Actemra

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Actemra (Tocilizumab) - What You Should Know

Actemra appears effective for Adult and Juvenile Rheumatoid Arthritis

By Carol & Eustice, About.com

Updated: March 27, 2008

About.com Health's Disease and Condition content is reviewed by the Medical

Review Board

What is Actemra?

Actemra (tocilizumab) is a monoclonal antibody under development by Roche for

the treatment of rheumatoid arthritis.

How Does Actemra Work?

The therapeutic goal of Actemra is to block inflammatory responses. It does this

by blocking interleukin-6. Actemra actually inhibits the interleukin-6 receptor,

thereby blocking interleukin-6. This is the first drug to do this, making it a

new treatment approach for RA. Classified as a cytokine, interleukin-6 is known

to play a role in immune and inflammatory responses.

How Has Actemra Performed in Clinical Trials?

An extensive clinical development program of 5 Phase III trials was designed to

evaluate Actemra. Four studies have been completed and reported meeting their

primary endpoints (goals). A fifth trial, called LITHE (Tocilizumab Safety and

the Prevention of Structural Joint Damage), is a 2-year trial that is currently

underway. Preliminary first-year data is expected for LITHE in 2008.

The 5 Phase III trials for Actemra are known as: OPTION (Tocilizumab Pivotal

Trial in Methotrexate Inadequate Responders), TOWARD (Tocilizumab in Combination

with Traditional DMARD Therapy), RADIATE (Research on Actemra Determining

Efficacy after Anti-TNF Failures), AMBITION (Actemra versus Methotrexate

Double-Blind Investigative Trial In Monotherapy), and LITHE.

What Was Learned About Actemra from the OPTION study?

In the OPTION study, reported in the March 22, 2008 issue of The Lancet, 622

patients with moderate to severely active rheumatoid arthritis were randomized

to receive 8 mg/kg Actemra, 4 mg/kg Actemra, or placebo intravenously every 4

weeks. Methotrexate was continued at pre-study dosages (10-25 mg/week). Study

results showed that at week 24, there were more patients receiving Actemra who

reached ACR20 than those on placebo. Of the study participants, 59% of patients

in the 8 mg/kg group vs. 48% in the 4 mg/kg group vs. 26% in the placebo group

achieved ACR20. Criteria for ACR20 include: 20% improvement in number of tender

and swollen joints; greater than or equal to 20% improvement in at least 3 of

the 5 following criteria:

physician assessment of disease

patient assessment of disease

C-reactive protein

pain

Health Assessment Questionnaire

Another study published in The Lancet on March 22, 2008 concluded that Actemra

is also effective for children with systemic juvenile arthritis -- a condition

that is often hard to treat.

How Is Actemra Given?

Actemra is given intravenously (through an IV). In the OPTION study, it was

given every 4 weeks.

What Side Effects Have Been Associated With Actemra?

According to drugmaker Roche, " The overall safety profile observed in the global

studies of Actemra is consistent and Actemra is generally well tolerated. The

serious adverse events reported in Actemra global clinical studies included

serious infections and hypersensitivity (allergic) reactions including a few

cases of anaphylaxis. The most common adverse events reported in clinical

studies were upper respiratory tract infection, nasopharyngitis, headache,

hypertension. Increases in liver function tests (ALT and AST) were seen in some

patients. These increases were generally mild and reversible, with no hepatic

injuries or any observed impact on liver function. "

Is Actemra FDA-Approved and Available?

As of March 2008, no. In November 2007, Roche submitted a biologics license

application (BLA) to the U.S. Food and Drug Administration (FDA) seeking

approval for Actemra to reduce the signs and symptoms in adults with moderate to

severe rheumatoid arthritis. Approval is expected within a few months.

What Concerns Some Critics of Actemra?

Critics of some of the clinical trials involving Actemra believe not enough has

been learned by comparing Actemra to placebo. Essentially, the critics said that

it's reasonable to assume Actemra would be better than nothing, but more useful

information would be gained by comparing Actemra to established treatments.