Tocilizumab Effective Regardless of Prior Therapy

KANANASKIS, ALTA. — The finding that the monoclonal antibody tocilizumab provided rapid and sustained improvement in the signs and symptoms of rheumatoid arthritis, regardless of patients' prior therapy, is not compelling enough to abandon methotrexate.

Dr. Robert McKendry said he was not convinced that he would turn to tocilizumab before methotrexate in rheumatoid arthritis patients.

“The difference between tocilizumab's efficacy and methotrexate's is real, but not necessarily dramatic,” according to Dr. McKendry, professor of medicine at the University of Ottawa.

“Moreover, most of these products—tocilizumab and others—work about 30% better when given with a background of methotrexate.

“So I think we're going to continue to do that until there's a reason not to,” Dr. McKendry said at the annual meeting of the Canadian Rheumatology Association.

Dr. McKendry made these remarks while presenting an analysis of data from more than 3,000 patients who used tocilizumab as monotherapy or in combination with disease modifying antirheumatic drugs (DMARDs) or methotrexate. The patients participated in any one of four phase III trials: TOWARD (Tocilizumab in Combination With Traditional DMARD Therapy), OPTION (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders), RADIATE (Research on Actemra [tocilizumab] Determining Efficacy After Anti-TNF [tumor necrosis factor] Failures), and AMBITION (Actemra Versus Methotrexate Double-Blind Investigative Trial in Monotherapy), he said.

“This product has a unique mechanism of action in that it blocks the [interleukin-6] receptor, which is very important in many aspects of inflammation,” he said.

Each of the trials was randomized and double-blinded, and consisted of a 24-week study period in patients with moderate to severe active rheumatoid arthritis; each patient received a standardized tocilizumab IV dose of 8 mg/kg.

In TOWARD, patients with inadequate prior response to DMARDs received tocilizumab or placebo in combination with DMARDs. OPTION included methotrexate patients who received tocilizumab or placebo plus 10–25 mg/wk methotrexate.

In RADIATE, patients with moderate to severe RA who had an inadequate response to at least one anti-TNF agent received either tocilizumab or placebo plus 10–25 mg/wk methotrexate.

Finally, AMBITION assessed the effects of tocilizumab monotherapy every 4 weeks or methotrexate monotherapy (escalating dosage, 7.5–20 mg/wk) in patients who had not failed previous methotrexate or biologic treatment.

It was found that in all four studies, differences between the tocilizumab and control groups became apparent by the first scheduled assessment at week 2, regardless of prior therapy.

“I emphasize that [tocilizumab] works quickly, compared with other biologics,” Dr. McKendry said in an interview. “You get a significant response within the first 2 weeks, the first time you see the patient.” The studies showed that 17%–25% of patients on tocilizumab achieved an ACR 20 response in the first 2 weeks, compared with 7%–10% of controls.

ACR 50 and ACR 70 responses were observed in a greater percentage of tocilizumab patients than controls from weeks 4 and 8 onward. Patients treated with tocilizumab also demonstrated greater DAS28 improvements from baseline than did controls; DAS28 remission rates were also greater in tocilizumab patients by week 2.

Dr. McKendry had no disclosures to report.

KANANASKIS, ALTA. — The finding that the monoclonal antibody tocilizumab provided rapid and sustained improvement in the signs and symptoms of rheumatoid arthritis, regardless of patients' prior therapy, is not compelling enough to abandon methotrexate.

Dr. Robert McKendry said he was not convinced that he would turn to tocilizumab before methotrexate in rheumatoid arthritis patients.

“The difference between tocilizumab's efficacy and methotrexate's is real, but not necessarily dramatic,” according to Dr. McKendry, professor of medicine at the University of Ottawa.

“Moreover, most of these products—tocilizumab and others—work about 30% better when given with a background of methotrexate.

“So I think we're going to continue to do that until there's a reason not to,” Dr. McKendry said at the annual meeting of the Canadian Rheumatology Association.

Dr. McKendry made these remarks while presenting an analysis of data from more than 3,000 patients who used tocilizumab as monotherapy or in combination with disease modifying antirheumatic drugs (DMARDs) or methotrexate. The patients participated in any one of four phase III trials: TOWARD (Tocilizumab in Combination With Traditional DMARD Therapy), OPTION (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders), RADIATE (Research on Actemra [tocilizumab] Determining Efficacy After Anti-TNF [tumor necrosis factor] Failures), and AMBITION (Actemra Versus Methotrexate Double-Blind Investigative Trial in Monotherapy), he said.

“This product has a unique mechanism of action in that it blocks the [interleukin-6] receptor, which is very important in many aspects of inflammation,” he said.

Each of the trials was randomized and double-blinded, and consisted of a 24-week study period in patients with moderate to severe active rheumatoid arthritis; each patient received a standardized tocilizumab IV dose of 8 mg/kg.

In TOWARD, patients with inadequate prior response to DMARDs received tocilizumab or placebo in combination with DMARDs. OPTION included methotrexate patients who received tocilizumab or placebo plus 10–25 mg/wk methotrexate.

In RADIATE, patients with moderate to severe RA who had an inadequate response to at least one anti-TNF agent received either tocilizumab or placebo plus 10–25 mg/wk methotrexate.

Finally, AMBITION assessed the effects of tocilizumab monotherapy every 4 weeks or methotrexate monotherapy (escalating dosage, 7.5–20 mg/wk) in patients who had not failed previous methotrexate or biologic treatment.

It was found that in all four studies, differences between the tocilizumab and control groups became apparent by the first scheduled assessment at week 2, regardless of prior therapy.

“I emphasize that [tocilizumab] works quickly, compared with other biologics,” Dr. McKendry said in an interview. “You get a significant response within the first 2 weeks, the first time you see the patient.” The studies showed that 17%–25% of patients on tocilizumab achieved an ACR 20 response in the first 2 weeks, compared with 7%–10% of controls.

ACR 50 and ACR 70 responses were observed in a greater percentage of tocilizumab patients than controls from weeks 4 and 8 onward. Patients treated with tocilizumab also demonstrated greater DAS28 improvements from baseline than did controls; DAS28 remission rates were also greater in tocilizumab patients by week 2.

Dr. McKendry had no disclosures to report.

KANANASKIS, ALTA. — The finding that the monoclonal antibody tocilizumab provided rapid and sustained improvement in the signs and symptoms of rheumatoid arthritis, regardless of patients' prior therapy, is not compelling enough to abandon methotrexate.

Dr. Robert McKendry said he was not convinced that he would turn to tocilizumab before methotrexate in rheumatoid arthritis patients.

“The difference between tocilizumab's efficacy and methotrexate's is real, but not necessarily dramatic,” according to Dr. McKendry, professor of medicine at the University of Ottawa.

“Moreover, most of these products—tocilizumab and others—work about 30% better when given with a background of methotrexate.

“So I think we're going to continue to do that until there's a reason not to,” Dr. McKendry said at the annual meeting of the Canadian Rheumatology Association.

Dr. McKendry made these remarks while presenting an analysis of data from more than 3,000 patients who used tocilizumab as monotherapy or in combination with disease modifying antirheumatic drugs (DMARDs) or methotrexate. The patients participated in any one of four phase III trials: TOWARD (Tocilizumab in Combination With Traditional DMARD Therapy), OPTION (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders), RADIATE (Research on Actemra [tocilizumab] Determining Efficacy After Anti-TNF [tumor necrosis factor] Failures), and AMBITION (Actemra Versus Methotrexate Double-Blind Investigative Trial in Monotherapy), he said.

“This product has a unique mechanism of action in that it blocks the [interleukin-6] receptor, which is very important in many aspects of inflammation,” he said.

Each of the trials was randomized and double-blinded, and consisted of a 24-week study period in patients with moderate to severe active rheumatoid arthritis; each patient received a standardized tocilizumab IV dose of 8 mg/kg.

In TOWARD, patients with inadequate prior response to DMARDs received tocilizumab or placebo in combination with DMARDs. OPTION included methotrexate patients who received tocilizumab or placebo plus 10–25 mg/wk methotrexate.

In RADIATE, patients with moderate to severe RA who had an inadequate response to at least one anti-TNF agent received either tocilizumab or placebo plus 10–25 mg/wk methotrexate.

Finally, AMBITION assessed the effects of tocilizumab monotherapy every 4 weeks or methotrexate monotherapy (escalating dosage, 7.5–20 mg/wk) in patients who had not failed previous methotrexate or biologic treatment.

It was found that in all four studies, differences between the tocilizumab and control groups became apparent by the first scheduled assessment at week 2, regardless of prior therapy.

“I emphasize that [tocilizumab] works quickly, compared with other biologics,” Dr. McKendry said in an interview. “You get a significant response within the first 2 weeks, the first time you see the patient.” The studies showed that 17%–25% of patients on tocilizumab achieved an ACR 20 response in the first 2 weeks, compared with 7%–10% of controls.

ACR 50 and ACR 70 responses were observed in a greater percentage of tocilizumab patients than controls from weeks 4 and 8 onward. Patients treated with tocilizumab also demonstrated greater DAS28 improvements from baseline than did controls; DAS28 remission rates were also greater in tocilizumab patients by week 2.

Dr. McKendry had no disclosures to report.