Rheumatoid Arthritis: Cush JJ

Cush JJ. · No affiliation provided · J Rheumatol. · Pubmed #15693079 links to  free full text

This publication has no abstract.

Kavanaugh A, Cohen S, Cush JJ. · No affiliation provided · J Rheumatol. · Pubmed #15468347 links to  free full text

This publication has no abstract.

Cush JJ. · Department of Clinical Rheumatology, Baylor Research Institute, Dallas, Texas 75231, USA. · J Rheumatol Suppl. · Pubmed #17985417 No free full text.

Abstract: The early diagnosis and treatment of nascent rheumatoid arthritis (RA) has become a prime objective for rheumatologists and clinicians who care for patients with arthritis. Population-based studies have consistently shown that patients with RA are at substantial risk for progressive joint damage, disability, and increased morbidity and mortality. These inevitable outcomes are closely linked to the consequences of rheumatoid inflammation, which begins early and is progressive in all. At issue is whether early diagnosis, coupled with aggressive therapy, might alter the natural history of this RA. If this "window of opportunity" exists, then outcomes should be substantially altered by delivering the right therapies at the right time. A growing body of evidence has emphasized the consistent clinical and radiographic benefits of early, aggressive treatment of RA. These studies confirm that all therapies - monotherapy, combination disease modifying antirheumatic drugs (DMARD), biologics - work better in early disease than in long-established RA. Earlier identification, referral, and an accurate diagnosis of RA can now be rewarded with highly effective DMARD or biologic therapies. Rheumatologists should rise to the challenge and educate clinicians about this window of opportunity, the potential for remission, and superior clinical responses when patients with early RA or undifferentiated arthritis are referred to and managed by experts in aggressive rheumatologic care.

Dao K, Cush JJ. · Rheumatology and Clinical Immunology Division, Presbyterian Hospital of Dallas, Dallas, TX 75231, USA. · Best Pract Res Clin Rheumatol. · Pubmed #16979530 No free full text.

Abstract: Arthritis is the most common cause of disability. Hence, prompt recognition and management of acute-onset polyarthritis are paramount to prevent progressive damage. When rheumatoid arthritis is considered as a prototypical example of polyarthritis, the stakes of early and accurate evaluation are evident. The challenge is in determining when undifferentiated polyarthritis ends and rheumatoid arthritis begins. This chapter reviews the evidence to help clinicians identify and manage patients who present with acute polyarticular inflammation.

Cush JJ. · Department of Rheumatology and Clinical Immunology, Presbyterian Hospital of Dallas, 8200 Walnut Hill Lane, Dallas, TX 75231-4496, USA. · Rheum Dis Clin North Am. · Pubmed #16287586 No free full text.

Abstract: In the next 12 months, 7500 Canadians and 75,000 Americans will be afflicted with the onset of rheumatoid arthritis. Little is known about the health care use of patients with early RA. Nonetheless, rheumatologists and outcomes researchers strongly endorse the need for early diagnosis and treatment of this population. This article reviews trends and impediments to early referral of new-onset arthritis patients. The slow growth of early arthritis clinics is summarized in a survey that characterizes 23 early arthritis programs in North America. Also, several screening tools and models to capture these early-onset arthritis patients are presented.

Cush JJ. · Rheumatology and Clinical Immunology, Presbyterian Hospital of Dallas, Texas 75231-4496, USA. · Clin Exp Rheumatol. · Pubmed #15552528 No free full text.

Abstract: Serious and unexpected adverse events, such as heart failure and drug-induced lupus, have been reported in patients receiving TNF inhibitor therapy. These events generally are easily recognizable, although they cannot be predicted nor avoided, other than by drug avoidance altogether Many patients have great benefit from anti-TNF therapies. Their intelligent use requires a firm understanding of these rare toxicities, so as to minimize the morbidity associated with their uncommon occurrence.

Cush JJ. · Presbyterian Hospital of Dallas, 8200 Walnut Hill Lane, Dallas, TX 75231, USA. · Rheum Dis Clin North Am. · Pubmed #15172038 No free full text.

Abstract: Beginning in 1998, a surge of new agents has expanded treatment options for rheumatoid arthritis (RA) patients. Although the disease modifying potential of these agents is encouraging, their use must be weighed against an evolving array of new safety concerns. Because of the popularity of these agents with patients and rheumatologists alike, clinicians must be prepared to discuss the potential risks associated with novel disease-modifying antirheumatic drugs and biologic therapies as they begin to appear with greater frequency in practice. This article discusses the safety issues arising from clinical trial and postmarketing experience with several new and commonly used agents, with specific emphasis on adalimumab, etanercept, infliximab, anakinra, and leflunomide.

Cush JJ. · Presbyterian Hospital of Dallas, University of Texas Southwestern Medical School, Dallas, Texas, USA. · Clin Exp Rheumatol. · Pubmed #14969055 No free full text.

Abstract: An early arthritis clinic (EAC) was established to identify early rheumatoid arthritis (RA) patients for clinical trials and to create a facile method of early patient referral from the practitioner to the rheumatologist. With minimal advertising and promotion, patients with less than 12 months of symptoms were easily referred if the primary care physician suspected a rheumatic condition. Of those patients who were appropriately referred one-third had synovitis, 20% had diagnostic cutaneous findings, 20% were diagnosed with lupus (or lupus-like disease), 12.5% had RA, and 10% were diagnosed with a spondyloarthropathy. An EAC was easily established, implemented and staffed and resulted in the prompt diagnosis and early treatment of many patients who may have otherwise waited months for appropriate rheumatologic diagnosis and treatment.

Wolfe F, Cush JJ, O'Dell JR, Kavanaugh A, Kremer JM, Lane NE, Moreland LW, Paulus HE, Pincus T, Russell AS, Wilskie KR. · National Data Bank for Rheumatic Diseases-Arthritis Research Center Foundation, Inc. and University of Kansas School of Medicine, Wichita, Kansas, USA. · J Rheumatol. · Pubmed #11409141 No free full text.

This publication has no abstract.

Cohen SB, Moreland LW, Cush JJ, Greenwald MW, Block S, Shergy WJ, Hanrahan PS, Kraishi MM, Patel A, Sun G, Bear MB, Anonymous00309. · Department of Rheumatology, St Paul Medical Center, Dallas, Texas 75235, USA. · Ann Rheum Dis. · Pubmed #15082469 links to  free full text

Abstract: OBJECTIVE: To assess the efficacy and safety of 100 mg daily anakinra (Kineret), a recombinant form of the naturally occurring interleukin 1 receptor antagonist, plus methotrexate (MTX) in reducing the signs and symptoms of rheumatoid arthritis (RA). METHODS: Patients with active RA (n = 506) despite current treatment with MTX were enrolled in this multicentre, double blind, randomised, placebo controlled study. Patients received subcutaneous injections of anakinra 100 mg/day or placebo. They were assessed monthly for 6 months for improvement in signs and symptoms of RA and for adverse events. The primary efficacy measure was the percentage of patients attaining ACR20 response at week 24. RESULTS: Significantly greater proportions of patients treated with anakinra compared with placebo achieved ACR20 (38% v 22%; p<0.001), ACR50 (17% v 8%; p<0.01), and ACR70 (6% v 2%; p<0.05) responses. The response to anakinra was rapid; the proportion of patients with an ACR20 response at the first study assessment (4 weeks) was twice as high with anakinra as with placebo (p<0.005). Clinically meaningful and statistically significant responses were also seen in individual components of the ACR response (for example, Health Assessment Questionnaire, pain, C reactive protein levels, and erythrocyte sedimentation rate). Anakinra was well tolerated, with a safety profile, similar to that of placebo with one exception: mild to moderate injection site reactions were more common with anakinra than with placebo (65% v 24%). CONCLUSIONS: This study confirms previous observations from a dose-ranging study showing that anakinra, in combination with MTX, is an effective and safe treatment for patients with RA who have inadequate responses to MTX alone.

Kremer JM, Genovese MC, Cannon GW, Caldwell JR, Cush JJ, Furst DE, Luggen ME, Keystone E, Weisman MH, Bensen WM, Kaine JL, Ruderman EM, Coleman P, Curtis DL, Kopp EJ, Kantor SM, Waltuck J, Lindsley HB, Markenson JA, Strand V, Crawford B, Fernando I, Simpson K, Bathon JM. · The Center for Rheumatology, LLP, 1367 Washington Avenue, Suite 101, Albany, NY 12206, USA. · Ann Intern Med. · Pubmed #12416946 links to  free full text

Abstract: BACKGROUND: Disease-modifying antirheumatic drugs may confer greater benefits when combined with the antimetabolite methotrexate. OBJECTIVE: To evaluate the efficacy and safety of leflunomide versus placebo when added to ongoing, stable-dose methotrexate therapy in patients with persistently active rheumatoid arthritis. DESIGN: 24-week, multicenter, randomized, double-blind, placebo-controlled trial. SETTING: 20 centers in the United States and Canada. PATIENTS: Patients with persistent rheumatoid arthritis, as defined by American College of Rheumatology (ACR) criteria, despite receiving methotrexate for at least 6 months. INTERVENTION: Leflunomide or matching placebo added to existing methotrexate therapy. MEASUREMENTS: The primary efficacy variable was the rate of achievement of 20% improvement in ACR criteria (ACR20) at the end of the study. The Health Assessment Questionnaire Disability Index was assessed at each visit, and the Medical Outcomes Study 36-Item Short Form was completed as an end point analysis. RESULTS: In the leflunomide and placebo groups, 46.2% and 19.5% of patients, respectively, met ACR20 criteria at 24 weeks (P < 0.001). Clinical improvement was demonstrated by statistically significant mean changes in individual components of the ACR20 response criteria. Discontinuation rates were similar in both treatment groups (23.1% in the leflunomide group and 24.8% in the placebo group), as were the overall incidences of adverse events (89.2% vs. 89.5%, respectively). Adverse events were predominantly mild or moderate. CONCLUSIONS: Combination therapy with leflunomide and methotrexate provides statistically significant clinical benefit in patients with active rheumatoid arthritis who are receiving methotrexate therapy. Leflunomide plus methotrexate is generally well tolerated and can be used safely with appropriate liver enzyme and hematologic monitoring.

Tao X, Cush JJ, Garret M, Lipsky PE. · Harold C. Simmons Arthritis Center, The University of Texas Southwestern Medical Center at Dallas, USA. · J Rheumatol. · Pubmed #11669150 No free full text.

Abstract: OBJECTIVE: To explore the efficacy and safety of ethyl acetate (EA) extracts of the Chinese herbal remedy Tripterygium wilfordii Hook F (TWHF) for treatment of patients with a variety of inflammatory and autoimmune diseases including rheumatoid arthritis (RA). METHODS: The roots of TWHF were extracted sequentially by ethyl alcohol and ethyl acetate and the content of the extract documented. An open label, dose escalation Phase I study was performed in 1993 in 13 patients with established RA. Clinical manifestations and laboratory findings were examined before and every 4 weeks after starting treatment with the EA extract. RESULTS: Three patients withdrew from the trial during the first 16 weeks of the dose escalation. These patients received a maximum dosage of 180 mg/day. There were no adverse effects or disease improvement observed in these patients. Nine of the remaining 10 patients tolerated the EA extract up to a dosage of 570 mg/day. There were no withdrawals related to adverse events in the trial except for one patient who developed diastolic hypertension at a dose of 180 mg/day of EA extract. Six of 10 patients treated with 180 mg/day of EA extract showed disease improvement. Eight of the 9 patients who received EA extract at doses > 360 mg/day experienced improvement in both clinical manifestations and laboratory findings. One patient met American College of Rheumatology criteria for remission. CONCLUSION: The EA extract of TWHF at dosages up to 570 mg/day appeared to be safe, and doses > 360 mg/day were associated with clinical benefit in patients with RA.

Cohen SB, Cohen MD, Cush JJ, Fleischmann RM, Mease PJ, Schiff MH, Simon LS, Weaver AL. · The University of Texas Southwestern Medical Center, Office of Continuing Education, 5323 Harry Hines Blvd., Dallas, TX 75390-9059. · J Rheumatol Suppl. · Pubmed #19193621 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic, multisystem, inflammatory disorder of the joints that affects about 1% of the world population. The ultimate goals of therapy include remission of disease and prevention of joint damage. Reaching these goals has become a realistic outcome for an increasing number of patients as treatment options have expanded over the past 3 decades. In addition to older therapies, such as methotrexate (MTX), other disease modifying drugs (DMARD), and tumor necrosis factor (TNF) inhibitors, newer biologic treatments have become available. For the substantial number of patients who experience an inadequate response to standard medications, biologic response modifiers (BRM) provide an important therapeutic alternative. The availability of multiple treatment options in the absence of clear definitions or criteria for remission and inadequate response, however, makes clinical decisions about measuring outcomes, predicting response to treatment, and prescribing pharmacologic therapies challenging. In this program, distinguished rheumatologists weigh the evolving body of clinical evidence to draw sound conclusions and resolve key issues in managing inadequate response to treatment and in achieving optimal outcomes in RA.

Cush JJ, Yazici Y. · Rheumatology and Clinical Immunology, Presbyterian Hospital of Dallas, 8200 Walnut Hill Lane, Dallas, TX 75231-4496, USA. · Clin Exp Rheumatol. · Pubmed #16273791 No free full text.

Abstract: The purpose of this report is to provide suggested guidance concerning the monitoring of TNF blocker therapy. Since the completion of randomized trials, several new long-term safety concerns have arisen, involving mycobacterial and opportunistic infections, cytopenias, lymphoma, demyelinating disease, drug-induced lupus, congestive heart failure and hepatotoxicity. Since these serious events are rare, widespread post-marketing use and prolonged follow-up have been required to analyze their prevalence. Monitoring of TNF inhibitors is necessary to reassure physicians and patients of the continued efficacy and safety of these drugs. No published recommendations on monitoring are available. The clinician must weigh the potential clinical benefits of TNF inhibition against potential adverse effects. Patients should be evaluated carefully for the risk or presence of infection, tuberculosis and other serious adverse events by regular visits, careful clinical assessments, and an assiduous, high index of suspicion for these rare events. Tuberculin skin testing using PPD is recommended before starting treatment with any TNF inhibitor.

Cush JJ. · Rheumatology and Clinical Immunology, Presbyterian Hospital of Dallas, 8200 Walnut Hill Lane, Dallas, TX 75231-4496, USA. · Ann Rheum Dis. · Pubmed #16239379 links to  free full text

Abstract: An estimated 20% of patients with rheumatoid arthritis (RA) receive tumour necrosis factor (TNF) inhibitor treatment. This paper presents the results of an online survey of US rheumatologists (1023 respondents) conducted in April 2005 on issues relating to use of TNF inhibitors in RA. The primary determinant of TNF inhibitor use among the participating rheumatologists was physician preference rather than patient preference or payor guidelines. Qualitative (rather than quantitative measures) assessments (physician overall assessment, symptom review, etc.) and laboratory measures were more frequently employed when assessing and treating patients with RA. Clinical assessments with hepatic enzymes and complete blood count as an additional safety tool were most commonly employed to monitor drug safety. Nearly all the rheumatologists (> or = 92%) felt that a partial purified derivative (PPD) test was indicated when using a TNF inhibitor, but were equally split with regard to those with a history of PPD positivity or BCG vaccination. The frequency of serious adverse events was estimated and included tuberculosis, systemic fungal infection, demyelinating disorders, cytopenia, drug induced lupus, lymphoma, and hepatic failure. Among 454 RA patients who became pregnant while receiving biological therapy there were 378 normal deliveries, 9 premature babies, 5 therapeutic abortions, and 25 miscarriages. It was concluded that a greater than expected number of US rheumatologists are familiar with biologicals and TNF inhibitor therapies, but uncertainties and educational gaps still exist regarding their use and monitoring.

Hansen KE, Hildebrand JP, Genovese MC, Cush JJ, Patel S, Cooley DA, Cohen SB, Gangnon RE, Schiff MH. · Division of Rheumatology, University of Wisconsin, Madison, Wisconsin, USA. · J Rheumatol. · Pubmed #15170921 No free full text.

Abstract: OBJECTIVE: To describe the degree of clinical benefit in patients with rheumatoid arthritis (RA) who receive infliximab therapy after lack of efficacy with etanercept. METHODS: In a retrospective study among 6 centers primarily designed to assess the safety of infliximab in combination with leflunomide, a standardized chart review form was used to collect data on 93 patients with RA. During that study, it was noted that some of these patients had switched from etanercept to infliximab. In this study, we compared the response of subjects switching from etanercept to infliximab (n = 20) to that of subjects receiving infliximab with no prior tumor necrosis factor (TNF) therapy (n = 73). RESULTS: The swollen and tender joint count, patient and physician global assessments, morning stiffness, and C-reactive protein all improved substantially in both groups, with no statistical difference in the degree of benefit between the groups. At the time of chart review, switchers had received a statistically higher dose of infliximab than controls (4.4 vs 3.19 mg/kg; p = 0.006) with a total of 5.7 and 5 infusions, respectively. CONCLUSION: In this retrospective study, previous lack of efficacy with etanercept did not predict lack of efficacy with infliximab. Indeed, the degree of clinical improvement was similar in both groups, although switchers were receiving a higher dose of infliximab at the time of chart review. Our findings suggest that clinical response may differ between anti-TNF agents, and lack of response to one agent may not predict a lack of response to another.

Cush JJ. · Arthritis Center, Presbyterian Hospital of Dallas and The University of Texas Southwestern Medical School at Dallas, Dallas, Texas 75231, USA. · Drugs Today (Barc). · Pubmed #12973433 No free full text.

Abstract: The need for new therapies for the treatment of rheumatoid arthritis (RA) has arisen during an era where clinicians have realized that RA is a far more ominous condition than was thought previously. The last decade has revealed numerous studies depicting the limited long-term efficacy and tolerability of conventional disease-modifying antirheumatic drug (DMARD) therapies. Moreover, DMARDs have not been shown to be truly capable of modifying articular, functional and radiographic outcomes in patients with RA. These issues have been raised amidst significant advances in our understanding of the immunopathogenesis of RA and advances in biotechnology. Such advances have led to a revised approach to using conventional DMARDs, while new pharmacologic and biospecific interventions are being developed. This chapter will discuss the clinical and biologic rationale for novel therapies for patients with RA and the hazards imposed by the therapeutic manipulation of various immune effector mechanisms in patients with RA.

Davis LS, Cush JJ, Schulze-Koops H, Lipsky PE. · The Harold C Simmons Arthritis Research Center and Rheumatic Diseases Division, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-8884, USA. · Arthritis Res. · Pubmed #11178127 links to  free full text

Abstract: CD4+ memory T cells (Tm) from rheumatoid arthritis peripheral blood (RAPB) or peripheral blood from normal donors produced IL-2, whereas fewer cells secreted IFN-gamma or IL-4 after a brief stimulation. RAPB Tm contained significantly more IFN-gamma producers than normal cells. Many rheumatoid arthritis (RA) synovial Tm produced IFN-gamma alone (40%) and fewer cells produced IL-2 or IL-4. An in vitro model was employed to generate polarized T-helper (Th) effectors. Normal and RAPB Tm differentiated into both IFN-gamma- and IL-4-producing effectors. RA synovial fluid (RASF) Tm demonstrated defective responsiveness, exhibiting diminished differentiation of IL-4 effectors, whereas RA synovial tissue (RAST) Tm exhibited defective generation of IFN-gamma and IL-4 producers.

Cush JJ. · Presbyterian Hospital of Dallas, University of Texas Southwestern Medical Center at Dallas, USA. · Bull Rheum Dis. · Pubmed #11100625 No free full text.

This publication has no abstract.

Cush JJ, Tugwell P, Weinblatt M, Yocum D. · University of Texas Southwestern Medical School, Dallas, USA. · J Rheumatol. · Pubmed #10332987 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that often leads to irreversible joint damage and loss of function. Although there are numerous treatment options, it is difficult to manage the disease in most patients. Use of cyclosporin A (CsA) for RA was first reported in 1979, and since that time many trials have investigated CsA use for this disease. Based on clinical evidence, CsA is an efficacious second-line agent for patients with active RA who have not responded adequately to methotrexate (MTX). In addition, CsA has been shown to provide clinical benefit when used in combination with MTX in patients responding inadequately to MTX monotherapy. Side effects associated with CsA treatment are manageable if dosing, monitoring, and intervention guidelines are followed. The purpose of this review is to provide recommendations for the use of CsA in severe RA to physicians experienced in the management of systemic immunosuppressive therapy for RA. Where possible and appropriate, recommendations are based on evidence available in the literature.