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Can anti-inflammatory drugs improve morning stiffness in rheumatoid arthritis?

Morning stiffness is a common problem for people with rheumatoid arthritis. A recently published article in Drugs & Aging reviewed the evidence that anti-inflammatory drugs can help lessen morning stiffness.

We depend on our immune system to defend us from bacteria and viruses. However, there are diseases in which the immune system turns against the body it is supposed to protect. In rheumatoid arthritis, the immune system targets the joints. With time, this can lead to joint damage, resulting in significant pain, impaired mobility, and a decreased quality of life.

The joint pain and stiffness that is experienced by those with rheumatoid arthritis tends to be worse in the morning. This morning stiffness can be severe and debilitating. There are many types of drugs that can reduce the severity of rheumatoid arthritis, and some of these may also lessen stiffness.

A rheumatologist from Hong Kong has written a review article that summarized the research into morning stiffness, and whether or not the most recently developed anti-inflammatory drugs can reduce its severity. The review was published in the scientific journal Drugs & Aging.

How serious is morning stiffness?

In one clinical study, more than two-thirds of rheumatoid arthritis patients experienced stiffness in the morning. A quarter of patients experienced morning stiffness for at least an hour. Another study found that half of the patients had stiffness that lasted longer than an hour. Interestingly, another study found that the duration of morning stiffness decreased in patients who had had rheumatoid arthritis for longer. The review also noted that studies on morning stiffness usually only measure the duration of stiffness, rather than the severity of pain, or degree of disability.

Morning stiffness can significantly impact an individual’s morning functions, as well as their daily living and social life. People who had severe morning stiffness were more likely to retire early, and patients with more severe morning stiffness were more likely to be unable to work at all.

In another study of retirees with rheumatoid arthritis, the majority said they had been forced to stop working prior to the regular retirement age. The majority of those early retirees said that morning stiffness was the main reason for their retirement. Almost half of working people with rheumatoid arthritis said that morning stiffness negatively affected work performance. Almost a third said that morning stiffness sometimes led to them being late for work.

Do new anti-inflammatory drugs alleviate morning stiffness?

Over-the-counter anti-inflammatory drugs such as aspirin or ibuprofen may temporarily relieve pain or stiffness, but they have no effect on the long-term prognosis of the underlying disease. Other drugs, such as methotrexate, have typically been used to treat rheumatoid arthritis. These work via a variety of biological mechanisms.

In recent decades, researchers have developed newer anti-inflammatory drugs that are designed to specifically target and inhibit individual proteins involved in inflammation and the immune response. The targeted nature of these drugs is intended to make them safer and more effective than previous treatments. These drugs include adalimumab (Humira), baricitinib, etanercept (Enbrel), infliximab (Remicade), rituximab (MabThera or Rituxan), sarilumab (Kevzara), and tocilizumab (Actemra).

Clinical trials have confirmed the effectiveness of these drugs for treating rheumatoid arthritis and morning stiffness. All of the drugs were found to decrease the average duration or severity of stiffness in the morning. Some of these trials also compared the drug’s effectiveness to either a placebo or a conventional anti-rheumatoid arthritis treatment. Sarilumab and baricitinib were both more effective than a placebo in reducing the duration or severity of morning stiffness. Infliximab and etanercept were both more effective at reducing the duration of morning stiffness compared to older drugs.

The studies were all of different designs and reported stiffness in different ways. It was therefore not possible to directly compare the results of each study to each other. For example, in one study testing tocilizumab, the average duration of morning stiffness was decreased by 50% (from 2.4 to 1.2 hours) after four weeks of treatment. Another study of tocilizumab found that the duration of morning stiffness was decreased in half of the treated patients, but only 19% of patients saw a reduction greater than 1 hour. Other studies reported even more impressive effects: for example, patients taking infliximab had the average duration of morning stiffness reduced by 70%.

Are anti-inflammatory glucocorticoids helpful for treating morning stiffness?

Glucocorticoids, such as prednisone, are a type of steroid hormone that suppress the immune system and decrease inflammatory activity. They are very effective at reducing the severity of rheumatoid arthritis, but long-term use can result in serious side effects, including an increased risk of death. This risk requires careful monitoring and attention to dosage, but the rapid effect of glucocorticoids means that they can be particularly effective when the administration of the drug is timed to coincide with morning stiffness. For example, recent studies have found that taking prednisone in the early morning, or delayed-release prednisone at bedtime, effectively decreased stiffness in the morning.

There are effective treatments for morning stiffness in rheumatoid arthritis

Physicians may not always be attentive to morning stiffness in their patients, preferring to rely on other measures of disease severity. Yet, stiffness in the morning makes a large contribution to the negative effects of rheumatoid arthritis on quality of life. For this reason, morning stiffness should be routinely assessed in the clinic. This is especially true given that medication can partially alleviate stiffness in the morning in many patients. However, there is no standard practice for assessing the severity of morning stiffness, with most clinical studies relying solely on duration, rather than quantifying the severity of the pain. Researchers and physicians need to develop a standardized method of measuring morning stiffness in order to better facilitate the treatment of this important consequence of rheumatoid arthritis.

Written by Bryan Hughes, PhD

Reference: Mok, C. C. Morning Stiffness in Elderly Patients with Rheumatoid Arthritis: What is Known About the Effect of Biological and Targeted Agents? Drugs & Aging (2018).

Bryan Hughes PhD
Bryan Hughes PhD
Bryan completed his Ph.D. in biology at McGill University, where he studied metabolism and the mechanisms of aging. He then worked at the University of Alberta as a Postdoctoral Research Fellow, investigating the causes of heart disease. After publishing many articles in scientific journals, he welcomes the opportunity to share the latest research findings with the wide audience of the Medical News Bulletin.


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