Rheumatoid Arthritis: Kavanaugh A

Keystone EC, Kavanaugh A. · No affiliation provided · Expert Opin Drug Saf. · Pubmed #15794709 No free full text.

Abstract: The introduction of TNF inhibitors into the clinic for the treatment of patients with rheumatoid arthritis and other systemic inflammatory conditions has revolutionised the approach to these diseases. Despite the substantial efficacy of these agents, a subset of patients either does not respond or has a suboptimal clinical response. Defining what constitutes 'failure' of this type of therapy is important in both clinical research and practice. For patients who fail to respond to TNF inhibitors, a number of promising avenues targeting other aspects of the immune system are under study, and may be brought to the clinic in the near future.

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

This publication has no abstract.

Boyle DL, Kavanaugh A. · Rheumatology, Allergy, Immunology Division, University of California, San Diego, California 92093, USA. · Curr Opin Rheumatol. · Pubmed #18525352 No free full text.

Abstract: PURPOSE OF REVIEW: Psoriatic arthritis pathogenesis is incompletely understood and the pathophysiologic role of the synovium is only beginning to be elucidated. Currently, approaches similar to those applied to rheumatoid arthritis are being applied to psoriatic arthritis synovia. RECENT FINDINGS: Synovitis is being re-examined along with efforts to better characterize the clinical phenotype and improve patient stratification. The dermatological perspective brings an alternative view of autoimmunity and the role of innate immunity. A pathogenetic basis for the differing roles of skin and synovium is suggested by a landmark animal study that demonstrated a psoriasis-like skin disease coupled with a T cell and B cell dependent arthritis. The histopathology of the synovio-entheseal complex has been described. Systematic methods for evaluating synovitis have been developed and cross-sectional evaluations of psoriatic arthritis synovia in the context of other arthritides have been performed. Fresh looks at psoriatic arthritis synovia suggest similarity to rheumatoid arthritis synovia. SUMMARY: Research into the pathophysiology of psoriatic arthritis is at an early, yet promising stage. Instruments are being developed to characterize and stratify psoriatic arthritis. The role of synovia remains unclear, but we now have a better understanding of the pathology of innate and adaptive immunity and are reminded that psoriatic arthritis is a systemic disease.

Castro-Rueda H, Kavanaugh A. · Center for Innovative Therapy, Division of Rheumatology, Allergy and Immunology, University of California, San Diego, California, USA. · Curr Opin Rheumatol. · Pubmed #18388524 No free full text.

Abstract: PURPOSE OF REVIEW: To describe current therapeutic trials with biologic agents for early rheumatoid arthritis, analyzing clinical and radiographic outcomes. RECENT FINDINGS: The use of tumor necrosis factor-alpha inhibitors in combination with disease-modifying antirheumatic drugs early after the diagnosis of aggressive rheumatoid arthritis seems to provide increased clinical benefit over methotrexate or tumor necrosis factor-alpha inhibitors as monotherapy, with better outcomes in terms of faster and more extensive clinical improvement. There also seems to be an increased likelihood of low-disease activity in some cases even after tapering therapy. Control of radiographic progression appears to be most effective among early rheumatoid arthritis patients treated with combination tumor necrosis factor-alpha inhibitors and methotrexate, although radiographic outcomes are better with tumor necrosis factor-alpha inhibitor monotherapy than with methotrexate alone. SUMMARY: The addition of antitumor necrosis factor-alpha agents to traditional disease-modifying antirheumatic drugs in early rheumatoid arthritis is a novel strategy which follows the principle of early and aggressive therapeutic intervention. Results from recent trials show greater levels of disease control. The impact on long-term safety and cost-efficacy are factors which will need to be better characterized over time.

Ackermann C, Kavanaugh A. · University of California, Center for Innovative Therapy, Divison of Rheumatology, Allergy and Immunology, San Diego, La Jolla, CA 92093-0943, USA. · Expert Opin Ther Targets. · Pubmed #18028004 No free full text.

Abstract: TNF-alpha is a crucial pro-inflammatory and immunoregulatory cytokine that is central to the pathogenesis of various inflammatory and autoimmune conditions. A number of controlled trials have shown effectiveness for TNF-alpha inhibitors in several diseases, in particular rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and Crohn's disease. These agents may also be useful in additional autoimmune conditions. The introduction of TNF-alpha inhibitors has revolutionized the therapeutic approach and treatment paradigms especially for patients with rheumatoid arthritis. Despite extensive investigation, the full profile of their mechanisms of action remain incompletely understood. Optimal use of these agents requires consideration of their possible adverse effects. In addition to the presently available TNF-alpha blockers, other agents targeting this key mediator are under study. Recent advances and future directions in anti-TNF-alpha therapy are discussed in this paper.

Kavanaugh A. · Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA 92093-0943, USA. · Best Pract Res Clin Rheumatol. · Pubmed #17870036 No free full text.

Abstract: Recent years have witnessed tremendous progress in the therapeutic approach to rheumatoid arthritis (RA). The introduction of novel biologic agents, in particular TNF inhibitors, has allowed clinicians to achieve improved outcomes for their patients. An important factor that has affected the utilization of novel therapies is their acquisition costs, which far exceed those for older antirheumatic drugs. Nevertheless, RA is a serious chronic condition which can cause substantial morbidity and even accelerated mortality for affected individuals. The notable sequelae of uncontrolled rheumatoid synovitis include joint damage and functional disability, which in turn, cause severe economic consequences not only to patients and their families, but also to society. Therefore, it is appropriate for pharmacoceconomic analyses to take into account all relevant costs, not only of the treatments, but of the disease itself. In this way, the value of therapies can be correctly estimated.

Kavanaugh A. · Center for Innovative Therapy, Division of Rheumatology, Allergy and Immunology, The University of California at San Diego, La Jolla, California 92093-0943, USA. · Bull NYU Hosp Jt Dis. · Pubmed #17708740 links to  free full text

Abstract: Interleukin 6 (IL-6), a pleiotropic cytokine with numerous and varied effects on the inflammatory cascade and immune response, appears to be an attractive target for novel immunomodulatory therapy for systemic inflammatory autoimmune diseases. Proof of principal for this approach has come from studies of the anti-IL-6 receptor monoclonal antibody, tocilizumab. Tocilizumab has been assessed in a number of studies in recent years, mainly in patients with rheumatoid arthritis (RA). Data from randomized controlled clinical trials demonstrate the efficacy of tocilizumab in improving the signs and symptoms of RA. In addition, it appears that such inhibition of IL-6 can have positive effects on functional status, an important outcome for RA patients. Finally, data suggest that treatment with this agent may also inhibit the progression of disease as assessed radiographically. Data from studies currently underway will help refine the ultimate use of this novel approach to treatment, and help clinicians optimize therapy using this approach.

Kavanaugh A. · University of California, San Diego, USA. · Am J Orthop. · Pubmed #17491580 No free full text.

This publication has no abstract.

Kavanaugh A. · Center for Innovative Therapy, Division of Rheumatology, Allergy, and Immunology, University of California San Diego, La Jolla, CA 92093-0943, USA. · Curr Opin Rheumatol. · Pubmed #17414954 No free full text.

Abstract: PURPOSE OF REVIEW: Pharmacoeconomic evaluations are increasingly important in all aspects of medicine. In rheumatology, such studies have become all the more relevant following the introduction of highly effective biologic agents. Brought to the clinic initially for the treatment of rheumatoid arthritis, biologic agents have found expanded indication in other rheumatic diseases. RECENT FINDINGS: Building upon a long tradition in rheumatology, recent studies have updated and expanded upon the costs of various rheumatic diseases. These studies set the stage for determining the value of newer therapies. As a result of the chronic nature of rheumatic diseases, pharmacoeconomic evaluations must be carried out over sufficiently long time frames. Therefore, methodologic issues continue to be an area of ongoing discussion. Finally, ongoing studies have estimated the cost-effectiveness of novel rheumatologic therapies, in particular the inhibitors of tumor necrosis factor. These studies have shown that in several clinical circumstances, tumor necrosis factor inhibitors can indeed have an incremental cost-efficacy within the range of generally accepted medical interventions. While many of these studies focused on rheumatoid arthritis, there is growing interest in pharmacoeconomic evaluations in other rheumatic diseases. SUMMARY: Pharmacoeconomic evaluations are crucial to the optimal use of new therapies in rheumatology.

Lee SJ, Kavanaugh A. · Division of Rheumatology, Allergy, and Immunology, The University of California, San Diego, USA. · Rheum Dis Clin North Am. · Pubmed #17410696 No free full text.

This publication has no abstract.

Tutuncu Z, Kavanaugh A. · Division of Rheumatology, Allergy and Immunology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0943, USA. · Rheum Dis Clin North Am. · Pubmed #17367692 No free full text.

Abstract: This article summarizes the different aspects of rheumatoid arthritis and the spectrum of diseases that can present as rheumatoid arthritis in the elderly population. With the ageing of the western population, different forms of inflammatory arthritis' prevalence and incidence are increasing in elderly persons. Difficulties in establishing the diagnosis and introducing new treatment modalities in this patient group pose a great challenge for clinicians. The management of inflammatory arthritis in the elderly requires special consideration in regard to the comorbidities and increased frequency of adverse events. There is substantial need for improving aspects of diagnostic and therapeutic interventions that will reduce the impact of inflammatory arthritis in the growing elderly population.

Kavanaugh A, Fransen J. · Center for Innovative Therapy, Division of Rheumatology, Allergy, and Immunology, University of California San Diego, La Jolla, CA 92093-0943, USA. · Clin Exp Rheumatol. · Pubmed #17083768 No free full text.

Abstract: Driven in part by the introduction of highly effective agents, there has been growing interest in the overall therapeutic approach to patients with psoriatic arthritis (PsA). As with any form of arthritis, the goal of treatment for PsA would be to improve the outcome to the greatest extent possible. In other conditions, such as rheumatoid arthritis, recent discussions have centered on how best to define "remission." For patients with PsA, the heterogeneity among disease manifestations as well as the need to validate outcome measures make definition of remission challenging. In this paper we present a number of key principles and considerations critical to laying the groundwork for defining remission in PsA.

Pincus T, Kavanaugh A, Aletaha D, Smolen J. · Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232-4500, USA. · Clin Exp Rheumatol. · Pubmed #17083755 No free full text.

Abstract: The rheumatology community has devoted increasing attention to the subject of remission over the past 2 decades, on the basis of greater appreciation of the long-term severity of inflammatory rheumatic diseases and availability of new therapies and approaches to improve outcomes. Nonetheless, description of remission in rheumatic diseases is complex, compared to many nonrheumatic diseases. Recognition of remission requires a set of measures or an index rather than a single "gold standard." Spontaneous remission is not infrequent in people with early inflammatory arthritis, including some who may meet criteria for rheumatoid arthritis (RA) over less than a few months, and may be confused with a drug-induced remission. Remission may be transient in many patients over short periods, and the length of time required to maintain remission status varies in different reports. Maintenance of a state of remission in autoimmune diseases that result from dysregulatory processes, rather than invasion of foreign cells or toxins, generally requires ongoing therapy indefinitely. Patients who have organ damage or functional disability may be described as "in remission," although they are free of disease activity only, but not necessarily free of disease consequences. A status of "low disease activity" or "near remission" with 70% to 90% of the features of an ideal remission may be adequate for many people with rheumatic diseases to avoid risks that may be required to reach 100% remission status. Thus, the subject of remission remains under active discussion in the rheumatology community.

Hata T, Kavanaugh A. · Department of Medicine, Division of Dermatology, University of California, San Diego School of Medicine, La Jolla, 92093-0943, USA. · Clin Dermatol. · Pubmed #16966022 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic progressive disorder characterized by symmetric inflammatory arthritis in association with systemic symptoms. Although considered a "joint disease," RA is associated with involvement in diverse organ systems, including the skin. Common manifestations include Raynaud phenomenon, rheumatoid nodules, and rheumatoid vasculitis. As with other extra-articular manifestations, dermatologic involvement tends to occur in patients with more severe RA. In addition to manifestations related to the disease, there are also sundry dermatologic reactions related to the medications used to treat RA. Understanding the etiology and therapy for cutaneous manifestations of RA will help optimize patient care.

Kavanaugh A. · Center for Innovative Therapy, Division of Rheumatology, Allergy, and Immunology, University of California San Diego, La Jolla, CA 92093, USA. · Nat Clin Pract Rheumatol. · Pubmed #16932716 No free full text.

This publication has no abstract.

Kavanaugh A. · Center for Innovative Therapy, Division of Rheumatology, Allergy, and Immunology, University of California, San Diego, La Jolla, California 92093-0943, USA. · Adv Ther. · Pubmed #16751154 No free full text.

Abstract: Rheumatoid arthritis (RA) has severe and lasting effects on quality of life. This review (1) describes the disease progression, disability, and joint destruction that seriously alter a patient's quality of life, and (2) explains how the interleukin-1 receptor antagonist (IL-1Ra), anakinra, retards the progress of disease, thereby improving outcomes. Relevant articles were reviewed with a focus on RA, anakinra, and functional and quality-of-life outcomes. In randomized, controlled trials, the IL-1Ra anakinra provided meaningful benefits for patients with active RA, such as decreased signs and symptoms of disease, slower radiographic disease progression, reduced disability, and improved health-related quality of life. The biologic agent, anakinra, provides to patients with RA a valuable treatment option that has a positive impact on both function and quality of life.

Kavanaugh A. · Division of Rheumatology, Allergy, and Immunology, University of California at San Diego, La Jolla, CA 92093-0943, USA. · Rheum Dis Clin North Am. · Pubmed #16504820 No free full text.

Abstract: Rheumatic diseases are common, serious conditions characterized by alterations in normal immune homeostasis with resultant end-organ injury. Although diverse in clinical expression and pathophysiologic basis, therapeutic approaches for these conditions frequently overlap. Over the past decade, several important new therapies have been introduced into the clinic for the treatment of many rheumatic conditions. Although these agents have proven highly effective, their higher costs have raised questions concerning their most appropriate use in the clinic. This issue has been analyzed in greatest detail in rheumatoid arthritis. Increasing data suggest that newer therapeutics may be cost-effective for rheumatoid arthritis and other rheumatic diseases.

Lee SJ, Kavanaugh A. · Division of Rheumatology, Allergy, and Immunology, and the Center for Innovative Therapy, the University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. · J Allergy Clin Immunol. · Pubmed #16455344 No free full text.

Abstract: Autoimmune diseases are distinct clinical syndromes characterized by various alterations in normal immune responsiveness, such that there is a loss of tolerance to particular host constituents. In most cases, despite years of intense investigation, the etiopathogenic antigens initiating these systemic inflammatory conditions remain undefined. However, a great deal has been learned about the changes in components of the immune response relevant to the propagation and sustenance of these often chronic disorders. In addition, various hormonal, environmental, physiologic, and other influences that affect their expression have been identified. The expression and ultimate clinical outcome of autoimmune diseases usually relate to inflammation-related damage to the target organ with subsequent dysfunction. Certain immune conditions, such as autoimmune thyroid disease, largely affect a single organ, whereas others, such as systemic lupus erythematosus, heterogeneously affect sundry organ systems. Autoantibodies directed against normal host antigens are a common feature of many autoimmune diseases. In some cases they are pathogenic, whereas in others they serve as markers for organ involvement or outcomes. Clinical descriptions of autoimmune diseases date back many decades in some cases. Recent efforts at formulating classification criteria have allowed clearer distinctions and more accurate stratification. Greater understanding of the immunopathogenesis of autoimmune conditions has led to the development and introduction into the clinic of novel immunomodulatory therapies and treatment paradigms that have substantially improved the outcomes for patients affected by these serious conditions.

Riedemann JP, Muñoz S, Kavanaugh A. · Department of Rheumatology and Clinical Epidemiology, Faculty of Medicine, Universidad de la Frontera, Temuco, Chile. · Clin Exp Rheumatol. · Pubmed #16273788 No free full text.

Abstract: OBJECTIVE: To evaluate the diagnostic properties and predictive value of the second generation of anti-CCP antibodies (anti-CCP2) in rheumatoid arthritis (RA) patients. METHODS: A systematic review of the published literature between January 2002 and June 2005 was performed. Data were extracted regarding the sensitivity and specificity of anti-CCP2 antibodies in making an accurate diagnosis of RA, predicting future development of RA, and predicting future radiological damage in RA patients. In addition, the prevalence of CCP2 antibodies in patients with other rheumatic diseases was examined. RESULTS: Among 38 studies initially identified, 27 provided information on the use of anti-CCP2 testing. Diagnostic properties were assessed in 13 studies; reported sensitivities ranged from 14.4% to 96%, and specificities from 88.9% to 100%. Odds ratios (OR) for the future development of RA varied from 15.9 among previously healthy individuals to 37.8 among a group of patients with undifferentiated arthritis. Several studies suggested that the presence of anti-CCP2 antibodies is highly predictive of current radiographic damage and further damage progression. CONCLUSIONS: Anti-CCP2 has a low sensitivity to be used as a screening test. However, a positive test is highly specific for RA. In addition, anti-CCP2 appears to be highly predictive of the future development of RA in both normal individuals and patients with undifferentiated arthritis. Finally, the presence of anti-CCP2 antibodies appears to predict radiographic damage and progression among patients with RA.

Kavanaugh A. · Center for Innovative Therapy and Division of Rheumatology, Allergy, and Immunology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0943, USA. · Ann Rheum Dis. · Pubmed #16239392 links to  free full text

Abstract: This paper discusses the pharmacoeconomics issues relating to the use of the newer therapies for rheumatoid arthritis (RA), namely the tumour necrosis factor (TNF) inhibitors. RESULTS: of recent studies have provided some evidence regarding the cost effectiveness of these agents. However, as the use of TNF inhibitors evolves--including their use in other systemic inflammatory diseases--this will be influenced by several factors including treatment of patients with early RA, longer term treatment, problems related to toxicity, quality of life, productivity, and market forces. Thus, pharmacoeconomic considerations are likely to remain a central factor in the use of novel therapies in rheumatology, and awareness about these will aid clinicians to select the most favourable therapies for their patients with arthritis.

Tutuncu Z, Kavanaugh A. · Division of Rheumatology, Allergy and Immunology, University of California-San Diego, La Jolla, CA 92093-0943, USA. · Clin Geriatr Med. · Pubmed #15911204 No free full text.

Abstract: This review summarizes the different aspects of rheumatoid arthritis and the spectrum of diseases that can present as rheumatoid arthritis-like arthritis in the elderly population. With the aging of Western population, different forms of inflammatory arthritis' prevalence and incidence are increasing in the elderly persons. Difficulties in establishing the diagnosis and introducing new treatment modalities in this patient group poses a great challenge for the clinicians. The management of inflammatory arthritis in the elderly requires special consideration in regard to the comorbidities and increased frequency of adverse events. There is definitely a substantial need for improving different aspects of diagnostic and therapeutic interventions that will reduce the impact of inflammatory arthritis in the growing elderly population.

Bieber J, Kavanaugh A. · The Center for Innovative Therapy, Division of Rheumatology, Allergy, and Immunology, The University of California San Diego School of Medicine, USA · Clin Exp Rheumatol. · Pubmed #15552526 No free full text.

Abstract: With the expanding use of biologic agents, in particular TNF inhibitors, tuberculosis and other opportunistic infections have become an important and growing concern in rheumatology. Clinicians using these therapies should have an understanding of the scope of the problem, the underlying scientific rationale, as well as the optimal approaches to screening, monitoring and treatment.

Pincus T, Sokka T, Kavanaugh A. · Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-4500, USA. · Clin Exp Rheumatol. · Pubmed #15552515 No free full text.

Abstract: Therapies for rheumatoid arthritis (RA) may be assessed according to relative levels of measures to compare efficacy to another therapy or to a placebo, as in the American College of Rheumatology (ACR) 20%, 50%, or 70% (ACR 20 ACR 50 and ACR 70) responses, or by absolute levels of measures, as in disease activity scores (DAS), ACR criteria for remission, or "target values" of specific measures. Regulatory considerations have emphasized primarily relative comparisons to a placebo or standard therapy, derived in part from the weak efficacy of traditional disease modifying anti-rheumatic drugs (DMARDs). While improvement compared to placebo certainly indicates efficacy, it is of concern that measures of inflammatory activity, such as swollen joints and the erythrocyte sedimentation rate (ESR), may be stable or improved over periods of 5-10 years, while measures of damage, such as joint deformity and radiographic changes, may progress over the same period in the same patients. These findings suggest that improvement at a level of 20% or 50% may deter but not prevent severe long-term outcomes of radiographic progression, functional declines, work disability, and premature mortality, seen in most patients until the middle 1990s. Outcomes appear to be improved at this time, associated with aggressive treatment strategies and more powerful therapies, including biologic agents. In the Finnish Rheumatoid Arthritis Combination Therapy Trial (FinRACo), no patient who was in remission after 6 months was receiving work disability payments 4 1/2 years later, compared to 22% of patients who had ACR 20 or 50 responses and 54% of patients who did not have ACR 20 responses after 6 months who were all receiving work disability payments after 5 years. These findings suggest that absolute targets, including remission, may be realistic contemporary goals, with aggressive treatment strategies and more effective DMARDs and biologic agents.

Lee SJ, Lenert L, Kavanaugh A. · Center for Innovative Therapy, UCSD, Division of Rheumatology, Allergy and Immunology, La Jolla, California 92093-0943, USA. · Clin Exp Rheumatol. · Pubmed #15552512 No free full text.

Abstract: Patient-derived measures have been increasingly recognized as a valuable means for monitoirng patients with rheumatoid arthritis. One advantage of this data is that it can be collected remotely. This would allow more frequent and more rapid assessments, which could optimize therapeutic intervention and patient outcome.

Pincus T, Sokka T, Kavanaugh A. · Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-4500, USA. · Clin Exp Rheumatol. · Pubmed #15552511 No free full text.

Abstract: Assessment of benefit/risk of therapies for any disease is best conducted according to quantitative data. In many diseases, such as hypertension or hyperlipidemia, a single quantitative measure serves as a "gold standard" for patient status, but no single measure can serve as a "gold standard' for all individual patients with rheumatoid arthritis (RA). Therefore, indices such as the American College of Rheumatology (ACR) Core Data Set and Disease Activity Score (DAS), are used in clinical trials and other clinical research. These indices include 3 types of measures, which are derived from a health professional [joint counts, global]; a laboratory [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)]; or a patient questionnaire [physical function, pain, global]. In most standard clinical care, the majority of clinicians do not collect joint count or patient questionnaire data at most visits. Therefore, assessment and management of most patients with RA is conducted empirically, with the only quantitative data from laboratory tests. Measures on a patient self-report questionnaire of physical function, pain, and global status, are as informative as joint counts, radiographic scores, laboratory tests, or any measure by a health professional to document status, estimate prognosis, and monitor responses to therapies. We suggest that quantitative measurement may be incorporated into standard clinical care most easily and effectively by asking each patient to complete a simple 1-page questionnaire at each visit to a rheumatologist.