RESEARCH - Comparison of tocilizumab monotherapy versus MTX monotherapy in patients with moderate to severe RA: AMBITION

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Ann Rheum Dis. 2009 Mar 17.

Comparison of tocilizumab monotherapy versus methotrexate monotherapy

in patients with moderate to severe rheumatoid arthritis: The AMBITION

study.

G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, Siri

DA, Tomsic M, Alecock E, Woodworth T, Genovese MC.

Menzies Centre for Population Health, Australia.

OBJECTIVES: The anti-IL-6 receptor antibody tocilizumab inhibits

signaling of IL-6, a key cytokine in rheumatoid arthritis (RA)

pathogenesis. The AMBITION study evaluated tocilizumab monotherapy

efficacy and safety vs. methotrexate in patients with active RA, who

had not previously failed methotrexate/biologics treatment.

METHODS: This 24-week, double-blind, double-dummy, parallel-group

study, randomized 673 patients to either tocilizumab 8 mg/kg every 4

weeks, or methotrexate, starting at 7.5 mg/week and titrated to 20

mg/week within 8 weeks, or placebo for 8 weeks followed by tocilizumab

8 mg/kg. The primary endpoint was the proportion of patients achieving

American College of Rheumatology (ACR) 20 response at Week 24.

RESULTS: The intent-to-treat analysis demonstrated that tocilizumab

was superior to methotrexate treatment with a higher ACR20 response

(69.9 vs. 52.5%; P<0.0001), and DAS28<2.6 rate (33.6 vs. 12.1%) at

Week 24. Mean high sensitivity C-reactive protein (hsCRP) was within

the normal range from Week 12 with tocilizumab, whereas levels

remained elevated with methotrexate. The incidence of serious adverse

events (AEs) with tocilizumab was 3.8% vs. methotrexate, 2.8%

(p=0.50), and of serious infections, 1.4% vs. 0.7%, respectively.

There was a higher incidence of reversible grade 3 neutropenia (3.1%

vs. 0.4%) and increased total cholesterol >/=240 mg/dL (13.2% vs.

0.4%), and a lower incidence of alanine aminotransferase elevations

>3x-<5x upper limit of normal (1.0% vs. 2.5%), respectively.

CONCLUSION: Tocilizumab monotherapy is superior to methotrexate

monotherapy, with rapid improvement in RA signs and symptoms, and a

favorable benefit-risk, in patients who have not previously failed

methotrexate or biologics treatment.

PMID: 19297346

http://www.ncbi.nlm.nih.gov/pubmed/19297346

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