Rheumatoid Arthritis: TNF Inhibitors Linked to Less Fatigue

Lara C. Pullen, PhD

November 03, 2014

Patients with rheumatoid arthritis (RA) report substantial improvement of fatigue after beginning anti–tumor necrosis factor α (TNF-α) therapy. In particular, employed women with a low level of disability were the most likely to experience an improvement in fatigue. Pain, however, was not a significant predictor of improvement in fatigue.

Although fatigue is generally considered a significant factor in RA, it is rarely a primary endpoint in clinical trials. Katie L. Druce, a PhD student from the Epidemiology Group, Institute of Applied Health Sciences, University of Aberdeen, United Kingdom, and colleagues published the results of their long-term observational cohort study online October 13 in Rheumatology. They sought to determine whether fatigue improved in patients with RA who were given anti-TNF-α (infliximab, etanercept, or adalimumab).

The investigators examined records from patients from the British Society of Rheumatology Biologics Register for Rheumatoid Arthritis biologics cohort who had a specific disease profile of high disease activity and RA refractory to traditional disease-modifying anti-rheumatic drug treatments. From this group, they selected and analyzed only patients with the highest level of baseline fatigue.

The researchers used the 36-item Short Form Health Survey (SF-36) vitality subscale to measure fatigue. They acknowledge that there is debate as to whether fatigue and vitality can be accurately placed on a continuum. Rheumatologist Daniel Furst, MD, professor of medicine, David Geffen School of Medicine at the University of California in Los Angeles, was not affiliated with the research but discussed it with Medscape Medical News, noting the misuse of the vitality subscale as a flaw in the article.

Nevertheless, the investigators measured fatigue using the SF-36 vitality subscale and defined severe baseline fatigue as a SF-36 vitality subscale score of 12.5 or less. Of the 6835 participants enrolled in the trial, 38.8% had severe baseline fatigue.

The team found that 70% of these patients reported clinically relevant improvement in fatigue when treated with anti-TNF-α and 66% of patients improved such that they could be categorized as having nonsevere fatigue. Women were more likely to improve than men (odds ratio, 1.3; 95% confidence interval, 1.01 - 1.7).

"Given the results from existing publications, which show that men tend to respond better to anti-TNF therapies, we were surprised that being female was a predictor of improvement. In the paper, we suggest that this may be due to the fact that females tend to report more fatigue, and so have a greater capacity for improvement, but we cannot explain this definitively," Druce told Medscape Medical News.

A majority (80%) of the patients who experienced improvement with fatigue also reported nonsevere fatigue after 1 year. Although the investigators describe predictors of patients most likely to experience an improvement in fatigue symptoms, they also acknowledge that many patients improved despite not having any of these characteristics.

"It is important that this work has supported anecdotal evidence from patients and the findings of [randomized control trials] and concludes that improvements in fatigue are common after anti-TNF therapy commencement. The identification of predictors of improvement can aid physicians to identify those commencing anti-TNF therapies who are most likely to improve. On the other hand, the identified predictors may also highlight those less likely to improve and act to guide discussions about the need for additional fatigue focused therapies," Druce told Medscape Medical News.

Patients with RA who begin anti-TNF-α therapy are eight times more likely than the general population to report severe fatigue, with women consistently reporting more fatigue than men. Druce pointed out, however, that anti-TNF-α therapy is not indicated for the treatment of fatigue, and thus cannot be prescribed specifically to treat fatigue.

"This article has some significant weaknesses," explained Dr Furst. That said, the conclusions support something that is generally known: "Treating with effective drugs...makes fatigue better."

The senior author of the study has received research support and/or served on advisory boards for Pfizer, MSD, and GSK. The other authors and Dr Furst have disclosed no relevant financial relationships.

Rheumatology. Published online October 13, 2014. Abstract

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