Abatacept efficacy differs in trials of giant cell and Takayasu’s arteritis

 

A pair of new studies offer mixed results regarding the use of the rheumatoid arthritis drug abatacept to treat two forms of large-vessel vasculitis: It appears to help patients with giant cell arteritis but not those with the rarer Takayasu’s arteritis.

 

“The results from the GCA [giant cell arteritis] study found that treatment with abatacept [Orencia] combined with prednisone resulted in a lower rate of relapse than treatment with prednisone alone,” said Carol A. Langford, MD, lead author of both studies, which were conducted by the Vasculitis Clinical Research Consortium. She is chair in rheumatic and immunologic diseases and director of the Center for Vasculitis Care and Research at the Cleveland Clinic.

In Takayasu’s arteritis (TAK), however, “abatacept was not found to provide additional benefit beyond prednisone,” Dr. Langford said in an interview.

Both studies appear online Jan. 30 in Arthritis & Rheumatology.

“GCA is the most common form of vasculitis with an estimated incidence of 19.8 per 100,000,” she said. “It occurs in people over the age of 50 with the average age of onset in the 70s.” Women are most affected by a 2:1 ratio.

She said the disease affects the cranium (causing headaches, scalp tenderness, and a risk of blindness) and causes signs of systemic inflammation.

“Almost one-third of patients with GCA can have large vessel involvement that specifically include thoracic aortic aneurysms and stenosis of the cervical and subclavian arteries,” she said. Fatal thoracic aneurysms are possible, she said, but “studies have shown that in GCA overall, while short-term mortality may be increased, long-term survival is similar to the age-matched general population.”

TAK is much rarer, she said, affecting 3-9 people per 1,000,000. “TAK has an average age of onset in the 20s with an even stronger female predisposition of up to 9:1.”

The condition affects the aorta, its main branches, and pulmonary arteries, she said, “Some of the more frequent vascular symptoms/signs can include extremity claudication, hypertension, chest pain, and features associated with cerebral hypoperfusion. TAK is associated with substantial morbidity which is influenced by a low rate of sustained remission in 28%-50% of patients. Up to 47% of patients experience permanent disability, which has a significant impact on this young population.”

The mortality from TAK is unclear, she said.

Glucocorticoids are the main treatment for both GCA and TAK, Dr. Langford said, but “while glucocorticoids effectively control disease, they do not prevent relapse and they are associated with significant toxicity.”

For GCA, methotrexate has shown a mild benefit at best, she said, while two studies show promise for tocilizumab (Actemra). As for TAK, she said doctors often turn to the use of immunosuppressants and tumor necrosis factor inhibitors, although their use is based on retrospective studies and small, open-label trials.

Dr. Langford and her colleagues launched the two randomized, double-blind, placebo-controlled, multicenter studies in parallel with the same protocols.

In the GCA trial (doi: 10.1002/art.40044), researchers enrolled 49 patients with newly diagnosed GCA or disease that had relapsed within the 2 prior months to prednisone 40-60 mg/day followed by a standardized tapering schedule plus abatacept 10 mg/kg IV on days 1, 15, 29, and week 8. At 12 weeks, 8 patients had withdrawn, relapsed, or were not in remission, and so 41 were randomized to receive placebo or monthly abatacept until they met criteria for early termination or 12 months had passed after the last patient was enrolled. At the time of the randomization at 12 weeks, all patients were taking prednisone 20 mg/day, which was tapered until discontinuation at week 28.

At 12 months, 48% of those who took abatacept survived without relapse, compared with 31% of those who took placebo (P = .049), and the median remission period was longer for abatacept (9.9 months) than placebo (3.9 months; P = .023).

“This difference between groups is clinically meaningful to patients with GCA, corresponding to a prolonged duration of remission during which time they are not exposed to glucocorticoids and their potential toxicities that can impact quality of life,” Dr. Langford said.

No patients died during the trial, and 23 serious adverse events were reported in 15 patients. The frequency and severity of adverse events and infections didn’t differ between the treatment and placebo groups.

The drug may work in GCA patients by blocking T-cell activation, Dr. Langford said. Physicians could consider the drug in clinical practice, she said, although more research is needed to understand the long-term effects of using the medication.

In the other study (doi: 10.1002/art.40037), researchers used the same protocol to treat 34 patients with TAK; 26 reached the 12-week midpoint and were randomized to placebo or continuing abatacept on a monthly basis.

At 12 months, the relapse-free rate was 22% for the abatacept group and 40% for the placebo group (P = .853). The median duration of remission was similar for the groups at 5.5 months for abatacept and 5.7 months for placebo (P = .125).

The researchers reported no difference in frequency or severity of adverse events such as infection.

Based on the study results, Dr. Langford said abatacept is not appropriate in clinical practice to treat TAK.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases funded the studies, and Bristol-Myers Squibb, which markets abatacept, provided the drug. Dr. Langford disclosed receiving research grants from Bristol-Myers Squibb, Genentech, and GlaxoSmithKline.

 

A pair of new studies offer mixed results regarding the use of the rheumatoid arthritis drug abatacept to treat two forms of large-vessel vasculitis: It appears to help patients with giant cell arteritis but not those with the rarer Takayasu’s arteritis.

 

“The results from the GCA [giant cell arteritis] study found that treatment with abatacept [Orencia] combined with prednisone resulted in a lower rate of relapse than treatment with prednisone alone,” said Carol A. Langford, MD, lead author of both studies, which were conducted by the Vasculitis Clinical Research Consortium. She is chair in rheumatic and immunologic diseases and director of the Center for Vasculitis Care and Research at the Cleveland Clinic.

In Takayasu’s arteritis (TAK), however, “abatacept was not found to provide additional benefit beyond prednisone,” Dr. Langford said in an interview.

Both studies appear online Jan. 30 in Arthritis & Rheumatology.

“GCA is the most common form of vasculitis with an estimated incidence of 19.8 per 100,000,” she said. “It occurs in people over the age of 50 with the average age of onset in the 70s.” Women are most affected by a 2:1 ratio.

She said the disease affects the cranium (causing headaches, scalp tenderness, and a risk of blindness) and causes signs of systemic inflammation.

“Almost one-third of patients with GCA can have large vessel involvement that specifically include thoracic aortic aneurysms and stenosis of the cervical and subclavian arteries,” she said. Fatal thoracic aneurysms are possible, she said, but “studies have shown that in GCA overall, while short-term mortality may be increased, long-term survival is similar to the age-matched general population.”

TAK is much rarer, she said, affecting 3-9 people per 1,000,000. “TAK has an average age of onset in the 20s with an even stronger female predisposition of up to 9:1.”

The condition affects the aorta, its main branches, and pulmonary arteries, she said, “Some of the more frequent vascular symptoms/signs can include extremity claudication, hypertension, chest pain, and features associated with cerebral hypoperfusion. TAK is associated with substantial morbidity which is influenced by a low rate of sustained remission in 28%-50% of patients. Up to 47% of patients experience permanent disability, which has a significant impact on this young population.”

The mortality from TAK is unclear, she said.

Glucocorticoids are the main treatment for both GCA and TAK, Dr. Langford said, but “while glucocorticoids effectively control disease, they do not prevent relapse and they are associated with significant toxicity.”

For GCA, methotrexate has shown a mild benefit at best, she said, while two studies show promise for tocilizumab (Actemra). As for TAK, she said doctors often turn to the use of immunosuppressants and tumor necrosis factor inhibitors, although their use is based on retrospective studies and small, open-label trials.

Dr. Langford and her colleagues launched the two randomized, double-blind, placebo-controlled, multicenter studies in parallel with the same protocols.

In the GCA trial (doi: 10.1002/art.40044), researchers enrolled 49 patients with newly diagnosed GCA or disease that had relapsed within the 2 prior months to prednisone 40-60 mg/day followed by a standardized tapering schedule plus abatacept 10 mg/kg IV on days 1, 15, 29, and week 8. At 12 weeks, 8 patients had withdrawn, relapsed, or were not in remission, and so 41 were randomized to receive placebo or monthly abatacept until they met criteria for early termination or 12 months had passed after the last patient was enrolled. At the time of the randomization at 12 weeks, all patients were taking prednisone 20 mg/day, which was tapered until discontinuation at week 28.

At 12 months, 48% of those who took abatacept survived without relapse, compared with 31% of those who took placebo (P = .049), and the median remission period was longer for abatacept (9.9 months) than placebo (3.9 months; P = .023).

“This difference between groups is clinically meaningful to patients with GCA, corresponding to a prolonged duration of remission during which time they are not exposed to glucocorticoids and their potential toxicities that can impact quality of life,” Dr. Langford said.

No patients died during the trial, and 23 serious adverse events were reported in 15 patients. The frequency and severity of adverse events and infections didn’t differ between the treatment and placebo groups.

The drug may work in GCA patients by blocking T-cell activation, Dr. Langford said. Physicians could consider the drug in clinical practice, she said, although more research is needed to understand the long-term effects of using the medication.

In the other study (doi: 10.1002/art.40037), researchers used the same protocol to treat 34 patients with TAK; 26 reached the 12-week midpoint and were randomized to placebo or continuing abatacept on a monthly basis.

At 12 months, the relapse-free rate was 22% for the abatacept group and 40% for the placebo group (P = .853). The median duration of remission was similar for the groups at 5.5 months for abatacept and 5.7 months for placebo (P = .125).

The researchers reported no difference in frequency or severity of adverse events such as infection.

Based on the study results, Dr. Langford said abatacept is not appropriate in clinical practice to treat TAK.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases funded the studies, and Bristol-Myers Squibb, which markets abatacept, provided the drug. Dr. Langford disclosed receiving research grants from Bristol-Myers Squibb, Genentech, and GlaxoSmithKline.

 

A pair of new studies offer mixed results regarding the use of the rheumatoid arthritis drug abatacept to treat two forms of large-vessel vasculitis: It appears to help patients with giant cell arteritis but not those with the rarer Takayasu’s arteritis.

 

“The results from the GCA [giant cell arteritis] study found that treatment with abatacept [Orencia] combined with prednisone resulted in a lower rate of relapse than treatment with prednisone alone,” said Carol A. Langford, MD, lead author of both studies, which were conducted by the Vasculitis Clinical Research Consortium. She is chair in rheumatic and immunologic diseases and director of the Center for Vasculitis Care and Research at the Cleveland Clinic.

In Takayasu’s arteritis (TAK), however, “abatacept was not found to provide additional benefit beyond prednisone,” Dr. Langford said in an interview.

Both studies appear online Jan. 30 in Arthritis & Rheumatology.

“GCA is the most common form of vasculitis with an estimated incidence of 19.8 per 100,000,” she said. “It occurs in people over the age of 50 with the average age of onset in the 70s.” Women are most affected by a 2:1 ratio.

She said the disease affects the cranium (causing headaches, scalp tenderness, and a risk of blindness) and causes signs of systemic inflammation.

“Almost one-third of patients with GCA can have large vessel involvement that specifically include thoracic aortic aneurysms and stenosis of the cervical and subclavian arteries,” she said. Fatal thoracic aneurysms are possible, she said, but “studies have shown that in GCA overall, while short-term mortality may be increased, long-term survival is similar to the age-matched general population.”

TAK is much rarer, she said, affecting 3-9 people per 1,000,000. “TAK has an average age of onset in the 20s with an even stronger female predisposition of up to 9:1.”

The condition affects the aorta, its main branches, and pulmonary arteries, she said, “Some of the more frequent vascular symptoms/signs can include extremity claudication, hypertension, chest pain, and features associated with cerebral hypoperfusion. TAK is associated with substantial morbidity which is influenced by a low rate of sustained remission in 28%-50% of patients. Up to 47% of patients experience permanent disability, which has a significant impact on this young population.”

The mortality from TAK is unclear, she said.

Glucocorticoids are the main treatment for both GCA and TAK, Dr. Langford said, but “while glucocorticoids effectively control disease, they do not prevent relapse and they are associated with significant toxicity.”

For GCA, methotrexate has shown a mild benefit at best, she said, while two studies show promise for tocilizumab (Actemra). As for TAK, she said doctors often turn to the use of immunosuppressants and tumor necrosis factor inhibitors, although their use is based on retrospective studies and small, open-label trials.

Dr. Langford and her colleagues launched the two randomized, double-blind, placebo-controlled, multicenter studies in parallel with the same protocols.

In the GCA trial (doi: 10.1002/art.40044), researchers enrolled 49 patients with newly diagnosed GCA or disease that had relapsed within the 2 prior months to prednisone 40-60 mg/day followed by a standardized tapering schedule plus abatacept 10 mg/kg IV on days 1, 15, 29, and week 8. At 12 weeks, 8 patients had withdrawn, relapsed, or were not in remission, and so 41 were randomized to receive placebo or monthly abatacept until they met criteria for early termination or 12 months had passed after the last patient was enrolled. At the time of the randomization at 12 weeks, all patients were taking prednisone 20 mg/day, which was tapered until discontinuation at week 28.

At 12 months, 48% of those who took abatacept survived without relapse, compared with 31% of those who took placebo (P = .049), and the median remission period was longer for abatacept (9.9 months) than placebo (3.9 months; P = .023).

“This difference between groups is clinically meaningful to patients with GCA, corresponding to a prolonged duration of remission during which time they are not exposed to glucocorticoids and their potential toxicities that can impact quality of life,” Dr. Langford said.

No patients died during the trial, and 23 serious adverse events were reported in 15 patients. The frequency and severity of adverse events and infections didn’t differ between the treatment and placebo groups.

The drug may work in GCA patients by blocking T-cell activation, Dr. Langford said. Physicians could consider the drug in clinical practice, she said, although more research is needed to understand the long-term effects of using the medication.

In the other study (doi: 10.1002/art.40037), researchers used the same protocol to treat 34 patients with TAK; 26 reached the 12-week midpoint and were randomized to placebo or continuing abatacept on a monthly basis.

At 12 months, the relapse-free rate was 22% for the abatacept group and 40% for the placebo group (P = .853). The median duration of remission was similar for the groups at 5.5 months for abatacept and 5.7 months for placebo (P = .125).

The researchers reported no difference in frequency or severity of adverse events such as infection.

Based on the study results, Dr. Langford said abatacept is not appropriate in clinical practice to treat TAK.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases funded the studies, and Bristol-Myers Squibb, which markets abatacept, provided the drug. Dr. Langford disclosed receiving research grants from Bristol-Myers Squibb, Genentech, and GlaxoSmithKline.