Update: B-Cells in Rheumatic Disease
Volume 4 | October 1, 2006 - Decmeber 31, 2006
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Highest Rated Articles
This important article presents data from the pivotal trial (REFLEX) that led to the approval of rituximab for the treatment of rheumatoid arthritis in patients who have had inadequate response to one or more TNF inhibitors. Data from this 2-year, randomized, double-blind, placebo-controlled trial are presented through week 24. The study group consisted of more than 500 patients with two-thirds of them (n = 311) receiving rituximab in standard doses (1,000 mg at weeks 0, 2) and the rest (n = 209) receiving placebo. The primary endpoint was ACR response at week 24. Results demonstrated ACR 20, 50, and 70 response rates of 51%, 27%, and 12% for rituximab compared with 18%, 5%, and 1% for placebo recipients.
What is truly impressive about this study is the disease severity in the study group. Overall, these patients averaged more than 22 swollen joints and 33 tender joints with all patients failing at least one TNF inhibitors, two-thirds failing at least two TNF inhibitors. Additional measures included fatigue and markers of quality of life, which all improved in the rituximab group. The study will serve as an ongoing source of information during the next 2 years regarding efficacy and safety of this recently approved biologic drug.
Smith
KG, Jones RB, Burns SM, Jayne DR. Long-term comparison of rituximab
treatment for refractory systemic lupus erythematosus and vasculitis:
remission, relapse, and re-treatment. Arthritis Rheum. 2006;54(9):2970-2982.
In
addition to rituximab's approved indication for the treatment of
rheumatoid arthritis in patients who have had an inadequate response
to one or more TNF inhibitors, the drug is in widespread use for
non-approved indications including systemic lupus erythematosis
(SLE) and vasculitis. Other B-cell targeting therapeutic strategies
are being examined for these conditions as well.
In this study, Smith and colleagues prospectively evaluated rituximab therapy in 11 patients with refractory SLE and 11 patients with refractory vasculitis, the latter of whom all had positive ANCA tests. The patients were followed for a median of 24 months. These investigators documented clinical remission in both groups followed by rapid B-cell depletion with response rates of 100% among SLE patients and 91% among vasculitis patients. Relapses occurred in about two-thirds of both groups. Attempts were made to correlate return of B-cells with relapse and this appeared to be the case in most patients, although exceptions were documented. Immunoglobulin G (IgG) and Immunoglobulin M (IgM) levels were maintained within the normal range. Infusion reactions were common, but overall safety was favorable.
This study adds to the open-trial literature on rituximab therapy for lupus and vasculitis. Clinicians should be reminded that safety concerns should predominate in these off-label uses. It also should be noted that in December 2006, the FDA notified all clinicians that an unexpected and fatal complication — progressive multifocal leukoencephalopathy (PML) — had been observed in two patients treated with rituximab for SLE. Both patients had received previous treatment with cyclophosphamide. Although there is causal proof of association at this time, caution should be exerted when using drugs of this nature for non-approved indications.
