Rituximab improves response in RA patients with initial incomplete B cell depletion

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Rituximab improves response in RA patients with initial incomplete B cell depletion
Key Take-Away: 

Rituximab is a biological therapy for Rheumatoid arthritis (RA) which reduces joint pain and swelling by removing B cells, responsible for inflammation. In this study, the investigators were able to produce fruitful results with an extra dose of rituximab to the RA patients with incomplete B cell depletion.

Since clinical non-response to 2×1000 mg rituximab has previously been found to be associated with incomplete B cell depletion, we determined, in a randomized controlled proof of concept study, whether patients with initial incomplete B cell depletion would benefit from an additional infusion of rituximab at week 4.

ABSTRACT: 
Background: 

Since clinical non-response to 2×1000 mg rituximab has previously been found to be associated with incomplete B cell depletion, we determined, in a randomized controlled proof of concept study, whether patients with initial incomplete B cell depletion would benefit from an additional infusion of rituximab at week 4.

Methods: 

Patients with active RA despite methotrexate received a first infusion of rituximab 1000 mg and were tested for persistent B cells using highly sensitive flow cytometry on day 15.

All received a second infusion of 1 g (according to license), but patients with persistent B cells were subsequently randomized double-blind to receive, 2 weeks later, either a third infusion of 1000 mg rituximab or placebo. Clinical response was determined by European League against Rheumatism (EULAR) and American College of Rheumatology (ACR) criteria.

Results: 

Baseline characteristics were balanced between groups. Treatment with 3×1000 mg rituximab resulted in significantly greater depletion (lower B cell and plasmablast numbers between 8 and 28 weeks) paralleled by significantly better EULAR and ACR20 response rates at 40 weeks (p=0.035 and p=0.027, respectively) and 52 weeks (p=0.021 and p=0.043, respectively) compared with 2×1000 mg.

Immunoglobulin titres remained stable in both arms, and adverse event rates were balanced.

Conclusion: 

In rituximab-treated patients with incomplete B cell depletion (predictive of poor response), an extra 1000 mg infusion of rituximab at 4 weeks produced both better depletion and clinical responses than placebo with no worsening of safety.

In rituximab-treated patients with incomplete B cell depletion (predictive of poor response), an extra 1000 mg infusion of rituximab at 4 weeks produced both better depletion and clinical responses than placebo with no worsening of safety. Degree of depletion is an important, but modifiable, determinant of response.

Ann Rheum Dis 2015; 74:1195-1201
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