Window of opportunity for managing fatigue

Many but not all people with rheumatoid arthritis achieve sustained fatigue improvement with intensive drug therapy, but early and effective treatment could mitigate this.

Rheumatoid arthritis is a chronic inflammatory disease that mainly affects a person’s joints, causing pain and disability among other symptoms. Rheumatoid arthritis can affect people of all ages, but it most often and generally starts between the ages of 40 and 60. It is more common in women than men. 

Fatigue is severe tiredness or exhaustion that is often but not always associated with excessive disease activity. Fatigue is common in people with rheumatoid arthritis. It is estimated that 40–80% of people with rheumatoid arthritis are affected by significant fatigue that does not get better with rest, compared to 10–20% of people in the general population. This is an important symptom. People with rheumatoid arthritis consistently say that improving fatigue is one of their most important goals for treatment. However, fatigue is a complicated symptom with many different factors. It can change over time and behave differently in different groups of people, particularly early after the diagnosis. 

The authors wanted to provide a better picture of how symptoms of fatigue behave and change over time in the early phase of a person’s rheumatoid arthritis. They also wanted to see how this is affected by drug treatment and disease activity.  

The study looked at people with newly diagnosed rheumatoid arthritis who were starting their first treatment. On average, people were in their early fifties, and over two-thirds were women. The average duration of symptoms was 8 months.

This analysis used data from a 2-year trial called CareRA, and its 3-year extension study (CareRA-plus). The trial included people who were newly diagnosed with rheumatoid arthritis and had not received disease-modifying antirheumatic drugs (DMARDs) up to that point. During the trial, several different measures of fatigue were collected. 

This information was used to identify different subgroups based on the way their symptoms of fatigue changed over time during the trial. The authors then looked for factors that could predict the changes in fatigue over time from early in the disease course. 

A second analysis looked at how fatigue symptoms relate to measures of disease activity or inflammation.

Although the majority of people achieved a good response to antirheumatic treatment, fatigue remained a persistent symptom. Only one in four people had lasting improvements in fatigue, despite intensive and targeted antirheumatic treatment, and 20% of those taking part even experienced worsening fatigue. 

However, the authors found that people with a good early response and who were in remission within the first 4 months of treatment had lower levels of fatigue. This continued over as much as 5 years of follow-up, even when disease activity worsened later on.

This seems to suggest that inflammation plays an important role in the fatigue experienced by people with rheumatoid arthritis. However, the second analysis showed that the relationship between disease activity and fatigue depended on pain, sleep quality, and psychosocial aspects rather than on inflammation itself.

The findings confirm that fatigue is very common in people with rheumatoid arthritis. and that it often does not improve to a large extent with antirheumatic treatment, as confirmed in earlier studies. 

As such, the paper adds to this knowledge by showing just how widespread the problem is, with fewer than 25% of people improving in fatigue despite treatment according to current standards. It is also a new finding that there seems to be an early window of opportunity during which achieving good disease control might positively affect the impact of fatigue for years to come. Another new finding is that pain, sleep, and psychosocial aspects seem to play a role in the experience of fatigue, and seem to be more important in this regard than pure disease activity or inflammation.

This was a post-hoc analysis of a randomised controlled trial. The type of study means the authors were able only to describe associations, and were not able to prove causal relationships. There are also possible limitations due to the study design, which meant that fatigue assessments were done only once every 6 months. However, the major advantage of the study setting is the very representative patient sample that was included, and the complex multidimensional measures of fatigue and wellbeing that were collected at regular time points. In this way, the trial provided a uniquely detailed picture of the complexity of fatigue in the early phase of rheumatoid arthritis. 

The authors are planning to investigate whether fatigue and psychosocial wellbeing can be improved with non-pharmacological treatments, including nurse-led interventions and apps to support self-management.

If you have rheumatoid arthritis, this study acknowledges that fatigue is an important but often-overlooked symptom. It is hoped that these results could provide guidance to healthcare professionals on how to improve fatigue in the long term for people with rheumatoid arthritis. Your treatment should aim to achieve good inflammatory disease control as early as possible. Depending on your own personal circumstances, this might include non-pharmacological interventions to help improve your fatigue when controlling your disease activity does not appear to be enough on its own.  

If you have any concerns about your disease or its treatment, you should talk to your doctor or a healthcare professional involved in your care.

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Date prepared: September 2022
Summary based on research article published on: 20 June 2022
From: Doumen M, et al. Longitudinal trajectories of fatigue in early RA: the role of inflammation, perceived disease impact and early treatment response. Ann Rheum Dis 2022;81(10):1385–91. doi:10.1136/annrheumdis-2022-222517

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