How safe and effective is tocilizumab (TCZ) for patients with giant cell arteritis (GCA)? John H. Stone, of Massachusetts General Hospital, Harvard Medical School, presented results of this Phase III GiACTA trial at the American College of Rheumatology annual meeting held in Washington, D.C. on Nov. 13.
The study looked at the safety and efficacy of TCZ, an IL-6 receptor-alpha inhibitor, in patients with GCA. It was a randomized, double-blind study using placebo controls and glucocorticoid regimens of variable dose and duration, obtaining data to week 52.
According to Genentech, there haven’t been any new GCA treatments in 50 years, and this is the largest GCA treatment Phase III trial conducted to date.
The study enrolled 251 patients ages 50 and older, with active GCA. They stratified the randomization by baseline prednisone dose (those getting more than 30 mg/day and those getting 30mg/day or less). Groups included:
-Group A: short course of prednisone (26 week prednisone taper) and weekly subcutaneous placebo;
-Group B: long course of prednisone (52 week prednisone taper) and weekly subcutaneous placebo;
-Group C: short course of prednisone (26 week prednisone taper) and weekly 162 mg subcutaneous TCZ;
-Group D: short course of prednisone (26 week prednisone taper) and every-other-week 162 mg subcutaneous TCZ.
Each investigator chose the patients’ baseline prednisone dose, ranging from 20-60 mg/day, though Prednisone doses less than 20 mg/day were blinded. If patients flared or couldn’t maintain their protocol’s prednisone tapering schedule, they were continued on the double-blind TCZ or placebo schedule, but given open-label prednisone escape therapy. Researchers looked for sustained remission at week 52, defined as no flare and C-reactive protein normalization at week 12, plus adhering to their specific protocol for prednisone taper.
During the study, researchers found that 56% of patients in Group C (weekly TCZ) and 53.1% in Group D (every-other-week TCZ) had sustained remission at 52 weeks, whereas only 14% achieved the same in Group A (placebo plus short course prednisone group), and 17.6% in Group B (placebo plus long course prednisone group). They found that those in the TCZ groups also had less than half of the median cumulative steroid exposure, compared to the long course prednisone group. Incidences of adverse events were similar for all four groups.
Researchers concluded the best results for GCA patients in this trial, were from those who received TCZ and a 26-week prednisone taper. Adding TCZ to the treatment also reduced the number of prednisone doses required for GCA control.
Dr. Stone and the study co-authors have ties with Roche, Genentech, Chugai, GlaxoSmithKline, Servier, Mundi Pharma, Napp Pharmaceuticals and UCB.
John H. Stone. "Efficacy and Safety of Tocilizumab in Patients with Giant Cell Arteritis: Primary and Secondary Outcomes from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial," Abstract number 911. 11:30 a.m., Nov. 13, 2016. ACR/ARHP 2016 Annual Meeting. http://acrabstracts.org/abstract/efficacy-and-safety-of-tocilizumab-in-patients-with-giant-cell-arteritis-primary-and-secondary-outcomes-from-a-phase-3-randomized-double-blind-placebo-controlled-trial/