• Posted November 9, 2021

Ultra-Low Dose of Rituximab Safely Eases Rheumatoid Arthritis Over Long Term: Study

"Ultra-low" doses of the drug rituximab may be enough to keep some patients' rheumatoid arthritis under control for several years, a new, preliminary study suggests.

Researchers found that among 118 patients, low doses of the drug were comparable to standard ones in controlling flare-ups for up to four years.

The findings, the researchers said, suggest that some patients can try lower doses -- possibly sparing themselves some side effects and spending less time in treatment.

"I think that patients who are doing well on higher doses of rituximab could certainly discuss the option of reducing the dose with their rheumatologist," said lead researcher Nathan den Broeder, a PhD student at Sint Maartenskliniek, in the Netherlands.

Rheumatoid arthritis is an autoimmune disease in which the immune system mistakenly attacks the lining of the body's joints, causing chronic inflammation. It generally affects multiple joints at once, including those in the wrists, hands and knees.

Rituximab, which targets certain immune system cells implicated in rheumatoid arthritis, has been used for years to help manage the disease. It's prescribed in combination with the drug methotrexate when patients do not respond to certain other medications, according to the American College of Rheumatology (ACR).

Rituximab is a lab-engineered antibody and has to be given by infusion. The traditional regimen involves two 1,000 milligram (mg) infusions, given two weeks apart, every six months.

But research in recent years has shown that giving just 1,000 mg every six months is just as effective as 2,000 mg.

And a 2019 trial tested the effects of ultra-low rituximab doses: 200 or 500 mg. The findings suggested the low doses were as effective as a 1,000 mg infusion, but they could not be proven "non-inferior" at the six-month mark.

In the new study, which is an extension of that trial, den Broeder and his colleagues followed 118 patients who were part of the original study for an average of three years, and up to four years.

Over that time, the investigators found, patients on either low-dose regimen had similar "disease activity" scores as patients given 1,000 mg doses. Those scores are based on the number of swollen, tender joints a patient has, measures of general health and other factors.

Only rarely did any patient need to take glucocorticoid medications, which are typically required to manage rheumatoid arthritis flare-ups.

"Based on these findings, I do think we should consider trying to lower the dose of patients with rheumatoid arthritis who do well on 1,000 mg, or even 2,000 mg, of rituximab," den Broeder said.

Giving patients higher-than-necessary doses almost always has downsides, he noted, including a greater chance of side effects. With rituximab, one potential adverse effect is vulnerability to infections, because it suppresses part of the immune system.

In the original trial, den Broeder said, patients on low-dose rituximab had about half the rate of infection, versus those on 1,000 mg.

Rituximab infusions also take time -- usually two to four hours, according to the ACR. Lower doses can trim that down, he added.

At the researchers' clinic in the Netherlands, "stepwise reduction" of rituximab doses has become a standard part of care, den Broeder said. If patients are doing well on 1,000 mg, they can "step down" to 500 mg.

The findings were presented Monday at the American College of Rheumatology annual meeting, held online. Studies released at meetings are generally considered preliminary until they are published in a peer-reviewed journal.

Dr. Arthur Kavanaugh is a rheumatologist and professor of medicine at the University of California, San Diego.

At this point, he said, it is fairly common to try stepping down to a single 1,000 mg dose of rituximab, rather than two, especially when patients are doing well.

But a more common tactic is to try spreading the interval, said Kavanaugh, who was not involved in the study.

"Rather than treat every six months," he said, "it has become common to wait until the disease becomes more active."

According to Kavanaugh, the new findings suggest "it may be possible to use a little less than the standard dose."

The big-picture point, he said, is that the more researchers and doctors learn about different rituximab doses, the more they can "personalize" rheumatoid arthritis patients' therapy.

More information

The American College of Rheumatology has more on rheumatoid arthritis.

SOURCES: Nathan den Broeder, MSc, PhD student, Sint Maartenskliniek, Nijmegen, the Netherlands; Arthur Kavanaugh, MD, professor, medicine, and director, Center for Innovative Therapy, division of rheumatology, allergy, immunology, University of California, San Diego; Nov. 8, 2021, presentation, American College of Rheumatology annual meeting, online