Patients With Rheumatoid Arthritis Have an Increased Risk of Multimorbidity Burden

March 2, 2021
Lana Dykes

Investigators believe inflammation, which is known to begin before rheumatoid arthritis (RA) symptoms appear, may be a main factor in the increased prevalence and incidence in multimorbidity for patients with RA.

Investigators discovered that patients with rheumatoid arthritis (RA) not only have a higher prevalence of multimorbidity at the time of diagnosis, but they also have an increased risk of incidence thereafter, according to a recent study published in The Journal of Rheumatology.1

Multimorbidity differs from comorbidity as it is limited to chronic conditions, as opposed to all comorbidities, and it is focused on patients instead of the disease index. “This concept is useful in patients with RA because it is reflective of patient complexity and the associated challenges in providing care for patients with RA who have multiple chronic conditions (eg, the influence of other chronic conditions on RA treatment response),” investigators stated.

The population-based study included data from patients with incident RA between January 1, 1999, and December 31, 2013, in Olmsted County, Minnesota, with all patients fulfilling the 1987 American College of Rheumatology (ACR) classification criteria for RA. Overall, investigators examined 597 RA patients and 594 non-RA patients.

Information collected from participants included age, sex, race and ethnicity, smoking status, body mass index, and obesity. Within the RA cohort, 70% of participants were female, 90% were Caucasian, 40% were obese, and the mean age was 55.5 years. The non-RA patients had incredibly similar statistics, as 70% were female, 91% were Caucasian, 39% were obese, and the mean age was 55.4 years.

Each patient with RA was matched with a subject without RA of similar age, sex, and calendar year. The calendar year was used to determine if there were any trends over time. The non-RA participant was assigned an index date relating to the incidence date of the RA subject.

Investigators created a list of comorbidities for both the general population and those with rheumatic diseases using a combination of the Charlson, Elixhauser, and Rheumatic Disease Comorbidity Indexes as well as diagnostic codes from health care providers in Olmsted County. Currently there is no set list of conditions used for assessing multimorbidity. Information on patients with RA were tracked from 4 years prior to incidence/index date (the date when the patient exhibited at least 4 of the 1987 criteria for RA) until the last follow-up. The 25 most common medical conditions for patients with RA included cancer, cardiovascular disease, diabetes mellitus, valvular disease, dementia, hypertension, depression, and hypothyroidism. Rheumatic diseases were not included as comorbidities. Multimorbidity (MM2+) was defined by investigators as the presence of 2 or more chronic conditions. Substantial multimorbidity (MM5+) was defined as patients with 5 or more chronic conditions.

The groups were compared using either the Chi-Square test, Fisher’s exact test, or Mann-Whitney/Wilcoxon rank-sum test. Incidence was adjusted for the risk of death for each comorbidity, MM2+, and MM5+, which helped account for any mortality rate differences between the cohorts. Throughout the study, 121 patients with RA and 92 non-RA patients died.

Even though investigators excluded hypertension, the most common comorbidity, the differences between both cohorts persisted. MM2+ at incidence/index date was higher in patients with RA than the non-RA cohort, with 228 (38%) versus 188 (32) P = 0.021, respectively. However, MM5+ was similar in both groups (5% and 4%, respectively). During the follow-up period, a larger percentage of patients with RA developed multimorbidity (214 versus 188, respectively). At the 10-year mark, multimorbidity for patients with RA was 56.5%, compared with only 47.9% of non-RA participants.

Further, patients with RA had an increased risk of having hypothyroidism and chronic pulmonary disease at the incidence/index date when compared with the non-RA cohort. During the study, patients with RA had increased incidence of deficiency anemias, depression, and liver disease.

Investigators believe inflammation, which is known to begin before RA symptoms appear, may be a main factor in the increased prevalence and incidence in multimorbidity for patients with RA, as it is a known contributor to cardiovascular disease as well as other comorbidities.

Strengths of the study included the duration of follow-up (11 years), which exemplified comorbidity over a long period of time. However, its retrospective design proved to be a limitation as only documented cases were eligible for assessment. Although it is unlikely that comorbidities of interest were missed, the accuracy of diagnoses may be lacking. To combat this, investigators required certain procedures, including the presence of 2 codes at least 30 days apart. Another limitation was that chronic conditions were used in defining multimorbidity burden, which tend to be unequal and underestimates the severity of certain conditions. Lastly, the limited diversity (90% Caucasian) may hinder generalizability.

“These findings underscore the complexity of caring for patients with RA, since a large proportion of these patients have multiple chronic conditions. The complexity makes healthcare decision-making more challenging than in patients without RA,” investigators concluded. “In addition, patients with rheumatic diseases are less likely to receive optimal health maintenance and preventive care services. Therefore, there is an increasing need for rheumatology care models that provide support for addressing multimorbidity and for improved coordination of healthcare between rheumatologists and primary care providers.”


Gunderson TM, Myasoedova E, Davis JM 3rd, Crowson CS. Multimorbidity Burden in Rheumatoid Arthritis: A Population-Based Cohort Study [published online ahead of print, 2021 Feb 15]. J Rheumatol. 2021;jrheum.200971. doi:10.3899/jrheum.200971