Rituxan Shows Durable Response for Refractory RA

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ACR: Rituxan Shows Durable Response for Refractory RA

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SAN DIEGO, Nov. 18 - Rheumatoid arthritis patients who get no relief

from DMARDs -- such as Remicade, Enbrel, or Humira -- may benefit

from Rituxan (rituximab), a B-cell-depleting chimeric monoclonal

anti-CD20 antibody used to treat non-Hodgkin's lymphoma.

Adding Rituxan (rituximab) to methotrexate appears to improve signs

and symptoms in RA patients who have failed other treatments,

researchers reported at the American College of Rheumatology meeting

here.

In a phase III trial, 51% of 298 patients randomized to methotrexate

plus Rituxan at 1,000 mg achieved at least a 20% improvement in the

ACR20 score versus just 18% of 201 patients in a methotrexate plus

placebo arm (P<0.0001).

Moreover, Rituxan demonstrated significant improvement in ACR50

score-27% versus 5% (P<0.0001)-and ACR70, with 12% of patients

reporting at least a 70% improvement in number of tender and/or

swollen joints (P<0.0001).

The researchers said the difference in the two treatment groups was

apparent after eight weeks and was sustained for six months after

only two infusions of Rituxan two weeks apart.

On average patients in the phase III REFLEX (Efficacy and Safety of

Rituximab in Active RA Patients who Experience an Inadequate

Response to one or more Anti-TNF-a Therapies) trial had failed 2.5

DMARDS and an average of 1.5 TNF inhibitors.

In a study published in the New England Journal of Medicine in 2004,

a single course of two infusions of Rituxan, alone or in combination

with either cyclophosphamide or continued methotrexate, provided

significant improvement in disease symptoms at both weeks 24 and 48

in patients with active rheumatoid arthritis despite methotrexate

treatment.

" While TNF blockers are an extremely beneficial therapy, from 20% to

40% of patients stop responding or don't respond to a TNF

inhibitor, " said REFLEX investigator Stanley Cohen, M.D., of Radiant

Research in Dallas. " For those patients, adding rituximab to the

treatment management plan may spell the difference in success. "

Matteson, M.D., a rheumatologist at the Mayo Clinic who was not

involved in the REFLEX trial, said he would try two TNF inhibitors

before moving to Rituxan, " We know that approximately 35%-40% of

patients who fail one TNF inhibitor will do well on another one.

After a second TNF failure, I would consider Rituxan. "

On days 1 and 15, patients were given placebo or a single

intravenous course of 1,000 mg of Rituxan. All patients received a

corticosteroid prior to each infusion and took a brief course of

oral glucocorticoids between the two injections. Every four weeks

for six months, patients were evaluated for evidence of toxicity and

efficacy.

The drug was generally well tolerated, said Keystone, M.D., a

rheumatologist at the University of Toronto, who participated in the

trial. He added that infusion reactions were slightly less with

Rituxan than what has been observed for Remicade (infliximab). Using

Rituxan for treatment of rheumatoid arthritis " is not like lymphoma

where they have big time infusion reactions [with Rituxan], " he

said.

Asked whether patients should get flu or pneumonia vaccinations

prior to Rituxan, Dr. Keystone said, " There is nothing that says you

should vaccinate first, but I would. "

Genentech, which markets Rituxan, has applied for FDA approval of

Rituxan for treatment of refractory RA. That Biologic License

Application (BLA) was filed last August, and it has been granted

priority review.

http://www.medpagetoday.com/Rheumatology/Arthritis/tb/2184