Longitudinal Course of Fatigue in Patients With Rheumatoid Arthritis on Biologic Treatment

doctor explaining prescription to patient
The researchers’ objective was to define the longitudinal course of fatigue in RA patients who initiate biological DMARD treatment and identify the predictors of those fatigue trajectories.

Among an initial group of 206 patients, 184 patients with long-standing rheumatoid arthritis (RA) treated with biologic disease-modifying antirheumatic drugs (bDMARDs), 53 still had clinically significant fatigue 12 months after introducing treatment, and the patients who experience improved fatigue most frequently did so within the first months, according to study results published in Rheumatic & Musculoskeletal Disease.

The objectives of the current study were to characterize the longitudinal course of fatigue in patients with RA following the introduction of bDMARD treatment and to identify potential predictors.

The study sample included 184 patients with RA who were started on bDMARD who completed a comprehensive assessment at baseline and 1, 2, 3, 6, and 12 months that included swollen and tender joint counts, patient-reported outcomes (PROMs), blood samples, and ultrasound examinations. The fatigue Numeric Rating Scale from the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire was used to assess fatigue in study participants.

Clinically significant fatigue was defined as RAID fatigue ≥ 4 and patients were classified into 1 of 3 fatigue trajectories: no fatigue (RAID fatigue ≤ 3 at 5 of 6 visits), improved fatigue (RAID fatigue ≥ 4 at baseline but ≤ 3 at follow-up), or continued fatigue (≥ 4 at 5 of 6 visits).

The study sample of 184 patients completed the RAID questionnaire for fatigue and missed ≤ 1 visits. Of these, 61 patients had no fatigue, defined as fatigue score ≤ 3 at baseline and at 4 of 5 follow-up visits. Improved fatigue was documented in 33 patients. In 34 patients there was no discernible pattern, and in 3 patients fatigue levels increased after initiating bDMARDs. Continued fatigue was seen in 53 patients (fatigue level ≥ 4 at 5 of 6 visits).

Comparison of baseline variables across trajectories of longitudinal fatigue revealed several predictors for the development of continued fatigue, compared to patients with no clinically significant fatigue, including female gender (88.68% vs 72.13%), presence of anti-citrullinated protein antibody (94.34% vs 72.13%) and rheumatoid factor (71.70% vs 52.45%), and lower levels of education (44.0% vs 63.93% had higher education).  Anti-citrullinated protein antibody (96.15% vs 81.25%), disease duration (11.71 years vs 8.12 years) and higher education (44.0% vs 63.93% had higher education) were also predictors of continued fatigue, compared to patients with improved fatigue. 

Patients with continued fatigue had higher levels of all PROMs compared to patients with no fatigue and higher levels of most PROMs compared to patients with improved fatigue. Compared to patients with no fatigue, those with improved fatigue had higher levels of patient global VAS, sleep disturbance, widespread pain, and pain catastrophizing.

The trajectories of continued fatigue were predicted by PROMs and not by inflammatory RA disease activity, as patients with continued fatigue had significantly higher levels of anxiety, sleep disturbance, pain, and pain catastrophizing, but there was no evidence of higher baseline inflammation compared with patients in the other fatigue trajectories.

The study had several limitations, including the use of a single instrument to assess fatigue and the limited number of variables that could be included in the regression models due to the sample size.

“PROMs are important determinants of continued fatigue and should be the focus of future interventions targeting this symptom,” wrote the researchers.


Provan SA, Michelsen B, Sexton J, Uhlig T, Hammer HB. Trajectories of fatigue in actively treated patients with established rheumatoid arthritis starting biologic DMARD therapy. RMD Open. 2020;6(3):e001372. doi:10.1136/rmdopen-2020-001372