Tocilizumab Beneficial in Moderate to Severe RA

BARCELONA — In a multicenter double-blind study, treatment with the interleukin-6 signaling blocker tocilizumab not only significantly reduced disease activity among patients with rheumatoid arthritis but also improved physical function, fatigue, and quality of life.

A total of 622 patients with moderate to severe rheumatoid arthritis (RA) were randomized to receive intravenous tocilizumab in doses of 4 mg/kg or 8 mg/kg every 4 weeks or placebo. They also received background methotrexate in doses of 10–25 mg/week and corticosteroids in doses of 10 mg/day or less, according to Dr. Rieke H.E. Alten of the Schlosspark Klinik, Berlin.

Patients' mean age was 51 years, and more than half were women. Mean disease duration was 7.5 years, and study participants had taken a mean of 1.5 disease-modifying antirheumatic drugs before undertaking the experimental regimen.

All patients had swollen joint counts of six or more and tender joint counts of at least eight.

By week 24, a significantly greater proportion of patients treated with tocilizumab achieved an American College of Rheumatology (ACR) 20 response than did those who received placebo. Among patients in the low-dose tocilizumab group, 13.5% achieved this level of response, as did 27.5% of those in the high-dose group. Among those receiving placebo, 0.8% reached an ACR20 level of response, Dr. Alten reported in a poster session at the annual European Congress of Rheumatology.

Tocilizumab treatment also resulted in a marked increase in the proportion of patients who achieved moderate or good response according to the criteria of the European League Against Rheumatism. A total of 61.9% and 79.5% of patients in the low- and high-dose groups, respectively, had moderate or good responses.

On the Health Assessment Questionnaire Disability Index (HAQ-DI), clinically relevant improvements were seen in patients in both tocilizumab groups, starting at week 4, and with greater mean reductions than the protocol-defined minimally clinically difference of −0.25.

Among patients in the tocilizumab 4 mg/kg and 8 mg/kg groups, 64.8% and 63.1%, respectively, had a 20% or greater improvement in HAQ-DI, compared with 47.5% of the placebo patients.

All treatment groups showed improvements in the physical and mental components of the Short Form-36 Health Survey.

Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale scores also improved in all treatment groups, but greater mean changes were consistently observed for patients in the tocilizumab groups, Dr. Alten wrote.

Moreover, the FACIT fatigue score increased by a clinically meaningful four points or more from baseline by week 4 in both tocilizumab groups.

RA is associated with functional disability, limitation of daily activities, and decreased quality of life. Fatigue is a particular problem, with more than 40% of patients reporting clinically important levels of fatigue, Dr. Alten noted.

The rationale for targeting IL-6 in RA lies in observations that this cytokine appears to play a role in the damage to periarticular bone and cartilage. It also activates T cells, B cells, and macrophages and is a central mediator of the hepatic acute phase response (Lancet 2007; [doi:10.1016/S0140-6736(07)60784-3]).

The study was sponsored by Hoffmann-La Roche Inc.

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BARCELONA — In a multicenter double-blind study, treatment with the interleukin-6 signaling blocker tocilizumab not only significantly reduced disease activity among patients with rheumatoid arthritis but also improved physical function, fatigue, and quality of life.

A total of 622 patients with moderate to severe rheumatoid arthritis (RA) were randomized to receive intravenous tocilizumab in doses of 4 mg/kg or 8 mg/kg every 4 weeks or placebo. They also received background methotrexate in doses of 10–25 mg/week and corticosteroids in doses of 10 mg/day or less, according to Dr. Rieke H.E. Alten of the Schlosspark Klinik, Berlin.

Patients' mean age was 51 years, and more than half were women. Mean disease duration was 7.5 years, and study participants had taken a mean of 1.5 disease-modifying antirheumatic drugs before undertaking the experimental regimen.

All patients had swollen joint counts of six or more and tender joint counts of at least eight.

By week 24, a significantly greater proportion of patients treated with tocilizumab achieved an American College of Rheumatology (ACR) 20 response than did those who received placebo. Among patients in the low-dose tocilizumab group, 13.5% achieved this level of response, as did 27.5% of those in the high-dose group. Among those receiving placebo, 0.8% reached an ACR20 level of response, Dr. Alten reported in a poster session at the annual European Congress of Rheumatology.

Tocilizumab treatment also resulted in a marked increase in the proportion of patients who achieved moderate or good response according to the criteria of the European League Against Rheumatism. A total of 61.9% and 79.5% of patients in the low- and high-dose groups, respectively, had moderate or good responses.

On the Health Assessment Questionnaire Disability Index (HAQ-DI), clinically relevant improvements were seen in patients in both tocilizumab groups, starting at week 4, and with greater mean reductions than the protocol-defined minimally clinically difference of −0.25.

Among patients in the tocilizumab 4 mg/kg and 8 mg/kg groups, 64.8% and 63.1%, respectively, had a 20% or greater improvement in HAQ-DI, compared with 47.5% of the placebo patients.

All treatment groups showed improvements in the physical and mental components of the Short Form-36 Health Survey.

Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale scores also improved in all treatment groups, but greater mean changes were consistently observed for patients in the tocilizumab groups, Dr. Alten wrote.

Moreover, the FACIT fatigue score increased by a clinically meaningful four points or more from baseline by week 4 in both tocilizumab groups.

RA is associated with functional disability, limitation of daily activities, and decreased quality of life. Fatigue is a particular problem, with more than 40% of patients reporting clinically important levels of fatigue, Dr. Alten noted.

The rationale for targeting IL-6 in RA lies in observations that this cytokine appears to play a role in the damage to periarticular bone and cartilage. It also activates T cells, B cells, and macrophages and is a central mediator of the hepatic acute phase response (Lancet 2007; [doi:10.1016/S0140-6736(07)60784-3]).

The study was sponsored by Hoffmann-La Roche Inc.

ELSEVIER GLOBAL MEDICAL NEWS

BARCELONA — In a multicenter double-blind study, treatment with the interleukin-6 signaling blocker tocilizumab not only significantly reduced disease activity among patients with rheumatoid arthritis but also improved physical function, fatigue, and quality of life.

A total of 622 patients with moderate to severe rheumatoid arthritis (RA) were randomized to receive intravenous tocilizumab in doses of 4 mg/kg or 8 mg/kg every 4 weeks or placebo. They also received background methotrexate in doses of 10–25 mg/week and corticosteroids in doses of 10 mg/day or less, according to Dr. Rieke H.E. Alten of the Schlosspark Klinik, Berlin.

Patients' mean age was 51 years, and more than half were women. Mean disease duration was 7.5 years, and study participants had taken a mean of 1.5 disease-modifying antirheumatic drugs before undertaking the experimental regimen.

All patients had swollen joint counts of six or more and tender joint counts of at least eight.

By week 24, a significantly greater proportion of patients treated with tocilizumab achieved an American College of Rheumatology (ACR) 20 response than did those who received placebo. Among patients in the low-dose tocilizumab group, 13.5% achieved this level of response, as did 27.5% of those in the high-dose group. Among those receiving placebo, 0.8% reached an ACR20 level of response, Dr. Alten reported in a poster session at the annual European Congress of Rheumatology.

Tocilizumab treatment also resulted in a marked increase in the proportion of patients who achieved moderate or good response according to the criteria of the European League Against Rheumatism. A total of 61.9% and 79.5% of patients in the low- and high-dose groups, respectively, had moderate or good responses.

On the Health Assessment Questionnaire Disability Index (HAQ-DI), clinically relevant improvements were seen in patients in both tocilizumab groups, starting at week 4, and with greater mean reductions than the protocol-defined minimally clinically difference of −0.25.

Among patients in the tocilizumab 4 mg/kg and 8 mg/kg groups, 64.8% and 63.1%, respectively, had a 20% or greater improvement in HAQ-DI, compared with 47.5% of the placebo patients.

All treatment groups showed improvements in the physical and mental components of the Short Form-36 Health Survey.

Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale scores also improved in all treatment groups, but greater mean changes were consistently observed for patients in the tocilizumab groups, Dr. Alten wrote.

Moreover, the FACIT fatigue score increased by a clinically meaningful four points or more from baseline by week 4 in both tocilizumab groups.

RA is associated with functional disability, limitation of daily activities, and decreased quality of life. Fatigue is a particular problem, with more than 40% of patients reporting clinically important levels of fatigue, Dr. Alten noted.

The rationale for targeting IL-6 in RA lies in observations that this cytokine appears to play a role in the damage to periarticular bone and cartilage. It also activates T cells, B cells, and macrophages and is a central mediator of the hepatic acute phase response (Lancet 2007; [doi:10.1016/S0140-6736(07)60784-3]).

The study was sponsored by Hoffmann-La Roche Inc.

ELSEVIER GLOBAL MEDICAL NEWS