How Fat Affects PsA

By Emily Delzell

Obesity and psoriatic arthritis (PsA) have a complicated relationship. Being overweight or obese is more common in people with PsA than in those without it. Research also shows that those with both conditions are more likely to develop other related diseases.

Estimates of obesity among people with PsA vary among studies, with some finding that up to 45% of people with PsA are obese. Rubén Queiro, MD, PhD, an associate professor of medicine in the Department of Rheumatology at Oviedo University in Asturias, Spain, published a study in 2019 in Medicine that found about 28% of participants with PsA were obese. His study also confirmed earlier proof that people with PsA had high rates of weight-related problems, such as high blood pressure, diabetes and high cholesterol.

Effect of Obesity on PsA
Carrying extra weight is linked to having more severe PsA and to getting less benefit from some medicines.

Body fat has what scientists call a “dose-dependent” effect on the disease’s activity and on the effectiveness of biologic medications . This means that PsA symptoms and damage increase along with rising obesity, while the ability of biologics to treat the disease falls.

The good news is that losing even a modest amount weight improves both skin and joint symptoms and boosts the effectiveness of biologics. Weight loss also can help manage many risk factors linked to heart disease, which occurs more often in people with PsA than in those without the disease, says Dr. Queiro.

Understanding the Connection
What’s the link between being overweight and more active, harder-to-treat PsA? The answer may lie in fatty tissue itself. Fat churns out proteins called cytokines, chemokines and adipokines, which promote inflammation.

Obesity is viewed by scientists as on ongoing state of low-grade inflammation that contributes to a number of diseases, including PsA, says Dr. Queiro.

“Fat tissue is not a mere reservoir of energy for humans. It is an active tissue that’s capable of creating proteins known to play a role in the development and disease activity of psoriatic arthritis,” he says. “Under the appropriate genetic circumstances, this chronic state of inflammation can predispose people to psoriasis and psoriatic arthritis.”

Carrying excess fat can also take a wear-and-tear toll on joints, says Eva Klingberg, MD, PhD, a rheumatologist at the University of Gothenburg in Sweden. “Increased body weight leads to stress on joints and tendons, an increased risk of [musculoskeletal] injury and subsequent inflammation during the healing,” she says.

How Fat Interferes with Biologics
A number of studies have shown that for people with PsA, being obese raises the chances of not improving with a biologic. Drugs that target and block tumor necrosis factor (TNF), an inflammatory protein that’s overactive in PsA, are particularly affected. Obesity also lowers the chances that a biologic will help people reach “minimal disease activity” (MDA), which is the current goal of PsA therapy.

Obesity was linked to a 60% greater chance of not responding to anti-TNF biologics in a review of 54 studies. The review, published in PLoS ONE in 2019, looked at the effects of anti-TNF biologics in people with PsA and other autoimmune diseases. It found that each 1-point increase in body mass index (BMI) upped the odds of not responding by 6.5%.

“Obesity may impact response to anti-TNF therapy in two ways,” says lead author Siddharth Singh, MD, assistant professor of clinical medicine at University of California, San Diego. “First, body weight, especially at extremes, may impact the way these drugs are absorbed, distributed, metabolized and cleared, with excess weight leading to less of the drug being available in the body.”

Secondly, adds Dr. Singh, because obesity is a “low-grade proinflammatory state” it adds to the body’s overall inflammatory load, making it harder for anti-TNF biologics to do their work. It’s likely that obesity also interferes with the action of other classes of biologics, such as those that target interleukin (IL) proteins, says Singh. It’s not yet known, says Singh, whether obesity blunts the therapeutic effects of small molecule drugs – newer medications for PsA that can be taken by mouth instead of injected or infused.

Losing Weight Helps
The 2018 American College of Rheumatology/National Psoriasis Foundation guidelines for treatment of PsA recommend weight loss for obese patients. There are few trials, however, that have put these patients on a diet and looked at the effects on disease activity.

Dr. Klingberg’s clinical trial did just that, however. Her research, published in Arthritis Research & Therapy in 2019, showed that weight loss over the course of seven months improved many PsA symptoms. Specifically, losing weight lowered participants’ pain, fatigue and number of tender and swollen joints. It also improved their overall health and measures of chronic inflammation. Participants lost between 8% and 35% of their starting weight; the more they lost, the more their symptoms improved.

A 2014 Annals of the Rheumatic Diseases study showed that smaller weight losses also reduce disease activity. In that study, overweight and obese people who lost 5% of their starting weight were significantly more likely to have MDA than those whose weight stayed the same. As with Dr. Klingberg’s study, more weight loss led to bigger benefits.

Dr. Queiro advises all his obese patients with PsA to lose weight. “We tell them that if they reduce their weight by 5–10%, they will notice clear benefits in their overall health, but especially in their skin and joint health,” he says.