TOCILIZUMAB IN COMBINATION WITH 8 WEEKS OF PREDNISONE FOR GIANT CELL ARTERITIS
Authors: Unizony S. et al.
The two RCTs about Tocilizumab to treat GCA documented a significant steroid-sparing effect. With the aim to further reduce glucocorticoid (GC) co-medication, John Stone and ourselves met in 2018 to discuss protocols addressing this issue. We decided to implement two independent studies. While we performed the GUSTO-study with three initial pulses of methyl-prednisolone only (published in Lancet Rheumatology in 7/2021), John Stone’s group decided for a GC co-medication of 8 weeks.
They 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 Identifier NCT03726749). Patients with active disease necessitating treatment within 6 weeks of baseline were included and received TCZ 162mg subcutaneously every week for 12 months and an 8-week prednisone taper starting between 20mg and 60mg daily. The primary endpoint was sustained prednisone-free remission; relapse was defined as the recurrence of symptoms of GCA requiring treatment intensification. 30 patients (mean age 74 years, 60% females, 50% new-onset disease, 77% temporal artery biopsy-proven, 47% imaging-proven) were enrolled. The mean ESR and CRP at screening were 45 mm/hour and 48 mg/L, respectively. Depending on the duration of prednisone treatment prior to study entry, patients started with doses between 20 and 60mg of prednisone/day. All patients entered remission within 4 weeks of baseline. The primary endpoint was achieved by 23 (77%) patients. 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. 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.
Based on their data, the authors conclude 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. The high and early recurrence rate of this 8-week co-medication study surprises, it contrasts to the results of the GUSTO study (no relapse up to week 52), and it needs further analysis. Variables of potential importance might be the inclusion of relapsing patients (GUSTO newly diagnosed patients only) and per os GC medication versus start with steroid-pulse therapy.