RESEARCH - IL-6 receptor inhibition with tocilizumab reduces disease activity in RA with inadequate response to DMARDs

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Arthritis Rheum. 2008 Sep 29;58(10):2968-2980.

Interleukin-6 receptor inhibition with tocilizumab reduces disease

activity in rheumatoid arthritis with inadequate response to

disease-modifying antirheumatic drugs: The tocilizumab in combination

with traditional disease-modifying antirheumatic drug therapy study.

Genovese MC, McKay JD, Nasonov EL, Mysler EF, da Silva NA, Alecock E,

Woodworth T, Gomez-Reino JJ.

Stanford University Medical Center, Palo Alto, California.

OBJECTIVE: To examine the efficacy and safety of the humanized

anti-interleukin-6 receptor antibody tocilizumab combined with

conventional disease-modifying antirheumatic drugs (DMARDs) in

patients with active rheumatoid arthritis (RA).

METHODS: A total of 1,220 patients were randomized (2:1 ratio) in the

phase III, double-blind, placebo-controlled, multicenter TOWARD

(Tocilizumab in Combination With Traditional DMARD Therapy) study.

Patients remained on stable doses of DMARDs and received tocilizumab 8

mg/kg or placebo (control group) every 4 weeks for 24 weeks.

RESULTS: At week 24, the proportion of patients achieving a response

according to the American College of Rheumatology criteria for 20%

improvement (ACR20) was significantly greater in the tocilizumab plus

DMARD group than in the control group (61% versus 25%; P < 0.0001).

Secondary end points including 50% or 70% improvement (ACR50/70), the

Disease Activity Score in 28 joints (DAS28), DAS28 remission responses

(DAS28 <2.6), European League Against Rheumatism responses, and

systemic markers such as the C-reactive protein and hemoglobin levels

showed superiority of tocilizumab plus DMARDs over DMARDs alone.

Seventy-three percent of patients in the tocilizumab group had >/=1

adverse event (AE), compared with 61% of patients in the control

group. AEs leading to withdrawal from the study were infrequent (4% of

patients in the tocilizumab group and 2% of those in the control

group). Serious AEs occurred in 6.7% and 4.3% of patients in the

tocilizumab and control groups, respectively, and serious infections

occurred in 2.7% and 1.9%, respectively. Elevations in the alanine

aminotransferase level, from normal at baseline to >3-fold the upper

limit of normal, occurred in 4% of patients in the tocilizumab group

and 1% of those in the control group, and elevated total cholesterol

levels were observed in 23% and 6% of patients, respectively. Sixteen

patients started lipid-lowering therapy during the study. Grade 3

neutropenia occurred in 3.7% of patients receiving tocilizumab and

none of the patients in the control group, and no grade 4 neutropenia

was reported.

CONCLUSION: Tocilizumab combined with any of the DMARDs evaluated was

safe and effective in reducing articular and systemic symptoms in

patients with an inadequate response to these agents.

PMID: 18821691

http://www.ncbi.nlm.nih.gov/pubmed/18821691

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