Donald Y. Young

The factors associated with mortality were examined in a prospective longitudinal study, over an average of 12 years, with 94% followup of patients diagnosed as having rheumatoid arthritis. Of 805 patients, 233 died during the period of the study. Survivorship of rheumatoid arthritis patients was approximately 50% less than that of population controls. Survivorship was decreased by the traditional demographic variables of greater age and male sex; however, a significant independent effect of variables reflecting disease severity (American Rheumatism Association functional class, rheumatoid factor titer, number of involved joints) was identified by multivariate analysis. Seventy-nine excess deaths (i.e., those that would not have been expected in a control population) were due in part to disease-related causes, to infections, and to gastrointestinal complications of therapy. Treatment with gold or prednisone did not seem to affect survivorship or cause of death, except for the clustering of deaths of patients with vasculitis within the prednisone group. Our findings indicate that rheumatoid arthritis, a chronic disabling disease, is also associated with a major decrease in survivorship.

Numerous methods for reading abnormalities of rheumatoid arthritis in hand and wrist radiographs have been proposed over the past several decades. There are many differences among these methods, one of the more striking of which is the variation in the number of joints that are scored. In this study, we tested the number of joints that need to be read in order to represent abnormalities accurately and reproducibly, using the scores of multiple observers. Thirteen rheumatologists and radiologists each read a set of 41 hand and wrist films from patients with rheumatoid arthritis. Ten of 13 readers scored 27 joints in each hand and wrist; the other 3 readers scored fewer areas. Fourteen combinations of joints were selected based on the frequency of involvement and the technical adequacy of routine films in assessing a given area. After testing these 14 different combinations, 1 scheme, which included 17 areas read for erosions and 18 areas read for joint space narrowing, was tested further. The correlation coefficients for 10 intraobserver scores derived from this modified scheme compared with the original scores were between 0.981 and 0.997. Seventy-one of 78 interobserver comparisons were better using the new scheme than using the original scheme. These data indicate that the simplified scheme, using a combination of 17 joints to score erosions and 18 to score joint space narrowing, more accurately reflects the extent of abnormalities perceived by a panel of experts than does the original scheme. This abbreviated number of joints shortens the amount of time required to read a set of films and simplifies the scoring of films, since a number of areas that are difficult to read are eliminated from radiographic assessment.

Six hundred eighty-one consecutive patients with rheumatoid arthritis were followed for an average of 11.9 years to identify initial factors that predicted subsequent disability. Of 39 potentially predictive variables obtained at study onset and studied by stepwise regression methods, age was found to be the most powerful single predictor of disability, followed by radiologic grade, sex, and initial functional class. The worst prognosis for disability was found in patients who were older women and who showed radiologic worsening and developed functional impairment early in the disease course. Both disability and radiologic progression of disease were found to develop most rapidly during the first years after disease onset and to assume a slow, nearly linear rate of increase after 10 years. Approximately 10% of patients did not develop significant disability. This study suggests that it is possible to identify, early in the disease course, those patients who are likely to develop severe disability, and that "disease-modifying" therapy might well be initiated earlier in such patients and used consistently throughout the subsequent treatment.

RATIONALE: Airway inflammation in asthma is associated with increased activated CD25(+) T cells, IL-2, and soluble IL-2 receptors (IL-2Rs). OBJECTIVES: A randomized, double-blinded, placebo-controlled study was used to evaluate the safety and efficacy of daclizumab, a humanized IgG1 monoclonal antibody against the IL-2R alpha chain (CD25) of activated lymphocytes, in adults with moderate to severe persistent asthma. METHODS: Patients with obstructive pulmonary functions, despite inhaled corticosteroids (ICS), were switched to equivalent dose inhaled triamcinolone acetate acetonide (TAA). Patients dependent on ICS were randomized (3:1) to daclizumab (intravenous loading dose, 2 mg/kg, then 1 mg/kg) or placebo every 2 weeks, added to stable-dose TAA through Week 12 (Treatment Period 1). Over Weeks 12-20 (Treatment Period 2), patients tapered TAA while on the study drug, and were followed for 16 weeks off the study drug. MEASUREMENTS AND MAIN RESULTS: Among 115 evaluable patients (88 daclizumab, 27 placebo), groups had similar age, disease duration, and length of ICS use. During Treatment Period 1, daclizumab improved FEV(1) (daclizumab, 4.4 +/- 1.80% vs. placebo, 1.5 +/- 2.39%; P = 0.05), and reduced daytime asthma symptoms (P = 0.018) and short-acting inhaled beta(2)-agonist use (P = 0.009). Daclizumab treatment prolonged time to exacerbation (P = 0.024). Adverse events were evenly distributed between groups, although there were more serious adverse events in the patients treated with daclizumab. CONCLUSIONS: Daclizumab improved pulmonary function and asthma control in patients with moderate to severe chronic asthma inadequately controlled on ICS. The mechanism of action likely involves inhibition of proinflammatory cytokine generation by IL-2R blockade in activated T cells. Clinical trial registered with www.clinicaltrials.gov (NCT00028288).

Forty-one coded radiographic films from 16 patients with rheumatoid arthritis were read by 13 observers, using 4 different methods for scoring abnormalities. Although absolute scores differed widely among individual observers, correlation coefficients were greater than 0.850 for approximately 2 of 3 comparisons. When films were ranked, using the median rank of all readers, 72% of individual ranks were within 10% of the median ranks. Among serial films on individual patients, 92% of comparisons between early and late films were interpreted as demonstrating progression of abnormalities when mean standardized scores showed an increase in scores of 15 units or greater. Films with lesser changes were interpreted inconsistently. This study shows good general agreement among readers in scoring radiologic abnormalities of hands and wrists, when applied to a film set showing a broad spectrum of severity, and defines the sensitivity of radiologic detection of disease progression.