Proceedings of the 2012 Rheumatology Winter Clinical Symposia

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    ncreasing numbers of rheumatologists in NorthAmerica have begun to evaluate whether the use ofmusculoskeletal ultrasound will enhance the overall

    e of their patients. To date, this has been focusedinly on the diagnosis of patients with inflammatoryhritis such as rheumatoid arthritis (RA) as well as mon-ring the response to therapy. Similar to magnetic reso-nce imaging and computed tomography scanning, ul-sound is able to detect changes in the synovium,tilage, and bone but at a much lower cost and without

    the synovium and bone, musculoskeletal ultrasound is agreat clinical tool that may be used in the diagnosis andmonitoring of other rheumatic conditions. Some of theconditions include seronegative arthropathies (eg, psori-atic arthritis, enthesitis), crystalline arthritis (eg, gout,pseudogout), polymyalgia rheumatica, temporal arteritis,scleroderma, Sjgrens syndrome, and fibromyalgia.

    Although the use of ultrasound in some of the aboveconditions is still in the early stages of clinical develop-ment, the use of more sensitive ultrasound transducersand a portable ultrasound machine will make these andother rheumatic conditions more readily assessable to thepracticing rheumatologists and to other physicians treat-ing patients with musculoskeletal disorders.A.F. Wells


    Idiopathic inflammatory myositis is a rare disorder thataffects 2 to 7 persons per million each year. Although thehistoric Bohan and Peter classification system remainsinstructive, new criteria and classifications have been fos-tered by the identification of well-characterized autoan-tibody subsets, including the antisynthetase antibodysyndrome. This overview also focuses on several un-usual myopathic disorders, including orbital myositis,

    SD Department of Medicine, La Jolla, CA.rmatology and Laser Center of Maui, Maui, Hawaii.partment of Medicine, Baylor Research University, Dallas, TX.partment of Medicine, Drexel University college of Medicine, Philadelphia, PA.partment of Medicine, University of Texas Southwestern Medical Center, Dallas,.C Medical School, Los Angeles, CA.ivision of Immunology/Rheumatology, Standford University, Palo Alto, CA.epartment of Medicine, Northwestern University School of Medicine, Chicago,

    osalind Franklin University of Medicine and Science, Chicago, IL.ddress reprint requests to John J. Cush, MD, Baylor Research Institute, 9900 N.tral Expressway, Suite 550, Dallas, TX 75231. E-mail:

    9239-0172/12/$-see front matter 2012 Elsevier Inc. All rights reserved.Rheumatology Wint

    Arthur Kavanaugh, MD,* GeorgeMartin J. Bergman, MD,

    Orrin M. Troum, MD,Eric M. Ruderman, MD, an

    Recent years have witnessed important developmstratification approaches, and treatment paradigmof rheumatologic and autoimmune diseases. In amedical disciplines that are relevant to the care owith these many developments is a challenge,methods to educate themselves about these advatology Winter Clinical Symposium was held.discussions and exchanged knowledge about newrheumatology patients. Excerpts from some of tical Symposium 2012 are included in this reviewtheir entirety at 2012 Elsevier Inc. All rights reserved. Semin:10.1016/j.semarthrit.2012.03.002linical Symposia

    in, MD, John J. Cush, MD,

    Fleischmann, MD,

    eke Strand, MD,**in F. Wells, MD, PhD

    n rheumatology. Novel diagnostic methods,e been brought into the clinic for a numbern, there have been developments in relatedents with rheumatic diseases. Keeping paceclinical rheumatologists have used variousIn January 2012, the 5th annual Rheuma-is meeting, faculty and participants heldtific data and how it may impact the care of

    tures from the Rheumatology Winter Clin-se and other presentations can be viewed in

    itis Rheum 41:923-926

  • focal myositis, inclusion body myositis, myositis ossi-ficpieareofintibmeencalrisbuluntumeCu







    released on the efficacy and safety of tofacitinib in com-binpafaistrapthusansafinceleofthththhibthdaeffiThabmutrePMlevmatiocoma




    924 Proceedings of the 2012 rheumatology winter clinical symposiaans, and necrotizing myositis related to statin thera-s. Although statin-induced myopathic complaintsquite common, it has been estimated that up to 6%

    myositis patients may have statin-induced necrotiz-g myositis that appears to be associated with an an-ody against a 100-kDa autoantigen (3-hydroxy-3-thylglutaryl coenzyme reductase). Another novel

    tity is dermatomyositis sine myositis, also known as clini-ly amyopathic dermatomyositis. Such patients have a lowk (10%) of developing systemic myositis and weaknesst may be at risk for severe interstitial lung disease. Chronicg disease, serious infections (25% to 35%), and oppor-

    nistic infections (10%) may complicate the manage-nt of idiopathic inflammatory myositis patients.J., MD


    less changed by the US Congress, in October 2013ere will be a dramatic change in how physicians in the

    code for work done, specifically, in how the diagnosesreported. At that time, the official coding system will

    itch from the current ICD9-CM to ICD-10. Theange has been a long time coming, being legislated asrt of the Health Insurance Portability and Accountabil-Act of 1996. The change will bring the USA in line

    th most of Europe and parts of Canada.The reasons for adopting these changes are multiple.e current ICD9-CM has limited numbers of codesproximately 13,000), is often nonspecific, and reflects

    e state of the art as regards medical knowledge fromout the 1970s. The new coding system, by being up todigits long, will allow for 68,000 codes, will be morexible and specific, and will allow for laterality. For ex-ple, M05.761 is the code for Seropositive RA involving

    e right knee (M05.7 seropositive RA without otheran system involvement; plus 6 knee; plus 1 right)

    d MA1A.9820 would indicate chronic gout of left toethout tophi (M1A.9 chronic gout unspecified etiol-y; plus 8 toe; plus 2 left; plus 0 no tophi).Making the switch from ICD9 to ICD-10 will be cum-rsome, but not impossible. Office practices, superbills,mputer software, and billing systems will need to bedated. Staff will need to be trained, particularly thoseponsible for coding and billing. It is estimated that theitch will take up to 36 months to complete and may cost400$46,000 to implement, depending on the size of thectice. However, the implementation of ICD-10 will oc-

    r, whether you are ready or not. The best time to startparing is now.J. M. Bergman, MD


    11 was an exciting year in the development of newerapeutics for the treatment of RA. Phase 3 results wereation with DMARDs and methotrexate, and com-red to adalimumab and in TNF inhibitor (TNFi)lures. Effects on radiographic inhibition were demon-ated. The safety profile has been better defined: therepears to be less liver test elevation when used as mono-erapy and the lipid elevation can be corrected with thee of lipid-lowering agents. Infections, including seriousd opportunistic, and herpes zoster have occurred. Theety of fostamatinib in phase 2 has been reported withreased diarrhea and hypertension noted, but no lipidvation. A report of a phase 2 study of another inhibitorJAK3/1, VX09-509-101, showed efficacy as mono-

    erapy with perhaps a slightly different safety profilean tofacitinib. The efficacy of tocilizumab as mono-erapy was presented; it is effective clinically and in in-iting radiographic progression, with less liver toxicity

    an when used with concomitant methotrexate. Phase 2ta were released on 2 new inhibitors of IL-6theircacy and safety appear to be similar to tocilizumab.e recently approved subcutaneous formulation of

    atacept has equivalent safety and efficacy as the IV for-lation. Screening for the JC virus, prior to rituximab

    atment, is not helpful in predicting the development ofL. It was reported from a French registry that IgG

    els do decrease over repetitive courses of RTX and thisy be related to increased frequency of serious infec-ns; this is different from what has been shown in thempany-sponsored long-term extensions.R. Fleisch-nn, MD


    esity now affects more than 30% of the US adult pop-tion. The WHO reports that worldwide there are ap-

    oximately 1 billion adults who are overweight and 300llion who are obese; of note, these numbers are ex-cted to rise. Increased body mass index is a major com-nent of the metabolic syndrome (common in psoriasisd psoriatic arthritis) and is associated with an adversediovascular risk profile. Obesity is regarded as a sys-ic, low-grade inflammatory state, characterized by el-

    ated levels of C-reactive protein, TNF-, IL-6, IL-1,d PAI-1. It is an unequivocal risk factor for the onsetd progression of knee osteoarthritis. It increases cardio-scular risk in RA and increases the risk of developingoriatic arthritis, as reported at the 2011 American Col-e of Rheumatology national meeting.Adipose tissue is a dynamic endocrine organ that re-ses cytokines and adipokines, including adiponectin,tin, resistin, visfatin, and chemerin, promoting inflam-tion and metabolic dysfunction. Additionally, obesityds to increased infiltration of immune cells into meta-lic tissues, increased ratio of CD8 to CD4 T cells,d decreased immunosuppressive T-regulatory cells, cre-ng a favorable environment for immune activation.

  • Therapeutic strategies in rheumatology should also ad-drpsRA







    use of novel therapeutic agents in rheumatology.A.Ka





    A. Kavanaugh et al. 925ess obesity as weight influences TNFi persistency inoriatic arthritis and also diminishes response to TNFi in

    patients.Orrin M. Troum, MD


    inical research is replete with ethical is certainly true in rheumatology, as the introductionhighly effective biologic agents has raised a number ofical questions concerning study design. For example,

    th these therapies available, what are the most appro-iate comparators for future studies of other new drugs?der what circumstances, if any, should the use of pla-os be permitted? What is the responsibility of the

    onsor or others to continue to provide expensive thera-s to patients who have participated in clinical studies?e approach toward achieving greater insight intoficult areas is to frame the discussion using several of

    e core principles of medical ethics: namely, patienttonomy, beneficence, nonmaleficence, and distribu-e justice.Many ethicists feel that patient autonomy may be theeeminent ethical principle. The tangible expression oftient autonomy in clinical research is the process oformed consent. Key components of adequate informednsent include decision-making capacity necessary toke a meaningful choice, and the freedom to make a

    cision to participate without coercion or other influ-ce. Given the complexity of the scientific advances nowing tested in the clinic, it can be challenging to presentch information to patients in a way they can under-nd. In many countries, patients impetus to participatea study may be driven by their lack of access to suchdicines by other meansthis can be viewed as a coer-e influence.The concept of beneficence is that clinicians will try toomplish benefit for their patients. Because clinical tri-are big business, with billions of dollars at stake, it isportant that investigators be free of conflict of interest,ich could result in bias.Nonmaleficence refers to the concept of keeping thetient free from harm. A relevant consideration in clin-l trials concerns the use of placebos in studies. Ques-ns on the ethical use of placebos (eg, duration) con-ue to generate intense debate in rheumatology,ecially as available therapies have improved.Distributive justice has become an increasingly impor-t consideration as clinical trials are done more broadly

    roughout the world. If the standard of care for the treat-nt of patients with rheumatic diseases is different in aen country, is it ethical to design a study based on thatndard, even if such a study would not be consideredical in another country with greater resources and aher standard of care? Consideration of ethical issues

    ll continue to be critical to the optimal assessment andvanaugh, MD


    is past year brought hope to patients suffering withge IV melanoma with the approval of Ipilimumab (Ye-y) in March 2011 and Vemurafenib (Zelboraf) in Au-

    st 2011. Until now, no therapy has demonstrated dur-phase III controlled trials increased survival in patients

    th stage IV disease. Ipilimumab, a human monoclonaltibody directed against CTLA-4, was found to increasee median and 1- and 2-year survival rates in stage IVtients, when used either alone or in combination with alanoma vaccine gp100. Autoimmune side effects,ile severe, are manageable. Vemurafenib targets mu-ed BRAF, a signaling molecule found in 50% of mela-mas. The majority of patients respond rapidly and dra-tically; however, resistance to therapy develops usually

    thin the first 6 months. Trials using both therapies inmbination are set to begin. External genital warts affect% of adults in the USA with approximately 500,000w cases annually. Imiquimod 3.75% (Zyclara), a toll-e receptor 7 agonist, when used topically daily for 8eks, produces significant responses in over half of maled female patients with complete remission in a largember of those patients. Actinic keratoses are part of thelogic continuum between photo-damaged skin and

    uamous cell carcinoma. Ingenol mebutate gel (Picato).015% applied daily 3 days to the face/scalp; 0.05%l applied daily for 2 days to trunk/extremities) was re-tly approved for the topical therapy of actinic kerato-

    . In addition to a direct cytotoxic effect, ingenol mebu-e upregulates IL-8 from keratinocytes and endothelialls, resulting in massive neutrophil infiltration into theatment areas. A new procedure involving harvestingroblasts from skin biopsies, culturing and reinjectingem into the dermis of cosmetic patients wanting a moreuthful appearance, was approved in 2011. The poten-l for this therapy to be used outside the cosmetic realmll prove interesting over the next few years. Move overabotulinumtoxin A (Botox). The marketplace now

    s Abobotulinumtoxin A (Dysport approved in 2009)d the recently approved Incobotulinumtoxin A (Xe-in approved in 2011). Wi...


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