Background The functional burden of disease in patients affected by Rheumatoid arthritis (RA), mainly caused by pain and swelling of joints, is often worsened by extra-articular manifestations, among which asthenia remains the most frequently reported. Most biologics have shown overall efficacy on fatigue, but whether this is due to overall improvement of disease or to more specific aspects of the disease like sleep disorders due to overnight pain and awakenings remains unknown.
Objectives The aim of this study was to evaluate potential predictive factors of improvement in related fatigue in RA patients newly receiving biologic therapy, and more specifically the potential influence of the improvement in sleep disorders.
Methods We conducted a multicenter prospective study in RA patients requiring initiation or change of biologic therapy. Sleep disorders, depression and the improvement in fatigue were respectively assessed by Spiegel scale, Beck Depression Inventory and the FACIT fatigue scale at inclusion (M0) and 3 months (M3) after the beginning of treatment. Clinical and biological characteristics were prospectively collected. Potential confounders like presence of anemia, thyroid dysfunctions, iron deficiency, psychotropic or corticosteroids medications were assessed and adjusted for. The association between evolution of fatigue (improvement/no improvement according to predefined validated cutoffs) and other characteristics were evaluated by univariate (Chi2) then multivariate (logistic regression) analyses.
Results We included 99 patients (72,7% women, aged 58,2±12,1 with initially active disease (DAS28 5,1±1,4). FACIT scores at inclusion revealed frequently reported fatigue: 89% with scores more severe than expected in general population, high prevalence of sleep disorders (95%: abnormal 68%, pathologic 27%) and depression (67%: mild 33%, moderate 24%, severe 11%). Anti-TNF drugs were started in 50 patients, other biologics in 49 patients (tocilizumab N=19, abatacept N=16, rituximab N=14). Clinical response was beneficial in most patients: 36% good EULAR response, 40% moderate, 24% no response. Improvement of fatigue, sleep quality and depression according to predefined cutoffs was observed in respectively 58.6%, 26.3% and 34.3% of cases. Significant factors associated with an improvement in fatigue at 3 months were an elevated sedimentation rate at M0 (OR=5.7[2.0-16.0], p=0.001) and a favorable EULAR response at M3 (OR=4.8[1.6-14.8], p=0.006). Furthermore, a number of swollen joints >5 at baseline (OR=0.3 [0.1-0.8]) and the use of psychotropic drugs (OR=0.2[0.04-0.9]) were predictive of an absence of improvement in fatigue. No significant association with the improvement in sleep disorders could be demonstrated: of 29 patients with improvement in sleep quality, 17 (58.6%) considered their level of fatigue had decreased, while 41/70 (58.6%) did so among those without correction of sleep disorders (p=0.9).
Conclusions Our study confirmed that fatigue in RA is frequent, as well as depression and sleep disorders, and is usually improved by effective treatment (i.e. via decrease in disease activity). Our results indicate that improvement of sleep disorders is more likely a surrogate of therapeutic efficiency rather than an independent outcome.
Disclosure of Interest None declared