Rheumatology
Rheumatoid Arthritis
Interleukin-6 in Rheumatoid Arthritis– Associated Pain, Fatigue and Mood
Overview
Therapeutic targeting of the interleukin-6 receptor (IL-6R) has been a major advancement in the effective treatment of rheumatoid arthritis (RA), as the IL-6R plays a key role in mediating the underlying disease pathophysiology and clinical manifestations of RA. Here, the focus is on the role of IL-6 in RA-associated pain, fatigue and mood.
Expert Commentary
Leonard H. Calabrese, DO
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“We reviewed the neuroendocrine and neurophysiological effects of IL-6 in RA, finding that inhibitors of IL-6 reduced pain and fatigue and improved mood.”
RA-associated symptoms and comorbidities are often intertwined and interdependent. For example, the chronic pain, fatigue, and disability from RA may adversely impact mental health and psychosocial function, Proinflammatory cytokines associated with RA are implicated strongly not only in the symptoms of pain and fatigue, but also in mood disorders, with related depressive and anxious symptomology. As such, we reviewed the neuroendocrine and neurophysiological effects of IL-6 in RA, finding that inhibitors of IL-6 reduced pain and fatigue and improved mood.
A variety of tools have been used to assess these symptoms in clinical trials; however, many clinical trials have not included these measurements. For instance, as of 2015, fatigue had only been specifically reported in 18% of randomized controlled trials (RCTs), despite published recommendations in 2007 to assess fatigue in RA trials.
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We are fortunate to have the following 2 IL-6 receptor antagonists available for use in the clinic: tocilizumab and sarilumab. In phase 3 RCTs of patients with moderate to severe RA, improvements in measures of pain, fatigue, and mood have been found with these IL-6 inhibitors. Improvements were observed in the setting of biologic monotherapy and in combination with conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDSs) such as methotrexate. No head-to-head data comparing sarilumab with tocilizumab are available at this time, but alleviation of fatigue appears to be one of the first beneficial effects that patients with moderate to severe RA may experience when using biologic therapies that block IL-6.
Currently, it is unclear whether the improvements in mood, pain, and fatigue observed with the IL-6 inhibitors are due to suppression of inflammation in RA (i.e. RA symptom relief) or are a direct effect of inhibiting IL-6. Further research should be prioritized to understand whether IL-6 inhibition confers additional advantages in alleviating these symptoms. If confirmed, patients with hyperalgesia, severe fatigue, or concomitant depression may derive greater benefits from IL-6 inhibition.
“Further research should be prioritized to understand whether IL-6 inhibition confers additional advantages in alleviating these symptoms. If confirmed, patients with hyperalgesia, severe fatigue, or concomitant depression may derive greater benefits from IL-6 inhibition.”
References
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