicine and Population and Quantitative Health Sciences
Timothy S. and Elaine L. Peterson Chair in Rheumatology
Director of Clinical Research, Rheumatology
University of Massachusetts Medical School
Worcester, MA

Leonard H. Calabrese, DO

Professor of Medicine
RJ Fasenmyer Chair of Clinical Immunology
Director, RJ Fasenmyer Center for Clinical Immunology
Vice Chair, Department of Rheumatic and Immunologic Diseases
Cleveland Clinic Foundation
Cleveland, OH

Vibeke Strand, MD, MACR, FACP

Adjunct Clinical Professor, Division of Immunology/Rheumatology
Stanford University School of Medicine
Biopharmaceutical Consultant
Palo Alto, CA

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