FDA approves tocilizumab, first therapy for GCA

June 13, 2017
Michelle Dalton, ELS
Michelle Dalton, ELS

The FDA recently granted regulatory approval for tocilizumab (Actemra, Genentech), the first approved therapy for the treatment of adults with giant cell arteritis.

The FDA recently granted regulatory approval for tocilizumab (Actemra, Genentech), the first approved therapy for the treatment of adults with giant cell arteritis.

Tocilizumab, a humanized interleukin-6 (IL-6) receptor antagonist, already is approved to treat various autoimmune disorders including rheumatoid arthritis (RA). 

GCA, a chronic and severe autoimmune condition that can result in vision loss (including irreversible blindness) and other systemic sequelae, is the common form of vasculitis in people over 50 years. It is characterized by an inflammation of the blood vessels branching off of the heart, including those supplying the scalp, neck, and arms.1

The eye care community is “well aware” of the devastating effects of GCA, also known as temporal arteritis, said Mark Robinson, MD, University of South Carolina Department of Ophthalmology, Columbia. “This disease is one of the well-known vision-threatening emergencies,” he added.

Permanent visual impairment may occur in about 20% of patients with GCA.2 Unfortunately, the cause of the disease is unknown, and no one single test is definitive.”

Before the tocilizumab approval, Dr. Robinson said the only successful treatment was high doses of glucocorticoids (usually prednisone) for many months, tapering to a moderate or lower doses for one to two years-if not longer.

But when patients taper off steroids, relapse rates can be high, said Anne Fung, MD, in private practice in San Francisco and associate group medical director, Genentech.

The lengthier amount of time spent on corticosteroids can lead to side effects, including hyperglycemia, insomnia, and bone fractures, she added.

Dr. Robinson noted GCA may initially present as a transient–but painless–vision impairment, or cause transient double vision. Symptoms that occur before or after vision loss are the onset of a new kind of headache, scalp tenderness, aching, and fatigue of the jaw while chewing (jaw claudication), weight loss, muscle aches, and fever.

“If suspicion is high enough based on the clinical presentation and laboratory values, the patient should be started on oral prednisone and referred for a temporal artery biopsy (perhaps bilaterally if the initial one is negative),” he said.

GiACTA

 

GiACTA

The GCA approval is based on the positive outcome of GiACTA, the phase III global, randomized, double-masked, placebo-controlled trial that enrolled 251 patients. GiACTA found that 52 weeks of subcutaneously injected tocilizumab, initially combined with a 6-month steroid (glucocorticoid) regimen, more effectively sustained remission through 1 year (56% in the tocilizumab weekly group and 53.1% in the tocilizumab bi-weekly group) compared to placebo combined with a 26-week steroid taper (14%) or placebo combined with a 52-week steroid taper (17.6%).3

“Four times the proportion of patients achieved sustained remission of GCA at 1 year in the (tocilizumab) arms compared to either of the study groups treated with corticosteroids alone,” Dr. Fung said. “This was achieved with about half the overall corticosteroid exposure in tocilizumab-treated patients.”

Further, Actemrathe overall safety profile observed in the tocilizumab-treatment groups was consistent with the known safety profile of tocilizumab. There was an overall higher incidence of infections in GCA patients relative to RA patients.

Keeping patients in remission while reducing their corticosteroid exposure “are two significant unmet medical needs in GCA,” Dr. Fung said.

How tocilizumab works

Tocilizumab has been approved in the United States since 2010, and was granted a Priority Review and Breakthrough Therapy designation. GCA marks the drug’s sixth U.S. approval.

Dr. Fung said interleukin-6 (IL-6) is a protein that is associated with the inflammation that leads to GCA. Tocilizumab “is believed to act by binding to the IL-6 receptor, thus blocking the effects of IL-6 and thereby reducing the inflammation associated with GCA,” she added.

During the phase III GiACTA study, subcutaneously administered tocilizumab was tested in combination with a tapering course of corticosteroids. Tocilizumab was dosed in combination with glucocorticoids initially and continued to be dosed alone after patients were rapidly tapered off steroids.

While “Actemra can be used without corticosteroids after the concomitant corticosteroid taper is finished,” Dr. Fung noted no studies have been undertaken to determine if tocilizumab can be used as a monotherapy initially.

The possibility of using tocilizumab in GCA started with research outside of Genentech, Dr. Fung said, where studies suggested that IL-6 plays a role in GCA.

“Initial case reports from clinicians who tried tocilizumab in GCA were also key,” she said. Outside GCA, “we have seen anecdotal preliminary data in other ocular diseases that would require larger studies to properly evaluate for safety and efficacy,” Dr. Fung said.

What this means

 

 

What this means

Due to the variability of symptoms, complexity of the disease and disease complications, GCA patients are seen by several physicians, including rheumatologists, ophthalmologists, and neurologists.

Bear in mind that GCA may not always present initially with permanent vision loss, Dr. Robinson said. “Patients over 50 years of age who have some of the other symptoms of GCA, or transient vision loss or transient double vision, also need to be evaluated,” he pointed out.

When clinicians do encounter these cases, Dr. Robinson recommends initiating prednisone treatment “without delay,” but he now refers patients to rheumatologists “specifically for consideration of treatment with tocilizumab to minimize a patient’s exposure to prednisone.”

 

References:

1.    National Library of Medicine, Medline Plus. Giant Cell Arteritis.http://www.nlm.nih.gov/medlineplus/giantcellarteritis.html#summary.

2.    Seetharaman M, et al. Giant Cell Arteritis (Temporal Arteritis). Medscape. http://emedicine.medscape.com/article/332483-overview.

3.    Stone JH, et al. Efficacy and Safety of Tocilizumab in Patients with Giant Cell Arteritis: Primary and Secondary Outcomes from a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10).

 

Anne Fung, MD

E: annefungmd@gmail.com

 

Mark Robinson, MD

P: (803) 434-2020

Dr. Fung is an employee of Genentech. Dr. Robinson has no financial disclosures regarding the contents of this article.