TOCILIZUMAB in COMBINATION with 8 WEEKS of PREDNISONE for GIANT CELL ARTERITIS

ABSTRACT

Background: Even with the use of tocilizumab (TCZ), signifcant glucocorticoid exposure (usually ≥ 6 months) continues to be an important problem in giant cell arteritis (GCA). Objectives: We aimed to evaluate the efficacy and safety of tocilizumab (TCZ) in combination with 2 months of prednisone in a group of patients with GCA. Methods: We conducted a prospective, single arm, open-label study of TCZ in combination with 2 months of prednisone for new-onset and relapsing GCA patients with active disease (ClinicalTrials.gov Identifer NCT03726749). GCA diagnosis required confrmation by temporal artery biopsy or vascular imaging. Active disease was defned as presence of cranial or polymyalgia rheumat-ica symptoms necessitating treatment within 6 weeks of baseline. All patients received TCZ 162 mg subcutaneously every week for 12 months and an 8-week prednisone taper starting between 20 mg and 60 mg daily (Figure 1). The primary endpoint, sustained prednisone-free remission, was defned as absence of relapse from induction of remission up to week 52 while adhering to the prednisone taper. Relapse was defned as the recurrence of symptoms of GCA requiring treatment intensifcation regardless of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. Safety was also evaluated. 8-week prednisone taper starting between 20 mg and 60 mg Primary endpoint Prednisone-free remission at week 52 Figure 1. Clinical Trial Schema Results: Between 11/2018 and 11/2020 we enrolled 30 patients (mean age 74 years, 60% females, 50% new-onset disease, 77% temporal artery biopsy-proven, 47% imaging-proven). The mean ESR and CRP at screening were 45 mm/hour and 48 mg/L, respectively. The initial prednisone dose was 60 mg (n = 7), 50 mg (n = 1), 40 mg (n = 7), 30 mg (n = 6) and 20 mg (n = 9). All patients entered remission within 4 weeks of baseline. The primary endpoint was achieved by 23 (77%) patients (Table 1). The mean (SD) cumulative prednisone dose in these 23 patients was 1052 (390) mg. After a mean period of 16 weeks, 7 (23%) patients relapsed (Table 1). All relapses but one occurred after the completion of the study prednisone taper. Overall, 6 of the 7 patients with relapse received a second prednisone taper over 8 weeks. Of these 6 patients, 4 achieved and maintained remission for the remainder of the trial period, and 2 withdrew from the study after having a second relapse. One patient with relapse received a second prednisone taper over 26 weeks and stayed in remission until the end of the study. The mean (SD) cumulative prednisone dose in the 7 patients with relapse was 1883 (699) mg (Table 1). Overall, 4 (13%) participants developed a serious adverse event (Table 1). No cases of ischemia-related visual symptoms including permanent vision loss occurred during the study. Table 1. Efficacy and Safety Outcomes GCA patients (n = 30) Efficacy Sustained, prednisone-free remission by week 52 23.0 (76.7) Cumulative prednisone dose (mg) at week 52, mean (SD) 1051.5 (390.3) Relapse 70 (23.3) Time to relapse, weeks mean (SD) 15.8 (14.7) Prednisone dose (mg/day) at relapse, mean (SD) 2.1 (5.2) Cumulative prednisone dose (mg), mean (SD) 1883.1 (699.2) Clinical manifestations at relapse Cranial symptoms 4 out of 7 patients schemic visual symptoms 0 out of 7 patients PMR symptoms 4 out of 7 patients Safety Serious adverse events 4.0 (13.3) Cellulitis 1 COVID-19 1 Fragility fracture 1 Cholecystitis 1 Values represent number and (%) unless otherwise specifed. SD, standard deviation;PMR, polymyalgia rheumatica Conclusion: These results suggest that 12 months of TCZ in combination with 8 weeks of prednisone could be efficacious for inducing and maintaining disease remission in patients with GCA. Confrmation of these fndings in a randomized controlled trial is required.