The main objective was to describe TCZ real life effect on fatigue over the first 4 months of treatment in RA patients.
PEPS is a multicenter non-interventional study assessing fatigue in real life in patients starting TCZ. Patients: RA patients requiring TCZ according to their physician. Treatment: TCZ as prescribed in real life. The first 5 infusions (4 months) were assessed. Primary endpoint: percentage of patients with variation of fatigue (FACIT-fatigue scale, 0-52, higher results indicate less fatigue) from inclusion to 4 months, above the minimal clinically important difference (MCID: 4 points) . Secondary endpoints: VAS fatigue, SF-36 vitality, HAQ, patient global, sleep, anxiety and depression by HADS, pain, DAS28, haemoglobin and tolerance. Analysis: patients with at least one TCZ infusion and FACIT score available at inclusion and at least once under TCZ were analysed. Last observation carried forward (LOCF) method was used to handle missing data on the primary criterion and DAS28. Survival analysis was performed to quantify the onset of action on fatigue. Univariate then multivariate logistic regressions were conducted to explain improvement of fatigue.
Result: 719 pts were included; 610 had analysable data: mean age 56±13 yrs, disease duration 12±10 yrs, 490 (81%) women, 463 (81%) rheumatoid factor or ACPA positive, 84% biologic IR. Mean (±SD) baseline DAS28 and FACIT-fatigue were respectively 5.3±1.1 and 24±10. At 4 months, TCZ reduced disease activity: mean DAS28 was 2.9±1.3, and improved fatigue: mean FACIT-fatigue was 33±11; 62% (n=378) patients reached MCID improvement for fatigue. Less fatigue was already observed at 2 weeks after treatment initiation. The mean percentage reduction of fatigue assessed by the FACIT score versus baseline was respectively 26% at week 2, and 37%, 52%, 61% and 59% at 1, 2, 3 and 4 months. The median time to reach FACIT-fatigue improvement >MCID with maintenance afterwards was 3 months.
In multivariate analysis, the only determinants of improvement of fatigue above MCID were high baseline level of fatigue (OR 3.2; 95% CI 2.0-5.1) and CRP (OR 1.01, 95% CI 1.00-1.03). When excluding baseline fatigue from the analysis, the significant determinants were baseline high levels of CRP (OR 1.01, 95% CI 1.00-1.03), of pain (OR 1.6, 95% CI 1.0-2.6) and baseline low SF36 vitality score (OR 2.0, 95% CI 1.2-3.2).
Safety profile was consistent with phase III results.
In these long-standing active RA patients, TCZ was efficacious on fatigue with rapid reduction seen as early as 2 weeks after the first infusion. Improvement in fatigue was mainly linked to high baseline fatigue, CRP and pain. In patients with disabling fatigue, TCZ may be a useful therapeutic option.
1: Smolen J et al:Lancet 2008; 371: 987–97
2: Cella D et al, J Rheumatol. 2005 May; 32(5):811-9
Disclosure: L. Gossec, Roche Pharmaceuticals, 5 ; S. Rouanet, Roche Pharmaceuticals, 3 ; G. Steinberg, Roche Pharmaceuticals, 3 ; B. G. Combe, Roche Pharmaceuticals, 5 .