With apologies to George Gershwin, I thought it might be nice to review with you the importance of the circadian rhythm in rheumatoid arthritis.
I am often asked by my patients why they have more pain and stiffness in the morning. After all, I never ask about "evening stiffness." It's always morning stiffness on my mind when I ask a patient how he or she is doing.
It appears that this is related to the circadian rhythm, which refers to the 24-hour biological cycles we all have, and which includes variations in hormone and nervous system activity. These variations in turn have a significant impact on disease, and thus the types of complaints a patient might have in the course of a day.
In past blogs I have written about the anti-tumor necrosis factor (TNF) drugs such as Enbrel, Humira and Remicade. And I have written about the anti-interleukin (IL)-6 drug Actemra. TNF and IL-6 are biochemicals which cause inflammation that leads to rheumatoid arthritis patients experiencing stiffness, joint pain, joint swelling and depression.
As you might expect, levels of TNF and IL-6 are higher in rheumatoid arthritis patients compared to healthy patients. And the levels remain elevated for a longer period of time in the morning, when they are at their peak.
The rheumatoid arthritis patient feels lousy in the morning. Those unfortunate to have more severe rheumatoid arthritis feel lousy all day.
The body does try to counter this onslaught of TNF and IL-6, by releasing cortisol, the body's natural anti-inflammatory "cortisone" type biochemical. Unfortunately, in rheumatoid arthritis patients, the cortisol response is overwhelmed by the large amounts of TNF and IL-6.
Studies show that the key is to fight the inflammation earlier in the day: One study has shown that giving prednisolone at 2:00 AM resulted in a much greater improvement in morning stiffness and pain, disease activity and IL-6 compared to the prednisolone being given at 7:30 AM (when most people would take their morning prescriptions). It appears from other studies that TNF must be "turned off" early, otherwise the amount of TNF becomes overwhelming for the immune system.
But it will be hard to arouse patients in the wee hours of the morning to take a dose of a rheumatoid arthritis drug. We would all rather be dreaming.
The key will be developing timed-release inflammatory biochemical neutralizers, which will follow the circadian rhythm of these causes of pain and swelling and stiffness. We might even be able to use the "old" drugs well-known to the rheumatologist, and simply repackage them in a form which will release them into the body at the ideal time, when their target is most vulnerable to being neutralized along the circadian highway.
Hopefully, researchers will follow the circadian rhythm to a cure.
Then we will all sleep a little better.
Published On: March 03, 2008