Glucocorticoid Dosages and Acute-Phase Reactant Levels at Giant Cell Arteritis Flare in a Randomized Trial of Tocilizumab

Abstract

Objective: This study was undertaken to evaluate glucocorticoid dosages and serologic findings in patients with giant cell arteritis (GCA) flares.

Methods: Patients with GCA were randomly assigned to receive double-blind dosing with either subcutaneous tocilizumab (TCZ) 162 mg weekly plus 26-week prednisone taper (TCZ-QW + Pred-26), every-other-week TCZ plus 26-week prednisone taper (TCZ-Q2W + Pred-26), placebo plus 26-week prednisone taper (PBO + Pred-26), or placebo plus 52-week prednisone taper (PBO + Pred-52). Outcome measures were prednisone dosage, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) at the time of flare.

Results: One hundred patients received TCZ-QW + Pred-26, 49 received TCZ-Q2W + Pred-26, 50 received PBO + Pred-26, and 51 received PBO + Pred-52. Of the 149 TCZ-treated patients, 36 (24%) experienced flare, 23 (64%) of whom were still receiving prednisone (median dosage 2.0 mg/day). Among 101 PBO + Pred-treated patients, 59 (58%) experienced flare, 45 (76%) of whom were receiving prednisone (median dosage 5.0 mg/day). Many flares occurred while patients were taking >10 mg/day prednisone: 9 (25%) in the TCZ groups and 13 (22%) in the placebo groups. Thirty-three flares (92%) in TCZ-treated groups and 20 (34%) in PBO + Pred-treated groups occurred with normal CRP levels. More than half of the PBO + Pred-treated patients had elevated CRP levels without flares. Benefits of the TCZ and prednisone combination over prednisone alone for remission induction were apparent by 8 weeks.

Conclusion: Most GCA flares occurred while patients were still receiving prednisone. Acute-phase reactant levels were not reliable indicators of flare in patients treated with TCZ plus prednisone or with prednisone alone. The addition of TCZ to prednisone facilitates earlier GCA control.

Trial registration: ClinicalTrials.gov NCT01791153.

Figure 1

Disease control during the first 52 weeks of treatment in all patients in the intent‐to‐treat population (A), and in patients with newly diagnosed (B) and relapsing (C) giant cell arteritis. Prespecified exploratory analysis of remission rates over time is shown. Remission was defined as absence of flare and did not include C‐reactive protein level in the definition. Patients who withdrew from the study or received escape therapy were excluded from that point. Patients with missing information on remission status were considered not in remission for that time point only. Responders (patients in remission) were analyzed; therefore, values at week 52 are slightly higher than the highest values for sustained remission, which accounts for patients not adhering to the protocol‐defined tapering regimen as nonresponders. PBO + Pred‐26 = placebo plus 26‐week prednisone taper; PBO + Pred‐52 = placebo plus 52‐week prednisone taper; TCZ‐QW + Pred‐26 = tocilizumab once weekly plus 26‐week prednisone taper; TCZ‐Q2W + Pred‐26 = tocilizumab once every 2 weeks plus 26‐week prednisone taper.

Figure 2

Sustained remission through week 52 according to baseline prednisone dosage. Percentages are based on number of patients receiving baseline dosage (*) and total number of patients in each treatment group at baseline (†). See Figure 1 for definitions. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.40876/abstract.

Figure 3

Kaplan‐Meier plot of time to first giant cell arteritis (GCA) flare according to starting prednisone dosage of >30 mg/day (A) and ≤30 mg/day (B) in the intent‐to‐treat population. Patients never in remission were censored at day 1, and patients who withdrew from the study before week 52 were censored from the time of withdrawal. See Figure 1 for definitions. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.40876/abstract.