The Promise Of A B-cell Biologic Therapy For Rheumatoid Arthritis

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The Promise Of A B-cell Biologic Therapy For Rheumatoid Arthritis

Drugs aimed at suppressing inflammation-provoking cytokines--

specifically those linked to T-cells--have improved the treatment of

rheumatoid arthritis (RA), a chronic, inflammatory autoimmune

disease. Still, the frequency of remission achieved by these biologic

agents remains below 50 percent. To increase the success rate of

biologic therapy for RA patients, researchers have honed in on a new

target: the B cell.

Rituximab, a biologic agent that selectively depletes B cells, has

been successfully used to treat non-Hodgkin's lymphoma. It has also

been shown to improve disease symptoms for RA patients, when injected

at aggressive levels for a two-week period. To investigate this

biologic's potential long-term therapeutic value, an international

team of scientists set out to compare the effectiveness and safety of

different rituximab doses over a 24-week period, with and without

steroids. Their study focused on 465 RA patients with moderate to

severe symptoms resistant to disease-modifying antirheumatic drugs

(DMARDs), including other biologics. The results, featured in the May

2006 issue of Arthritis & Rheumatism (http://

www.interscience.wiley.com/journal/arthritis), indicate the promise

of low-dose rituximab to achieve remission for RA patients, without

serious side effects and without the need for prescribing harsh

steroids.

Drawn from outpatient populations in California, Texas, Arizona,

Switzerland, Sweden, Poland, and England, the subjects were randomly

divided into nine treatment groups. Three groups received a 1,000 mg.

dose of rituximab--two infusions two weeks apart--with either

intravenous steroid, oral steroid, or placebo. Three groups received

a 500 mg. dose of rituximab--two infusions two weeks apart--with

either intravenous steroid, oral steroid, or placebo. Three groups

received a placebo with either intravenous steroid, oral steroid, or

another placebo. All subjects received the DMARD methotrexate (MXT).

All subjects were evaluated every four weeks for changes in the

Disease Active Score (DAS), a 28-joint assessment for swelling and

tenderness, as well as for overall disease improvement, with the goal

of meeting the American College of Rheumatology (ACR) 20 percent

improvement criteria.

At the 24-week culmination, 54 percent of the subjects in three

rituximab 1,000 mg. X 2 groups and 55 percent of the subjects in the

three rituximab 500 mg. X 2 groups had achieved the desired ACR20

response, compared with 28 percent of the subjects in the three

placebo groups. The different dosages of rituximab did not have a

statistically significant impact on the odds of achieving an ACR20

response, and analyses of the proportions of patients who achieved

higher ACR improvement scores--50 percent and 70 percent--showed

similar patterns. Changes in DAS28 at week 24 reflected the ACR

response findings, as did the subjects reports of relief from joint

pain and stiffness. What's more, subjects in the rituximab groups

showed gains toward disease remission earlier in the course of

treatment than subjects in the placebo group.

Steroids, whether received intravenously or orally, showed no

significant correlation with disease improvement scores among the

rituximab groups. Intravenous steroid, however, showed a positive

correlation to improved tolerability during the first rituximab

infusion in both dosage groups. Overall, adverse events associated

with rituximab were mild and easily managed. Headache was the most

common complaint.

Confirming the role of B cells in the inflammatory processes behind

RA, this study demonstrates the effectiveness and safety of a unique

biologic therapy, in moderate doses and independent of steroids. Yet,

as its leading author, Dr. Emery, notes, further studies are

needed before applying the results to the routine treatment of RA

patients. " Both doses of rituximab explored in this study warrant

further differential exploration and longer-term followup, " he stresses.