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Biomedical subjects

M H Weisman

Publications and source records attributed to M H Weisman.

At least 19 recordsLinked to original sources
PubMed2006

Development and validation of the revised Cedars-Sinai health-related quality of life for rheumatoid arthritis instrument.

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.

Arthritis, Rheumatoid↗
PubMed2006

The Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT): results of radiographic analyses after 1 year.

OBJECTIVE: Infliximab is effective in improving signs and symptoms of joint/skin involvement, functional status, and quality of life in patients with psoriatic arthritis (PsA). Using IMPACT trial data, we assessed the effect of infliximab (IFX) on structural damage in PsA. METHODS: Patients with active PsA were randomly assigned to receive placebo (PBO/IFX) or infliximab 5 mg/kg (IFX/IFX) at weeks 0, 2, 6, and 14, with the primary endpoint at week 16. The PBO group received infliximab loading doses at weeks 16, 18, and 22. Thereafter, all patients received infliximab 5 mg/kg every 8 weeks through week 50. Hand/feet radiographs were obtained at weeks 0 and 50. Total radiographic scores were determined using the PsA modified van der Heijde-Sharp (vdH-S) score. Projected annual rate of progression was calculated by dividing x ray score by disease duration (years). RESULTS: As reported previously, 65% of infliximab treated patients versus 10% of PBO treated patients achieved an ACR20 response at week 16 (p<0.001). At week 50, 69% of patients achieved an ACR20 response. Radiographs (baseline and week 50) were available for 72/104 patients. At baseline, estimated mean annual rate of progression was 5.8 modified vdH-S points/year. Mean (median) changes from baseline to week 50 in the total modified vdH-S score were -1.95 (-0.50) for PBO/IFX and -1.52 (-0.50) for IFX/IFX patients (p = NS). At week 50, 85% and 84% of patients in the PBO/IFX and IFX/IFX groups had no worsening in the total modified vdH-S score. CONCLUSION: Infliximab inhibits radiographic progression in patients with PsA through week 50.

Antibodies, Monoclonal↗
PubMed2005

Long term safety of etanercept in elderly subjects with rheumatic diseases.

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.

Adult↗
PubMed2004

Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate.

OBJECTIVE: To evaluate the efficacy and safety of repeated administration of infliximab plus methotrexate (MTX) over a 2-year period in patients with rheumatoid arthritis (RA) who previously experienced an incomplete response to MTX. METHODS: Four hundred twenty-eight patients were randomly assigned to receive MTX plus placebo or infliximab at a dose of 3 or 10 mg/kg plus MTX for 54 weeks, with an additional year of followup. The protocol was later amended to allow for continued treatment during the second year. Of 259 patients who entered the second year of treatment, 216 continued to receive infliximab plus MTX for 102 weeks. Ninety-four of these 259 patients experienced a gap in therapy of >8 weeks before continuing therapy. Infusions were administered at weeks 0, 2, and 6, followed by treatment every 4 weeks or every 8 weeks (alternating with placebo infusions in the interim 4-week visits) at a dose of 3 or 10 mg/kg for a total of 102 weeks (including the gap in therapy). For safety and efficacy assessments, data on the patients who were randomized to receive treatment, irrespective of whether treatment was administered for 102 weeks, were evaluated using all actual observations available. The efficacy measures included the Health Assessment Questionnaire (HAQ) (physical function), Short Form 36 health survey (SF-36) (health-related quality of life), total radiographic scores (structural damage), and the American College of Rheumatology 20% improvement criteria (ACR20) (signs and symptoms). RESULTS: The infliximab plus MTX regimens resulted in significantly greater improvement in HAQ scores (P < or = 0.006) and SF-36 physical component summary scores (P < or = 0.011) compared with the MTX-only group. There also was stability in the SF-36 mental component summary score among patients who received the infliximab plus MTX regimens. Median changes from baseline to week 102 in the total radiographic score were 4.25 for patients who received the MTX-only regimen and 0.50 for patients who received the infliximab plus MTX regimen. The proportion of patients achieving an ACR20 response at week 102 varied from 40% to 48% for the infliximab plus MTX groups compared with 16% for the MTX-only group. CONCLUSION: Throughout 102 weeks of therapy, infliximab plus MTX provided significant, clinically relevant improvement in physical function and quality of life, accompanied by inhibition of progressive joint damage and sustained improvement in the signs and symptoms of RA among patients who previously had an incomplete response to MTX alone.

Antibodies, Monoclonal↗
PubMed2003

Validation of a rheumatoid arthritis health-related quality of life instrument, the CSHQ-RA.

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.

Arthritis, Rheumatoid↗
PubMed2002

Rheumatoid Arthritis Severity Scale: a brief, physician-completed scale not confounded by patient self-report of psychological functioning.

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.

Adaptation, Psychological↗
PubMed2002

Potential therapeutic uses of interleukin 1 receptor antagonists in human diseases.

OBJECTIVE: To review publications relating to the blocking of interleukin 1 (IL1) as a strategy for treating human disease, ranging from rheumatoid arthritis (RA) to Alzheimer's disease. METHODS: The National Library of Medicine's PubMed database was searched for articles about pharmaceutical agents that reduce the biological actions of IL1. RESULTS: Fish oils and corticosteroids were identified as non-selective pharmacological interventions that reduce the activity of IL1, whereas a recombinant human IL1 receptor antagonist (anakinra) and a soluble recombinant type I IL1 receptor act selectively. To date, anakinra is the only selective intervention that has been shown in controlled clinical trials to be effective and well tolerated in the treatment of a specific human disorder, RA. In controlled clinical trials, anakinra provided significant clinical improvement and slowed radiographic disease progression in patients with active RA. Moreover, addition of anakinra to existing methotrexate treatment significantly reduced signs and symptoms of active disease. CONCLUSIONS: The clinical use of anakinra has been demonstrated in the management of RA, but blocking of IL1 in other human disorders, as well as the safety of the use of these blocking agents in chronic diseases, still needs to be defined by controlled clinical investigations.

Animals↗
PubMed2002

Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group.

Classification criteria for Sjögren's syndrome (SS) were developed and validated between 1989 and 1996 by the European Study Group on Classification Criteria for SS, and broadly accepted. These have been re-examined by consensus group members, who have introduced some modifications, more clearly defined the rules for classifying patients with primary or secondary SS, and provided more precise exclusion criteria.

Decision Making↗
PubMed2002

Celecoxib for systemic lupus erythematosus: case series and literature review of the use of NSAIDs in SLE.

The primary objectives of this study were to evaluate the safety and efficacy of the cyclooxygenase-2 inhibitor celecoxib in systemic lupus erythematosus (SLE) patients both with and without a self-reported sulfa drug allergy and to review the literature on the use of nonsteroidal agents in SLE subjects. A retrospective review of medical records was performed for 50 SLE patients seen by a community-based rheumatologist and treated with open label celecoxib in doses of 200-400 mg/day for a period of 1-9 months. A MEDLINE search of all articles pertaining to the use of NSAIDs in patients with SLE since 1966 was undertaken. We noted that, in this cohort of celecoxib-treated SLE patients from an office rheumatology practice, the majority demonstrated some improvement, and little toxicity was observed. SLE patients with self-reported sulfa allergies were not more likely to have adverse reactions to celecoxib than non-sulfa allergic patients. The literature review performed herein reveals that, although NSAID toxicity should be a continuing concern in an SLE population, structural dissimilarities between celecoxib and the sulfonamide antimicrobials may make true cross-allergenicity less likely to be a clinical problem. These results suggest that patients with SLE can be safely and effectively treated with celecoxib; however, further studies are needed to assess the effectiveness and safety of all NSAIDs in SLE.

Adult↗
PubMed2001

Cigarette smoking and rheumatoid arthritis.

OBJECTIVES: To examine and explore the potential relationships among the following: the incidence/severity of rheumatoid arthritis (RA), the extra-articular manifestations of RA, vascular disease, certain specific malignancies, the p53 tumor suppressor gene, and cigarette smoking. METHODS: The medical literature was reviewed from 1985 to 2001 with the assistance of a MEDLINE search using the key words vascular disease, smoking, protein p53, RA, rheumatoid vasculitis, cancer, and malignancies. A qualitative review was performed after all articles were abstracted and new information summarized. RESULTS: Cigarette smoking has been increasingly shown in epidemiologic and case-control studies to be an important risk factor for both the incidence and severity of RA, especially in seropositive men. Further, there is evidence of a downward trend in incidence of extra-articular manifestations of RA, especially RA vasculitis, observed with a decrease in worldwide tobacco use and overall improved mortality in RA. The association of cigarette smoking with lung and other cancers and its link to vascular disease (including Buerger's disease) and atherosclerosis appears secure. Mutations or alterations in p53, a suppressor gene that regulates cell growth, have been found in certain cancers, cigarette smokers, and in patients with RA. CONCLUSIONS: Cigarette smoking appears to have an undeniable link to the pathogenesis of vascular disease of many types, including the possibility of a strong causal connection to rheumatoid vasculitis. The observations worldwide of decreasing tobacco use along with secular trends of diminished RA vasculitis and extra-articular manifestations, and with improved survival, points to a better outcome for our patients. The example of p53 may be a first step in the discovery of additional links between environmental triggers and phenotypic expression of chronic illness.

Arthritis, Rheumatoid↗
PubMed2001

Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study.

OBJECTIVE: To measure soluble factors having a possible role in fibromyalgia (FM) and compare the profiles of patients with recent onset of the syndrome with patients with chronic FM. METHODS: The production of cytokines, cytokine-related molecules, and a CXC chemokine, interleukin (IL)-8, was examined. Fifty-six patients with FM (23 with <2 yr and 33 with >2 yr of symptoms) were compared with age- and sex-matched healthy controls. Cytokines and cytokine-related molecules were measured in sera and in supernatants of peripheral blood mononuclear cells (PBMC) that were incubated with and without lectins and phorbol myristate acetate (PMA). RESULTS: No differences between FMS and controls were found by measuring IL-1beta, IL-2, IL-10, serum IL-2 receptor (sIL-2R), interferon gamma (IFN-gamma), and tumour necrosis factor alpha (TNF-alpha). Levels of IL-1R antibody (IL-1Ra) and IL-8 were significantly higher in sera, and IL-1Ra and IL-6 were significantly higher in stimulated and unstimulated FM PBMC compared with controls. Serum IL-6 levels were comparable to those in controls, but were elevated in supernatants of in vitro-activated PBMC derived from patients with >2 yr of symptoms. In the presence of PMA, there were additional increases in IL-1Ra, IL-8 and IL-6 over control values. CONCLUSIONS: In patients with FM we found increases over time in serum levels and/or PBMC-stimulated activity of soluble factors whose release is stimulated by substance P. Because IL-8 promotes sympathetic pain and IL-6 induces hyperalgesia, fatigue and depression, it is hypothesized that they may play a role in modulating FM symptoms.

Cytokines↗
PubMed2001

Benefits of leflunomide in systemic lupus erythematosus: a pilot observational study.

The objective of this study was to retrospectively explore the safety and efficacy of leflunomide (LEF) in outpatients with systemic lupus erythematosus (SLE). Eighteen SLE females received LEF, open label, 100 mg/day loading dose for 3 days followed by 20 mg per day. Patients were evaluated for safety and efficacy after 2-3 months of therapy. The mean age was 42.6 y and mean disease duration 7.9 y. ACR criteria were met by 15/18. Four patients stopped LEF during the observation period. Ten of 14 LEF-treated patients had subjective improvement with 9/14 patients achieving lower SLEDAI scores. The mean SLEDAI decreased by 2.1 (P=0.005) and the mean ESR decreased by 9mm/h (P=0.02). Prednisone dosages could be reduced in 2/5 subjects without a flare. No organ-threatening or life-threatening side effects were seen in our patients. Diarrhea occurred in seven patients (two stopped LEF), rash occurred in one patient (stopped LEF), one patient stopped LEF for reasons not related to therapy. Blood pressure was unchanged. Leflunomide was efficacious and safe in this cohort of SLE patients after 2-3 months of therapy. Placebo-controlled trials of longer duration are indicated.

Adult↗
PubMed2001

Pre-treatment affinity for LJP 394 influences pharmacodynamic response in lupus patients.

Five prospective clinical studies in lupus patients have shown that LJP 394 can reduce circulating anti-dsDNA antibody levels without causing generalized immunosuppression. The compound is currently being evaluated in a phase III clinical trial for the prevention of renal flares in patients with high-affinity antibodies to LJP 394 and a history of lupus nephritis. The current study analyzed the affinity of patient IgG for LJP 394 prior to and following 4 months of treatment with LJP 394 to determine if pretreatment affinity influenced pharmacodynamic response. Patient serum samples from a multicenter, double-blind, placebo-controlled trial were evaluated prior to and following 4 months of weekly, biweekly or monthly treatment with placebo (n = 9) or weekly treatment with 10 mg LJP 394 (n = 6) or 50 mg LJP 394 (n = 4). After treatment there was a dose-dependent reduction in affinity in the 10 mg/week and 50 mg/week groups (P < 0.05 and P < 0.01, respectively), whereas the placebo group was unchanged. This study demonstrates that weekly treatment with LJP 394 produces a dose-dependent reduction in titer-weighted average affinity. These results suggest it may be possible to use an affinity assay to define prospectively patients that are most likely to exhibit the desired pharmacodynamic response to LJP 394.

Antibodies, Antinuclear↗
PubMed2001

Treatment of systemic lupus erythematosus with LJP 394.

OBJECTIVE: LJP 394 is a novel therapy under development for the treatment of systemic lupus erythematosus (SLE). We investigated the optimal LJP 394 dosing regimen required to maximally reduce serum dsDNA antibodies. We also evaluated the safety and tolerability of repeated doses of LJP 394 as well as the effects of therapy on SLE related disease activity and health related quality of life. METHODS: This was a multicenter, partially randomized, placebo controlled, double blind, dose-ranging trial. Study drug or placebo was administered at weekly, biweekly, or monthly intervals for a total of 17, 9, or 5 doses, respectively. Fifty-eight patients were randomly assigned to receive 1, 10, or 50 mg LJP 394 or placebo. After a 2 month pretreatment period, dosing visits continued for 16 weeks, after which there was a 2 month posttreatment period. RESULTS: The greatest reductions in mean dsDNA antibody titers were observed in the group of patients who received 50 mg LJP 394 weekly (38.1% and 37.1 % at Weeks 16 and 24, respectively). A reduction (29.3%) in dsDNA antibody titers was also observed at Week 24 in the group of patients who received 10 mg LJP 394 weekly. The frequencies of adverse events were comparable in the placebo and active treatment groups. CONCLUSION: This clinical trial, in which a large number of patients with SLE were treated with LJP 394, expanded the safety profile of LJP 394 and demonstrated its capacity to reduce dsDNA antibodies.

Adolescent↗
PubMed2001

Disease status predicts fatigue in systemic lupus erythematosus.

OBJECTIVE: To investigate the relative contributions of disease status, helplessness, and depression to fatigue in patients with systemic lupus erythematosus (SLE) in a path-analytic framework. METHODS: The disease status of 81 patients with SLE was evaluated by a clinical rheumatologist using the Systemic Lupus Activity Measure. Patients completed self-report measures of psychosocial data, depression, helplessness, and fatigue at 2 assessment periods, 3 months apart. SLE diagnoses were confirmed with patients' physicians. RESULTS: The model proposed that SLE disease status would predict fatigue directly, and indirectly, through helplessness and depression. At Time 1, disease status, helplessness, and depression were significantly correlated with each other and with fatigue, with helplessness and depression partially mediating the relationship between disease status and fatigue. Longitudinal analyses showed that disease status at Time 1 predicted fatigue, regardless of helplessness and depression operating as mediators at either Time 1 or Time 2. CONCLUSION: The cross sectional findings revealed direct and indirect relationships between disease status and fatigue, with helplessness and depression as mediating variables. However, disease status was the only predictor of fatigue over time. Disease status also predicted Time 2 helplessness, which, in turn, was associated with Time 2 depression. Fatigue amelioration may be an important result of successful management of the underlying SLE process.

Adult↗