Tocilizumab Looks Promising For the Toughest Patients

PARIS — The anti-interleukin-6 monoclonal antibody tocilizumab may offer a new alternative for the most refractory patients with rheumatoid arthritis, including those who have failed antitumor necrosis factor drugs.

Both interleukin (IL)-6 and tumor necrosis factor (TNF)-? play major roles in the development and maintenance of rheumatoid arthritis (RA), explained Dr. Paul Emery, Arthritis Research Campaign Professor of Rheumatology and head of the academic section of musculoskeletal diseases at the University of Leeds (England). He gave his presentation at the annual European Congress of Rheumatology.

“While anti-TNF therapies have become established treatments for RA, significant proportions of patients do not achieve an adequate response or become refractory to them,” Dr. Emery said. Inhibiting the ubiquitous cytokine IL-6, which drives the acute phase response among other effects, may offer an additional way of achieving disease control, he said.

In the Research on Actemra Determining Efficacy after Anti-TNF Failure (RADIATE) trial, 498 patients who had previously failed anti-TNF therapy were randomized to receive placebo or tocilizumab in doses of 4 mg/kg or 8 mg/kg administered intravenously every 4 weeks for 24 weeks. A total of 160 were randomized to placebo, 163 to 4 mg/kg, and 175 to 8 mg/kg.

Patients also were receiving stable doses of methotrexate, 10-25 mg/week, and corticosteroids, 10 mg or less/day.

Mean age of patients was 53 years and mean disease duration was 11 years. Most were seropositive, and disease activity scores (DAS) were high, at a mean of 6.8.

Approximately half the patients had failed one anti-TNF agent, another third had failed two, and 12%-18% had failed three prior agents, he said. The study design allowed for escape at 16 weeks. A total of 60% of the controls had withdrawn or were on 8-mg/kg rescue therapy by week 24, as had 34% of the 4-mg group and 25% of the 8-mg group.

ACR 20 responses were seen in 50% of patients receiving the 8-mg/kg dose, according to Dr. Emery, who was lead investigator of the trial, funded by Roche.

Significantly greater improvements were also seen in the 8-mg/kg group on other end points.

“Probably the most impressive finding was that one-third of patients who had previously failed the best we had to offer were able to get into remission, which is a much higher rate than previously has been seen in patients failing TNF,” Dr. Emery said. Remission was defined as a DAS28 score below 2.6.

“This is our worst population, for whom we have no easy options, and the results were equal to or better than what we've seen before,” he added.

Serious adverse events were seen in 11%, 7%, and 6% of the placebo, 4-mg/kg, and 8-mg/kg groups, respectively. Infections occurred in 41%, 47%, and 50% of the placebo, 4-mg, and 8-mg patients, while serious infections were seen in 3%, 2%, and 5%, respectively. There were no opportunistic infections or cases of tuberculosis.

Over the past 12 months, there have been research reports that tocilizumab improves quality of life in RA (RHEUMATOLOGY NEWS, May 2008, p. 6); lessens the articular and systemic manifestations of RA when used with disease-modifying antirheumatic drugs (RHEUMATOLOGY NEWS, January 2008, p. 1); and was beneficial in moderate to severe RA (RHEUMATOLOGY NEWS, October 2007, p. 20). The drug remains investigational both in the United States and Europe.

Dr. Emery has received consulting fees from Roche.

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PARIS — The anti-interleukin-6 monoclonal antibody tocilizumab may offer a new alternative for the most refractory patients with rheumatoid arthritis, including those who have failed antitumor necrosis factor drugs.

Both interleukin (IL)-6 and tumor necrosis factor (TNF)-? play major roles in the development and maintenance of rheumatoid arthritis (RA), explained Dr. Paul Emery, Arthritis Research Campaign Professor of Rheumatology and head of the academic section of musculoskeletal diseases at the University of Leeds (England). He gave his presentation at the annual European Congress of Rheumatology.

“While anti-TNF therapies have become established treatments for RA, significant proportions of patients do not achieve an adequate response or become refractory to them,” Dr. Emery said. Inhibiting the ubiquitous cytokine IL-6, which drives the acute phase response among other effects, may offer an additional way of achieving disease control, he said.

In the Research on Actemra Determining Efficacy after Anti-TNF Failure (RADIATE) trial, 498 patients who had previously failed anti-TNF therapy were randomized to receive placebo or tocilizumab in doses of 4 mg/kg or 8 mg/kg administered intravenously every 4 weeks for 24 weeks. A total of 160 were randomized to placebo, 163 to 4 mg/kg, and 175 to 8 mg/kg.

Patients also were receiving stable doses of methotrexate, 10-25 mg/week, and corticosteroids, 10 mg or less/day.

Mean age of patients was 53 years and mean disease duration was 11 years. Most were seropositive, and disease activity scores (DAS) were high, at a mean of 6.8.

Approximately half the patients had failed one anti-TNF agent, another third had failed two, and 12%-18% had failed three prior agents, he said. The study design allowed for escape at 16 weeks. A total of 60% of the controls had withdrawn or were on 8-mg/kg rescue therapy by week 24, as had 34% of the 4-mg group and 25% of the 8-mg group.

ACR 20 responses were seen in 50% of patients receiving the 8-mg/kg dose, according to Dr. Emery, who was lead investigator of the trial, funded by Roche.

Significantly greater improvements were also seen in the 8-mg/kg group on other end points.

“Probably the most impressive finding was that one-third of patients who had previously failed the best we had to offer were able to get into remission, which is a much higher rate than previously has been seen in patients failing TNF,” Dr. Emery said. Remission was defined as a DAS28 score below 2.6.

“This is our worst population, for whom we have no easy options, and the results were equal to or better than what we've seen before,” he added.

Serious adverse events were seen in 11%, 7%, and 6% of the placebo, 4-mg/kg, and 8-mg/kg groups, respectively. Infections occurred in 41%, 47%, and 50% of the placebo, 4-mg, and 8-mg patients, while serious infections were seen in 3%, 2%, and 5%, respectively. There were no opportunistic infections or cases of tuberculosis.

Over the past 12 months, there have been research reports that tocilizumab improves quality of life in RA (RHEUMATOLOGY NEWS, May 2008, p. 6); lessens the articular and systemic manifestations of RA when used with disease-modifying antirheumatic drugs (RHEUMATOLOGY NEWS, January 2008, p. 1); and was beneficial in moderate to severe RA (RHEUMATOLOGY NEWS, October 2007, p. 20). The drug remains investigational both in the United States and Europe.

Dr. Emery has received consulting fees from Roche.

ELSEVIER GLOBAL MEDICAL NEWS

PARIS — The anti-interleukin-6 monoclonal antibody tocilizumab may offer a new alternative for the most refractory patients with rheumatoid arthritis, including those who have failed antitumor necrosis factor drugs.

Both interleukin (IL)-6 and tumor necrosis factor (TNF)-? play major roles in the development and maintenance of rheumatoid arthritis (RA), explained Dr. Paul Emery, Arthritis Research Campaign Professor of Rheumatology and head of the academic section of musculoskeletal diseases at the University of Leeds (England). He gave his presentation at the annual European Congress of Rheumatology.

“While anti-TNF therapies have become established treatments for RA, significant proportions of patients do not achieve an adequate response or become refractory to them,” Dr. Emery said. Inhibiting the ubiquitous cytokine IL-6, which drives the acute phase response among other effects, may offer an additional way of achieving disease control, he said.

In the Research on Actemra Determining Efficacy after Anti-TNF Failure (RADIATE) trial, 498 patients who had previously failed anti-TNF therapy were randomized to receive placebo or tocilizumab in doses of 4 mg/kg or 8 mg/kg administered intravenously every 4 weeks for 24 weeks. A total of 160 were randomized to placebo, 163 to 4 mg/kg, and 175 to 8 mg/kg.

Patients also were receiving stable doses of methotrexate, 10-25 mg/week, and corticosteroids, 10 mg or less/day.

Mean age of patients was 53 years and mean disease duration was 11 years. Most were seropositive, and disease activity scores (DAS) were high, at a mean of 6.8.

Approximately half the patients had failed one anti-TNF agent, another third had failed two, and 12%-18% had failed three prior agents, he said. The study design allowed for escape at 16 weeks. A total of 60% of the controls had withdrawn or were on 8-mg/kg rescue therapy by week 24, as had 34% of the 4-mg group and 25% of the 8-mg group.

ACR 20 responses were seen in 50% of patients receiving the 8-mg/kg dose, according to Dr. Emery, who was lead investigator of the trial, funded by Roche.

Significantly greater improvements were also seen in the 8-mg/kg group on other end points.

“Probably the most impressive finding was that one-third of patients who had previously failed the best we had to offer were able to get into remission, which is a much higher rate than previously has been seen in patients failing TNF,” Dr. Emery said. Remission was defined as a DAS28 score below 2.6.

“This is our worst population, for whom we have no easy options, and the results were equal to or better than what we've seen before,” he added.

Serious adverse events were seen in 11%, 7%, and 6% of the placebo, 4-mg/kg, and 8-mg/kg groups, respectively. Infections occurred in 41%, 47%, and 50% of the placebo, 4-mg, and 8-mg patients, while serious infections were seen in 3%, 2%, and 5%, respectively. There were no opportunistic infections or cases of tuberculosis.

Over the past 12 months, there have been research reports that tocilizumab improves quality of life in RA (RHEUMATOLOGY NEWS, May 2008, p. 6); lessens the articular and systemic manifestations of RA when used with disease-modifying antirheumatic drugs (RHEUMATOLOGY NEWS, January 2008, p. 1); and was beneficial in moderate to severe RA (RHEUMATOLOGY NEWS, October 2007, p. 20). The drug remains investigational both in the United States and Europe.

Dr. Emery has received consulting fees from Roche.

ELSEVIER GLOBAL MEDICAL NEWS