Background Achieving disease remission or low disease activity is the therapeutic goal in rheumatoid arthritis' (RA) treatment. Disease activity is defined through established criteria most of them requiring the evaluation of patient global assessment (PGA). PGA is considered a limiting factor for achieving remission definition, as it can be influenced by many factors not RA-related, namely fatigue which is commonly reported in RA and has been correlated with increased levels of interleukin-6 (IL-6).
Objectives To evaluate the relation between PGA and fatigue, and whether fatigue influences disease remission definition in RA patients treated with tocilizumab (TCZ), an anti-IL-6 receptor monoclonal antibody.
Methods We prospectively recruited 18 consecutive patients with RA (ACR/EULAR 2010 criteria), on TCZ treatment (≥3 months), from a single referral centre. Disease activity was evaluated by disease activity score for 28-joints (DAS28), and the ACR/EULAR Boolean-based criteria for remission were calculated. Visual Analog Scale for Fatigue (VASF) and Multidimensional Assessment of Fatigue scale (MAF) were used to measure fatigue.
Results 89% of the patients were female and mean age was 55.5±13.8 years (yrs). Mean disease duration was 8.8±6.8yrs and mean duration of TCZ treatment was 2.3±1.3yrs (50% 1st line). Mean PGA score was 3.3±2.0 (0-best health) and mean DAS28 C-reactive protein (CRP) was 2.27. According to DAS28-CRP 44% of the patients were in remission, 22% had low disease activity and 33% had moderate activity. 3 patients (17%) fullfield the ACR/EULAR Boolean criteria for remission. Considering all the composits of the Boolean criteria, PGA was the only reason for not achieving remission in 10 patients (56%). The mean fatigue scores were: VASF 6.6±2.3 (0-best health), Global Fatigue Index (GFI), calculated through MAF scale, 24.3±14.9 (1-best health). Amongst the 18 patients, PGA correlated with higher fatigue scores on VASF (r=0.50, p=0.00951) and on GFI (r=0.49, p=0.037). In the group of patients not fulfilling Boolean remission, a similar correlation between PGA and higher fatigues scores was found (VASF: r=0.54, p=0.036; GFI: r=0.79, p=0.00041). In the sub-group of patients in which PGA was the only factor for not achieving Boolean remission, there was a significant correlation between PGA and fatigue scores (GFI: r=0.79, p=0.009), that was not present in the other patients (GFI: r=0.24; p=0.49).
Conclusions We found a positive correlation between higher PGA and fatigue scores in RA patients treated with TCZ. PGA was the major limiting factor for not achieving ACR/EULAR Boolean remission criteria, and in this sub-group of patients the same positive correlation between higher PGA and fatigue scores was found, not present in the rest of the cohort. These results enhance the influence of fatigue in patients' perspectives of disease and reinforce the limitations of using PGA to define RA activity and remission. Furthermore, considering the influence of TCZ in fatigue mechanisms, by blocking IL-6 receptor, we still found high fatigue scores in this cohort, which can enhance the complex physiopathology of fatigue in chronic inflammatory diseases, and the role of several other cytokines (IL-1, TNF-α). This effect and comparison with RA patients treated with anti-TNF-α can be explored further in larger prospective studies.
Disclosure of Interest None declared