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M E Weinblatt

Publications and source records attributed to M E Weinblatt.

At least 19 recordsLinked to original sources
PubMed2002

Immune function in patients with rheumatoid arthritis treated with etanercept.

Etanercept, a recombinant human tumor necrosis factor (TNF) inhibitor that binds both soluble and cell-bound TNF, has been shown to reduce disease activity and inhibit joint destruction when administered to patients with rheumatoid arthritis (RA). Because TNF receptors are found on many types of cells that modulate the immune response, we evaluated the general immune function of a subset of RA patients in a blinded clinical study. No significant differences were seen between patients treated with etanercept or placebo in the surface antigen phenotypes of peripheral blood leukocytes, T cell proliferative responses, neutrophil function, delayed-type hypersensitivity (DTH) reactions, serum immunoglobulin levels, or incidence of infections. Although this observational study was relatively small and could detect only major changes in immunological status, the stability of immune function over time in patients receiving etanercept corroborates the findings in clinical studies, which suggest that etanercept does not alter overall global immune function.

Adult↗
PubMed2001

Rheumatoid arthritis.

Rheumatoid arthritis is a systemic inflammatory disorder that mainly affects the diarthrodial joint. It is the most common form of inflammatory arthritis, and has a substantial societal effect in terms of cost, disability, and lost productivity. Although the pathogenesis of rheumatoid arthritis remains incompletely understood, much insight into the cellular and molecular mechanisms involved has been gained in the past decade. On the basis of these insights, new therapies have been developed, and clinical trials have shown the efficacy of aggressive treatment of patients with active disease. In this review, we discuss improvements in our understanding of the pathophysiology of inflammatory synovitis in rheumatoid arthritis, and improvements in therapy for patients with the disorder. The past decade has seen substantial advances in these areas. Future studies will be directed at improving methods for early diagnosis and identification of patients with progressive disease, and at improving methods to identify candidates for subclasses of disease-modifying antirheumatic drugs (DMARDs). Long-term safety and efficacy data for the new DMARD agents and combination regimens will also further delineate efficacy and toxicity and thus the appropriate clinical context for use of these therapeutic approaches. The continuing elucidation of pathophysiological pathways relevant in rheumatoid arthritis, coupled with continuing advances in biotechnology and rational drug design, offer substantial hope for the continued development of increasingly potent and specific pharmacotherapy for treatment of rheumatoid arthritis.

Adult↗
PubMed2000

Amyloid myopathy masquerading as polymyositis.

OBJECTIVE: It is not well appreciated that the clinical presentation of amyloid myopathy can mimic that of polymyositis. By retrospective clinicopathologic analysis we determined distinctive features of amyloid myopathy that differentiate the 2 diseases. METHODS: Two patients with clinical and histologic evidence of an inflammatory myopathy had fatal outcomes despite appropriate treatment for polymyositis. Their clinical course and original pathologic specimens were reviewed. In addition, original tissue samples were obtained and analyzed using Congo red staining and immunoperoxidase. RESULTS: The initial diagnosis of polymyositis was supported in both cases by muscle biopsies showing inflammatory infiltrates and elevations of creatine phosphokinase and by classic electromyography. Retrospective evaluation of the initial muscle biopsies disclosed subtle but incontrovertible evidence of vascular amyloid. Further analysis of the original specimens confirmed the presence of immunoglobin light chain (AL) amyloid. CONCLUSION: Amyloid myopathy can mimic polymyositis. Both can have similar clinical symptoms, as well as inflammatory infiltrates on muscle biopsy. Failure to recognize amyloid myopathy deprives patients of potentially life prolonging treatment. Congo red staining and immunohistochemical analysis of tissue could prevent misdiagnosis.

Aged↗
PubMed1999

Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial.

BACKGROUND: In a phase II study, etanercept (recombinant human tumor necrosis factor receptor [p75]:Fc fusion protein) safely produced rapid, dose-dependent improvement in rheumatoid arthritis over 3 months. OBJECTIVE: To confirm the benefit of etanercept therapy of longer duration and simplified dosing in patients with rheumatoid arthritis. DESIGN: Randomized, double-blind, placebo-controlled trial with blinded joint assessors. SETTING: 13 North American centers. PATIENTS: 234 patients with active rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs. INTERVENTION: Twice-weekly subcutaneous injections of etanercept, 10 or 25 mg, or placebo for 6 months. MEASUREMENTS: The primary end points were 20% and 50% improvement in disease activity according to American College of Rheumatology (ACR) responses at 3 and 6 months. Other end points were 70% ACR responses at 3 and 6 months and other measures of disease activity at 3 and 6 months. RESULTS: Etanercept significantly reduced disease activity in a dose-related fashion. At 3 months, 62% of the patients receiving 25 mg of etanercept and 23% of the placebo recipients achieved 20% ACR response (P < 0.001). At 6 months, 59% of the 25-mg group and 11% of the placebo group achieved a 20% ACR response (P < 0.001); 40% and 5%, respectively, achieved a 50% ACR response (P < 0.01). The respective mean percentage reduction in the number of tender and swollen joints at 6 months was 56% and 47% in the 25-mg group and 6% and -7% in the placebo group (P < 0.05). Significantly more etanercept recipients achieved a 70% ACR response, minimal disease status (0 to 5 affected joints), and improved quality of life. Etanercept was well tolerated, with no dose-limiting toxic effects. CONCLUSIONS: Etanercept can safely provide rapid, significant, and sustained benefit in patients with active rheumatoid arthritis.

Algorithms↗
PubMed1999

A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate.

BACKGROUND: Patients treated with methotrexate for rheumatoid arthritis often improve but continue to have active disease. This study was undertaken to determine whether the addition of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein (TNFR:Fc), to methotrexate therapy would provide additional benefit to patients who had persistent rheumatoid arthritis despite receiving methotrexate. METHODS: In a 24-week, double-blind trial, we randomly assigned 89 patients with persistently active rheumatoid arthritis despite at least 6 months of methotrexate therapy at a stable dose of 15 to 25 mg per week (or as low as 10 mg per week for patients unable to tolerate higher doses) to receive either etanercept (25 mg) or placebo subcutaneously twice weekly while continuing to receive methotrexate. The primary measure of clinical response was the American College of Rheumatology criteria for a 20 percent improvement in measures of disease activity (ACR 20) at 24 weeks. RESULTS: The addition of etanercept to methotrexate therapy resulted in rapid and sustained improvement. At 24 weeks, 71 percent of the patients receiving etanercept plus methotrexate and 27 percent of those receiving placebo plus methotrexate met the ACR 20 criteria (P<0.001); 39 percent of the patients receiving etanercept plus methotrexate and 3 percent of those receiving placebo plus methotrexate met the ACR 50 criteria (for a 50 percent improvement) (P<0.001). Patients receiving etanercept plus methotrexate had significantly better outcomes according to all measures of disease activity. The only adverse events associated with etanercept were mild injection-site reactions, and no patient withdrew from the study because of adverse events associated with etanercept. CONCLUSIONS: In patients with persistently active rheumatoid arthritis, the combination of etanercept and methotrexate was safe and well tolerated and provided significantly greater clinical benefit than methotrexate alone.

Adult↗
PubMed1999

Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis.

OBJECTIVE: To examine the safety and pharmacokinetics of and clinical response to leflunomide, a de novo pyrimidine synthesis inhibitor, when administered to patients with active rheumatoid arthritis (RA) who have been receiving long-term methotrexate therapy. METHODS: This was an open-label, 52-week study in which 30 patients with RA that remained active despite therapy with methotrexate at 17+/-4 mg/week (mean +/- SD) for > or =6 months were given leflunomide, 10-20 mg/day. Patients were assessed for adverse effects, pharmacokinetic measurements of leflunomide and methotrexate, and clinical response by American College of Rheumatology (ACR) 20% response criteria. RESULTS: Twenty-three patients completed 1 year of treatment. No significant pharmacokinetic interactions between leflunomide and methotrexate were noted. This combination therapy was generally well tolerated clinically, with the exception of elevations of liver enzyme levels. Seven patients withdrew from the treatment regimen: 2 withdrawals were voluntary, 3 were due to persistent elevation of plasma transaminase levels, and 2 were due to lack of efficacy. Of the patients, 16 (53%) met ACR 20% response criteria. Two met ACR criteria for remission after 1 year. CONCLUSION: The combination of methotrexate and leflunomide has therapeutic potential in RA.

Adult↗
PubMed1999

Sulfasalazine treatment for rheumatoid arthritis: a metaanalysis of 15 randomized trials.

OBJECTIVE: To assess the efficacy and safety of sulfasalazine (SSZ) compared to placebo and other disease modifying drugs. METHODS: A metaanalysis was performed on 15 randomized clinical trials of rheumatoid arthritis (RA) that included SSZ (2 g/day average dose, 36 weeks average followup) as a treatment. Eight trials included a placebo group (PL), 2 hydroxychloroquine (HCQ) (350 mg/day average dose), 3 D-penicillamine (D-Pen) (667 mg/day average dose), and 4 gold sodium thiomalate or aurothioglucose (GST) (25 mg, 1 g/wk). RESULTS: Compared to PL, SSZ was superior for improvement in erythrocyte sedimentation rate (ESR) (SSZ 37%, PL 14%; p < 0.0001), morning stiffness duration (SSZ 61%, PL 33%; p = 0.008), pain visual analog scale (SSZ 42%, PL 15%; p < 0.0001), articular index (SSZ 46%, PL 20%; p < 0.0001), number of swollen joints (SSZ 51%, PL 26%; p < 0.0001), number of painful joints (SSZ 59%, PL 33%; p = 0.004), and patient global assessment (SSZ 26%, PL 14%; p = 0.02). Withdrawals from study because of adverse drug reactions were increased (SSZ 24%, PL 7%; p < 0.0001), but lack of efficacy dropouts were decreased (SSZ 8%, PL 21%; p < 0.0001). Compared to HCQ, SSZ tended to have fewer lack of efficacy dropouts (SSZ 5%, HCQ 15%; p = 0.055) and improved ESR (SSZ 43%, HCQ 26%; p = 0.10) and morning stiffness duration (SSZ 59%, HCQ 40%; p = 0.09). Compared to GST, adverse drug reaction dropouts were significantly fewer (SSZ 12%, GST 29%; p < 0.0001), while withdrawals due to lack of efficacy were greater (SSZ 13%, GST 4%; p = 0.006). More patients tended to complete treatment taking SSZ (SSZ 69%, GST 61%; p = 0.09). CONCLUSION: Over all, the metaanalysis provides data that support the effectiveness of SSZ as a treatment for RA.

Antirheumatic Agents↗
PubMed1999

The role of current strategies in the future treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a serious, chronic, debilitating disease for which no cure is available. Therapeutic aims for patients with RA are to alleviate symptoms, slow disease progression and optimize quality of life. In recent years, measures to achieve these goals have changed, and the development of new drugs will probably result in new treatment regimens. Two drugs with an extensive record of clinical experience are methotrexate and cyclosporin. Methotrexate is widely used because of its efficacy and high therapy retention rate. Both drugs have been shown to slow the progression of RA, but not without side-effects that sometimes preclude their use. As neither drug generally induces remission, improved treatments are needed. Combination therapy using drugs with different mechanisms of action is beginning to be evaluated, as are biological response modifiers targeted to specific mediators of the immune response. The future treatment of RA should provide more effective relief with fewer side-effects.

Antirheumatic Agents↗
PubMed1998

Longterm prospective study of methotrexate in rheumatoid arthritis: conclusion after 132 months of therapy.

OBJECTIVE: To conclude observations of efficacy of longterm methotrexate (MTX) treatment of rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA entered a prospective study of MTX in 1983. The study was completed after 132 months of therapy. RESULTS: Significant improvement (p < 0.001) was noted in the number of painful joints, swollen joints, and physician and patient global assessments. There was 50% improvement in the joint pain index and joint swelling index in > 65% of the patients. A significant reduction in prednisone dose was achieved. Sixteen patients withdrew from the study. Toxicity led to 3 drug related withdrawals of study patients (alopecia 1; pneumonitis 2). At 132 months, 10 patients (38%) had completed the study; 3 patients (11%) discontinued due to MTX toxicity. CONCLUSION: MTX was an effective treatment for RA in this 132 month prospective study.

Arthritis, Rheumatoid↗
PubMed1997

Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group.

BACKGROUND: Toxicity limits the use of methotrexate. OBJECTIVE: To identify risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. DESIGN: Case-control study. SETTING: One private and five academic rheumatology practices. PARTICIPANTS: Methotrexate recipients with rheumatoid arthritis with and without lung injury. MEASUREMENTS: Potential risk factors examined were sociodemographic and lifestyle characteristics, medical history, clinical and ancillary features and treatment of rheumatoid arthritis before methotrexate therapy, and characteristics of methotrexate therapy. Cases of lung injury were defined according to the modified criteria of Searles and McKendry. RESULTS: Ninety-four percent of the study participants were white, and 67% were women. Case-patients (n = 29) were older than controls (n = 82) (61.5 compared with 54.5 years of age). The strongest predictors of lung injury, after adjustment for other variables, were older age (odds ratio [OR], 5.1 [95% CI, 1.2 to 21.1]), diabetes (OR, 35.6 [CI, 1.3 to infinity]), rheumatoid pleuropulmonary involvement (OR, 7.1 [CI, 1.1 to 45.4]), previous use of disease-modifying antirheumatic drugs (OR, 5.6 [CI, 1.2 to 27.0]), and hypoalbuminemia (OR, 19.5 [CI, 3.5 to 109.7]). Previous use of disease-modifying antirheumatic drugs and hypoalbuminemia had very large attributable risks. CONCLUSION: Knowledge of the risk factors that predispose patients with rheumatoid arthritis to the toxic effects of methotrexate on the lung may provide a rationale for monitoring high-risk patients and may facilitate their management.

Antirheumatic Agents↗
PubMed1997

Clinical, laboratory, radiographic, and histopathologic features of methotrexate-associated lung injury in patients with rheumatoid arthritis: a multicenter study with literature review.

OBJECTIVE: To describe the clinical, laboratory, radiologic, and histopathologic features of methotrexate (MTX)-induced lung injury in a combined cohort of selected patients with rheumatoid arthritis (RA) and all cases reported in the English-language literature. METHODS: Retrospective combined cohort review and abstraction from the medical literature. Case reports were obtained from 6 centers that had 4 or more cases of potential MTX lung injury per site. RA patients who were seen between 1981 and 1993 and who satisfied predetermined criteria for the presence of MTX lung injury were identified. RESULTS: Twenty-seven patients satisfied the criteria for definite MTX lung injury, and 2 for probable MTX lung injury. Predominant clinical features of MTX lung injury included shortness of breath in 27 patients (93.1%), which was present for 23.5 +/- 22.3 days (mean +/- SD), cough in 24 (82.8%), present for 26.9 +/- 28.5 days, and fever in 20 (69.0%), present for 10.4 +/- 12.8 days. Five patients (17.2%) died, compared with 12 of 68 (17.6%) reported in the medical literature. Four of the 6 patients who were re-treated with MTX after an initial pulmonary event developed recurrent lung toxicity, resulting in 2 deaths, compared with a recurrence rate of 3 of 6 in the literature. CONCLUSION: MTX lung injury is most often a subacute process, in which symptoms are commonly present for several weeks before diagnosis. Approximately 50% of the cases are diagnosed within 32 weeks from initiation of MTX treatment. A patient who recovers from MTX lung injury should not be re-treated. Earlier recognition and drug withdrawal may avoid the serious and sometimes fatal outcome that has been observed in this and other studies.

Aged↗
PubMed1997

Histologic liver abnormalities in an autopsy series of patients with rheumatoid arthritis.

A retrospective review was performed on 188 autopsied cases of rheumatoid arthritis at our institutions during 1958-1985, prior to the widespread use of methotrexate. Hepatic histology was reported in 182 cases. All available microscopic liver slides from cases in which the autopsy report described portal tract inflammation, fibrosis, cirrhosis, tumour, amyloid, vasculitis, or infections involving the liver were examined and graded by a hepatic pathologist blinded to the original diagnosis, along with a representative sample of cases with reports describing fatty change or no hepatic pathologic abnormalities. Ninety normal and abnormal cases were reviewed from the 182 for which hepatic histology was available. Fifteen cases of diffuse fibrosis were identified upon blinded review. Two cases were graded as severe fibrosis (grades 3 or 4 on a scale of 0-4) without an identifiable pathologic cause, in both of which the liver disease was suspected premortem (alcohol abuse and viral hepatitis). Although the incidence of fibrosis in this series is slightly higher than that previously described, serious fibrotic liver disease was rare. These results support the current practice of limiting pre-treatment liver biopsies prior to methotrexate therapy to patients with suspected liver disease.

Adult↗
PubMed1997

False-positive FDG-PET imaging of the thymus of a child with Hodgkin's disease.

During the evaluation of a child who had completed treatment for Hodgkin's disease, a PET study strongly suggested recurrent disease in the mediastinum. Biopsies were obtained and revealed normal thymic tissue only, with no evidence of recurrent disease. The ongoing difficulty in establishing accurate disease status in patients treated for Hodgkin's disease is discussed, along with recommendations for treating pediatric patient populations.

Child↗
PubMed1996

N-[4-hydroxyphenyl] retinamide in rheumatoid arthritis: a pilot study.

OBJECTIVE: To evaluate the efficacy and tolerability of N-[4 hydroxyphenyl] retinamide (4-HPR), a synthetic retinoid, in the treatment of rheumatoid arthritis (RA). METHODS: An uncontrolled, open clinical trial with synovial biopsy pre- and postmedication to evaluate the clinical effects of 4-HPR as well as its effects on metalloproteinase gene expression. RESULTS: Twelve patients with severe, longstanding RA were enrolled in this study. Six patients withdrew before study completion, 2 because of drug toxicity, 2 because of a flare of RA, and 2 because of intercurrent medical problems. No patient met predetermined Paulus criteria treatment response, and there was no improvement in the laboratory parameters, except for a modest decrease in C-reactive protein. No decrease in messenger RNA for the metalloproteinases collagenase and stromelysin was seen in the 2 patients in whom paired synovial biopsies were obtained. CONCLUSION: No beneficial clinical effect was observed with the retinoid 4-HPR in the treatment of severe, longstanding RA at the 300 mg/day dosage studied. The use of higher dosages is precluded by the observed toxicities. The effect of this drug in patients with early or mild disease was not studied. Although this particular retinoid was not effective in this pilot study, the use of other retinoids in RA should still be considered.

Antineoplastic Agents↗