AT THE ACR ANNUAL MEETING

WASHINGTON (FRONTLINE MEDICAL NEWS) – Tocilizumab treatment every week or every other week for 52 weeks with a 26-week prednisone taper was superior to a short and long course of tapered prednisone and also cut the rate of steroid use in half when compared with long-course prednisone in patients with giant cell arteritis in the largest-ever trial of patients with the disease.

The treatment represents a milestone in the treatment of giant cell arteritis (GCA), “a chronic, often devastating, difficult to manage disease,” John Stone, MD, said in his presentation of the results of the randomized, double-blind, placebo-controlled GiACTA trial at the annual meeting of the American College of Rheumatology.

“Our study had three conclusions. There is a new treatment for GCA at last! Tocilizumab [Actemra] has a powerful steroid-sparing effect. The era of unending glucocorticoid treatment with no viable alternative is over,” stated lead author Dr. Stone, a rheumatologist at Massachusetts General Hospital, Boston.

Tocilizumab, an IL-6 receptor-alpha inhibitor, is approved by the Food and Drug Administration for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis.

The difficulty in treating GCA is made evident by the fact that “at least 10% of patients with GCA lose their vision, and the long-term morbidity of glucocorticoid treatment – the only treatment thus far for this disease – is substantial,” he said. “For more than 65 years, no true steroid-sparing treatment has been proven effective.”

Remissions rise while flares and steroid use decline

GiACTA enrolled 251 GCA patients over 22 months from 14 countries and 76 sites (61 in Europe and 15 in North America). Median age was 69 years; 74% were female; and 97% were white.

“This trial was 2.5 times as large as any trial conducted in GCA,” Dr. Stone said.

Patients with GCA were eligible for the study if they met modified 1990 ACR classification criteria for GCA as follows: elevated C-reactive protein (CRP) with unequivocal cranial symptoms or unequivocal symptoms of polymyalgia rheumatica; and imaging evidence of large-vessel vasculitis (ultrasound was not permitted).

Patients were randomized to one of four treatment arms: Group 1, prednisone with 6-month taper until week 52 on no other therapy; Group 2, prednisone with 52 weeks of taper; Group 3, weekly tocilizumab injection plus the same steroid taper as Group 1; and Group 4, tocilizumab every other week with same steroid taper as Group 1.

Investigators were blinded to the prednisone taper regimen and the treatment.

Dr. Stone reported 52-week results for the primary endpoint of GiACTA (i.e., sustained remission from week 12 to 52 for tocilizumab versus prednisone 26-week taper). The study is continuing open-label for another year.

The rates of sustained remission at 52 weeks were significantly higher for both weekly tocilizumab (56% of 100 patients; P less than .0001) and every-other-week tocilizumab (53% of 49 patients; P = .0002) versus 14% for short-course prednisone (14% of 50 patients). The rate of sustained remission at 52 weeks was 18% of 51 patients for long-course prednisone.

“The inclusion of CRP did not affect the outcome. After removing CRP from the primary analysis, both endpoints were highly statistically significant for the tocilizumab groups,” Dr. Stone noted.

The same pattern was evident for time to first flare following clinical remission, with the best results in Group 3 and Group 4 – the two tocilizumab groups. The weekly tocilizumab group had a sustained response following the cessation of prednisone, but the every-other-week tocilizumab group had a drop-off after stopping prednisone. More flares were seen in Groups 1 and 2.

Flares were defined as recurrence of GCA signs or symptoms; increased erythrocyte sedimentation rate greater than 30 mm/h attributed to GCA; or two consecutive CRP elevations. Flares were treated by increase in prednisone dose. The cumulative dose of prednisone was cut in half in both tocilizumab arms, compared with the long-course prednisone treatment arm.

“The reduction in prednisone use in patients taking tocilizumab was clinically significant,” Dr. Stone said.

According to the Short-Form 36, a patient-reported outcomes measure, tocilizumab improved global quality of life while quality of life declined in both prednisone taper groups.

There were no new safety signals related to tocilizumab reported during the trial. No cases of vision loss and no deaths occurred. Two malignancies were reported in the prednisone groups.

“Adverse events were not disproportionate in the tocilizumab-treated groups,” Dr. Stone said.

Some of the investigators had financial relationships with Roche, which sponsored the study, or other pharmaceutical companies. Several investigators were employees of Roche or its wholly-owned subsidiary, Genentech.

rhnews@frontlinemedcom.com

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