Rheumatoid Arthritis: Weisman MH

Moder KG, Wener MH, Weisman MH, Ishimori ML, Wallace DJ, Buckeridge DL, Homburger HA. · Department of Rheumatology, Mayo College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. · J Rheumatol. · Pubmed #17407218 No free full text.

Abstract: OBJECTIVE: We conducted a prospective, multicenter evaluation of autoantibody testing by multiplex immunoassay in patients with known or suspected connective tissue diseases (CTD). We evaluated agreement between multiplex immunoassay and enzyme immunoassay (EIA) and assessed the diagnostic utility of autoantibody profiles. METHODS: Samples from 908 patients with suspected CTD seen in rheumatology clinics were collected prospectively at 3 tertiary care centers. Diagnoses were established according to recognized classification criteria. Tests for autoantibodies were obtained by multiplex immunoassay and by EIA. The results of the multiplex immunoassay were analyzed using a previously validated interpretative algorithm, MDSS (Medical Decision Support Software), that suggests possible disease associations based on the pattern of results for the autoantibodies. RESULTS: The median patient age was 49.7 years; 83% were female. The most common diagnoses were rheumatoid arthritis in 352 patients and systemic lupus erythematosus (SLE) in 332 patients. Agreement between multiplex and EIA testing ranged from a high of 99% (95% CI 98% to 100%) for Jo-1 to a low of 79% (95% CI 76% to 82%) for antinuclear antibodies. The MDSS algorithm suggested an appropriate disease association in 75% to 100% of patients with SLE. The results varied depending on the disease and the autoantibodies present. CONCLUSION: These results suggest that patterns of autoantibodies detected by multiplex immunoassay testing, when analyzed by an interpretative algorithm, are useful in the evaluation of patients with CTD in situations of high disease prevalence. Further testing is necessary to determine its utility in settings of low disease prevalence.

Chiou CF, Sherbourne CD, Cornelio I, Lubeck DP, Paulus HE, Dylan M, Chang CH, Weisman MH. · Cerner LifeSciences, Beverly Hills, California, USA. · Arthritis Rheum. · Pubmed #17139661 links to  free full text

Abstract: OBJECTIVE: To improve accuracy and content coverage of the original 33-item Cedars-Sinai Health-Related Quality of Life for Rheumatoid Arthritis Instrument (CSHQ-RA). METHODS: A total of 312 RA patients from 55 sites were screened in a 24-week trial. Patients completed an expanded 48-item version of the CSHQ-RA, Medical Outcomes Study Short Form 36 (MOS SF-36), and Stanford Health Assessment Questionnaire (HAQ) Disability Index at 5 visits. The revised CSHQ-RA was created based on response frequencies and distributions, item-to-item correlation, factor and Rasch analysis, and input from experts. Psychometric evaluation included internal consistency, test-retest reliability, convergent and discriminant validity, and responsiveness. Minimum clinically important difference (MCID) was also measured. RESULTS: Response rates were 93% at baseline and 71% at 12 weeks. Eighty-one percent of respondents at baseline were women, mean +/- SD age was 52 +/- 12 years, and mean +/- SD duration of RA was 10.8 +/- 10.4 years. The revised CSHQ-RA included 36 items measuring 7 domains (4 original and 3 new). All Cronbach's alpha coefficients were >0.8, indicating good internal consistency. Test-retest reliability measured intraclass correlation coefficients, which ranged from 0.86 to 0.95. All 7 domains correlated significantly with the MOS SF-36 and HAQ, indicating good convergent validity. Analysis of variance of disability group scores showed good discriminant validity (P < 0.0001). The MCIDs ranged from 6.2 for social well-being to 14.8 for pain/discomfort. CONCLUSION: The revised CSHQ-RA was validated using a broader RA patient population. It captures 3 additional domains (social well-being, pain/discomfort, and fatigue), which allow for measuring all important aspects of health-related quality of life.

Lee W, Terk MR, Hu B, Garber EK, Weisman MH. · Division of Rheumatology, Department of Radiology, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. · J Rheumatol. · Pubmed #17080513 No free full text.

Abstract: Geodes are noted frequently in rheumatoid arthritis (RA), but large geodes of the femur are uncommon. We describe a patient with RA and a large geode in his femur; histological findings were consistent with a rheumatoid nodule and chronically inflamed synovium. We review the literature of large femoral geodes and what this particular manifestation may reflect about the pathogenesis of RA.

Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Emery P, Keystone EC, Schiff MH, van Riel PL, Weinblatt ME, Weisman MH. · David Geffen School of Medicine, UCLA - RM 32-59, 1000 Veteran Avenue, Los Angeles, CA 90025, USA. · Ann Rheum Dis. · Pubmed #17038465 No free full text.

This publication has no abstract.

Weisman MH, Furst DE, Park GS, Kremer JM, Smith KM, Wallace DJ, Caldwell JR, Dervieux T. · Cedars-Sinai Medical Center, Los Angeles, California, USA. · Arthritis Rheum. · Pubmed #16447238 links to  free full text

Abstract: OBJECTIVE: Methotrexate (MTX) is an antifolate agent that is often associated with toxicity. This study investigated whether risk genotypes for folate-dependent enzymes are associated with the toxicity of MTX in patients with rheumatoid arthritis (RA). METHODS: Blood was collected for analysis in a muticenter, cross-sectional study of RA patients who had been receiving MTX for at least 1 month prior to enrollment, and side effects occurring at the time of a single study visit were recorded. Low-penetrance risk genotypes in methylenetetrahydrofolate reductase (MTHFR) 677TT, thymidylate synthase (TSER) *2/*2 (variable number of tandem repeats), amino imidazole ribonucleotide transformylase (ATIC) 347GG, and serine hydroxymethyltransferase (SHMT1) 1420CC were measured and summed to constitute the toxicogenetic index specific to each patient. Statistical analyses consisted of logistic regression models with clustered-center effects, and associations with risk genotypes were expressed as adjusted odds ratios (ORs). RESULTS: Among 214 patients enrolled at 4 study sites, a total of 67 patients (31%) presented with a side effect (gastrointestinal event, headache, lethargy, alopecia, cough, or dyspnea). Risk genotypes associated with side effects in the central nervous system were MTHFR 677TT (OR 3.3, P < 0.01) and SHMT1 1420CC (OR 2.4, P < 0.05). ATIC 347GG was associated with gastrointestinal side effects (OR 3.0, P < 0.01), while TSER*2/*2 (OR 5.4, P < 0.01) and SHMT1 1420CC (OR 3.2, P < 0.01) were associated with alopecia. The toxicogenetic index ranged from 0 to 3 (median 1). An index of 3 was associated with an approximately 7-fold higher likelihood of having a side effect compared with an index of 0 (P < 0.01). CONCLUSION: These data suggest that a composite index of the cumulative risk genotypes in folate-dependent enzymes may be an effective means of profiling RA patients who develop side effects to MTX.

Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, Sharp J, Perez JL, Spencer-Green GT. · Department of Rheumatology, Leiden University Medical Centre, Albinusdreef 2, C4-R Postbox 9600, Leiden 2300 RC, The Netherlands. · Arthritis Rheum. · Pubmed #16385520 links to  free full text

Abstract: OBJECTIVE: To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment. METHODS: This was a 2-year, multicenter, double-blind, active comparator-controlled study of 799 RA patients with active disease of < 3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co-primary end points at year 1 were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score. RESULTS: Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at 1 and 2 years. There was significantly less radiographic progression (P < or = 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28-joint Disease Activity Score <2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups. CONCLUSION: In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission.

Fleischmann R, Baumgartner SW, Weisman MH, Liu T, White B, Peloso P. · University of Texas Southwestern Medical Center at Dallas, 5939 Harry Hines Boulevard, Dallas, Texas 75235, USA. · Ann Rheum Dis. · Pubmed #16150792 links to  free full text

Abstract: OBJECTIVES: To determine the long term safety profile of the tumour necrosis factor (TNF) antagonist etanercept in subjects with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) aged > or =65 years in comparison with subjects aged <65 years. METHODS: Safety data from an integrated database of 4322 subjects enrolled in 18 RA trials, 2 PsA trials, and 2 AS trials were analysed. Safety end points included subject incidence of all adverse events (AE), serious adverse events (SAE), infectious events (IE), medically important infections (MII), and deaths. Events of particular interest in subjects treated with TNF modulating biological treatments, including demyelinating diseases, tuberculosis, lymphomas, and cardiovascular diseases, were also evaluated. RESULTS: The incidence of AE, SAE, IE, MII, and malignancies was not significantly raised in elderly subjects in comparison with subjects aged <65 years. No cases of tuberculosis were reported in the trials. Demyelinating diseases were seen only in subjects aged <65 years. The incidence and types of death in the elderly subjects were consistent with the expected rates for subjects of comparable age. CONCLUSIONS: Etanercept is a generally safe and well tolerated biological agent for treatment of rheumatological diseases in the elderly, and the risk of AE in these studies was no greater in subjects aged > or =65 years than in younger subjects.

Russak SM, Sherbourne CD, Lubeck DP, Paulus HD, Chiou CF, Sengupta N, Borenstein J, Ofman J, Moadel A, Weisman MH. · Division of Rheumatology, Cedars-Sinai Health System, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. · Arthritis Rheum. · Pubmed #14673966 links to  free full text

Abstract: OBJECTIVE: To test the validity and reliability of a newly developed disease-specific multidimensional quality of life instrument: the Cedars-Sinai Health-Related Quality of Life Instrument (CSHQ-RA). METHODS: A total of 350 rheumatoid arthritis (RA) patients were asked to complete the CSHQ-RA at 2 time points (4 weeks apart). Patients also completed the Medical Outcomes Study Short Form 36 (SF-36) and the Stanford Health Assessment Questionnaire (HAQ) Disability Index (DI) at the second time point. Construct validity was tested, using Pearson's correlations, by comparing subscale scores on the CSHQ-RA to those obtained from the mental component summary (MCS) and physical component summary (PCS) of the SF-36. HAQ DI scores were used to assess the discriminant validity of the CSHQ-RA. Intraclass correlation coefficients (ICCs) were used to assess test-retest reliability. RESULTS: Response rates for the first and second survey were 83% (291) and 93% (276), respectively; 84% of respondents were women, and mean age was 57 years. Mean scores +/- SDs on instruments were: HAQ 0.73 +/- 0.69; MCS 49 +/- 12; and PCS 33 +/- 11. Pearson's correlations between the CSHQ-RA subscale scores and the SF-36 scores ranged from 0.55 to 0.76 (P < 0.001). Analysis of variance indicate that scores on the CSHQ-RA discriminated between levels of physical disability as measured by the HAQ (P < 0.001). Test-retest reliability was demonstrated in the instrument's subscale scores (ICC 0.70-0.90). CONCLUSION: These results support the construct validity, discriminant validity, and reliability of the CSHQ-RA as a measure that captures the impact of RA on patients' health-related quality of life.

Weisman MH, Gano AD, Gabriel SE, Hochberg MC, Kavanaugh A, Ofman JJ, Prashker M, Suarez-Almazor ME, Yelin E, Nakelsky SD, Croft JD, Anonymous00394. · Evidence-Based Medicine Working Groups in Rheumatology, Beverly Hills, CA, USA. · J Rheumatol. · Pubmed #12913929 No free full text.

Abstract: OBJECTIVE: To describe and compare the relative attributes (reliability, ease of use, applicability, and relevance) of different assessment tools for economic analyses as they pertain to rheumatoid arthritis (RA) literature. METHODS: An expert panel, comprising rheumatology researchers and clinicians, operationalized 2 economic appraisal instruments and applied them to 11 articles used for analysis. Each expert reviewed 3 articles, with each article independently reviewed by a pair of experts. A summary score for each article per appraisal instrument was calculated by dividing the number of items that received a "positive" response by the total number of items in the appraisal instrument. RESULTS: Scores for each article were similar across reviewers and appraisal instruments. CONCLUSION: There is a need for a more comprehensive approach for evaluating this rapidly growing body of economic literature that is not only valid and reliable, but also easy to apply and understand. Although consistency between reviewers was good on both guidelines, inter-guideline discrepancies were noted and reviewers reported some difficulty in using the operationalized format.

Weisman MH, Paulus HE, Russak SM, Lubeck DP, Chiou CF, Sengupta N, Ofman JJ, Borenstein J, Moadel AB, Sherbourne CD, Paulus HD. · Cedars-Sinai Health System, Los Angeles, California 90048, USA. · Arthritis Rheum. · Pubmed #12579597 links to  free full text

Abstract: OBJECTIVE: To update and complement existing instruments, we developed a multidimensional disease-specific instrument, intended to reflect the impact of rheumatoid arthritis (RA) with modern treatment options on patient's Health-Related Quality of Life (HRQOL). METHODS: Items were developed from a systematic review of published HRQOL measures and transcripts of RA patient focus groups. Items were refined by an expert panel and administered to 350 patients for psychometric testing. RESULTS: The systematic review identified 228 potential items, and the focus group transcripts identified 96 additional items. Expert review and pilot testing resulted in an initial 58-item instrument. Twenty-six items were excluded due to floor/ceiling effects, poor response rates, or high item-item correlations. Factor analysis identified a 5-factor structure (eigenvalues >or=1). Multi-trait scaling performed on both completed surveys confirmed the 5 sub-scale structure (Cronbach's > 0.87). CONCLUSION: The CSHQ-RA consists of 33 items that address 5 HRQOL domains, each with high internal consistency. Additional testing will assess the instrument's validity and responsiveness.

Weisman MH. · Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Ann Rheum Dis. · Pubmed #11874827 links to  free full text

This publication has no abstract.

Bardwell WA, Nicassio PM, Weisman MH, Gevirtz R, Bazzo D. · Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0804, USA. · Rheumatology (Oxford). · Pubmed #11792878 links to  free full text

Abstract: OBJECTIVE: The purpose of this study was to develop a brief measure of severity for rheumatoid arthritis (RA) that would not be seriously confounded by psychological functioning. The Rheumatoid Arthritis Severity Scale (RASS), designed for use by physicians on their own patients, consists of three visual analogue scales: Disease Activity, Functional Impairment and Physical Damage. METHODS: Ninety-four RA outpatients completed the Health Assessment Questionnaire (HAQ) Disability, Pain Severity, Health State subscales and the Symptom Checklist-90-Revised (SCL-90-R) Anxiety, Depression and Somatization subscales. Rheumatologists completed the RASS on their own patients. RESULTS: Results suggest that the RASS is internally consistent (alpha=0.85) and valid. RASS Disease Activity, Functional Impairment, Physical Damage correlated with HAQ Disability (r=0.40, 0.68, 0.61; P<0.01), Pain (r=0.37, 0.34, 0.34; P<0.01) and Health State (r=-0.27, -0.36, -0.27; P<0.01). RASS Physical Damage uniquely predicted longer illness duration (years with RA). In contrast to the HAQ, RASS subscales shared less variance with anxiety, somatization and depression scores. CONCLUSIONS: Preliminary data suggest that the RASS may be a quick, reliable, valid physician-completed RA severity scale that compares favourably with the longer, patient-completed HAQ.

Burt RK, Furst DE, Weisman MH, Sullivan KE. · Northwestern University, Feinberg School of Medicine, Chicago, IL 60208, USA. · Clin Immunol. · Pubmed #15885633 No free full text.

This publication has no abstract.