Arthur Kavanaugh

La Jolla Institute for Allergy & Immunology, لا هویا, California, United States

Are you Arthur Kavanaugh?

Claim your profile

Publications (390)2187.68 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the efficacy and safety of ustekinumab through 2years in adult patients with active psoriatic arthritis (PsA). A total of 615 adult patients with active PsA were randomized to placebo, ustekinumab 45mg, or ustekinumab 90mg, at wks0, 4, and every 12 weeks through wk88 (last dose). At wk16, patients with <5% improvement in both tender/swollen joint counts entered blinded early escape (placebo to 45mg, 45mg to 90mg, 90mg to 90mg). All remaining placebo patients crossed over to ustekinumab 45mg at wk24. Clinical efficacy measures included: ≥20% improvement in the American College of Rheumatology criteria (ACR20), 28-joint count disease activity score using C-reactive protein (DAS28-CRP), and ≥75% improvement in psoriasis area and severity index (PASI75). Radiographic progression was evaluated using the van der Heijde-modified Sharp (vdH-S) score. At week100, ACR20, DAS28-CRP moderate/good response, and PASI75 rates ranged from 56.7%-63.6%, 71.9%-76.7%, and 63.9%- 72.5%, respectively, across treatment groups. In both ustekinumab groups, the median percent improvement in dactylitis and enthesitis was 100% at wk100. The mean changes in vdH-S from week52-100 were similar to those observed from wk0-52 in the ustekinumab groups. Through week108, 70.7% and 9.7% of patients had an AE or SAE, respectively. The rates and type of AEs were similar between the dose groups. Clinical and radiographic benefits from ustekinumab treatment were maintained through wk100 in PSUMMIT 1. No unexpected safety events were observed; the safety profile of ustekinumab in this population was similar to that previously observed in psoriasis patients treated with ustekinumab. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    06/2015; DOI:10.1002/acr.22645
  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess salivary gland ultrasonography (US) as a diagnostic tool for secondary Sjögren syndrome (sSS) in patients with rheumatoid arthritis (RA). Salivary gland US images from 30 patients with RA were graded using a validated semiquantitative scoring system. Sicca symptoms, oral health, and RA disease activity were assessed. US changes consistent with SS were found in 40% of patients. Patients with higher US scores had more sicca symptoms as well as higher RA activity and poorer oral health. Salivary gland US may aid the diagnosis of sSS in patients with RA.
    The Journal of Rheumatology 05/2015; DOI:10.3899/jrheum.141149 · 3.17 Impact Factor
  • Minyoung Her, Arthur Kavanaugh
    [Show abstract] [Hide abstract]
    ABSTRACT: With the advent of biologic agents such as TNF inhibitors, the treatment paradigm for autoimmune systemic inflammatory diseases has progressed tremendously. Despite some distinct treatments, similarities exist in several aspects of the treatment of autoimmune inflammatory diseases such as rheumatoid arthritis (RA), IBD and psoriasis. With a so-called treat-to-target strategy aiming at remission, the intensive and early application of disease-modifying antirheumatic drugs within a 'window of opportunity', and in combination with TNF inhibitors, has become the overarching principle of RA therapy. In this Perspective, the concept of treatment approaches using immunomodulatory agents and the latest advances of therapies in autoimmune systemic inflammatory diseases, especially RA, are overviewed from a rheumatology perspective to provide insights into possible approaches to the treatment of inflammatory gastrointestinal disease.
    Nature Reviews Gastroenterology &#38 Hepatology 04/2015; 12(6). DOI:10.1038/nrgastro.2015.65 · 10.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The main objective of this study was to compare disease burden in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (ax-SpA). In this cross-sectional study, all the RA (1093), PsA (365) and ax-SpA (333) patients who visited the out-patient clinic of the Hospital of Southern Norway Trust during the year 2013 were included; the RA patients all had a RA diagnosis verified by the treating rheumatologist, the PsA patients all fulfilled the ClASsification for Psoriatic ARthritis (CASPAR) criteria and the ax-SpA patients all fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for ax-SpA. Patient-reported health status, demographic variables, medications, and composite scores of disease activity were assessed. The main analyses were performed using General Linear Models adjusted for age, sex and multiple comparisons. Correlation analyses were performed using Spearman's rho. The reported pain, joint pain, patient's global assessment and fatigue were similar in PsA and ax-SpA, but significantly lower in RA. The 28-joint Disease Activity Score (DAS28) (0.3±0.1, p = 0.003), Clinical Disease Activity Index (CDAI) (1.0±0.4, p = 0.028) and Routine Assessment of Patient Index Data 3 (RAPID3) (0.4±0.1, p = 0.004) were all significantly higher in PsA vs. RA. RAPID3 showed moderate to high correlation with DAS28 (rho = 0.521, p<0.001) and CDAI (rho = 0.768, p<0.001) in RA and PsA, and with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (rho = 0.902, p<0.001) and Bath Ankylosing Spondylitis Functional Index (BASFI) (0.865, p<0.001) in ax-SpA and PsA. In conclusion, patient- reported outcome measures were similar in our population of PsA and ax-SpA patients, but significantly lower for the RA patients. Composite disease activity measures were lower in RA than in PsA and ax-SpA, but the magnitude of these differences was small and probably not of clinical significance. Our study indicates that disease burden in RA, PsA and ax-SpA may be more similar than previously demonstrated.
    PLoS ONE 04/2015; 10(4):e0123582. DOI:10.1371/journal.pone.0123582 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adalimumab (ADA) was evaluated for its efficacy in patients with moderate to severely active psoriatic arthritis (PsA) and for the presence of correlations in disease change variables. Patients with inadequate response to standard PsA therapy were given 40 mg of ADA every other week for up to 12 weeks or 20 weeks. Outcome variables encompassed tender joint count (TJC), swollen joint count (SJC), physician's global assessment (PGA) of psoriasis, Health Assessment Questionnaire (HAQ), patient's global assessment (PtGA) of disease activity and pain, C-reactive protein, as well as composite measures of disease activity. Patients with inactive skin disease symptoms at baseline were excluded from the remission analyses. Of 268 patients with active baseline joint and skin disease and data available at Week 12 following open-label ADA therapy, 73 achieved joint remission (27.2%, TJC ≤ 1 + SJC ≤ 1) and 144 achieved skin remission criteria (53.7%, PGA = clear/almost clear). Simultaneous joint and skin remission criteria were achieved in 16.0% and 24.8% of patients at weeks 12 and 20, respectively. In patients who did not achieve skin and/or joint remission, 12-week ADA treatment improved mean clinical and functional scores. Joint remission was more frequently associated with achieving clinically relevant outcomes including HAQ, PtGA disease activity, and PtGA pain compared to skin remission. No correlation between improvement in skin and joint disease was observed. ADA was effective in achieving strict criteria for remission in joint or skin disease in many patients with active PsA within 12 weeks and sustained through 20 weeks. (NCT00235885).
    The Journal of Rheumatology 04/2015; 42(6). DOI:10.3899/jrheum.140312 · 3.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To compare the presence of cardiovascular (CV) risk factors and established CV disease in patients with psoriatic arthritis (PsA) and the general population and to compare the 10-year risk of a fatal CV event calculated by the Systematic Coronary Risk Evaluation (SCORE) algorithm. Patients with PsA (n=338) and controls (n=50 468) were recruited from the Nord-Trøndelag Health Study 3. Age-adjusted and sex-adjusted prevalence rates of CV risk factors and comorbidity were calculated and the SCORE algorithm was applied. There was an increased prevalence of angina pectoris (5.0% vs 3.6%, p=0.01), history of percutaneous coronary intervention (2.4% vs 1.4%, p=0.04), hypertension (45.3% vs 39.3%, p=0.01), obesity (32.0% vs 22.4%) and tobacco smoking (21.3% vs 16.4%, p=0.02) in patients with PsA compared with controls. Patients with PsA had elevated levels of C reactive protein (CRP; p<0.001), body mass index (BMI; p<0.001) and triglycerides (p=0.01). The median calculated CV risk in patients with PsA was low and comparable with controls (0.87 vs 0.83, p=0.24). The distribution across CV risk classes was similar among patients with PsA and controls. Patients with PsA have a higher risk of CV disease than the background population, although there was no difference between groups in 10-year risk of a fatal CV event estimated by SCORE. However, patients with PsA had elevated levels of CV risk factors not included in the SCORE algorithm, such as BMI, triglycerides and CRP. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the rheumatic diseases 03/2015; DOI:10.1136/annrheumdis-2014-206824 · 9.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Evaluate long-term outcomes in psoriatic arthritis (PsA) patients who achieved or did not achieve minimal disease activity (MDA) through 5 years of golimumab treatment in GO-REVEAL. The GO-REVEAL trial was a phase 3, randomized, double-blind trial with placebo-control through wk24 followed by an open-label extension of golimumab 50/100mg treatment up to 5 years. In these post-hoc analyses, MDA was defined by the presence of ≥5/7 PsA outcome measures (≤1 swollen joint, ≤1 tender joint, Psoriasis Area and Severity Index [PASI] ≤1, patient pain score ≤15, patient global disease activity [PtGA] score ≤20 (0-100), Health Assessment Questionnaire-Disability Index [HAQ-DI] ≤0.5, and ≤1 tender enthesis point). Treatment with golimumab yielded significantly higher MDA response rates versus patients randomized to placebo at wk14 (23.5% vs. 1.0%; p<0.0001), wk24 (28.1% vs. 7.7%; p<0.0001), and wk52 (42.4% vs. 30.2%; p=0.037). MDA was achieved at least once by ∼50% of golimumab-treated patients overall. Irrespective of treatment randomisation, achievement of MDA at ≥3 and ≥4 consecutive visits was associated with significantly less radiographic progression and more improvement in MDA components allowing specific assessment of physical function (HAQ-DI) and overall disease activity (PtGA) at wk256 versus patients not achieving MDA. Logistic regression analyses indicated that a 1-unit higher baseline HAQ-DI score yielded a significantly lower likelihood of achieving MDA at ≥3 (odds ratio [95%CI]=0.514 [0.321,0.824]; p=0.006) and ≥4 (odds ratio [95%CI]=0.480 [0.290,0.795]; p=0.004) consecutive visits. Among golimumab-treated PsA patients, better long-term functional improvement, patient global assessment, and radiographic outcomes were observed when patients achieved persistent MDA. This article is protected by copyright. All rights reserved. © 2015 American College of Rheumatology.
    Arthritis Care and Research 03/2015; DOI:10.1002/acr.22576 · 4.04 Impact Factor
  • Renata Baronaite Hansen, Arthur Kavanaugh
    [Show abstract] [Hide abstract]
    ABSTRACT: Certolizumab pegol (CZP) is a TNF-α inhibitor approved for the treatment of psoriatic arthritis in 38 countries, including many European countries and the USA. It is a pegylated humanized anti-TNF-α antigen-binding fragment, administered subcutaneously. As other TNF-α antibodies, CZP binds to and neutralizes both soluble and membrane TNF-α. In contrast to whole antibodies and etanercept, CZP does not activate antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity, as it does not have an Fc piece. CZP showed efficacy in improving skin scores and patient reported outcomes in a Phase II study of 176 adults with moderate-to-severe plaque psoriasis. In a Phase III study of CZP in 409 psoriatic arthritis patients, CZP treatment resulted in improvements in peripheral arthritis, as well as dactylitis, enthesitis, nail disease and quality of life. The safety profile of CZP appears to be similar to that of other TNF-α inhibitor.
    Expert Review of Clinical Immunology 02/2015; 11(3):1-12. DOI:10.1586/1744666X.2015.1009897 · 3.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, over 52 weeks in patients with active psoriatic arthritis (PsA) despite prior treatment. Patients were randomized to placebo (n = 168), apremilast 20 mg BID (n = 168), or apremilast 30 mg BID (n = 168). Patients whose swollen and tender joint counts had not improved by ≥ 20% at Week 16 were considered nonresponders and were required to be re-randomized (1:1) to apremilast 20 mg BID or 30 mg BID if they were initially randomized to placebo, or continued their initial treatment of apremilast dose. At Week 24, all remaining patients treated with placebo were re-randomized to apremilast 20 mg BID or 30 mg BID. An American College of Rheumatology 20 (ACR20) response at Week 16 was attained by significantly more patients receiving apremilast 20 mg BID (30.4%, p = 0.0166) or 30 mg BID (38.1%, p = 0.0001) than placebo (19.0%). Among patients receiving apremilast continuously for 52 weeks (n = 254), ACR20 response at Week 52 was observed in 63.0% (75/119, 20 mg BID) and 54.6% (71/130, 30 mg BID) of patients. Response was also maintained across secondary outcomes, including measures of PsA signs and symptoms, skin psoriasis severity, and physical function. The nature, incidence, and severity of adverse events were comparable over the 24-week and 52-week periods. The most common adverse events, diarrhea and nausea, generally occurred early and were self-limited. Continuous apremilast treatment resulted in sustained improvements in PsA for up to 52 weeks. Apremilast had an acceptable safety profile and was generally well tolerated. Clinical trial registration: NCT01172938.
    The Journal of Rheumatology 01/2015; 42(3). DOI:10.3899/jrheum.140647 · 3.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is increasing interest in discontinuing biological therapies for patients with rheumatoid arthritis (RA) achieving good clinical responses, provided patients maintain clinical benefit. We assessed patients with RA from the Corrona registry who discontinued treatment with their first tumour necrosis factor inhibitor (TNFi) while in low-disease activity (LDA) or lower levels of disease activity. Patients were followed until they lost clinical benefit, defined as increased disease activity or change in RA medications. Duration of maintenance of clinical benefit was estimated using the Kaplan-Meier method. Cox proportional hazard models were assessed to identify factors related to maintenance of benefit. We identified 717 eligible patients with RA from 35 656 in the Corrona registry. At discontinuation, patients had a median RA duration of 8 years, mean clinical disease activity score of 4.3±0.11; 41.8% were using TNFi as monotherapy. 73.4% of patients maintained benefit for >12 months after discontinuing therapy and 42.2% did so through 24 months. Factors predictive of maintaining clinical benefit in multivariate analysis included lower disease activity, less pain and better functional status at the time of TNFi discontinuation. Among 301 patients initiating their first TNFi within the registry, faster responders (ie, those who achieved LDA in 4 months or less) did better than slower responders (HR 1.54 (95% CI 1.17 to 2.04)). RA disease duration did not affect maintenance of clinical benefit. Discontinuation of a first course of TNFi may be associated with persistent clinical benefit. Half of patients maintained response through 20 months. Several patient characteristics may help predict persistent benefit. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the Rheumatic Diseases 12/2014; 74(6). DOI:10.1136/annrheumdis-2014-206435 · 9.27 Impact Factor
  • Source
    12/2014; 66(12). DOI:10.1002/acr.22404
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). The pathways affected by tofacitinib and the effects on gene expression in situ are unknown. Therefore, tofacitinib effects on synovial pathobiology were investigated.
    Annals of the Rheumatic Diseases 11/2014; 72(Suppl 3). DOI:10.1136/annrheumdis-2014-206028 · 9.27 Impact Factor
  • 11/2014; 67(3). DOI:10.1002/acr.22516
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nail involvement in psoriatic diseases causes significant physical and functional disabilities. Evaluating, measuring, and treating nail involvement is important in improving the health outcomes and quality of life among patients with psoriasis and psoriatic arthritis (PsA). We performed a systematic analysis of the literature on nail psoriasis to help inform an update of treatment recommendations by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).
    The Journal of Rheumatology 11/2014; 41(11):2306-14. DOI:10.3899/jrheum.140881 · 3.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Psoriatic arthritis (PsA) is a chronic systemic inflammatory disorder characterized by the association of arthritis and periarticular inflammation in patients with psoriasis. In addition to a heterogeneous and variable clinical course, PsA is complex and multifaceted and may include prominent involvement in the peripheral and axial diarthrodial joints, the skin and nails, and in periarticular structures such as entheses. Simultaneous inflammation in the skin and musculoskeletal structures in a single patient, a relatively common scenario, often leads to marked decrease in function and quality of life. Thus, it is essential for the clinician to document the extent of disease involvement and craft a therapeutic plan that addresses the different domains of disease. In an effort to update previous treatment recommendations developed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), several evidence-based, systemic reviews of therapies for PsA were completed, analyzed, and circulated for consensus.
    The Journal of Rheumatology 11/2014; 41(11):2273-2276. DOI:10.3899/jrheum.140875 · 3.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective. Our 24-week study (NCT01197755; OSKIRA-3) compared the efficacy and safety of fostamatinib versus placebo in patients taking background methotrexate treatment with active rheumatoid arthritis (RA) and an inadequate response to a single tumor necrosis factor-alpha antagonist. Methods. Adult patients were randomized (1: 1: 1) to fostamatinib [100 mg bid for 24 weeks (n = 105; Group A)], or 100 mg bid for 4 weeks, then 150 mg qd (n = 108; Group B), or to placebo (n = 110; Group C) for 24 weeks. Nonresponders at Week 12 could enter a longterm extension study. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at Week 24. Results. Baseline characteristics were well balanced. Significantly more patients in fostamatinib Group A (36.2%; p = 0.004), but not B (27.8%; p = 0.168), achieved ACR20 at Week 24 versus placebo (21.1%). Frequently reported adverse events were diarrhea, hypertension, and headache. Elevated blood pressure (>= 140/ 90 mm Hg) at >= 1 visit was observed in 46.7%, 51.9%, and 26.6% of patients, respectively. There were 2 deaths in the study, 1 in Group B and 1 in the placebo group. Conclusion. Fostamatinib 100 mg bid, but not fostamatinib 100 mg bid for 4 weeks then 150 mg qd, achieved statistical improvements in ACR20 at 24 weeks versus placebo. Because of efficacy and safety results from the phase III clinical program, the companies developing fostamatinib have decided not to study it further in RA at this time.
    The Journal of Rheumatology 09/2014; 41(11). DOI:10.3899/jrheum.140238 · 3.17 Impact Factor
  • Renata Baronaite Hansen, Arthur Kavanaugh
    [Show abstract] [Hide abstract]
    ABSTRACT: Current treatment options for patients with active psoriatic arthritis (PsA) include synthetic disease-modifying antirheumatic drugs and biologic agents. Propelled by increased understanding of immunopathogenesis of PsA, new therapeutic agents targeting different biologic pathways have been evaluated. This article discusses novel small-molecule, orally available treatments that are currently in clinical development for the treatment of psoriasis and PsA. This includes the phosphodiesterase 4 inhibitor apremilast and Janus kinase (JAK) inhibitors. Apremilast has demonstrated significant improvements in patients with moderate to severe psoriasis and PsA in phase II and III clinical trials and has recently been approved for the treatment of PsA. Tofacitinib, an oral inhibitor of JAK3, JAK1, and, to a lesser degree, JAK2, approved for the treatment of rheumatoid arthritis in several countries, has demonstrated positive results in psoriasis in phase II studies. Studies in PsA are ongoing. With these new developments, treatment options will continue to improve in the future.
    Current Rheumatology Reports 09/2014; 16(9):443. DOI:10.1007/s11926-014-0443-6 · 2.45 Impact Factor
  • Clinical and experimental rheumatology 09/2014; 32 Suppl 85(5):1. · 2.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study assessed the impact of simultaneous achievement of clinical, functional and structural efficacy, herein referred to as comprehensive disease control (CDC), on short-term and long-term work-related outcomes, health-related quality of life (HRQoL), pain and fatigue.
    Annals of the Rheumatic Diseases 08/2014; DOI:10.1136/annrheumdis-2014-205302 · 9.27 Impact Factor
  • DoQuyen Huynh, Arthur Kavanaugh
    [Show abstract] [Hide abstract]
    ABSTRACT: PsA is a systemic inflammatory condition that affects 20-30% of patients with psoriasis. It is characterized by potential involvement of diverse tissues, including peripheral and axial joints, enthesitis, dactylitis and skin and nail disease. The degree of involvement in each domain can vary over time in individual patients and can differ substantially between PsA patients. The clinical heterogeneity along with the varying extent of severity and activity can pose significant challenges to treatment. Although some studies had suggested immunopathophysiological similarities between PsA and RA, more recently important distinctions have been defined. Similarly, although some immunomodulatory therapies have proved effective for both PsA and RA, recent data suggest distinct responses to certain targeted therapies. Herein, current DMARDs and biologic agents as well as the potential role of emerging therapeutics will be reviewed.
    Rheumatology (Oxford, England) 08/2014; 54(1). DOI:10.1093/rheumatology/keu237 · 4.44 Impact Factor

Publication Stats

12k Citations
2,187.68 Total Impact Points

Institutions

  • 2003–2015
    • La Jolla Institute for Allergy & Immunology
      • Division of Cell Biology
      لا هویا, California, United States
  • 2000–2015
    • University of California, San Diego
      • Division of Rheumatology, Allergy and Immunology
      San Diego, California, United States
  • 2014
    • University Center Rochester
      Рочестер, Minnesota, United States
  • 2013
    • University of Toronto
      Toronto, Ontario, Canada
    • Medical University of Vienna
      Wien, Vienna, Austria
  • 2005–2013
    • Leiden University Medical Centre
      • Department of Rheumatology
      Leyden, South Holland, Netherlands
    • Toronto Western Hospital
      Toronto, Ontario, Canada
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      Erlangen, Bavaria, Germany
  • 2012
    • Inje University
      Kŭmhae, South Gyeongsang, South Korea
  • 2011
    • VA San Diego Healthcare System
      San Diego, California, United States
  • 2008–2009
    • National University (California)
      San Diego, California, United States
    • CSU Mentor
      Long Beach, California, United States
    • University of Otago
      • Department of Medicine (Dunedin)
      Taieri, Otago, New Zealand
    • Goethe-Universität Frankfurt am Main
      Frankfurt, Hesse, Germany
  • 2007
    • Johnson & Johnson
      New Brunswick, New Jersey, United States
  • 2006
    • Radboud University Medical Centre (Radboudumc)
      Nymegen, Gelderland, Netherlands
    • Albany Medical College
      Albany, New York, United States
    • University of San Diego
      San Diego, California, United States
  • 2004–2006
    • Stanford University
      • • Division of Rheumatology
      • • Division of Immunology
      Palo Alto, CA, United States
  • 1991–2002
    • University of Texas Southwestern Medical Center
      • Department of Internal Medicine
      Dallas, TX, United States
  • 2001
    • Virginia Mason Medical Center
      Seattle, Washington, United States
  • 1994–2000
    • University of Texas at Dallas
      Richardson, Texas, United States