RESEARCH - Trial of IL-6 receptor antagonist, tocilizumab, in RA patients who had an incomplete response to MTX

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Arthritis Rheum. 2006 Aug 31;54(9):2817-2829 [Epub ahead of print]

Double-blind randomized controlled clinical trial of the interleukin-6

receptor antagonist, tocilizumab, in European patients with rheumatoid

arthritis who had an incomplete response to methotrexate.

Maini RN, PC, Szechinski J, Pavelka K, Broll J, Balint G, Emery P,

Raemen F, sen J, Smolen J, Thomson D, Kishimoto T.

Kennedy Institute of Rheumatology Division, Imperial College, London, UK.

OBJECTIVE: To establish the safety and efficacy of repeat infusions of

tocilizumab (previously known as MRA), a humanized anti-interleukin-6 (IL-6)

receptor antibody, alone and in combination with methotrexate (MTX), for the

treatment of rheumatoid arthritis (RA). METHODS: The study group comprised

359 patients with active RA in whom the response to MTX was inadequate.

During a stabilization period, these patients received their current dose of

MTX for at least 4 weeks. Following stabilization, they were randomized to 1

of 7 treatment arms, as follows: tocilizumab at doses of 2 mg/kg, 4 mg/kg,

or 8 mg/kg either as monotherapy or in combination with MTX, or MTX plus

placebo. RESULTS: A 20% response (improvement) according to the American

College of Rheumatology criteria (ACR20 response) was achieved by 61% and

63% of patients receiving 4 mg/kg and 8 mg/kg of tocilizumab as monotherapy,

respectively, and by 63% and 74% of patients receiving those doses of

tocilizumab plus MTX, respectively, compared with 41% of patients receiving

placebo plus MTX. Statistically significant ACR50 and ACR70 responses were

observed in patients receiving combination therapy with either 4 mg/kg or 8

mg/kg of tocilizumab plus MTX (P < 0.05). A dose-related reduction in the

Disease Activity Score in 28 joints was observed from week 4 onward, in all

patients except those receiving monotherapy with 2 mg/kg of tocilizumab. In

the majority of patients who received 8 mg/kg of tocilizumab, the C-reactive

protein level/erythrocyte sedimentation rate normalized, while placebo plus

MTX had little effect on these laboratory parameters. Tocilizumab was mostly

well tolerated, with a safety profile similar to that of other biologic and

immunosuppressive therapies. Alanine transaminase and aspartate transaminase

levels followed a sawtooth pattern (rising and falling between infusions).

There were moderate but reversible increases in the nonfasting total

cholesterol and triglyceride levels and reversible reductions in the

high-density lipoprotein cholesterol and neutrophil levels. There were 2

cases of sepsis, both of which occurred in patients who were receiving

combination therapy with 8 mg/kg of tocilizumab plus MTX.

CONCLUSION: These results indicate that targeted blockade of IL-6 signaling

is a highly efficacious and promising means of decreasing disease activity

in RA.

PMID: 16947782

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6947782

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