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Biomedical subjects

Arthur Kavanaugh

Publications and source records attributed to Arthur Kavanaugh.

At least 19 recordsLinked to original sources
PubMed2007

The modified Nail Psoriasis Severity Index: validation of an instrument to assess psoriatic nail involvement in patients with psoriatic arthritis.

OBJECTIVE: Patients with psoriasis and psoriatic arthritis (PsA) commonly have nail involvement. There is no validated psoriatic nail assessment tool. Recently, investigators developed the Nail Psoriasis Severity Index (NAPSI). Beginning with NAPSI, our goal was to validate a psoriatic nail assessment tool for use in clinical trials, and investigate correlations between nail and other PsA features. METHODS: Fingernails of 29 patients with PsA were photographed and scored. Clinical data were collected. Using the original NAPSI, analysis revealed high interrater variability of nail scores. Twenty patients' photographs were regraded using the modified NAPSI (mNAPSI). RESULTS: The mNAPSI scores had excellent interrater reliability (Cronbach's alpha 0.98). Nail scores and physicians' global nail severity visual analog scores showed good inter- and intrarater correlations (Spearman's rho 0.85 and 0.90-0.99, respectively; p < 0.01). Several clinical measures correlated with nail scores. CONCLUSION: The mNAPSI demonstrated excellent interrater reliability and construct validity, and may be a valuable tool.

Adult↗
PubMed2006

Effect of infliximab therapy on employment, time lost from work, and productivity in patients with psoriatic arthritis.

OBJECTIVE: To examine the effect of infliximab on employment status, time lost from work, and productivity in a double-blind, placebo-controlled study of patients with active psoriatic arthritis (PsA). METHODS: Two hundred adult patients with PsA were randomized to intravenous infusions of either infliximab 5 mg/kg or placebo at Weeks 0, 2, 6, 14, and 22, with early escape at Week 16. Employment status, workdays missed, and productivity were assessed at baseline and at Week 14. The effect of PsA on daily productivity was assessed using a visual analog scale. RESULTS: At baseline, similar percentages of patients in both treatment groups were employed and similar percentages missed workdays; the mean productivity score at baseline was similar between groups (roughly 3 on a scale of 0 to 10). At Week 14, median productivity increased significantly in the infliximab group compared with the placebo group (67.5% vs 9.2%; p < 0.0001). Compared with the placebo group, higher proportions of patients in the infliximab group improved employment status from unemployed at baseline to employed at Week 14 (11.5% vs 0%; p = 0.084) and from part-time to full-time employment (30.0% vs 10.0%; p = 0.582). Among patients employed at baseline and Week 14, a lower proportion of patients in the infliximab group than in the placebo group had missed workdays in the 4 weeks prior to Week 14 (p = 0.138). CONCLUSION: After 14 weeks of treatment, infliximab improved productivity in patients with active PsA. There was also a trend toward increased employment and reduced time lost from work for patients treated with infliximab.

Adult↗
PubMed2006

The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial.

OBJECTIVE: To examine the efficacy and safety of different rituximab doses plus methotrexate (MTX), with or without glucocorticoids, in patients with active rheumatoid arthritis (RA) resistant to disease-modifying antirheumatic drugs (DMARDs), including biologic agents. METHODS: A total of 465 patients were randomized into 9 treatment groups: 3 rituximab groups (placebo [n = 149], 500 mg [n = 124], or 1,000 mg [n = 192] on days 1 and 15) each also taking either placebo glucocorticoids, intravenous methylprednisolone premedication, or intravenous methylprednisolone premedication plus oral prednisone for 2 weeks. All patients received MTX (10-25 mg/week); no other DMARDs were permitted. RESULTS: Significantly more patients who received 2 500-mg or 2 1,000-mg infusions of rituximab met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 24 (55% and 54%, respectively) compared with placebo (28%; P < 0.0001). ACR50 responses were achieved by 33%, 34%, and 13% of patients, respectively (P < 0.001), and ACR70 responses were achieved by 13%, 20%, and 5% of patients (P < 0.05). Changes in the Disease Activity Score in 28 joints (-1.79, -2.05, -0.67; P < 0.0001) and moderate to good responses on the European League Against Rheumatism criteria (P < 0.0001) reflected the ACR criteria responses. Glucocorticoids did not contribute significantly to the primary efficacy end point, ACR20 response at 24 weeks. Intravenous glucocorticoid premedication reduced the frequency and intensity of first infusion-associated events; oral glucocorticoids conferred no additional safety benefit. Rituximab was well tolerated; the type and severity of infections was similar to those for placebo. CONCLUSION: Both rituximab doses were effective and well tolerated when added to MTX therapy in patients with active RA. The primary end point (ACR20 response) was independent of glucocorticoids, although intravenous glucocorticoid premedication improved tolerability during the first rituximab infusion.

Antibodies, Monoclonal↗
PubMed2006

4. Autoimmunity, vasculitis, and autoantibodies.

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.

Animals↗
PubMed2006

The pharmacoeconomics of newer therapeutics for rheumatic diseases.

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.

Antirheumatic Agents↗
PubMed2006

Recent developments in diet and gout.

PURPOSE OF REVIEW: Gout is the most common inflammatory arthritis in men, affecting approximately 1-2% of adult men in Western countries. United States gout prevalence has approximately doubled over the past two decades. In recent years, key prospective epidemiological and open-labeled dietary studies, coupled with recent advances in molecular biology elucidating proximal tubular urate transport, have provided novel insights into roles of diet and alcohol in hyperuricemia and gout. This review focuses on recent developments and their implications for clinical practice, including how we advise patients on appropriate diets and alcoholic beverage consumption. RECENT FINDINGS: Studies have observed an increased risk of gout among those who consumed the highest quintile of meat, seafood and alcohol. Although limited by confounding variables, low-fat dairy products, ascorbic acid and wine consumption appeared to be protective for the development of gout. SUMMARY: The most effective forms of dietary regimen for both hyperuricemia and gout flares remains to be unidentified. Until confirmed by a large, controlled study, it is prudent to advise patients to consume meat, seafood and alcoholic beverages in moderation, with special attention to food portion size and content of non-complex carbohydrates which are essential for weight loss and improved insulin sensitivity.

Beer↗
PubMed2006

Update on anti-tumor necrosis factor therapy in the spondyloarthropathies including psoriatic arthritis.

PURPOSE OF REVIEW: The introduction of the macromolecule tumor necrosis factor inhibitors etanercept, infliximab, and adalimumab has proven very successful for patients with spondyloarthropathies. The greatest experience has accrued in ankylosing spondylitis and psoriatic arthritis. This paper reviews data from clinical trials with tumor necrosis factor inhibitors in ankylosing spondylitis and psoriatic arthritis. RECENT FINDINGS: Treatment with tumor necrosis factor inhibitors has not only resulted in substantial improvement in the signs and symptoms of arthritis but has also improved functional status and quality of life in ankylosing spondylitis and psoriatic arthritis. Improvements in associated inflammatory features, such as enthesitis in psoriatic arthritis and uveitis in ankylosing spondylitis, have also been observed. Moreover, treatment has been shown to inhibit the progression of radiographic joint damage in psoriatic arthritis and to attenuate spinal inflammation in ankylosing spondylitis. The notable success of tumor necrosis factor inhibitors has not only changed the treatment paradigms for these conditions but has also stimulated studies aimed at improving diagnosis, prognostic stratification, and other aspects of clinical care. SUMMARY: The introduction of tumor necrosis factor inhibitors for patients with ankylosing spondylitis and psoriatic arthritis has had a tremendous impact on daily clinical care.

Adalimumab↗
PubMed2005

Psoriatic arthritis: pathogenesis and novel immunomodulatory approaches to treatment.

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy characterized by the association of arthritis and psoriasis. PsA runs a variable course, from mild synovitis to severe, progressive, erosive arthropathy. The pathogenesis of PsA involves alteration in the components of the immune response, although the exact cause of PsA is unknown. A number of patients with severe peripheral arthritis fail to respond to standard conventional therapy. Advances in biotechnology and in our understanding of the immunopathogenesis of PsA have led to great interest and progress in regards to biologic treatments for PsA. Notable success achieved with recently introduced biologic therapies has paved the way for further research and development of additional therapies that should improve outcomes for affected patients.

Journal Article↗
PubMed2005

Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT).

OBJECTIVE: To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis (PsA). METHODS: One hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug (DMARD) had failed were recruited into this investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial. During the initial blinded portion of the study, patients received infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and 14. After week 16, patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50, while patients initially randomized to infliximab continued to receive active treatment at the same dose through week 50. The primary efficacy outcome was achievement of the American College of Rheumatology 20% criteria for improvement in rheumatoid arthritis (ACR20) at week 16. Additional predefined clinical efficacy assessments included the Psoriasis Area and Severity Index (PASI) score, the ACR50 and ACR70 criteria, the Disease Activity Score in 28 joints, the Health Assessment Questionnaire, ratings of enthesitis and dactylitis, and the Psoriatic Arthritis Response Criteria score. RESULTS: The proportion of infliximab-treated patients who achieved an ACR20 response at week 16 (65%) was significantly higher than the proportion of placebo-treated patients who achieved this response (10%). In addition, 46% of infliximab-treated patients achieved an ACR50 response, and 29% achieved an ACR70 response; no placebo-treated patient achieved these end points. Among patients who had PASI scores of >/=2.5 at baseline, 68% of infliximab-treated patients achieved improvement of >/=75% in the PASI score at week 16 compared with none of the placebo-treated patients. Continued therapy with infliximab resulted in sustained improvement in articular and dermatologic manifestations of PsA through week 50. The incidence of adverse events was similar between the treatment groups. CONCLUSION: Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis, psoriasis, dactylitis, and enthesitis in patients with active PsA that had been resistant to DMARD therapy. With continued infliximab treatment, benefits were sustained through 50 weeks. The benefit-to-risk ratio appeared favorable in this study population.

Adult↗
PubMed2005

Fcgamma receptor type IIIA polymorphisms influence treatment outcomes in patients with inflammatory arthritis treated with tumor necrosis factor alpha-blocking agents.

OBJECTIVE: To determine whether polymorphisms in Fcgamma receptor type IIIA (FcgammaRIIIA) correlate with clinical efficacy in patients with rheumatoid arthritis (RA) and patients with psoriatic arthritis (PsA) being treated with tumor necrosis factor alpha (TNFalpha) inhibitors. METHODS: The study group comprised 30 patients with RA and 5 patients with PsA. Patients were classified as being very good responders (n = 23) or nonresponders (n = 12) to therapy with TNF blocking agents. Whole blood was obtained from all patients, and DNA was extracted for FcgammaRIIIA analysis. The FcgammaRIIIA-158 polymorphism was determined using an allele-specific polymerase chain reaction assay. RESULTS: The distribution of FcgammaRIIIA-158 genotypes was as follows: for F homozygous (F/F), 31.5%; for V homozygous (V/V), 11.5%; and for V/F heterozygous (V/F), 57%. Among very good responders, the distribution of alleles was as follows: for F/F, 48%; for V/V, 13%; and for V/F, 39%. Among nonresponders, the distribution of alleles was as follows: for F/F, 0%; for V/V, 8%; and for V/F, 92%. The low-affinity F/F homozygous genotype was found to be significantly associated with response to TNF inhibitor therapy (P < 0.01 by Fisher's exact test). CONCLUSION: These results suggest that FcgammaRIIIA-158 polymorphisms may affect the outcome of treatment with TNF blocking agents. Better understanding of the factors affecting responses to these agents could result in improved outcomes of treatment.

Adalimumab↗
PubMed2005

Outcome measures in psoriatic arthritis.

Psoriatic arthritis (PsA) is an important condition that significantly impacts affected patients. The introduction of novel therapeutic agents for PsA has generated great interest in clinical trials as well as in clinical care. Therefore, there is a great need for standardized outcome measures that can accurately assess the activity of disease and response to therapy. Because it is a heterogeneous and multifaceted condition, defining outcome measures has been a challenge. To date, such measures have largely been adapted from other similar diseases. With further research, the most appropriate outcome measures specific for PsA will be delineated.

Anti-Inflammatory Agents↗
PubMed2005

Rheumatic disease in the elderly: rheumatoid arthritis.

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.

Age of Onset↗
PubMed2005

Adverse reactions to biologic agents: focus on autoimmune disease therapies.

In recent years, a growing number of biologic agents have become available for the treatment of various autoimmune, neoplastic, cardiovascular, infectious, allergic, and other conditions. Their introduction has resulted in marked clinical improvements for many patients. Nevertheless, a variety of adverse reactions have been observed with these agents. Because many biologic agents affect key components of sundry physiologic processes, a number of important adverse reactions might be considered mechanism based. Other adverse reactions relate to the agent rather than the target, including hypersensitivity reactions. As a means of exploring the spectrum of potential adverse effects related to biologic agents and their mechanisms, this review will focus on the experience to date with biologic agents used for the treatment of autoimmune disorders. An understanding of the spectrum and types of reactions possible with biologic agents, as well as the mechanisms underlying such reactions, will help clinicians use them optimally.

Abatacept↗
PubMed2005

Novel therapies for rheumatoid arthritis.

Recent years have witnessed significant advancements in the therapeutic approach to rheumatoid arthritis. The introduction of biologic agents, in particular inhibitors of tumor necrosis factor (TNF), has ushered a new era in which the goal of therapy has become achieving very low levels of disease activity. Success achieved with the TNF inhibitors has reinvigorated research into targeting other componenets of the dysregulated immune system in RA. A number of approaches, targeting various cytokines, other inflammatory mediators, and populations of immunocompetent cells, seem promising.

Journal Article↗
PubMed2005

What to do with TNF failures.

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.

Abatacept↗
PubMed2005

Factors affecting rheumatoid arthritis patients' decisions to participate in clinical trials.

OBJECTIVE: To delineate the personal, psychosocial, and disease-related factors that may influence rheumatoid arthritis (RA) patients' decisions to participate in clinical trials. METHODS: A total of 191 patients with RA were asked to participate in this survey. The questionnaire collected information on demographics, RA disease-related factors, and the importance of several factors that might influence patients' willingness to participate in clinical trials. Patients were then asked if they would consider participating in a hypothetical study. RESULTS: Participants were 88% female with a mean age of 40.5 years. The ethnic composition was 57% Hispanic, 25% Caucasian, 12% Asian, and 6% African American, with 71% having a family income < $20,000/year. Factors that patients considered important for participation in a clinical study included: the opportunity to help others, the possibility of improved health, early access to new therapy, the availability of free treatments, unknown side effects of the study drug, and the need to stop current therapy. There were strong correlations between the rank order importance weights between Hispanics and Caucasians, suggesting fundamental similarities in preferences. The most important factor was the opportunity to help others. In general, the more important factors were associated with preferences for trial participation. CONCLUSION: This questionnaire identified factors that may affect RA patients' willingness to participate in a study. Patient participation in trials is driven by diverse factors that include altruism and the opportunity for healthcare and improved health. Consideration of these factors may facilitate the inclusion of more diverse patient populations into trials and enhance the applicability of trial results.

Adult↗