A proposed 30-45 minute 4 page standard protocol to evaluate rheumatoid arthritis (SPERA) that includes measures of inflammatory activity, joint damage, and longterm outcomes.

A proposed 4 page, 30-45 minute standard protocol to assess rheumatoid arthritis (SPERA) is described that includes all relevant measures of inflammatory activity such as joint swelling, measures of joint damage such as joint deformity, and outcomes such as joint replacement surgery, to monitor patients in longterm observational studies. Forms are included: (1) a patient self-report modified health assessment questionnaire (MHAQ) to assess function, pain, fatigue, psychological distress, symptoms, and drugs used; (2) assessor-completed forms: "RA clinical features" --criteria for RA, functional class, family history, extraarticular disease, comorbidities, joint surgery, radiographic score, and laboratory findings. (3) A 32 joint count with 5 variables: (a) a "shorthand" normal/abnormal so that normal joints require no further detailed assessment; (b) tenderness or pain on motion; (c) swelling; (d) limited motion or deformity; (e) previous surgeries; physical measures of function, i.e., grip strength, walk time, and button test. (4) Medication review of previous disease modifying antirheumatic drugs (DMARD), work history, and years of education. The forms allow cost effective acquisition of all relevant measures of activity, damage, and outcomes in routine clinical care, and allow recognition that measures of activity may show similar or improved values over 5-10 years, while measures of damage and outcomes indicate severe progression in the same patients. The SPERA is feasible to acquire most known relevant measures of activity, damage, and outcomes in RA in 30-45 min in usual clinical settings, to provide a complete database for analyses of longterm outcomes.

Combination treatment of severe rheumatoid arthritis with cyclosporine and methotrexate for forty-eight weeks: an open-label extension study. The Methotrexate-Cyclosporine Combination Study Group.

OBJECTIVE: To determine whether the clinical benefit and favorable safety profile previously noted with the combination of cyclosporine (CSA) and methotrexate (MTX) given for 24 weeks in patients with rheumatoid arthritis (RA) would be maintained for a further 24 weeks, and whether the addition of CSA in patients who had previously been randomized to receive placebo + MTX would result in clinical benefit. METHODS: Eligible subjects from the initial study (weeks 0-24), in which the addition of placebo or CSA to MTX therapy was compared in patients with RA that was partially responsive to MTX, were enrolled. Patients who had received CSA + MTX continued this regimen for a further 24 weeks (weeks 24-48) (group 1; n = 48), and patients who had initially received placebo + MTX now received CSA + MTX for 24 weeks (weeks 24-48) (group 2; n = 44), in an open-label extension study. The primary outcome measures were the number of tender joints, number of swollen joints, physician and patient global assessments, pain, functional disability as measured by the modified Health Assessment Questionnaire, and erythrocyte sedimentation rate. RESULTS: Of the 92 patients enrolled, 80 (87%) completed the extension study. In patients in group 1, the clinically and statistically significant improvement in response outcomes previously noted at week 24, ranging from 25% to 50%, was maintained through week 48. In patients in group 2, the addition of CSA resulted in significant clinical improvement. By week 48, most outcome measures in group 2 patients were similar to those in group 1 patients. CSA treatment resulted in a small increase in serum creatinine levels, but only 1 patient was withdrawn from the study for this reason. CONCLUSION: The clinical improvement previously observed in patients treated with the CSA + MTX combination for 24 weeks was maintained for 24 subsequent weeks, without serious adverse effects, and was also observed in the patients whose treatment was switched from placebo + MTX to CSA + MTX.

Comparison of 3 quantitative measures of hand radiographs in patients with rheumatoid arthritis: Steinbrocker stage, Kaye modified Sharp score, and Larsen score.

OBJECTIVE: To compare 3 quantitative hand radiograph scores, Steinbrocker stage, Larsen score, and Sharp score modified by Kaye, to one another and to other measures of clinical status in a cross sectional analysis of hand radiographs of 173 patients with rheumatoid arthritis (RA). METHODS: Radiographs were scored and compared to other measures of clinical status according to correlation and cross tabulation analyses. RESULTS: In these cross sectional studies, radiographic scores according to all 3 methods were correlated at high levels (r(s) > 0.5) with one another and duration of disease, as well as with scores for physical joint deformity and limited motion; at lower levels (0.3 < r(s) < 0.5) with physical joint swelling scores, functional status, and age; and at low levels of marginal or no clinical importance (r(s) < 0.3) with physical joint tenderness scores, laboratory data, and pain scores. CONCLUSION: The 3 scoring methods give similar quantitative information concerning hand radiographs of patients with RA. The Larsen and modified Sharp scores are preferred measures, as the detailed information facilitates comparison of different patients and monitoring of individual patients over time.

Measures of activity and damage in rheumatoid arthritis: depiction of changes and prediction of mortality over five years.

OBJECTIVE: To analyze various quantitative measures of inflammatory activity and joint damage, including articular, radiographic, laboratory, questionnaire, and physical function measures, in regard to changes in status in surviving patients and prediction of mortality in non-survivors over 5 years in a cohort of patients with rheumatoid arthritis (RA) monitored in the mid-1980s and early 1990s. METHODS: A comprehensive evaluation, which included a complete joint count, radiograph, laboratory tests, physical measures of function, and self-report questionnaire scales, was performed at baseline and 5 years later in 210 consecutive patients with RA. RESULTS: Five years after baseline, 206 of the 210 patients were accounted for: 37 had died, 130 had a comprehensive repeat assessment, and 39 had a more limited repeat assessment. In surviving patients, most measures of activity were generally unchanged or somewhat better, including joint tenderness, pain on motion, and swelling; erythrocyte sedimentation rate and rheumatoid factor; as well as questionnaire scores for pain, global status, helplessness, and difficulty in performing 8 activities of daily living (ADL) according to a modified Health Assessment Questionnaire (MHAQ). By contrast, measures of damage, including joint deformity, grip strength, walk time, and radiographic scores, indicated worse status. Mortality over 5 years was predicted significantly in univariable analyses by American College of Rheumatology (formerly the American Rheumatism Association) Functional Class, limited joint motion, scores for MHAQ, global status, helplessness, grip strength, walk time, button time, and number of comorbidities and duration of diseases, as well as the sociodemographic measures of age and formal education. In multivariable Cox regressions, age, comorbidities, MHAQ, and other measures of functional status were the most effective predictors of 5-year mortality. CONCLUSION: In patients with RA, most measures of inflammatory activity were unchanged and sometimes better, while measures of damage indicated worse status in the same patients over 5 years. Measures indicating functional disability, as well as age and comorbidities, predict 5-year mortality more effectively than radiographic and laboratory data. Measures of inflammatory activity may underestimate long-term outcomes in RA, and long-term studies should include measures of damage.

A double-blind, placebo-controlled study of anti-CD5 immunoconjugate in patients with rheumatoid arthritis. The Xoma RA Investigator Group.

OBJECTIVE: To evaluate the efficacy of an anti-CD5 ricin-linked immunoconjugate (CD5-IC) in patients with rheumatoid arthritis (RA). METHODS: A total of 104 evaluable patients were enrolled in a multicenter, double-blind, multiple-dose, placebo-controlled study of CD5-IC. RESULTS: Treatment with CD5-IC in doses up to 8 mg/m2/day for 4 days in 1 month failed to produce marked or prolonged T cell depletion and was no more effective than placebo in ameliorating disease manifestations. An unexpectedly high placebo response was observed in 48% of the patients. Adverse events were correlated with the dose of CD5-IC, but the treatment was generally well-tolerated. CONCLUSION: At the doses used in this study, CD5-IC was ineffective for treating RA.

Phase II of the AHCPR-sponsored heart failure guideline: translating practice recommendations into review criteria.

BACKGROUND: In 1992, under the sponsorship of the U.S. Agency for Health Care Policy and Research, RAND assembled an expert panel to develop the Heart Failure Clinical Practice Guideline. Phase II of the effort was intended to identify which of the guideline's recommendations the panel felt were suitable for use in retrospective utilization review and quality assessment programs and to develop review criteria, performance measures, and standards of quality for use in monitoring compliance with those recommendations. SELECTION OF RECOMMENDATIONS: Selecting guideline recommendations for translation into review criteria and ultimately into standards of care was a multistep process comprising (1) identification of 34 recommendations from the guideline, (2) rating them on the basis of importance to quality of care and feasibility of monitoring, (3) review by a subcommittee and the full guideline panel, (4) translation into review criteria, and (5) further review and input by panelists and peer and pilot reviewers. Finally, standards of care (the minimum proportion of cases expected to be in accordance with guideline recommendations) were determined to be 90%-95% for six of the final criteria and 75%-80% for the other two. CONCLUSION: Despite some reservations, physicians and other health care professionals agreed to be held accountable for following a core set of guideline recommendations for the treatment of heart failure. Substantial progress was made in identifying recommendations that panelists and reviewers were willing to endorse in utilization review activities, including adoption of improved documentation standards. The review criteria's major impact may be the knowledge that the criteria are in place and that care is being monitored based on those standards.

Comparison of hydroxychloroquine and placebo in the treatment of the arthropathy of mild systemic lupus erythematosus.

OBJECTIVE: To compare the relative safety and efficacy of hydroxychloroquine (HCQ) and placebo (Pl) in the treatment of the articular complaints of systemic lupus erythematosus (SLE). METHODS: Seventy-one patients with mild SLE requiring < or = 10 mg of prednisone or equivalent daily and with arthritis or arthralgias were entered into a 48-week prospective, controlled, double blind multicenter trial and randomly assigned to either HCQ or Pl. RESULTS: Both HCQ and Pl were well tolerated in the 48-week trial. There were no remissions. With the exception of the patient assessment of joint pain, all other joint measures were similar between the groups. Twenty-nine patients withdrew before the end of the trial although only 2 patients withdrew for adverse drug effects. CONCLUSION: Our study found subjective pain relief as the only statistically significant difference in joint count variables from HCQ in the treatment of the articular manifestations of SLE.

Prediction of long-term mortality in patients with rheumatoid arthritis according to simple questionnaire and joint count measures.

OBJECTIVE: To describe mortality over 15 years in a cohort of patients with rheumatoid arthritis, according to a simple questionnaire and joint count. DESIGN: A cohort study with 15 years of follow-up. SETTING: University hospital outpatient clinic. PATIENTS: A cohort of 75 patients with rheumatoid arthritis. MEASUREMENTS: Quantitative baseline measures: demographic, articular (joint counts), clinical, questionnaire, and physical measures, including modified questionnaire and joint count measures with substantially fewer items. RESULTS: Although few deaths were seen in the first 3 years after baseline, the standard mortality ratio over 15 years was 1.62, similar to findings in other series. Significant predictors of mortality included age, formal education level, joint count, activities-of-daily-living questionnaire scores, disease adjustment scores, morning stiffness, comorbid cardiovascular disease, grip strength, modified walking time, and button test. Five-year survival in patients with the poorest status according to these quantitative measures was 40% to 60%, comparable to expected survival at that time of patients with three-vessel coronary artery disease or with stage 4 Hodgkin disease. Simplified measures, including a count using only 28 joints and a questionnaire using only 8 activities of daily living, were similar to the more elaborate traditional measures for predicting mortality. CONCLUSION: Higher mortality rates in patients with rheumatoid arthritis are predicted by more severe clinical disease, as in other chronic diseases. Severe rheumatoid arthritis may be identified using quantitative functional status questionnaires and joint counts, which can be ascertained in about 10 to 15 minutes in any clinical setting.

Comparison of naproxen and acetaminophen in a two-year study of treatment of osteoarthritis of the knee.

OBJECTIVE: To compare the relative safety and efficacy of naproxen and acetaminophen in the treatment of osteoarthritis (OA) of the knee. The major outcome measures were radiographic progression and withdrawal from the trial due to lack of efficacy. METHODS: One hundred seventy-eight patients with OA of the knee were enrolled in a 2-year prospective, controlled, double-blind multicenter trial and were randomly assigned to receive acetaminophen (ACT) or naproxen (NPX) treatment. RESULTS: After 6 weeks of treatment, modest improvement in pain on motion and in physician's global assessment was seen in both the ACT and the NPX groups, and the NPX group also had modest improvement in pain at rest and in 50-foot walk time. Sixty-two patients completed the 2-year study. Among these patients, radiographic progression was similar in the 2 treatment groups. Withdrawal from the trial due to lack of drug efficacy was slightly more frequent among patients in the ACT group (22% versus 16%), but withdrawal due to adverse drug effects was slightly more common in the NPX group (23% versus 18%). CONCLUSION: The efficacy of ACT treatment and NPX treatment was similar, although it was slightly better for NPX. The toxicity rate was slightly lower with ACT. However, the high rate of withdrawal in both treatment groups suggests that neither is satisfactory for the treatment of OA.

Variability of immunologic and clinical features in patients with rheumatoid arthritis studied over 24 hours.

Disease activity measures in patients with rheumatoid arthritis (RA) are influenced by many factors. Bedrest has been long recognized to effect decreased disease activity. In addition, most patients note maximal levels of pain and stiffness in the early morning hours with improvement in the afternoon. Cytokines and hormones with circadian rhythms may also contribute to variability in disease status during the day. Our purpose was to investigate variability of clinical and immunologic measures over a 24-h period of hospitalization in patients with RA. Production of rheumatoid factors and immunoglobulins, joint counts and questionnaire evaluations were measured 3 to 6 times over a 24-h period of hospitalization in 10 patients with RA who were not receiving steroids or second line drugs. Total joint counts were significantly decreased as soon as 4 h after admission, and continued to decrease during the 24-h period of observation. Significant decreases in mononuclear cell proliferation and antibody synthesis were also observed. Our findings are consistent with the presence of decreased levels of immunostimulatory mediators in hospitalized patients especially during late afternoon or evening hours.

Comparison of auranofin, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial.

OBJECTIVE: To compare the relative safety and efficacy of auranofin (AUR), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA). METHODS: Three hundred thirty-five patients with active RA were entered into a 48-week, prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups. RESULTS: Two hundred eleven patients completed the trial. No remissions were seen, and there were no statistically significant differences among the treatment groups in the clinical or laboratory variables measured. Patients taking AUR alone had a slower onset of response than did patients taking MTX alone or in combination. Withdrawals because of adverse drug reactions were slightly more common for those taking combination therapy, but the differences were not statistically significant. Withdrawals because of lack of response were more common for single-drug therapy, with the difference between AUR and the combination reaching statistical significance. No unexpected adverse drug effects were identified, and all reactions resolved without sequelae. CONCLUSION: Except for fewer withdrawals because of lack of response, combination therapy did not demonstrate any advantage in efficacy over single-drug treatment within the time frame of the study.

IgM-rheumatoid factor and responses to second-line drugs in rheumatoid arthritis.

We have examined the relationship between IgM-rheumatoid factor (RF) and responses to second-line drugs in patients with rheumatoid arthritis (RA). Patients with active RA who were beginning treatment with gold, methotrexate or both were studied. Clinical responses were assessed with ESR, joint count, grip strength and activities of daily living questionnaire scores. Production of IgM-RF by peripheral blood mononuclear cells in vitro and plasma levels of IgM-RF were measured by ELISA. Overall, 31 of 44 patients completing more than 6 months treatment improved including 10 treated with gold, 12 with MTX and 9 with both. Production of IgM-RF by peripheral blood mononuclear cells was decreased by 59% in patients who improved on treatment, but increased 2-fold in the unimproved group. Plasma levels of IgM-RF were decreased from 121 to 66 micrograms/ml in the improved group after 6 months of treatment, with similar decreases seen for each of the three treatments. In contrast, plasma IgM-RF levels in the unimproved group did not decrease until 1 year of treatment was completed. Nine patients converted to seronegativity, and all but one of these were in the improved group. The results suggest that IgM-RF is correlated with responses to second-line drug in RA patients.

Reliability of grip strength, walking time and button test performed according to a standard protocol.

Excellent interobserver and intraobserver reliability (reproducibility) was seen for the grip strength, walking time and button test measures in 40 patients with rheumatoid arthritis (RA), when measurement was performed according to a standard protocol. Evidence of reliability, coupled with the observation that baseline measures predict longterm morbidity and mortality in individual patients, suggests that these measures might be more widely used in general rheumatologic care.

A simplified twenty-eight-joint quantitative articular index in rheumatoid arthritis.

We describe a joint index that includes only 28 joints: 10 proximal interphalangeal joints of the fingers, 10 metacarpophalangeal joints, and the wrists, elbows, shoulders, and knees. These joints are evaluated for swelling, tenderness, and limited motion, with the findings scored as abnormal or normal. The 28-joint index is considerably easier to use than traditional methods, and appears to yield as much information in terms of correlation with other measures of clinical status, including hand radiograph scores, American Rheumatism Association functional class, grip strength, walking time, and activities of daily living questionnaire scores (r = 0.25-0.53, P less than 0.001). Simplified joint counts might facilitate acquisition of quantitative articular data in research and clinical rheumatologic settings.

Self-report questionnaire scores in rheumatoid arthritis compared with traditional physical, radiographic, and laboratory measures.

STUDY OBJECTIVE: To assess whether scores on a simple self-report questionnaire to depict the clinical status of patients with rheumatoid arthritis are correlated with traditional measures of physical, radiographic, laboratory, functional, and global status. DESIGN: The self-report questionnaire was administered at the same time the following variables were assessed: American Rheumatism Association functional class, joint count, hand radiograph, erythrocyte sedimentation rate, rheumatoid factor titer, walking time, grip strength, button test, and global self-assessment. SETTING: University rheumatology clinic, the rheumatology clinic of a Veterans Administration hospital, and a private rheumatology practice. PATIENTS: The study included 259 patients who met the criteria of the American Rheumatism Association for a diagnosis of definite or classic rheumatoid arthritis. INTERVENTIONS: Standard rheumatologic care for patients with rheumatoid arthritis. MEASUREMENTS AND MAIN RESULTS: Self-report questionnaire scores were significantly correlated with the joint count, radiographic score, erythrocyte sedimentation rate, grip strength, button test, walking time, American Rheumatism Association functional class, and global self-assessment. Patients were categorized into five questionnaire score categories of 1.00, indicating no dysfunction, and 1.01 to 1.50, 1.51 to 2.00, 2.01 to 3.00, and 3.01 to 4.00, indicating progressive dysfunction. In these five categories, more than ten involved joints were seen in 11%, 37%, 67%, 79%, and 100% of patients, respectively, and erythrocyte sedimentation rates greater than 20 mm/h in 29%, 49%, 64%, 74%, and 85% of patients, respectively. Similar results were seen for other physical and radiographic measures. The questionnaire score was as effective in explaining other measures of clinical status as was any other available measure. CONCLUSIONS: A simple self-report questionnaire provides information similar to many traditional measures in rheumatoid arthritis and appears to be an attractive, cost-effective approach to assessing and monitoring quantitatively the status of an individual patient.

Further analysis of learned helplessness in rheumatoid arthritis using a "Rheumatology Attitudes Index".

A Rheumatology Attitudes Index (RAI) has been modified from the Arthritis Helplessness Index to assess the psychological construct of learned helplessness. The validity of the RAI was established in comparisons to the Arthritis Helplessness Index. The external criterion validity of the RAI was established by identification of statistically significant correlations between RAI scores and physical measures of disease status, including joint count, grip strength, walking time, and button test, as well as with questionnaire self-report scores for difficulty, dissatisfaction and pain in activities of daily living (ADL). Any variation in RAI scores which could be explained by available disease status measures was explained entirely by ADL self-report scores, with no additional explanation by traditional physical measures. Responses to individual RAI statements were significantly correlated with either questionnaire or physical measures of disease status for only 6 of the 15 RAI statements.

Associations of HLA-DR4 with rheumatoid factor and radiographic severity in rheumatoid arthritis.

Possible associations between HLA-DR4 and laboratory, radiographic, joint count, functional, and demographic measures of clinical status were analyzed in 154 white patients with rheumatoid arthritis. Overall, 65 percent of the patients were HLA-DR4 positive, similar to other series. HLA-DR4 was associated significantly with the presence of rheumatoid factor and more severe radiographic changes. HLA-DR4 was not associated with significant differences in demographic, joint count, or functional measures of clinical status. HLA-DR1 was not associated significantly with differences in the presence of rheumatoid factor, radiographic changes, or other measures of clinical status. Selective associations of HLA-DR4 with rheumatoid factor and radiographic scores were more marked in men than in women. Patients who were putatively homozygous for HLA-DR4 were all seropositive and had more severe radiographic changes than patients who were heterozygous for HLA-DR4.

Radiographic and joint count findings of the hand in rheumatoid arthritis. Related and unrelated findings.

Radiographic and physical joint count findings of the hands and wrists of 148 patients with rheumatoid arthritis (RA) were analyzed in a cross-sectional study. Quantitative radiographic scores for joint space narrowing, erosion, and malalignment were correlated highly with joint count scores for limitation of motion and deformity, and were correlated at considerably lower levels with joint swelling scores. Radiographic scores, however, were not correlated at all with joint count tenderness scores. That 2 of the most widely used indices of RA disease activity, radiographic erosion scores and joint count scores for tenderness, were independent of one another at a selected timepoint, should be considered in the design of clinical trials and long-term observation of patients with RA.

Rheumatoid arthritis: explanatory power of specific radiographic findings for patient clinical status.

Radiographs of the hands and wrists of 201 patients with rheumatoid arthritis (RA) were scored for erosion, joint space narrowing, and malalignment. The explanatory power of these findings for measures of clinical status was studied with stepwise multiple linear regression analyses. Radiographic scores explained 59.2% of variation in physical joint count deformity scores, 58.5% of variation in limited motion scores, 22.5% of variation in grip strength scores, 20.5% of variation in button test scores, and 13.5% of variation for the American Rheumatism Association (ARA) Functional Class. Malalignment scores best explained variation in physical deformity, limited motion, and button test scores; joint-space-narrowing scores best explained variation in grip strength; erosion scores best explained variation in ARA Functional Class. When age, duration of disease, erythrocyte sedimentation rate, and rheumatoid factor titer were included in the regression analyses, results were similar to those without these variables. Therefore quantitative scores of specific radiographic findings are in themselves explanatory for measures of clinical status.