Health-related quality of life improved significantly among patients with giant cell arteritis (GCA) treated with tocilizumab (Actemra), analysis of data from a phase III clinical trial found.
Among patients enrolled in a randomized study that compared tocilizumab with placebo with two different steroid taper regimens, those receiving tocilizumab weekly plus a 26-week prednisone taper had a least squares mean change from baseline in the Physical Component Summary (PCS) of the Short Form (SF)-36 Health Survey of 4.18, according to John H. Stone, MD, of Harvard Medical School in Boston, and colleagues.
That represented a significant difference compared with the changes from baseline on the PCS for patients receiving placebo plus a 26-week prednisone taper and for those given placebo with a 52-week prednisone taper (-0.98 and -0.40, respectively, P<0.01 for both), the researchers reported online in Arthritis Research & Therapy.
GCA is a systemic vasculitis involving the aorta, its primary branches, and other arteries connecting the brain and eyes. Its most dreaded complications include vision loss and aortic aneurysms.
Conventional treatment has relied on glucocorticoids, often in high doses and for extended periods, even though recommendations call for prednisone to be tapered as rapidly as possible. In the yearlong GiACTA study, 56% of patients receiving the weekly subcutaneous interleukin (IL)-6 receptor-α inhibitor tocilizumab plus short-course prednisone were in remission at week 52 compared with only 14% of those given placebo plus short-course prednisone. That led to the drug’s approval in 2017 for GCA.
Little is known, however, about the effects of treatment on health-related quality of life, so Stone and colleagues conducted an analysis of patient-reported outcomes among GiACTA participants. This analysis included 201 patients whose mean age was 69. Three-quarters were women, and almost all were white.
Patients in the two placebo groups had approximately twice the cumulative prednisone dose compared with the tocilizumab group. The median cumulative dose was 3,296 mg in the placebo plus 26-week prednisone taper group and 3,817.5 mg in the placebo plus 52-week taper group compared with 1,862 mg in the tocilizumab group (P<0.001).
At baseline, the PCS and Mental Component Summary (MCS) scores were similar in the tocilizumab and placebo groups, being approximately one standard deviation below the age- and sex-matched normative scores of 50. On the MCS, change from baseline at week 52 was 8.10 in the tocilizumab group, 5.25 in the placebo plus 26-week prednisone taper group, and 1.89 in the placebo plus prednisone 52-week taper group.
At week 52, changes from baseline on four of the individual domains of the SF-36 (physical function, role physical, general health, and vitality) were significantly higher in the tocilizumab group than in the placebo plus 26-week prednisone taper group, while scores for six individual domains of the SF-36 (role physical, bodily pain, general health, vitality, social function, and mental health) were higher in the tocilizumab group than in the placebo plus 52-week prednisone taper group.
Patients in the tocilizumab group also had significantly greater increases in their scores on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue measurement compared with the placebo plus 26-week placebo taper (5.30 vs 0.09), and compared with the placebo plus 52-week taper (-0.42, P<0.001 for both). They also more often reported clinically meaningful improvements on the Patient Global Assessment of disease activity (-17.14 vs -7.19 and -7.56).
“Even more striking” was the finding that by week 52, patients in the tocilizumab group showed improvements in every individual domain of the SF-36 that met or exceeded age- and sex-matched normative values, the authors observed.
For instance, the normative value for the physical function domain of the SF-36 was 67.56. At week 52, the value in the tocilizumab group was 78.28, compared with 63.48 and 65.44 in the placebo plus 26-week prednisone taper and the 52-week taper groups, respectively. On the mental health domain, the normative value was 77.16, and the values at 1 year were 77.94, 73.60, and 66.33 in the tocilizumab, placebo plus 26-week taper, and placebo plus 52-week taper groups, respectively.
“These findings are unprecedented in other health-related quality of life analyses across rheumatic diseases and highlight the importance of IL-6 in the underlying pathophysiology of GCA,” the investigators stated.
Recent research has demonstrated that IL-6 is involved not only in inflammation, but also plays a role in mediation of pain, fatigue, and mood, possibly through upregulation of the hypothalamic-pituitary axis.
“Our findings support the concept that one mechanism whereby IL-6 inhibition improves health-related quality of life is through an elevating effect on mood,” Stone and colleagues noted.
The study was funded by Roche.
The authors reported financial relationships with Genentech/Roche, AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, CORRONA, Crescendo, EMD Serono, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Protagen, Regeneron, Samsung, Sandoz, Sanofi, and UCB.