Health-Related Quality of Life in Patients With Giant Cell Arteritis Treated With Tocilizumab in a Phase 3 Randomised Controlled Trial

Vibeke Strand; Sophie Dimonaco; Katie Tuckwell; Micki Klearman; Neil Collinson; John H. Stone


Arthritis Res Ther. 2019;21(64) 

In This Article


The set of analyses reported here represents the most detailed investigation to date of fatigue and HRQOL in patients with GCA and the first report of such data from an RCT. Patients with GCA in all treatment groups reported lower FACIT-Fatigue, SF-36 PCS, MCS and domain scores compared with A/G norms at baseline, highlighting the impact of GCA itself on HRQOL. However, weekly TCZ treatment resulted in substantial and clinically meaningful decreases in patients' fatigue and improvements in their HRQOL. Patients receiving TCZ-QW + Pred-26 reported statistically significantly greater improvements in SF-36 PCS, MCS, domain and FACIT-Fatigue scores than those in the PBO + Pred-26 and PBO + Pred-52 groups. Even more striking was the finding that improvements in the TCZ-QW + Pred-26 group met or exceeded A/G norms across every SF-36 domain. These findings are unprecedented in other HRQOL analyses across rheumatic diseases and highlight the importance of IL-6 in the underlying pathophysiology of GCA.

Data from these analyses underscore important differences between the two TCZ regimens used in this RCT. Patients treated with TCZ-QW + Pred-26 reported consistent and unequivocal improvements in HRQOL measures compared with patients in the PBO + Pred-26 and PBO + Pred-52 groups. In contrast, such improvements were not evident among patients treated with the every-other-week TCZ regimen (i.e., TCZ-Q2W + Pred-26). Thus, although both every week and every-other-week-TCZ treatment demonstrated clinical efficacy with regard to sustained GCA remission, the differences in HRQOL and fatigue observed between these two TCZ regimens argue in favour of weekly TCZ treatment.

Significant improvements in FACIT-Fatigue scores exceeding A/G norms were also reported for the TCZ-QW + Pred-26 group compared with both PBO + Pred groups. There also appeared to be a difference between the TCZ-QW + Pred-26 group and both PBO + Pred groups in PtGA scores, though these differences did not achieve statistical significance. One potential explanation for this is that patients who received prednisone escape therapy (i.e., had higher cumulative prednisone doses) were included in the current analyses. Glucocorticoids have the potential to make patients feel better by alleviating some disease symptoms without necessarily improving HRQOL or fatigue. In fact, patients in the PBO + Pred-52 group reported deterioration in SF-36 bodily pain and general health domains, a finding likely due to the relative excess of cumulative prednisone use in this group. PRO improvements reported in the TCZ-QW + Pred-26 group might have resulted not only from the effects of TCZ treatment on the symptoms of GCA but also from the lower cumulative glucocorticoid exposures enabled by TCZ treatment.

The observation that patients in the TCZ-QW + Pred-26 group reported improvements in HRQOL to levels exceeding A/G norms deserves further comment. A substantial body of research in recent years indicates that IL-6 is a crucial mediator not only of inflammation but also of pain, fatigue and even mood.[26] For example, injection of IL-6 into healthy persons is known to induce lowered moods.[27] The mechanism whereby IL-6 may mediate such changes is unclear, but one purported mechanism is through activation of the hypothalamic-pituitary axis.[28] Our findings support the concept that one mechanism whereby IL-6 inhibition improves HRQOL is through an elevating effect on mood.