An extra dose of rituximab improves clinical response in rheumatoid arthritis patients with initial incomplete B cell depletion: a randomised controlled trial.

Abstract

OBJECTIVES:

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 randomised 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 rheumatoid arthritis 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 randomised 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.

CONCLUSIONS:

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.

• Authors: Edward M Vital, Shouvik Dass, Maya H Buch, Andrew C Rawstron, Paul Emery
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 74 Issue 6 Pg. 1195-201 (Jun 2015) ISSN: 1468-2060 [Electronic] England
• PMID: 24443001 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Antirheumatic Agents
• Rituximab
• Methotrexate

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Murine-Derived (administration & dosage)
• Antirheumatic Agents (administration & dosage, therapeutic use)
• Arthritis, Rheumatoid (drug therapy, immunology)
• B-Lymphocytes (cytology)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Lymphocyte Count
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Rituximab
• Treatment Outcome