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

Results

Patients

One hundred patients were randomly assigned to TCZ-QW + Pred-26, 50 to TCZ-Q2W + Pred-26, 50 to PBO + Pred-26 and 51 to PBO + Pred-52. One patient assigned to the TCZ-Q2W group did not receive any study treatment and was not included in the ITT population. Baseline demographics and disease characteristics for all patients have been reported[16,25] and are shown for the TCZ-QW + Pred-26, PBO + Pred-26 and PBO + Pred-52 groups in Table 1. In the ITT population, patients in both PBO + Pred groups received approximately twice the cumulative dose of prednisone as patients receiving TCZ-QW + Pred-26 over 52 weeks. The median (minimum–maximum) cumulative prednisone doses were 1862.0 mg (630.0–6602.5) for TCZ-QW + Pred-26, 3296.0 mg (932.0–9777.5) for PBO + Pred-26 and 3817.5 mg (822.5–10,697.5) for PBO + Pred-52 (p < 0.001 for comparisons). Among patients in the escape population who remained in the study until week 52, the median (minimum–maximum) cumulative prednisone doses over 52 weeks were 3129.8 mg (2009.0–5680.5, n = 18) for TCZ-QW + Pred-26, 4023.5 mg (2583.5–8695.0, n = 29) for PBO + Pred-26 and 5389.5 mg (2700–10,697.5, n = 24) for PBO + Pred-52. In summary, in the ITT and escape populations, cumulative prednisone doses were far higher in both PBO + Pred groups than in the TCZ-QW + Pred-26 group.

SF-36

At baseline, PCS and MCS scores were similar across treatment groups and approximately 1 standard deviation (SD) below the A/G-matched normative scores of 50. Patients in the TCZ-QW + Pred-26 group reported greater LSM improvements from baseline to week 52 in PCS scores than patients in both PBO + Pred groups (p < 0.01). LSM improvement in MCS was significant in the TCZ-QW + Pred-26 group compared with the PBO + Pred-52 group (p < 0.01). Changes from baseline exceeded the MCID in both PCS and MCS scores in the TCZ-QW + Pred-26 group. Change from baseline in MCS score to week 52 exceeded the MCID in the PBO + Pred-26 group (Table 2).

Baseline domain scores reflected impaired HRQOL, which was the most impacted in the role physical, vitality, social function, role emotional and mental health domains. Scores were lowest in the PBO + Pred 52 group, reflecting decrements of 16–25 points below A/G norms (Table 3, Figure 1). At week 52, LSM changes from baseline with TCZ-QW + Pred-26 treatment exceeded those in the PBO + Pred-26 group in four domains (physical function, role physical, general health and vitality; p < 0.01 for all) and exceeded those in the PBO + Pred-52 group in six domains (role physical, bodily pain, general health, vitality, social function and mental health; p < 0.01 for all) (Table 3, Figure 1). Reported improvements across all domains exceeded the MCID in the TCZ-QW + Pred-26 group compared with five of eight domains in the PBO + Pred-26 group and none in the PBO + Pred-52 group (Table 3).

Figure 1.

SF-36 domain scores at baseline and week 52. SF-36 domain scores are shown for the TCZ-weekly group compared with the placebo-26-week taper (a) and compared with the placebo-52-week taper (b) groups. Values shown in parentheses are the numbers of patients. *p < 0.01 TCZ-QW + Pred-26 vs PBO + Pred group. A/G age/gender, BL baseline, BP bodily pain, GH general health, MH mental health, PBO placebo, PF physical function, Pred-26 26-week prednisone taper, Pred-52 52-week prednisone taper, QW every week, RE role emotional, RProle physical, SF social function, SF-36 36-Item Short-Form Health Survey, TCZ tocilizumab, VT vitality

SF-6D Utility Scores

The SF-6D utility score (a quantitative measure of SF-36) was low in each treatment group at baseline, reflecting impaired HRQOL. Changes in SF-6D utility scores from baseline to week 52 exceeded the MID of 0.041 in the TCZ-QW + Pred-26 group (0.080) but in neither of the two PBO + Pred groups (0.034 for PBO + Pred-26 and 0.029 for PBO + Pred-52) (Table 3).

Patient Global Assessment and FACIT-fatigue Scores

Reported improvements in LSM PtGA scores from baseline to week 52 with TCZ-QW + Pred-26 treatment were not statistically significantly different from those of either PBO + Pred group. LSM changes exceeded the MCID[19] only in the TCZ-QW + Pred-26 group (Figure 2).

Figure 2.

Change from baseline to week 52 in PtGA VAS and FACIT-Fatigue scores. Improvement is indicated by a negative change in PtGA and a positive change in FACIT-Fatigue score. *p < 0.001 vs TCZ-QW + Pred-26, upper dashed line = FACIT-Fatigue MCID, lower dashed line = PtGA MCID. FACIT Functional Assessment of Chronic Illness Therapy, MCID minimum clinically important difference, PBO placebo, Pred-26 26-week prednisone taper, Pred-52 52-week prednisone taper, PtGA Patient Global Assessment of Disease Activity, QW every week, TCZ tocilizumab

LSM increases in FACIT-Fatigue scores from baseline to week 52 in the TCZ-QW + Pred-26 group were significantly greater than in both PBO + Pred groups (p < 0.001) and exceeded the MCID[24] (Figure 2).

Patients Reporting Clinically Meaningful Improvements

The proportions of patients who reported improvements that met or exceeded the MCID from baseline to week 52 in SF-36 PCS and MCS, PtGA and FACIT-Fatigue scores ranged from 43 to 72% in the TCZ-QW + Pred-26 group and were numerically higher than in either PBO + Pred group with the exception of PBO + Pred-52 for FACIT-Fatigue (Figure 3a). Statistically significant differences in the percentages of patients reporting clinically meaningful improvements in PtGA (p = 0.0029) and SF-36 MCS (p = 0.0012) scores were observed in the TCZ-QW + Pred-26 group compared with the PBO + Pred-26 group, resulting in numbers needed to treat (NNTs) of 3.5 and 3.15, respectively. NNTs represent the number of patients who required treatment with an intervention, in this case TCZ-QW + Pred-26, to effect a clinically meaningful improvement in HRQOL (met or exceeded MCID) for one patient. Across SF-36 domain scores, 31 to 61% of patients receiving TCZ-QW + Pred-26 reported improvements that met or exceeded the MCID compared with 12 to 49% receiving PBO + Pred-26. The difference was statistically significant in the general health domain (40 vs 12%, p = 0.0010, NNT = 3.53) (Figure 3b).

Figure 3.

Proportions of patients reporting changes from baseline to week 52 meeting or exceeding MCID. MCIDs are based on patients with RA and SLE, and data are shown for PROs (a) and SF-36 domain scores (b) and proportions of patients reporting scores meeting or exceeding A/G-matched normative values in PROs (c) and SF-36 domain scores (d) at week 52. A/G age/gender, BL baseline, BP bodily pain, FACIT Functional Assessment of Chronic Illness Therapy, GH general health, MCID minimal clinically important difference, MCS Mental Component Summary, MH mental health, PBO placebo, PCS Physical Component Summary, PF physical function, Pred-26 26-week prednisone taper, Pred-52 52-week prednisone taper, PROs patient-reported outcomes, QW every week, RA rheumatoid arthritis, RE role emotional, RP role physical, SF social function, SF-36 36-Item Short-Form Health Survey, SLE systemic lupus erythematosus, TCZ tocilizumab, VT vitality

The proportions of patients reporting clinically meaningful improvements in SF-36 domain scores were numerically higher with TCZ-QW + Pred-26 than with PBO + Pred-52 (Figure 3b). These differences were statistically significant in role physical (57 vs 27%, p = 0.0016, NNT = 3.42) and general health (40 vs 16%, p = 0.0053, NNT = 4.11) domains.

Comparisons With age- and Gender-matched Normative Values

Impaired HRQOL at baseline compared with A/G norms was evident across SF-36 PCS, MCS, domain and FACIT-Fatigue scores across all treatment groups, and few patients in any treatment group reported baseline scores that met or exceeded A/G norms across these PROs (Table 3, Figs. 1 and 3c, d).

The proportions of patients reporting scores that met or exceeded A/G norms in SF-36 PCS, MCS and FACIT-Fatigue increased from baseline to week 52 in the TCZ-QW + Pred-26 group, with generally smaller improvements in both PBO + Pred groups (Figure 3c). The TCZ-QW + Pred-26 group demonstrated statistically significant differences in the proportions of patients reporting scores that met or exceeded A/G norms compared with the PBO + Pred-26 group in FACIT-Fatigue score (p = 0.008, Figure 3c). Week 52 domain scores exceeded A/G norms in five of eight domains with TCZ-QW + Pred-26 (physical function, role physical, bodily pain, vitality and social function; Figure 1) and met A/G norms in the remaining three domains. The proportions of patients reporting SF-36 physical function domain scores that met or exceeded A/G norms was significantly higher in the TCZ-QW + Pred-26 group than in the PBO + Pred-26 group (p = 0.002). The proportions of patients reporting bodily pain, general health, vitality, social function and mental health domain scores that met or exceeded A/G norms were lowest in the PBO + Pred-52 group. The patients in the PBO + Pred-52 group actually reported deterioration in the bodily pain and general health domains at week 52 (Figure 3d).

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