Tocilizumab After Ultra-Short Course Steroids Promising for Newly Diagnosed Giant Cell Arteritis

By Marilynn Larkin

July 16, 2021

NEW YORK (Reuters Health) - Tocilizumab (TCZ) induced a slow and lasting remission after an ultra-short pulse (three days) of steroids in newly diagnosed giant cell arteritis (GCA) patients, a proof-of-concept trial shows.

His early research on cytokines and glucocorticoids led Dr. Peter Villiger of Medical Center Monbijou in Bern to find ways to reduce steroid use, he told Reuters Health by email. "I have always been concerned about the potential problems of combination therapy with TCZ and glucocorticoids, and was looking forward to substantially shortening the co-medication with steroids."

His team went on to publish, among others, the first case series on TCZ for the treatment of GCA ( and the first randomized controlled trial of TCZ for induction and maintenance of remission in GCA using a very rapid reduction scheme of prednisone (, he said.

For the current study, Dr. Villiger and colleagues evaluated the efficacy and safety of TCZ monotherapy after ultra-short-term glucocorticoid treatment in patients with new-onset GCA. As reported in The Lancet Rheumatology, the single-arm, single-center, open-label, proof-of-concept GUSTO (giant cell arteritis treatment with ultra-short glucocorticoids and tocilizumab) trial enrolled 18 patients (median age, 72; 67%, women; 100% white).

Participants received IV methylprednisolone 500 mg for three consecutive days only, followed by a single infusion of IV tocilizumab (8 mg/kg bodyweight) and weekly subcutaneous tocilizumab injections (162 mg) thereafter, until week 52.

The primary endpoint was the proportion of patients who experienced remission within 31 days and showed no relapse at week 24.

Overall, 15 of the 18 patients had cranial symptoms; 10 had polymyalgia rheumatica symptoms; and 13 showed a positive histopathology.

At 31 days, three (25%) of 12 patients were in remission. The null hypothesis could not be rejected, and the study was futile with respect to the primary endpoint.

However, 14 (78%) of 18 patients were in remission within 24 weeks (mean time to first remission 11.1 weeks) and 13 (72%) had no relapses up to 52 weeks. The mean time to the first partial remission was 6.2 weeks. No patients relapsed after induction of remission.

Overall, three did not respond to treatment and two discontinued the study due to an adverse event (hepatopathy in one case; diverticulitis in the other). Anterior ischemic optic neuropathy occurred in one patient.

Dr. Villiger said, "The next study should be a multicenter trial testing a protocol for clinical use - i.e., co-medication with low-dose glucocorticoids over six weeks to control residual symptoms."

Dr. Maria Cid of the University of Barcelona, coauthor of a related editorial, commented in an email to Reuters Health, "Although the primary endpoint - remission at 31 days - was not achieved, the GUSTO has demonstrated, indeed, that 78% of patients achieve remission within 24 weeks with tocilizumab monotherapy following three IV methyl-prednisolone pulses. Moreover in 72% of patients, remission was sustained through the trial duration."

"However," she noted, "remission was substantially slower than in the standard of care and one patient suffered GCA-related permanent visual loss."

"Results of the GUSTO trial are preliminary and this treatment regimen cannot be recommended," she said. "However, the trial provides proof of concept that glucocorticoid exposure can be further reduced in some patients receiving TCZ. The extent of reduction, its efficacy and safety in the short and in the long-term need to be explored in larger clinical trials with extended follow-up."

The study was funded by Bern University Hospital, University of Bern and F. Hoffmann-LaRoche, Dr. Villiger and another coauthor have received fees from Hoffmann-LaRoche and one coauthor is an employee and shareholder.

SOURCE: The Lancet Rheumatology, online July 2, 2021.