Single Rituximab Injection Delays RA in High-Risk Patients

Pam Harrison

June 17, 2016

LONDON — A single infusion of the anti-CD20 antibody rituximab (Rituxan, Genentech, Inc) can delay the onset of rheumatoid arthritis for up to a year in individuals at high risk of developing the disease, results from the PRAIRI study show.

"When we set up this study, we thought that if we knocked out the B cells longer term, we could actually have a complete cure of the disease," said Danielle Gerlag, MD, PhD, an employee of GlaxoSmithKline in Cambridge, the United Kingdom.

"Unfortunately, we only saw a preventative effect of 12 months from rituximab, but this still proves that you can influence the usual trajectory towards the first clinical signs and symptoms of arthritis," he told Medscape Medical News. "And I do think 12 months is clinically meaningful."

The study was presented here at the European League Against Rheumatism (EULAR) Congress 2016.

The PRAIRI study involved 81 participants selected for high-risk features who were expected to develop rheumatoid arthritis. Participants had to have arthralgia and had to have tested positive for both anti–citrullinated protein antibodies (ACPA) and rheumatoid factor.

Patients also had to have a C-reactive protein level of at least 3 mg/L or signs of subclinical synovitis on ultrasound or MRI of the hands.

Forty-one patients received a single infusion of 1000 mg of rituximab, and 40 patients received an infusion of placebo. All patients were treated with 100 mg of methylprednisolone prior to treatment to prevent infusion-type reactions.

At a median follow-up of 29 months, 30 of the total 81 participants developed arthritis: 16 in the placebo group (40%) after a median of 11.5 months, and 14 in the rituximab group (34%) after a median of 16.5 months.

Although the difference between the two groups was not statistically significant, rituximab delayed the occurrence of rheumatoid arthritis, Dr Gerlag explained. Those who received the anti-CD20 antibody and who went on to develop rheumatoid arthritis did so at 24 months, compared with 12 months for patients receiving placebo, a difference that was statistically significant (P < .0001).

Slowed Disease Onset

Assuming a 40% background incidence in rheumatoid arthritis in this cohort, as was observed in patients receiving placebo, rituximab reduced the risk of developing the disease by 55% at 12 months' follow-up, he said.

Asked how B-cell depletion might delay the onset of rheumatoid arthritis in high-risk patients, Dr Gerlad said one explanation is that "knocking B cells out of the system hopefully leads to less plasma cells, less autoantibody production, and less antigen production."

The problem with using a single dose of rituximab is that the treatment has only a temporary effect on the B-cell population. The population restores itself, and the B cells come back, she added.

"We're currently looking into this to see if this is the reason why as many people who received rituximab ended up with arthritis as people treated with placebo," she said. "If so, perhaps we can think of retreatment with rituximab."

The PRAIRI study is one of the first clinical trials to test the ability of any therapy to prevent arthritis in patients who are not experiencing clinically apparent joint swelling but who are at high risk for future rheumatoid arthritis, Karim Raza, PhD, from the University of Birmingham, the United Kingdom, told Medscape Medical News.

"Whilst we have good treatments for rheumatoid arthritis, if therapy is commenced once the disease is fully established, patients need lifelong treatment to keep the disease under control," he explained.

"An increased understanding of the phases of disease that lead up to rheumatoid arthritis development allows us to identify treatments which may potentially prevent the disease in the first place," he added.

Although results from the PRAIRI study showed that a single infusion of rituximab does not prevent arthritis, "it does slow down the rate at which arthritis develops," said Dr Raza. This "may indeed be clinically relevant, given the severe nature of rheumatoid arthritis, in particular, the type of rheumatoid arthritis associated with both ACPA and rheumatoid factor."

Dr Gerlag is an employee of and holds shares in GlaxoSmithKline. Dr Raza reports financial relationships with AbbVie, BMS, Pfizer, and Roche.

European League Against Rheumatism (EULAR) Congress 2016: Abstract OP0182. Presented June 9, 2016.

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