In RA Patients, Multiple Comorbidities Lower Odds of Disease Control

Ted Bosworth

August 23, 2021

An increasing number of comorbidities in patients with rheumatoid arthritis correlates with a lower likelihood of reaching treatment targets, according to an analysis conducted with a series of large real-world datasets and presented in a symposium sponsored by the Rheumatology Research Foundation.

Dr Bryant England

When compared to those with the lowest burden of comorbidity in one of these analyses, those with the highest had a nearly 50% lower likelihood (odds ratio, 0.54; 95% confidence interval [CI], 0.34-0.85) of achieving low disease activity or remission, according to Bryant England, MD, PhD, assistant professor in the division of rheumatology at the University of Nebraska, Omaha.

"Patients with more comorbidities struggle to reach treatment targets," England said. In the treatment of RA, "we typically focus only on the joints, but these data suggest we need to begin to think more holistically about managing these patients."

Both the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) endorse a treat-to-target management approach in RA guidelines, but only a proportion of patients reach their targets, according to England. In his series of analyses, England has been exploring the role of comorbidities as one of the contributing factors.

Looking for real-world data, England evaluated comorbidities in the Veterans Affairs Rheumatoid Arthritis Registry, which has a male predominant population, the National Databank for Rheumatic Diseases, which is female predominant, the Truven Health Analytics MarketScan Database, and the Rheumatology Informatics System for Effectiveness Registry (RISE).

Comorbidities Accrue More Quickly in RA Patients

All of these real-world data support the premise that comorbidities are higher in patients with RA than in those without, and show that the burden of comorbidities rises more quickly in patients with RA. For example, the average number of comorbidities in the MarketScan database of recently diagnosed RA patients was 2.6. Five years later, the average doubled to more than 5. For those without RA, the average at the baseline evaluation was 1.6 and remained below 3 at 5 years.

For the burden of comorbidities in RA, England prefers the term "multimorbidity" because he believes it captures the interconnections of these chronic diseases, many of which trigger or exacerbate others. When he looked at health history 2 years before the RA diagnosis, multimorbidities were already somewhat higher, but he found that burden "takes off" in the peri-diagnostic period and climbs steeply thereafter.

"The data tell us that multimorbidity becomes more problematic throughout the RA disease course," said England, who published some of these data only a few weeks prior to his presentation.

In one effort to evaluate how multimorbidity affects treatment choices and outcome, he selected patients with persistently active disease from the RISE registry, a group expected to be candidates for a treatment change or escalation. The data suggested patients with multimorbidity were less likely than were those without to receive a change of therapy in response to their active disease, but it also demonstrated that patients with multimorbidity were less likely to achieve remission or low disease activity even if the medications were changed.

Each Comorbidity Lowers Odds of Remission

When relative burden of comorbidities was assessed by RxRisk score, a validated medication-based measure of chronic disease that recognizes 46 categories of chronic conditions, there was about a 5% lower odds ratio for each RxRisk unit of increase in comorbidity. The relationship was consistent across various cohorts of patients evaluated, according to England.

When looking for patterns of comorbidities in these large datasets using machine learning, England reported that there were "striking" relationships between organ systems. This included a pattern of cardiometabolic multimorbidity, cardiopulmonary multimorbidity, and mental health and chronic pain multimorbidity. Surprisingly, the same patterns could be identified in those with or without RA, but the prevalence differed.

"RA was closely associated with all of these different multimorbidity patterns, but the odds of having these patterns were one- to threefold greater," England reported.

"The multimorbidity pattern most closely associated with RA was mental health and chronic pain," he added, noting that the same results were observed across the datasets evaluated.

The implication of this work is that multimorbidity exerts an adverse effect on the course of RA and might be an appropriate target of therapies to improve RA outcomes. Although England called for better tools to measure multimorbidity and consider how it can be addressed systematically in RA patients with the intention of improving RA control, he believes this is an important direction of research.

"What our data show is that we need to begin to think more holistically about these other diseases in RA patients," he said.

Others Support Targeting of Comorbidities

Vanessa L. Kronzer, MD, a rheumatology fellow at Mayo Clinic, Rochester, Minn., agreed. An author of a study that identified 11 comorbidities significantly associated with RA, either as conditions that predispose to RA or that commonly develop in patients with RA, Kronzer has drawn the same conclusion in regard to targeting comorbidities in the RA patient.

"Based on mounting evidence that multimorbidity is associated with RA and RA disease activity, taking a broader view of the patient as a whole and his or her comorbidities may help us to not only predict RA but also achieve over disease-specific goals," Kronzer said in an interview.

"I suspect that certain comorbidities, perhaps depression as an example, may play a particularly strong role in perpetuating high RA disease activity," she added. She considers this a ripe area of study for improving clinical strategies in RA.

"Finding out which ones [perpetuate RA] and targeting them could be a reasonable approach to moving forward," Kronzer said.

England and Kronzer reported having no potential conflicts of interest.

This article originally appeared on, part of the Medscape Professional Network.


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