Cecil O. Samuelson

Second-Line Antirheumatic Drugs in the Elderly with Rheumatoid Arthritis: A Post Hoc Analysis of Three Controlled Trials

This study assessed the relative efficacy and toxicity of second‐line antirheumatic drugs in patients 65 years of age or older compared to younger counterparts. The results of three prospective, double‐blind, parallel, randomized, multicenter trials were reanalyzed, stratifying outcomes by intervention and patient age. Efficacy was assessed by categorizing patient responses as follows: important improvement, no meaningful change, or progressive disease. Toxicity was analyzed by comparing withdrawal rates due to adverse effects. The three trials compared the following treatments: (1) d‐penicillamine 10–12 mg/day versus azathioprine 1.25‐1.5 mg/kg/day; (2) gold sodium thiomalate 50 mg intramuscularly weekly versus auranofin 6 mg/day versus placebo; and (3) pulse oral methotrexate 7.5–15.0 mg weekly versus placebo. At baseline, 103 patients age 65 or older were similar to 485 patients less than 65 years of age, with the exception of disease duration in all studies and erythrocyte sedimentation rate in one study. For patients completing each study, efficacy outcomes based on age were not significantly different. Withdrawal rates due to adverse drug reactions were also not significantly different.

Chlorambucil therapy in rheumatoid arthritis: Clinical experience in 28 patients and literature review

Our clinical experience in 28 patients receiving chlorambucil for rheumatoid arthritis (RA) and the reports on chlorambucil therapy are reviewed. Our study population and other reports generally represent patients with severe RA who had either failed to improve or developed significant toxicity during previous treatment with conventional slow acting anti-rheumatic drugs (SAARDs). Seventy-two percent of patients had a significant clinical improvement during chlorambucil therapy and reports of complete remission are given, although the incidence of remission is unknown. Hematologic complications are often reported, but appeared more frequently in our experience than previously reported. Hematologic toxicity required that chlorambucil be discontinued in the majority of our cases. Two deaths from suspected drug induced malignancies are reported. Although chlorambucil appears to be effective in the control of active RA, the potential for drug induced toxicity and malignancies may outweigh the benefit of continued use of this experimental therapy in RA.

Spontaneous nasal septal perforation in patients with rheumatoid arthritis

SummaryNasal septal perforation is known to be associated with various traumatic and disease states, yet spontaneous nasal septal perforation (SNSP) is relatively rare. SNSP has been reported in three patients with seropositive rheumatoid arthritis (RA) and we report an additional seven patients with SNSP and RA, four of whom were seronegative and none of whom had Raynauds, in contrast to those reported previously. Manifestations of overt infectious, neoplastic or granulomatous disease have not been found in our seven patients over several years of close follow-up. We have identified no obvious pathogenesis or specific etiology for SNSP. We suggest that SNSP may represent an unusual manifestation of RA previously not well recognized.

Circulating immune complexes containing secretory IgA in jejunoileal bypass disease.

Thirteen patients were studied after jejunoileal bypass (JIB) surgery. Seven developed arthritis and six did not. Circulating immune complexes containing IgG and IgA were detected in the sera of patients with and without arthritis. IgA complexes were shown to contain secretory component, a protein predominantly associated with intraluminal IgA, in significantly higher levels in patients with arthritis. Analytical ultracentrifugation showed complexes of approximately 10 X 8S, consistent with the size of secretory IgA. Arthritis after JIB appears to be associated with circulating immune complexes containing secretory IgA.

Auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis Cooperative systematic studies of rheumatic diseases

SummaryTwo hundred eight patients were studied in a prospective, controlled, double-blind multicenter trial comparing auranofin (AUR), gold sodium thiomalate (GST), and placebo. One hundred sixty-one patients completed at least 20 weeks of therapy. Response to a variety of measures of efficacy was generally modest for both gold treatment groups although improvement was continuing in both groups at the end of the study. There was statistically significant improvement with both gold preparations compared to placebo for the number of tender joints, the joint tenderness score, and physician assessment of disease severity. GST was also significantly better than placebo for the joint swelling score. GST demonstrated more improvement in patients with anemia and thrombocytosis compared to the other treatment groups and both gold preparations were superior to placebo in improvement of an elevated erythrocyte sedimentation rate. Twenty-seven percent of patients on GST were withdrawn from the study for adverse drug reaction with rash and stomatitis being the predominant cause. Only 6% of patients on AUR were withdrawn for untoward drug effect. The time of onset of the adverse reactions is discussed. The two gold preparations were similar in efficacy although AUR was better tolerated.

Comparison of Clinical and Hemodynamic Assessment of Cardiac Disability

Clinical versus hemodynamic assessment of cardiac disability was compared in 187 patients with either coronary artery or valvular disease classified using the New York Heart Association classification (excluding class IV). The following variables were analyzed during rest and exercise: arteriovenous oxygen content difference (CavO2), cardiac index (CI), pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP), pulmonary arteriolar resistance index (PARI) and heart rate (HR). 180 comparisons of variables were made. Hemodynamic evaluation paralleled clinical evaluation only 19 times during rest and 12 during exercise. There were 5 instances of clinical and hemodynamic distinction between class I and II, 14 between class I and III and 12 between class II and III. Correlation was best in mitral stenosis. The most useful variable was CI followed by PAP and CavO2. HR was not helpful. This study emphasizes that subjective clinical disability may not correlate with physiologic derangement in certain patients.