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

Disclosures

Arthritis Res Ther. 2019;21(64) 

In This Article

Patients and Methods

Patients

The GiACTA RCT (ClinicalTrials.gov, NCT01791153) design and enrolment criteria have been published.[16,17] Briefly, patients ≥ 50 years of age with newly diagnosed or relapsing active GCA confirmed by temporal artery biopsy or cross-sectional imaging and a history of elevated erythrocyte sedimentation rate attributable to GCA were randomly assigned (2:1:1:1) to one of four 52-week regimens: (1) weekly subcutaneous TCZ 162 mg plus a 26-week prednisone taper (TCZ-QW + Pred-26), (2) every-other-week subcutaneous TCZ 162 mg plus a 26-week prednisone taper (TCZ-Q2W + Pred-26), (3) weekly subcutaneous placebo plus a 26-week prednisone taper (PBO + Pred-26) or (4) placebo plus a 52-week prednisone taper (PBO + Pred-52). The trial was conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. All patients provided written informed consent as approved by the institutional review board or ethics committee. The primary outcome (sustained disease remission to week 52) and secondary and exploratory PRO outcomes (SF-36, FACIT-Fatigue and PtGA) were analysed at 1 year.

Patient-reported Outcome Assessments

We analysed data by SF-36 PCS and MCS and all eight individual domains. These domains are physical function, role physical, bodily pain, general health, vitality, social function, role emotional and mental health. We also analysed PtGA by visual analogue scale (VAS) and FACIT-Fatigue score. We used MCIDs previously validated in patients with rheumatoid arthritis and systemic lupus erythematosus because such values have never been defined in GCA.

Least square mean (LSM) changes from baseline to week 52 in SF-36 PCS and MCS scores were assessed using a range of 0 to 50, with normative scores of 50 and a standard deviation of ± 10; higher scores indicate better HRQOL.[18] Change ≥ 2.5 in PCS and MCS was considered the MCID.[19] SF-36 domain scores ranging from 0 to 100 were compared with A/G norms matched to the study population. LSM changes from baseline to week 52 were depicted using spydergrams.[20] An MCID of 5.0 was used for changes in domain scores.[19] Overall changes in SF-36 scores in spydergrams were quantified using the SF-6D utility score based on mean scores across all eight domains[21,22] and the previously defined minimally important difference (MID) for an SF-6D utility score of 0.041.[23] Changes from baseline to week 52 in PtGA, ranging from 0 to 100, were assessed by VAS using the generally accepted MCID of 10.0.[19] FACIT-Fatigue was assessed on a scale of 0 to 52, with higher scores representing less fatigue, using an MCID of 4.0.[24]

Statistical Analysis

The current analyses compared PROs between the TCZ-QW + Pred-26 group and the PBO + Pred-26 and PBO + Pred-52 groups. These comparisons were selected to correspond with the primary and key secondary analyses of sustained remission from baseline to week 52 in the GiACTA trial.[16] Comparisons of SF-36 PCS and MCS scores between the TCZ-Q2W + Pred-26 group and the two PBO + Pred groups were not statistically significant at the pre-specified 1% level. Therefore, data from that group were not assessed further. Our analyses focused on the TCZ-QW + Pred-26 group, the PBO + Pred-26 group and the PBO + Pred-52 group.

All patients in the intent-to-treat (ITT) population, including those who experienced disease flare, were included in the current analyses. This approach contrasts with the analytical approach used previously, in which data obtained after use of escape therapy were censored.[16] Statistical significance was set as p < 0.01. All analyses presented were performed after unblinding and are considered exploratory.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....