Lead Investigator Discusses Implications of the GiACTA Trial for GCA Treatment

Rheumatology Advisor speaks with John Stone, MD, MPH, Edward Fox Chair in Medicine at Massachusetts General Hospital who is the lead investigator of a phase III, double-blind, randomized trial evaluating the safety and efficacy of tocilizumab for giant cell arteritis

For people who suffer from giant cell arteritis (GCA) — estimated to be more than 200 in every 100 000 US adults over age 50 — steroids have been the mainstay of treatment for more than 50 years. However, steroid use is associated with adverse effects such as diabetes, hypertension, fractures, and cataracts in approximately 80% of GCA patients who use them for the long term. 

But given the risk of blindness, stroke, and aortic aneurysms without them, patients have no other choice. However, results from the largest clinical trial of patients with GCA to date suggest that this will likely change in the near future.¹

The phase III, double-blind, randomized, controlled trial A Study of RoActemra/Actemra (Tocilizumab) in Patients With Giant Cell Arteritis (GiACTA, ClinicalTrials.gov Identifier: NCT01791153) included 251 patients from 76 sites across 14 countries. 

The investigators reported tocilizumab (Actemra^®, Genentech) paired initially with a 6-month steroid regimen, more effectively sustained remission through 1 year compared with a 6 or 12-month steroid-only regimen in those with newly diagnosed and relapsing GCA. 

No new safety signals have been observed thus far, and similar adverse events were observed as in prior tocilizumab trials.

Rheumatology Advisor spoke with lead investigator John H. Stone, MD, MPH, about what led to the trial, its promising results thus far, and next steps in the investigation.

Rheumatology Advisor: What prompted this inquiry into the efficacy of tocilizumab for GCA?

John H. Stone, MD, MPH: In 2010, I was consulted urgently by the cardiovascular surgeons at my hospital about a 65 year-old man with GCA who had developed a life-threatening aneurysm at the aortic arch. His GCA had been refractory to high doses of prednisone for approximately 9 months. Their reason for consulting me was simple: “Cool his disease down so that we can operate on him.”

I was not confident at the time that we had ANY means of cooling his GCA, particularly in the time frame that would be required to get him to surgery when he needed it. Methotrexate and tumor necrosis factor inhibition had failed in clinical trials, and no anecdotal experience strongly supported the efficacy of any other agent. 

However, knowing that interleukin-6 (IL-6) is produced by macrophages — among other cells — within the blood vessel wall of temporal arteries from patients with GCA, I had wanted to use IL-6 receptor blockade for a number of years in this disease.

So here was the perfect opportunity. The clinical situation was desperate, and there was literally no other treatment option that was feasible. We used the entire supply of tocilizumab that the inpatient pharmacy had on hand and waited with bated breath to see if the patient would respond. 

Two days after he had received tocilizumab, his acute phase reactant began to fall steadily and we began to lower his prednisone dose swiftly, with the goal of getting him to 7.5 mg/day by the time of surgery. The patient felt better clinically after tocilizumab administration and even as we decreased his prednisone substantially every day, the levels of his acute phase reactants fell steadily toward normal.

Finally, on day 12 after receiving tocilizumab, the patient went to surgery. He survived a 13-hour operation with no adverse consequences and was discharged from the hospital 1 month after the day I met him. Nearly 6 years later, he remains in complete remission on tocilizumab and has not taken a single milligram of prednisone since the time of his hospital discharge.

Of course, this single anecdotal case — impressive though it was — did not prove that IL-6 receptor blockade worked in GCA. We had to conduct a rigorous clinical trial to prove that. But my experience with this first patient led directly to the GiACTA trial. Right after I presented the story of this patient at the American College of Rheumatology Annual Meeting in 2010, a representative of Roche approached me and said, “We need to talk.”

Rheumatology Advisor: Regarding these latest reported findings, what are the current and future treatment implications for rheumatologists?

Dr Stone: IL6-receptor blockade is the first treatment confirmed to be effective in GCA since cortisone was invented more than 65 years ago in 1948. The results of the GiACTA trial demonstrated quite clearly the powerful steroid-sparing effects of tocilizumab. As a consequence, assuming that tocilizumab is approved for this indication, physicians will have a major new weapon in their fight against GCA, a potentially devastating and chronic disease that tends to afflict middle-aged to elderly individuals.

Patients will be the greatest beneficiaries, of course. The most despised aspect of GCA for most patients is the need for long courses of glucocorticoids — and all of their attendant side effects — to treat GCA and try to prevent blindness and other disease complications.

Summary & Clinical Applicability

A new phase III clinical trial shows the efficacy of tocilizumab in treating GCA. It was found to be more effective than steroids, which have been the treatment mainstay for GCA for more than 50 years.

Reference

1. Business Wire. Press Release: Phase III Study Shows Genentech’s Actemra^® (tocilizumab) Maintained Steroid-Free Remission in People With Giant Cell Arteritis (GCA). Published online June 6, 2016. Accessed July 6, 2016.