HSS Rheumatology Research News: 2012 ACR Meeting
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Transcript of HSS Rheumatology Research News: 2012 ACR Meeting
New Discoveries. Latest Studies.
HSS Rheumatology Research News
Tap Here to See the News
HSS Authors:Yurii Chinenov, PhDRebecca GupteJana Dobrovolna, PhDJamie R. Flammer, PhDBill LiuFrancesco E. MichelassiInez Rogatsky, PhD
Inez Rogatsky, PhD, and her lab
discovered that without GRIP1,
glucocorticoids (GC) fail
to control inflammation.
The team found that without GRIP1, the GC
receptors on macrophages fail to repress NFkB
activity. Transcription is “on”, pro-inflammatory
cytokines keep being produced. Until now, the
key molecular mechanisms of how GC stop
inflamation had not been known.Inez Rogatsky, PhD, HSS Associate Scientist
Revealing How Steroids Work
GRIP1 Required
The Role of Transcriptional Coregulator
Glucocorticoid hormone Receptor Interacting Protein-1 (GRIP1)
in the Anti-inflammatory Actions of Glucocorticoids (GC)
Published in PNAS, July, 2012Full Details now on HSS.edu
previous next study
Full details on HSS.edu
AuthorsHSS:Anna Yarilina MD, PhDKai XuChunhin ChanLionel B. Ivashkiv MD
Rheumatoid arthritis prevents the immune system from
effectively using its “off switch” in the inflammatory
process. Cytokines – the messenger proteins that carry
action signals to cells – just can’t seem to communicate
“no”. The cells that are supposed to halt inflammation
don’t. The cells promoting inflammation continue
unstopped. Joints deteriorate, pain increases.
But now, for the first time, HSS scientists and rheuma-
tologists have pinpointed what seems to be a key
component of that crucial “no”: the immunoreceptor
tyrosine-based activation motif coupled receptors - the
ITAM pathway. The researchers observed the ITAM
pathway fully stopping the inflammatory process.
“It completely turns things off,” reports HSS Associate
Chief Scientific Officer Lionel Ivashkiv, MD, who led the
multi-center study. “What we saw was the ITAM pathway
triggering a complete inhibition of the inflammatory response.”
At the outset, the team knew the ITAM pathway was involved
in regulating inflammation. It had been shown to suppress
so-called Toll-like receptors on pathways that promote
inflammation. But no one knew exactly how. What’s more,
the ITAM pathway had never been established - or even
studied - as specifically involved in rheumatoid arthritis.
“
– Lionel Ivashkiv, MD,Associate Chief Scientific Officer,
David H. Koch Chair in Arthritis and Tissue Degeneration
New Discovery: A Pathway That Can Completely Stop Inflammation in Rheumatoid Arthritis
In the 20 years or so I have been studying regulation of inflammation, this seems to be
the most potent inhibitory mechanism we have ever seen.”
“
HSS RheumatologyClick here for more on HSS.edu
Next
How JAK InhibitorsStop Inflammation
in Rheumatoid Arthritis
Published in Arthritis & Rheumatism, (epub in advance of print)August, 2012.
Lionel B. Ivashkiv MDAssociate Chief Scientific Officer
It has not been completely understood exactly how JAK inhibitors
suppress inflammation in RA. Now, an HSS study of two JAK inhibitors (tofacitinib
and ruxolitinib) has revealed key mocleular mechanisms.
The drugs are able to suppress macrophage activation and attenuate tumor necrosis factor (TNF) responses.
Cytokine/chemokine production is diminished.
The research team also found thatJAK inhibitors partially interfered with
transcription factor NF-KB, blocking the expression of genes that encode pro-
inflammatory cytokines.
Regulation of
Inflammatory Responses in
Tumor Necrosis Factor-activated
and RA Synovial Macrophages by
Janus Kinase Inhibitors
HSS and Seoul National University College of Medicine:Kyung-Hyun Park-Min, MDEun Young Lee
Authors
Weill CornellMedical College:Chuanxin Huang, PhDAri M Melnick, MD
HSS:Neal K Moskowitz, MD, PhDElisha LimEdward Purdue, PhDSteven R Goldring, MDLionel B Ivashkiv, MD
University of Connecticut Health Center:Sun-Kyeong Lee, PhDJoseph A Lorenzo, MD
Negative Regulation of
Osteoclast Precursor Differentiation by CD11band
β2 integrin-BCL6 Signaling.
The molecular mechanisms that directly suppress osteoclastogenesis have not been well understood.
Now, a recent collaboration has uncovered a key finding
In the study, CD11b suppressed induction of NFATc1 by the complementary mechanisms of downregulation
of RANK expression and induction of recruitment of the transcriptional repressor BCL6 to the NFATC1 gene.
CD11b was identified as a negative regulator of the earliest stages of osteoclast differentiation.
New Discovery: Key Mechanism of Negative Regulation
of Osteoclastgenesis
Steven A. Goldring, MDChief Scientific Officer
Richard L. Menschel Research Chair
Lionel B. Ivashkiv, MDAssociate Chief Scientific Officer
David M. Koch Chair
Edward Purdue, PhDHSS Associate Scientist
Director, HSS Osteolysis Lab
Published in Journal of Bone Mineral Research,
(Epub ahead of print) August, 2012
Coming Soon: Full details on
HSS.edu
Authors from HSS:Elana J. Bernstein, MDJessica K. Gordon, MD, MScRobert F. Spiera, MDLisa A. Mandl, MD, MPHEvelyn M. Horn, MD
Presented at the2012 ACR Annual Meeting
Full details on HSS.edu
New, Non-invasive Test May Help Diagnose
Pulmonary Hypertension in Scleroderma
A new, noninvasive stress test called SHAPE™ that uses a 5.5 inch high step on which patients step up and down
for 3 minutes has showed promising results for use in diagnosing pulmonary hypertension (PH) in scleroderma.
End tidal carbon dioxide monitored during SHAPE™ had significant negative correlation to the mPAP of right heart catherization (RHC), the current gold standard diagnostic
test. RHC is both expensive and invasive.
SHAPE™ stands for Submaximal Heart And Pulmonary Evaluation. Further, wider studies will help determine how SHAPE™ can help non-invasively diagnose PH,
a leading cause of death in SSc.
(left to right) Robert F. Spiera, MD Jessica K. Gordon, MD, MScLisa A. Mandl, MD, MPH
The presence of lupus anticoagulant (LAC) is the primary predictor of adverse pregnancy outcome after 12
weeks’ gestation in aPL-associated pregnancies. Other antibodies in the same family, thought to cause pregnancy
complications, do not put women at increased risk.
Anticardiolipin antibody and anti-β2 GPI – if LAC is not also present – do not predict adverse pregnancy
outcome. These findings are from the first clinical research publication of PROMISSE – the largest ever study of
pregnancy outcomes in women with lupus and/or aPL.
Published in Arthritis & Rheumatism, July 2012.
Full Details on study and PROMISSE on HSS.edu
Jane E. Salmon, MD
Collette Kean Research Chair;
Co-director, Mary Kirkland
Center for Lupus Research at HSS
Michael A.Lockshin, MDDirector, Barbara Volcker Center for Women and Rheumatic Disease; Co-director, Mary Kirkland Center for Lupus Research at HSS
PROMISSE Study OvERtuRnS COMMOn BElIEf
LAC Strongest Indicator of Advese Outcome in aPL-Associated Pregnancies
Full Details now on HSS.edu
Testing New Drugs to Treat SSc: Results of Open Label Trials of Imatinib Mesylate (Gleevec™)
Systemic sclerosis (SSc) – or scleroderma – has many debilitating manifestations and few reliably effective treatments. Research at HSS is hoping to help change that. Clinical trials at HSS have been testing the tyrosine kinase inhibitor (TKI) Imatinib Mesylate (Gleevec™) to treat SSc.
At the 2012 ACR Annual Meeting, HSS doctors are reporting on a 24-month trial extension involving 17 patients with early diffuse SSc. The patients had already completed an initial 12-month trial. The target daily dose of 400mg of Gleevec™ was the same in both trials.
The group started the extension with a median Modified Rodnan Skin Score (MRSS) score of 24, which reflected a 22% average improvement from the first 12 month trial.
At the end of the 24-month extension, the median group MRSS had improved to 18. Results must be interpreted cautiously, as patients with SSc can have spontaneous improvements in their skin scores, especially with longer duration of disease.
While both trials showed acceptable safety and tolerability, adverse events did occur. Imantinib is a powerful drug and is not for everyone. Testing at HSS has been a long, careful process. Further, wider testing is warranted on a drug that can provide some benefit for some people, especially when so few alternatives exist.
Robert F. Spiera, MD HSS Attending Rheumatologist Director, HSS Vasculitis and Scleroderma Program
HSS Authors:Jessica K. Gordon, MD
Morgana L. DavidsKamini Doobay
Jamie N. MerstenStephen L. Lyman, PhDMary K. Crow, MDRobert F. Spiera, MD
Recent collaborations of HSS physicians and surgeons using the extensive HSS Total Joint Replacement Registries have
revealed that patients with lupus and RA can experience pain relief and beneficial results from total joint arthroplasty (TJA).
Drug treatments for RA have changed dramatically in recent years, and the investigators wanted to see if that change affected
patient outcomes in joint replacement. Matching each of 159 contemporary patients with RA having total knee replacement
(TKR) to two patients undergoing TKR for osteoarthritis (OA), the collaboration demonstrated that patients with RA can expect
TKR benefits and outcomes similar to patients with OA.
HSS Rheumatologists & Orthopedic Surgeons Overturn Common Beliefs
New Findings on Joint Replacement for Patients with SLE or RA
Additonal Authors and Full Details on HSS.edu
Studies presented at the 2012 ACR Annual Meeting
Another investigation matched each of 101 patients with lupus undergoing either TKR or total hip arthroplasty (THA) to two similar patients having the same surgery for OA.
Patients with lupus experienced far fewer adverse events than previously expected. Two years after surgery, pain and function outcomes were similiar
for patients with and without lupus.
HSS Authors, Both Studies:Lisa A. Mandl MD MPH (right)Assistant Attending Physician
Susan M Goodman, MD (left)Assistant Attending Physician
Mark P. Figgie, MD (pictured on next page)
Chief, Surgical Arthritis Service
Morbid Obesity is Not a Risk Factor for Poor Pain and Function Two
Years After Total Knee Replacement
Almost 90% of referring physicians think obesity increases the likelihood of poor outcomes after total knee replacement (TKR).
However, current data are conflicting.
A recent collaboration of HSS rheumatologists and orthopedic surgeons found that although obese patients have worse pain and function at the time they elect TKR, their outcomes at 2 years are not clinically
significantly different than other patients. However, race and educational attainment were significantly associated with poor outcomes.
The study anaylzed data from 2524 patients in the HSS Total Joint Replacement Registry who underwent TKR between 2007 and 2009.
Findings showed that obese patients have similar expectations and are as satisfied as patients with lower BMI. While more research is needed on the effect of race and education on TKR outcomes, morbid obesity should not
be regarded as a risk factor for poor outcomes after primary TKR.
Authors HSS:Susan M. Goodman, MDMark P. Figgie, MD,Alejandro Gonzalez Della Valle, MDMichael M. Alexiades, MDLisa A. Mandl MD, MPH
Presented at 2012 ACR Annual Meeting
Full details on HSS.eduMark P. Figgie, MD
Chief, Surgical Arthritis ServiceAlejandro Gonzalez Della Valle, MD
Associate Attending Orthopaedic Surgeon
Pilot Nutrition Education Program
Receives High Marks from
Culturally Diverse Teens with Lupus and their Families
A recent HSS study shows promising results for a hospital-based education program specially designed for a culturally diverse group of teens with lupus and
their families to learn about healthy nutrition together.
The curriculum focused on learning about the nutritional benefits of whole grains/fiber, calcium/
vitamin D, fruits/vegetables, protein foods, and snacks/fast foods. Several key topics were included throughout
all 5 sessions, including portion control, food labels, sodium and culturally appropriate recipe examples.
94% of participants rated overall content as excellent. 94% of the participants reported that the program led
them to include more nutritious foods in their diet.
The benefits of this pilot series will be further expanded in future programs, which will consider
adding more communication tools and social media.
AuthorsHSS:Jillian A. Rose, LMSW (above left)Roberta Horton, LCSW, ACSW(above right)Dariana M. PichardoDana Friedman, MPHRobyn Wiesel, CHESSandra Goldsmith, MA, MS, RDSotiria Everett, MS, RD, CDN, CSSD
Morgan Stanley Children’s Hospital, New York-PresbyterianColumbia University Medical Center:Lisa F. Imundo, MD
Presented by Jillian Rose, LMSW, at 2012 ACR Annual Meeting
Full details on HSS.edu
Test of a Systematic Two Drug Regimen Shows Prolonged Improvement in Lupus
Full Details Coming Soon to HSS.edu
Thomas J.A. Lehman, MDChief, Pediatric Rheumatology
A carefully supervised, systematic regimen of twopowerful drugs was found to significantly reduce steroid dosage while improving a patient’s lupus condition.
15 patients, ranging in age from 10 to 22, with active lupus, who had been dependent on steroids for control of the condition, received a systematic regimen ofrituximab and cyclophosphamide administered at three intervals – at the start of the trial, then again at 6 months, and a third time at 18 months.
All 15 patients experienced improvements in 6 standard indicators of lupus disease level in their blood tests. Note these powerful drugs, used in chemotherapy, must not be administered without careful supervision from doctors familiar with the medications.
Study presented by Dr. Lehman at 2012 ACR Annual Meeting
Authors:HSS:Thomas J. A. Lehman, MDEmily BairdAnusha Ramanathan, MDRisa Alperin, MDEmma J. MacDermott, MDAlexa B. Adams, MD
Maimonides Medical Center:Laura V. Barinstein, MD
Robert Wood Johnson-UMDNJ:Lakshmi N. Moorthy, MD
Patient Self-Assessments and Patient Reported Outcomes May Reliably Identify Disease Flare in Early RA
AuthorsHSS:Vivian P. Bykerk, BSc, MD, FRCPC
Johns Hopkins University:Clifton O. Bingham III, MD
Cardiff University School of Medicine, UK:Ernest Choy, MD, FRCP
Mount Sinai Hospital, Toronto:Juan Xiong, PhD
CHUS - Sherbrooke University, Quebec:Gilles Boire, MD, MSc
University of Manitoba, Winnipeg:Carol A. Hitchon, MD, FRCPC, MSc
University of Western Ontario:Janet E. Pope, MD, MPH, FRCPC
Southlake Regional Health Centre, Ontario:J. Carter Thorne, MD, FRCPC
University of Montreal Hospital Research Centre: Boulos Haraoui, MD, FRCPC
University of Toronto: Edward Keystone, MD, FRCPC
McGill University, Montreal: Susan J. Bartlett, PhD
Patients reporting a rheumatoid arthritis (RA) flare have clinical indices reflecting worsening
disease activity. Using criteria of pain, function, stiffness, coping, participation, and fatigue, patient
reported outcomes (PROs) significantly discriminated between patients reporting flare vs. no flare.
These findings were uncovered in a recent investigation involving data from 512 patients in
the CATCH (Canadian early ArThritis CoHort) study, comparing patient and doctor assessment of
symptoms and clinical status in a flare.
There is modest agreement between patients and MDs regarding flare status. Flare patients
identify more swollen and tender joints than MDs.
PROs and patient joint counts may reliably identify
Study presented by Dr. Bykerk at the 2012 ACR Annual Meeting
Full Details With Chart of Patient/MD ConcordancesComing soon to HSS.edu
disease flare, but some ratings are higher inpatients than MDs. More research is
needed to identify predictors of concordance and discrepancy
between patients and providers in flare assessment.
Vivian P. Bykerk, BSc, MD, FRCPC
Hospital-Based Exercise Program
Shown to Decrease Pain
and Improve Life for Patients
with Arthritis
A recent HSS study has shown that a low-cost, hospital-based, exercise program of weekly classes significantly decreased pain and the severity and frequency of falls, as well as improved enjoyment of life and balance among the participants.
Of the 200 study participants, 53% indicated pain relief. Further analysis showed that in a subet of 66 participants who complete both pre and post program surveys, 62% experienced pain relief. Pain intensity dropped from 4.5 to 2.7 with 0 being “no pain” and 10 “worst pain imaginable.
Weekly classes, part of the HSS Osteoarthritis Wellness Initiative, included Tai Chi, yoga, mat and chair pilates, yoga-lates and dance fitness. Instructors tailored programs where necessary for patients with osteoarthritis.
AuthorsHSS:
Sandra Goldsmith, MA MS RDDana Friedman, MPHLinda Roberts, LCSW
Dana Sperber Laura Robbins, DSW, CSW, MSW
Linda Russell, MD
Low cost, community exercise programs can play an important role
in fighting OA with minimal resources.
Full details on HSS.edu
Presented at the 2012 ACR Annual Meeting
Testing New Drugs for SSc: A Single Group, Open Label,
Pilot Clinical Trial of Nilotinib (Tasigna™)
AuthorsHSS:Jessica K. Gordon, MDMorgana L. DavidsKamini DoobayStephen L. Lyman, PhDMary K. Crow, MDRobert F. Spiera, MD
Weill-Cornell Medical Center:Cynthia Magro, MDHoratio F. Wildman, MD
Presented by Dr. Gordon (pictured) at the 2012 ACR Annual Meeting
Second generation tyrosine kinase inhibitor (TKI) drugs aim to be more
efficacious with less side effects. A recent pilot study of one such TKI called nilotinib
(Tasigna™) was completed by 7 patients with diffuse cutaneous (dc) systemic sclerosis (SSc) for less than 3 years.
The twice daily 400 mg oral dose of nilotinib was tolerated by the majority
of patients in the study. Tolerability was limited primarily by mildly prolonged
QTc, which is a known side effect of nilotinib and an exclusion criterion for
continuation in this study.
Modified Rodnan Skin Score (MRSS) improved significantly with 6 months of
treatment in this very early and active group of patients.
Further testing in randomized placebo controlled trials will ultimately be necessary to determine whether the benefits seen were truly related to the
medication tested.
Full Details on HSS.edu
Stories of Health & Humanity
to HealRheum
Full Detailson HSS.edu
back to page 1
A New, Online, Narrative Journal By and For People Living with Rheumatic Conditions and their Physicians
and Caregivers
Rheum to Heal will use the power of words and images,
combined with the nurturing balm of community, to transform
all who share them. The frequently common emotional impact
of chronic rheumatic disease, once creatively expressed,
has the ability to unite and heal.
Stories, Poems, Artwork, Healingfrom patients, doctors & caregivers
Coming Soon from HSS