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17 Articles in Volume 20, Issue #1
20/20 with Lynn Webster, MD
Analgesics of the Future: Peripheral Kappa Opioid Receptor Agonists
Correspondence: Opioid-Induced Hyperalgesia; Pain Care in Older Adults
Don’t Discount the Role of Diet for Chronic Pain Relief
Editorial: Why Haven’t There Been More Breakthrough Analgesics?
Gasping for Air: Sleep-Disordered Breathing and Chronic Opioids
How can botulinum toxin be used in chronic pain syndromes?
Neurodestructive Interventions for Cancer Pain
Obesity and Pain Care: Multifaceted Considerations for Treatment
Obesity and Rheumatoid Arthritis: What Clinicians Should Know
Sickle Cell Pain Crisis: Clinical Guidelines for the Use of Oxygen
The Complexity of Sickle Cell Pain: An Overview
The Perseverance Loop: The Psychology of Pain and Factors in Pain Perception
The Rapid Rise of Non-Opioid Pain Policies
Treating Pain by Overcoming Communication Barriers
Visual Artists Tackle What Pain Looks Like
Will 2020 Be the Year of Patient Education?

Obesity and Rheumatoid Arthritis: What Clinicians Should Know

There are important links between obesity and RA, including risk and drug effectiveness.
Pages 45-46

A long-standing concern in the medical community, obesity is known to affect more than 90 million adults in the United States and often results in widely known health consequences, such as heart disease, stroke, and type 2 diabetes.1 More recently, obesity has been linked to inflammatory diseases, such as rheumatoid arthritis (RA), as well as widespread chronic pain.2,3

“There are important links between obesity and RA. Not only is obesity a risk factor for RA, but being overweight makes the drugs less effective,” Eric Matteson, MD, MPH, chair of the rheumatology department at the Mayo Clinic in Rochester, MN, told PPM. “As well, adipose [fat] cells contain inflammatory proteins which we think are important in the inflammatory process.”

Chronic, systemic, and autoimmune-based, RA is most commonly characterized by symmetric pain, swelling, and stiffness of the joints. These symptoms result from inflammation, a phenomenon that may result from obesity as well.4

Some studies have substantiated the role of obesity in the course of rheumatoid arthritis. (Image: iStock)

Obesity as a Risk Factor for Rheumatoid Arthritis

According to a systematic review published in Autoimmunity Reviews, individuals who are obese are at an increased risk of developing RA.5 The authors of this review suggested that the accumulation of white adipose tissue that results from obesity contributes to this finding, given that this tissue secretes adipokines, such as leptin, adiponectin, resistin, and visfatin, all of which may be involved in immunity and inflammation. These findings are supported by an additional systematic review and meta-analysis published in Arthritis Research and Therapy, demonstrating an increased risk of RA in individuals with a higher body mass index (BMI).6

A more recent study published in Arthritis Care and Research by researchers from Denmark showed an increased risk of developing RA from higher body fat percentage, higher waist circumference, and obesity. However, unlike the aforementioned analyses, this finding was noted in women, but not men.7 “It remains unknown whether the association of the development of RA with excess adipose tissue simply reflects the presence of inflammatory activity as a part of the metabolic syndrome or whether it contributes to the development of autoimmune inflammatory joint disease,” the authors suggested.7

BMI and Risk for Other Chronic Pain Conditions

“Obesity can also have an impact on chronic, widespread pain and fibromyalgia, which is present in about 20% of RA patients,” added Don Goldenberg, MD, a rheumatologist and professor emeritus at Oregon Health Services University. He pointed to research by Neuman, et al, which found that patients who were both obese and had fibromyalgia syndrome displayed higher pain sensitivity and lower levels of quality of life (QOL).8 Related research has supported links between severe obesity (BMI ≥ 35.0 kg/m2) and symptom severity/QOL in patients with fibromyalgia9 and with chronic pain overall.10


Editor's Note: See also how anxiety and psychiatric disorders affect people with rheumatoid arthritis.

The Role of Obesity in Disease Course

In addition to increasing the likelihood of an individual developing RA, obesity may negatively affect the disease course for individuals with obesity.5 Dr. Matteson provided one plausible reason for this finding: “The extra weight is especially bad for hips, knees, and ankles, and accelerates the development of arthritis in these joints already due to mechanical stress."

A recently published cross-sectional study of patients with RA evidenced a direct association between elevated BMI and increased swelling of lower extremity joints. Furthermore, participating patients showed a higher disease activity score, specifically with the validated DAS-44 disease activity measure.11

Other studies have substantiated the role of obesity in the course of rheumatoid arthritis. In an investigation of the histological and transcriptional features of synovial tissue in patients with RA, a team of scientists demonstrated that patients with RA who were also overweight or obese had higher degrees of synovitis both at disease onset and after achieving remission. Based on their results, the team recommended that patients with RA aim to manage their weight throughout the course of their disease.2 (More on diet for inflammation)

Another systematic review and meta-analysis out of Canada found that obesity in fact “decreases the odds of achieving remission in RA” and negatively impacts “patient-reported outcomes during therapy.” The research team proposed that interventions to reduce BMI in these patients be investigated for their ability to improve disease outcomes.12

Treatment Complications and Goals

There has been a rapid development of new therapies for RA over the past several years. Per the 2015 American College of Rheumatology clinical practice guidelines, clinicians have several pharmacologic options available to manage patients with RA, including traditional disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and medications such as tofacitinib, each regimen personalized to the clinical scenario.13

However, emerging studies suggest that obese patients with RA may require further individualization of treatment plans. A 2019 systematic review and meta-analysis published in Joint Bone Spine showed that treatment efficacy was diminished for certain medications in patients who are obese. These findings were specific to anti-tumor necrosis factor agents, with the authors noting that the efficacy of certain agents, including abatacept and tocilizumab, remained unaffected. “[A] personalized treatment strategy should be considered for obese patients,” the authors recommended.3

Overall, suggested Dr. Matteson, “Physicians must advise their patients in a compassionate but frank way about the problems related to obesity. This also includes the extra risk patients have for developing heart disease. Patients with RA are already at increased risk for heart disease and being overweight is a further burden for them. Patients want to live well and do well, so understanding these connections is vital,” he said. 

Last updated on: May 11, 2021
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