New Options Explored for Sarcopenia in Rheumatic Diseases

New efforts — including the development of drugs that target mitochondrial pathways and others that target androgen receptors selectively — are underway for treating sarcopenia in rheumatic diseases, but so far the results have been mixed, an expert said at the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting, held recently as a virtual event.

Addressing the problem of reduced muscle mass — experienced by many patients with rheumatic diseases, owing in part to the processes of inflammation and to pain interfering with exercise — is bound to help with outcomes, inasmuch as lean mass and fat mass are linked with disability and early mortality, said Joshua Baker, MD, associate professor of medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Elamipretide, which works by stabilizing mitochondrial pathways that are disrupted in people with sarcopenia, in particular those with mitochondrial disorders, might be the most promising of the therapies being developed. In a study published last year, patients with mitochondrial myopathy experienced significant improvement in gait speed, fatigue, and physical function after 4 weeks, Baker said.

It’s “an interesting and exciting approach that we need to see more studies about in the future,” he said.

Studies of selective androgen receptor modulators (SARMs), which are similar to anabolic steroids but only target certain androgen receptors so as to prevent side effects, have been a letdown, Baker said. The idea with SARMs is to enhance growth of certain tissue, such as muscle, but without causing side effects in other tissues. Previous trials found that although this approach increased muscle mass, it didn’t produce improvements in measures of physical function.

A myostatin/activin type II receptor blocker, bimagrumab, recently was found to boost lean mass but without improvement in physical function or gait speed.

Still, the focus on improving sarcopenia is an encouraging development, Baker said.

“New therapies are in the pipeline, and let’s be optimistic and hope that in the future we’ll have lots of options for these patients,” he said.

For now, resistance training remains the best way to tackle the problem. However, the need to have access to trainers, equipment, and gyms, as well as the presence of comorbidities, can make exercise difficult, he said. In addition, routine nutritional supplements, such as with vitamin D, have not been found to improve outcomes, he noted.

The sheer number of people with sarcopenia should make the search for better inventions a priority, suggested Maria Lorena Brance, MD, PhD, professor of medicine at the National University of Rosario, in Argentina.

“Prevalence of sarcopenia is very high in autoimmune disease, with representation between 20% and 30%, depending on the pathology,” she said. “So it’s very important to study the presence of sarcopenia.”

Identifying the problem — by first noticing symptoms and then confirming with tests of muscle strength, such as grip tests — would be a big step, the panelists said. Baker said that among patients with obesity, sarcopenia is more likely to be overlooked, because such patients might not be weak in an absolute sense but might be weak relative to their size.

Brance said that it’s important to differentiate the value of vitamin D for someone with normal levels in comparison with someone who has a deficiency. Although evidence does not support the use of vitamin D supplements across the board, supplements have been shown to be helpful for patients with low vitamin D levels, she said.

Xavier Ricardo, MD, PhD, professor at Federal University of Rio Grande, in Brazil, suggested that sarcopenia may differ from what meets the eye. At his hospital, researchers are studying sarcopenia in patients with systemic sclerosis and have found that in about 20% to 25% of patients, it is present in levels similar to those that occur in patients with rheumatoid arthritis. Researchers are now examining tissue from biopsies to see whether there are differences between the two conditions in the processes of muscle wasting.

“So far, we’re a little bit surprised,” he said. “We expected to have more sarcopenia in these patients, because they do look more frail, more cachexic sometimes.”

Baker has received consulting fees from Bristol-Myers Squibb, Burns-White, and Gilead. Ricardo has received consulting fees, speaker fees, or both from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, and UCB. Brance has disclosed no relevant financial relationships.

Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting: Presented August 14, 2021.

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