Tocilizumab Reduces Disease Activity in Rheumatoid Arthritis

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Tocilizumab Reduces Disease Activity in Rheumatoid Arthritis

Arthritis Rheum 2008;58:2968-2980.

The anti-interleukin-6 (IL-6) receptor antibody tocilizumab, combined with

conventional disease-modifying antirheumatic drugs (DMARDs), reduces

articular and systemic symptoms in patients with active rheumatoid

arthritis, results of a multinational phase III clinical trial indicate.

According to lead author Dr. Mark C. Genovese of Stanford University Medical

Center, Palo Alto, California, and colleagues, IL-6 is a " proinflammatory

cytokine produced by a variety of cell types including lymphocytes,

monocytes, and fibroblasts... and is involved in multiple immunologic

processes such as T cell activation, B cell proliferation, initiation of

acute-phase protein " and others.

" Of particular relevance to rheumatoid arthritis, " they explain in the

October issue of Arthritis & Rheumatism, " IL-6 induces osteoclast

differentiation, contributing to joint destruction and osteoporosis. "

The Tocilizumab in Combination With Traditional DMARD Therapy (TOWARD) study

included 1216 patients with moderate-to-severe rheumatoid arthritis in whom

response to DMARD therapy was inadequate; none had received treatment with

anti-TNF therapy. Patients were randomly assigned in a double-blind manner

to tocilizumab (n = 803) or to placebo (n = 413) while continuing DMARD

treatment. Tocilizumab 8 mg/kg or placebo was administered by intravenous

infusion every 4 weeks.

At the end of the 24-week trial, significantly more patients in the

tocilizumab arm achieved American College of Rheumatology (ACR) 20 (61% vs

25%), ACR 50 (38% vs 9%), and ACR 70 responses (21% vs 3%, p < 0.0001 for

each).

Tocilizumab was also associated with significantly greater improvement in

function, as well as decreased levels of inflammatory markers (C reactive

protein and erythrocyte sedimentation rate) and increased hemoglobin

concentration.

" Tocilizumab was well tolerated in combination with conventional DMARDs, and

the safety profile was not affected by the type or number of DMARDS used, "

Dr. Genovese and associates report.

Transient elevations in liver enzymes to > 3-fold the upper limit of normal

occurred in 4% of patients in the tocilizumab group and in 1% of the control

group. Total cholesterol levels were higher in the tocilizumab group, a low

rate of serious infection was similar in both groups, and there were no

cases of tuberculosis.

Patients treated with tocilizumab were more prone to transient neutropenia,

including grade 3 neutropenia, which occurred in 3.7% of the tocilizumab

group and in none of the control group. However, decreases in neutrophil

count did not correlate with the occurrence of infections.