RESEARCH - Rituximab effective in RA: DANCER study published

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Rituximab effective in RA: DANCER study published

Rheumawire

May 4, 2006

Gandey

Leeds, UK - Results of a phase 2b trial show that rituximab (Rituxan,

Roche/Genentech) is generally well tolerated when added to methotrexate

therapy in patients with active rheumatoid arthritis (RA). The study, known

as the Dose-Ranging Assessment International Clinical Evaluation of

Rituximab in RA (DANCER) trial, is published online April 28, 2006 in

Arthritis and Rheumatism [1]. The DANCER results " are significant because

they confirm the ability of rituximab to provide substantial relief of

symptoms following just a short course of therapy, " lead author Dr

Emery (Chapel Allerton Hospital, Leeds, UK) told journalists during a press

briefing at the European League Against Rheumatism (EULAR) meeting last

June, when the trial was first presented.

As previously reported by rheumawire, these results also show that oral

steroids are not needed for efficacy, which Emery says is good news,

considering many patients don't like taking steroids and others, such as

those with osteoporosis or diabetes, can't take them. But his group also

found that premedication with intravenous glucocorticoid reduced the

frequency and intensity of first-infusion-associated events.

The researchers report that the data are also reassuring with regard to

safety, and rituximab didn't show an increase in the risk of infection-a

concern that stems from the action of the drug. " Rituximab was well

tolerated and the type and severity of infections were similar to those for

placebo, " they write.

But during an interview with rheumawire when the findings were first

presented, Emery emphasized that further studies are needed before the

results can be applied to the routine treatment of RA patients. " Both doses

of rituximab explored in this study warrant further differential exploration

and longer-term follow-up, " he stressed.

In March, the US Food and Drug Administration (FDA) approved rituximab for

the treatment of moderate to severe RA in adults who have had inadequate

responses to one or more TNF inhibitors. Rituximab joins abatacept (Orencia,

Bristol-Myers Squibb), which was approved in December, as RA-treatment

approaches with mechanisms entirely different from those of the TNF

inhibitors.

Abatacept is a selective T-cell costimulation modulator. Rituximab is a

monoclonal antibody that selectively depletes CD20-positive B lymphocytes.

Although RA had traditionally been thought of as a T-cell-mediated disease,

more recent research highlighted the role of B cells in joint inflammation

and led to RA trials for rituximab.

In the present industry-sponsored trial, researchers looked at 465 patients

randomized to nine treatment groups. More than half of patients who received

two 500-mg or two 1000-mg infusions of rituximab met the American College of

Rheumatology (ACR) 20% improvement criteria at week 24 (55% and 54%,

respectively, compared with 28% for placebo).

ACR50 responses were achieved by 33% of patients taking 500 mg, 34% of those

taking 1000 mg, and 13% of patients taking placebo (p<0.001), and ACR70

responses were achieved by 13%, 20%, and 5% of the same groups of patients

(p<0.05). The researchers report that changes in the disease activity score

in 28 joints (-1.79, -2.05, -0.67; p<0.0001) and moderate to good responses

on the EULAR criteria (p<0.0001) reflected the ACR-criteria responses.

" The DANCER trial has confirmed that a single course of rituximab, provided

as two infusions two weeks apart, is highly effective over 24 weeks in the

treatment of active RA in those who have shown incomplete response to

methotrexate, " Emery and colleagues write. " The present study corroborates

earlier studies that support a role for B cells in the inflammatory

processes that underlie RA. "

The researchers point out that radiologic outcomes were not measured in this

study, and they maintain that this issue will be addressed in future

studies. They add that follow-up of these patients beyond the primary end

point is ongoing.

Source:

1. Emery P, Fleischmann R, Filipowicz-Sosnowska A, et al. The

efficacy and safety of rituximab in patients with active rheumatoid

arthritis despite methotrexate treatment: Results of a phase IIB randomized,

double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum 2006;

54:1390-1400.

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Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

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