Objective. To determine the safety and efficacy of additional courses of rituximab in patients with rheumatoid arthritis (RA).Methods. An open-label extension analysis of RA patients previously treated with rituximab was conducted. Patients who had participated in any of 3 double-blind trials were eligible for additional courses (2 infusions of 1,000 mg given 2 weeks apart) if they exhibited a swollen joint count and tender joint count of >8 with >16 weeks elapsing after the previous course. Safety was assessed in patients receiving all or a portion of a rituximab course. Efficacy was assessed 24 weeks after each course, using the American College of Rheumatology 20% criteria for improvement (ACR20), ACR50, ACR70, European League Against Rheumatism (EULAR) response criteria, Disease Activity Score in 28 joints, the disability index of the Health Assessment Questionnaire, and Short Form 36 scores, stratified according to prior tumor necrosis factor (TNF) inhibitor exposure.Results. A total of 1,039 patients received >1 course of rituximab. Of these, 570 received 2 courses, 191 received 3 courses, and 40 received 4 courses, for a ClinicalTrials.gov identifier: NCT00074438/NCT00468377.

Two courses of rituximab about 6 months apart resulted in improved and sustained efficacy at 1 year, compared with 1 course, with a similar safety profile.

Antibody to native DNA was measured by five techniques: the Crithidia luciliae immunofluorescence (CL-IF) test; filter radioimmunoassays using either untreated human KB DNA, endonuclease-treated KB DNA, or a synthetic polynucleotide (poly dAT); and the Farr immunoprecipitation assay using KB DNA. The specificity and sensitivity of the CL-IF assay was similar to that of the filter radioimmunoassay procedures using KB DNA. The CL-IF test showed an increased frequency of positive tests in patients with active disease and severe renal involvement. In patients with severe renal involvement, high titers of serum nDNA antibodies were measured by this procedure. A unique advantage of the CL-IF test was its ability to identify complement-fixing nDNA antibody. The presence of such antibody was correlated with high antibody titer and the presence of severe renal disease. The CL-IF assay is a simple and useful procedure for measurement of anti-nDNA.

A young black woman with clinical and serologic features of mixed connective tissue disease (MCTD) developed myocarditis with congestive heart failure and ventricular ectopic activity. Despite treatment with steroids and cyclophosphamide, progressive myocarditis resulted in death 20 months after cardiomegaly first developed. Necropsy findings in the myocardium included multiple areas of extensive lymphocytic infiltration and patches of fibrosis. Myocarditis has not previously been described in the adult with MCTD but may be an important complication in patients with a high titer of antibody to nuclear ribonucleoprotein.

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