Fatigue in rheumatoid arthritis: quantitative findings on the efficacy of tocilizumab and on factors associated with fatigue. The French multicentre prospective PEPS Study.
OBJECTIVE
Fatigue is an important aspect of rheumatoid arthritis (RA). The objective was to assess fatigue levels and its determinants over the first 4 months of tocilizumab (TCZ) treatment in RA patients.


METHODS
We performed a multicentre prospective study of RA patients treated with intravenous TCZ in open-label prescription conditions. The first 5 infusions (4 months) were assessed. The primary endpoint was the percentage of patients with variation of the FACIT fatigue scale from inclusion to 4 months, above the minimal clinically important difference (MCID) of 4 points. Fatigue was also assessed by the patient acceptable symptom state for fatigue (PASS) question. Variables related with fatigue and with fatigue improvement including other patient reported outcomes, depression and anxiety, and disease activity, were assessed before and after treatment.


METHODS
univariate and multivariate logistic regressions.


RESULTS
Of 719 patients, 610 had evaluable data: mean age 56±13 years, disease duration 12±10 years, 490 (81%) women. At baseline, fatigue levels were high: 73% patients had unacceptable fatigue. At 4 months, 378 patients (62%) reached MCID improvement for fatigue. Fatigue reduction was rapid, seen as early as after 2 weeks. Fatigue was mainly related to functional status (HAQ score), depression and anxiety, both before and after TCZ treatment. Moderate predictors of fatigue improvement were evidenced.


CONCLUSIONS
In these long-standing RA patients, fatigue levels were high and mainly explained by HAQ and psychological distress but improved with treatment indicating a link with disease activity. The pathophysiological basis of RA fatigue should be further explored.
Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, and AP-HP, Pitié Salpêtrière Hospital, Department of rheumatology, Paris, France. laure.gossec@aphp.fr.
Laure
L
Gossec
Medical Department, Roche, France.
Ghislaine
G
Steinberg
eXYSTAT, Paris, France.
Stephanie
S
Rouanet
Rheumatology Department, Lapeyronie Hospital, Montpellier CHRU, and Université Montpellier I, Montpellier, France.
Bernard
B
Combe
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D004334:Drug Administration Schedule; D005221:Fatigue / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D005260:Female; D005602:France; D006801:Humans; D007262:Infusions, Intravenous; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012074:Remission Induction; D012307:Risk Factors; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab