This document summarizes evidence-based care of women with rheumatoid arthritis (RA). It discusses that RA is a chronic inflammatory disorder that principally affects the synovial joints. It is characterized by a proliferative response in the synovium leading to bone and cartilage destruction. The document reviews who is affected by RA, common articular features, characteristic deformities, and extra-articular manifestations. It also discusses the natural history of RA and whether there are any gender differences. Current management approaches from 2012 are presented, including early diagnosis, prompt initiation of traditional DMARDs, and appropriate use of biological DMARDs.
Presentation I gave during the 22nd PRA Annual Meeting held at the Iloilo Convention Center, Iloilo City, Philippines. I gave this talk during Day 1 of the Convention.
This talk was given by Dr. Grant Schulert Cincinnati Children's Hospital to a group of patient families, at Systemic Juvenile Idiopathic Arthritis (or SJIA) Family Day on July 22nd, 2017.
This talk was given by Dr. Daniel Lovell of Cincinnati Children's Hospital to a group of patient families, at Systemic Juvenile Idiopathic Arthritis (or SJIA) Family Day on July 22nd, 2017.
Presentation I gave during the 22nd PRA Annual Meeting held at the Iloilo Convention Center, Iloilo City, Philippines. I gave this talk during Day 1 of the Convention.
This talk was given by Dr. Grant Schulert Cincinnati Children's Hospital to a group of patient families, at Systemic Juvenile Idiopathic Arthritis (or SJIA) Family Day on July 22nd, 2017.
This talk was given by Dr. Daniel Lovell of Cincinnati Children's Hospital to a group of patient families, at Systemic Juvenile Idiopathic Arthritis (or SJIA) Family Day on July 22nd, 2017.
This presentation by Gavin Giovannoni looks at the new treatment paradigm for MS. It includes: arguments for early treatment in multiple sclerosis, the effect of MS on quality of life and whether highly-effective treatments stabilise MS.
It was presented at the MS Trust Annual Conference in November 2013.
This talk was given by Dr. Jennifer Huggins of Cincinnati Childrens Hospital, at the Systemic Juvenile Idiopathic Arthritis (or SJIA) Family Day, on July 22nd, 2017.
Evidence based management of osteoarthritis in primary care - Dr Jonathan Quickepcsciences
Dr Jonathan Quicke is an NIHR Academic Clinical Lecturer in Physiotherapy (Keele University). Dr Quicke presented at the 2017 Musculoskeletal Education Day, where he discussed how we can ensure that best practice can be implemented within general practice for patients suffering with osteoarthritis
Rare Pulmonary Diseases in Systemic JIA. This presentation tracks the increased use of biologics to treat SJIA and observes the trends in rare pulmonary diseases.
The evaluation of back pain can be a pain in the neck or a back-breaking exercise, so to speak. However, the diagnosis hinges always on a focused History and Physical Exam and not really on labs or imaging. Knowing what to ask and where to look can make the evaluation of this all-too-common condition manageable for the internist.
This lecture focuses on the evaluation of low back pain and will guide the reader on the key points in the Hx and PE and prevent unnecessary testing/imaging. It also presents 3 "unusual" cases of low back pain which may be disabling if not recognized immediately.
Vertebral Fracture Identification presented by Dr Andrew Pearson, Consultant Radiologist, Borders Hospital, Melrose at the fracture liaison service champions' summit 2016. #flschampions
A great deal is happening in lupus-related research. This presentation will update participants on recent research developments and their impact on those affected by lupus. Dr. Petri will provide an overview of current lupus research and the prospects for the future of lupus treatments. Learn how to better manage your lupus and make knowledgeable decisions regarding your treatment plan.
Chlamydia-induced Reactive Arthritis research project. Discusses pathogenesis, symptoms, and etiology. Summarizes possible treatment plans and includes questions for further research.
This presentation by Gavin Giovannoni looks at the new treatment paradigm for MS. It includes: arguments for early treatment in multiple sclerosis, the effect of MS on quality of life and whether highly-effective treatments stabilise MS.
It was presented at the MS Trust Annual Conference in November 2013.
This talk was given by Dr. Jennifer Huggins of Cincinnati Childrens Hospital, at the Systemic Juvenile Idiopathic Arthritis (or SJIA) Family Day, on July 22nd, 2017.
Evidence based management of osteoarthritis in primary care - Dr Jonathan Quickepcsciences
Dr Jonathan Quicke is an NIHR Academic Clinical Lecturer in Physiotherapy (Keele University). Dr Quicke presented at the 2017 Musculoskeletal Education Day, where he discussed how we can ensure that best practice can be implemented within general practice for patients suffering with osteoarthritis
Rare Pulmonary Diseases in Systemic JIA. This presentation tracks the increased use of biologics to treat SJIA and observes the trends in rare pulmonary diseases.
The evaluation of back pain can be a pain in the neck or a back-breaking exercise, so to speak. However, the diagnosis hinges always on a focused History and Physical Exam and not really on labs or imaging. Knowing what to ask and where to look can make the evaluation of this all-too-common condition manageable for the internist.
This lecture focuses on the evaluation of low back pain and will guide the reader on the key points in the Hx and PE and prevent unnecessary testing/imaging. It also presents 3 "unusual" cases of low back pain which may be disabling if not recognized immediately.
Vertebral Fracture Identification presented by Dr Andrew Pearson, Consultant Radiologist, Borders Hospital, Melrose at the fracture liaison service champions' summit 2016. #flschampions
A great deal is happening in lupus-related research. This presentation will update participants on recent research developments and their impact on those affected by lupus. Dr. Petri will provide an overview of current lupus research and the prospects for the future of lupus treatments. Learn how to better manage your lupus and make knowledgeable decisions regarding your treatment plan.
Chlamydia-induced Reactive Arthritis research project. Discusses pathogenesis, symptoms, and etiology. Summarizes possible treatment plans and includes questions for further research.
Dr. Swamy Venuturupalli talks about Rheumatoid Arthritis, Early Diagnosis and Treatment at the James R. Klinenberg symposium on Rheumatic diseases in Pasadena, CA.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
1. Evidence-Based Care of Women
with Rheumatoid Arthritis
Marc C. Hochberg, MD, MPH
Professor of Medicine and Epidemiology and Public Health
Head, Division of Rheumatology & Clinical Immunology
University of Maryland School of Medicine
Baltimore, MD
2. Disclosures
• Dr. Hochberg receives research support
from the National Institutes of Health
• He has served as a consultant to the
following commercial entities:
– Abbott Laboratories, Amgen, Astra-Zeneca Pharmaceutical
Co., Bristol Myers Squibb Company, CORRONA,
Genentech/Roche, Merck & Co. Inc., NicOx S.A., Novartis
Pharma AG, Pfizer Inc., Pozen Inc., Theralogix LLC and
UCB Inc.
3. “So much to do; so little time.”
The White Rabbit, “Alice in Wonderland”
Slide provided by Daniel E. Furst, M.D.
4. Rheumatoid Arthritis (RA)
• A chronic, systemic inflammatory
disorder that principally affects the
synovial joints
• Characterized by a proliferative
response in the synovial membrane
leading to bone and cartilage
destruction and joint deformity
Hochberg MC, et al: Rheumatoid arthritis. Mosby/Elsevier, Philadelphia, 2009.
5. Who is Affected by RA?
• Most commonly presents
between the ages of
45 and 64 years1
• Overall lifetime risk of RA2
– 3.6% for women
– 1.7% for men
• For women with a first-
degree relative with RA,
lifetime risk of RA
approaches 18%2
1. Silman AJ and Hochberg MC. In: Rheumatoid Arthritis; 2010, 1st ed. 2. Crowson CS, et al. Arthritis
Rheum. 2011;63:633-639.
6. Common
Articular Features
• Additive, symmetric
inflammatory arthritis
– Typically involves small
joints of the hands
(PIPs, MCPs), wrists,
elbows, shoulders,
knees, ankles, and feet
(MTPs)
– DIPs, hips and spine
usually spared
DIP, distal interphalangeal; MCP, metacarpophalangeal;
MTP, metatarsophalangeal; PIP, proximal interphalangeal.
11. Extra-articular Manifestations
Affected tissue or
Comments
organ
Infections Association with RA due to disease, medications; important
implications for vaccination
Cardiovascular Pericarditis, endocarditis, myocarditis, MI; association due to
underlying inflammatory disease, medications, reduced exercise,
genetics
Nervous system Depression; PML (rare but often fatal in immunosuppressed; more
common with biologics such as rituximab)
Skin Subcutaneous nodules
Pulmonary Pulmonary nodules; interstitial lung disease
Eyes Scleritis, episcleritis, retinal vasculitis
Other Secondary Sjogren’s syndrome, anemia, thrombocytosis,
vasculitis, diabetes, GI bleeding, cancer (e.g., lymphoma)
GI, gastrointestinal; MI, myocardial infarction; PML, progressive multifocal leukoencephalopathy.
13. Natural History of RA:
Any Gender Differences?
• Baseline measures of disease activity slightly
higher in women1
– Higher swollen/tender joint count
– Higher scores for pain and fatigue
– Worse physician and patient global assessment of
disease activity
• No gender differences in treatment response2
DMARD, disease-modifying antirheumatic drug; MTX, methotrexate; TNF, tumor necrosis factor.
1. Sokka T, et al. Arthritis Res Ther. 2009;11:R7. 2. Kristensen LE, et al. Rheumatology. 2008;47:495-499.
14. Management of RA: 2012
• Early correct diagnosis
• Prompt initiation of traditional DMARDs
– Methotrexate alone
– Triple therapy (MTX, SSZ, HCQ)
• Appropriate use of biological DMARDs
– Anti-TNF agents as 1st line biologics
– What to use in inadequate responders?
DMARD, disease-modifying antirheumatic drug; HCQ, hydroxychloroquine; MTX, methotrexate; SSZ,
sulfasalazine; TNF, tumor necrosis factor.
Saag KG, et al. Arthritis Rheum. 2008;59:762-784.
15. Early Diagnosis of RA
• Prompt referral of patients with 1 or more
swollen joints (“early arthritis”) by the PCP to
a rheumatologist
• Evaluation by the rheumatologist to determine
correct diagnosis
• Apply 2010 ACR/EULAR Classification
Criteria to identify those with early arthritis
who do not have another diagnosis
Aletaha D, et al. Arthritis Rheum. 2010;62:2569-2581.
16. 2010 ACR/EULAR
RA Classification Criteria
• Classification as ‘definite RA’ based on:
– Confirmed presence of synovitis in at least
one joint
– Absence of an alternative diagnosis better
explaining the synovitis
Aletaha D,D et al: Arthritis Rheum 2010;62:2569-81.
*Aletaha et al. Arthritis Rheum. 2010;62:2569-2581.
17. 2010 ACR/EULAR
Classification Criteria for RA
JOINT DISTRIBUTION (0-5)
1 large joint 0
2-10 large joints
1-3 small joints (large joints not counted)
1
2
≥6 = definite RA
4-10 small joints (large joints not counted) 3
>10 joints (at least one small joint) 5
SEROLOGY (0-3) What if the score is <6?
Negative RF AND negative ACPA 0
Low positive RF OR low positive ACPA 2
Patient might fulfill the criteria…
High positive RF OR high positive ACPA 3
SYMPTOM DURATION (0-1) Prospectively over time
<6 weeks 0 (cumulatively)
≥6 weeks 1
ACUTE PHASE REACTANTS (0-1) Retrospectively if data on all
Normal CRP AND normal ESR 0 four domains have been
Abnormal CRP OR abnormal ESR 1 adequately recorded in the past
Aletaha D, et al. Arthritis Rheum. 2010;62:2569-2581.
18. Classification Tree
• >10 joints (≥1 small joint)
– Positive serology or duration ≥6 wks or abnormal acute
phase reactant (APR)
• 4-10 small joints
– Positive serology (if low titer, then duration ≥6 wks or
abnormal APR)
• 1-3 small joints
– Positive serology and duration ≥6 wks or abnormal APR (if
low titer, then duration ≥6 wks and abnormal APR)
• 2-10 large joints (no small joints)
– Positive serology and duration ≥6 wks and abnormal APR
Aletaha D,D et al: Arthritis Rheum 2010;62:2569-81.
*Aletaha et al. Arthritis Rheum. 2010;62:2569-2581.
19. Classification Criteria in Practice
Aletaha D,D et al: Arthritis Rheum 2010;62:2569-81.
*Aletaha et al. Arthritis Rheum. 2010;62:2569-2581.
20. Rationale for Early Institution
of Traditional DMARDs
• Early onset of functional limitation and
reduced health-related quality of life
• Early onset of joint damage
– Rate of progression of joint damage is
greater in early c/w late disease
Saag KG, et al. Arthritis Rheum. 2008;59:762-784.
21. RA: Typical Course
• Damage occurs early in most patients
• 50% show joint space narrowing or
erosions in the first 2 years
• Disease activity and damage are
associated with functional limitation and
work disability
– By 10 years, 50% of young working
patients are “work disabled”
Aletaha D, et al. Arthritis Rheum. 2010;62:2569-2581.
22. Critical Elements of Management:
Staging RA
• Assess disease activity
• AM stiffness, synovitis (#P/T and swollen joints),
pain, ESR and/or CRP
• Document the degree of damage
• Joint space narrowing and erosions on imaging
• Functional status (HAQ-DI)
• Document extra-articular manifestations
• Nodules, sicca symptoms, vasculitis
• Assess prior Rx responses and side effects
23. Imaging Tools for Assessing Early
Joint Damage
• Plain radiographs
– Views of hands and feet at baseline visit
– Low sensitivity for early erosive disease
• Ultrasound (gray scale and power Doppler)
– Tenosynovitis common
– Correlates with active disease
• Magnetic resonance imaging
– Gadolinium enhancement for synovitis
Aletaha D, et al. Arthritis Rheum. 2010;62:2569-2581.
24. Grayscale and Power Doppler Ultrasound
Images of Synovial Hypertrophy in RA
Brown AK, et al. Nat Rev Rheumatol. 2009;5:698-706.
26. MRI in Early RA
Mak W, et al. J Musculoskel Med. 2009;26:478-486.
27. Approaches to Traditional
DMARD Therapy
• Single agent (MTX as anchor drug)
– Leflunomide or SSZ in patients with a
contraindication to MTX
• Triple therapy (MTX, SSZ, HCQ)
– More efficacious than MTX alone at 6 months1
– More efficacious than MTX with either SSZ or
HCQ after 2 years2
DMARD, disease-modifying antirheumatic drug; HCQ, hydroxychloroquine; MTX, methotrexate; SSZ,
sulfasalazine.
1. O’Dell J, et al. N Engl J Med. 1996;334:1287-1291. 2. O’Dell J, et al. Arthritis Rheum. 2002;46:1164-1170.
28. Triple DMARD Therapy in RA:
ACR Responses at 2 Years
ACR, American College of Rheumatology; HCQ, hydroxychloroquine; MTX, methotrexate; SSZ, sulfasalazine.
O’Dell J, et al. Arthritis Rheum. 2002;46:1164-1170.
29. Treat to Target (T2T)
• Treatment should be targeted at achieving a
state of clinical remission
– A state of low disease activity may be an
acceptable alternative goal, particularly in patients
with established disease
• Therapy should be adjusted at least every 3
months, as needed
• Decisions should be based on validated
composite measures of disease activity
Smolen JS, et al. Ann Rheum Dis. 2010;69:631-637.
31. ACR/EULAR Definition of
Remission in RA
• Patient must satisfy all of the following:
– Tender joint count ≤ 1
– Swollen joint count ≤ 1
– C-reactive protein ≤ 1 mg/dl
– Patient global assessment ≤ 1 (0-10 scale)
• Patient must have an SDAI score ≤ 3.3
ACR, American College of Rheumatology; EULAR, European League Against Rheumatism; SDAI, Simplified
Disease Activity Index.
Felson DT, et al. Ann Rheum Dis. 2011;70:404-413.
32. Options for Inadequate
Response to Methotrexate
• Add additional traditional DMARDs
– Azathioprine, cyclosporin, leflunomide,
sulfasalazine + hydroxychloroquine
• Add biologic DMARD
– TNF inhibitors are agents of choice for
initial biologic therapy in patients with RA
DMARD, disease-modifying antirheumatic drug; TNF, tumor necrosis factor.
Saag KG, et al. Arthritis Rheum. 2008;59:762-784.
33. Current Biological Targets in RA
CTLA-4Ig / abatacept
Anti-CD20 / rituximab
Pro-inflammatory cytokines
targeted hitherto:
•TNF/ INF, ETN, ADA, GO, CP
IL- 6
•IL-1/ Anakinra
IL-6 receptor/ tocilizumab
ADA, adalimumab; CP, certolizumab pegol;
CTLA-4, cytotoxic T-lymphocyte antigen 4; IL,
interleukin; INF, interferon; ETN, etanercept; GO,
golimumab; TNF, tumor necrosis factor.
Smolen JS, et al. Nature Rev Drug Disc. 2003;2:473-488.
34. Anti-TNF Therapy in Early RA:
Swefot Trial
• 487 patients with early RA enrolled
• 145 achieved LDA with MTX
• 258 randomly assigned to either
infliximab or SSZ + HCQ added to MTX
HCQ, hydroxychloroquine; LDA, low disease activity; MTX, methotrexate; RA, rheumatoid arthritis;
SSZ, sulfasalazine; TNF, tumor necrosis factor.
van Vollenhoven RF, et al. Lancet 2009;374:459-466.
35. Swefot: Triple DMARD vs. MTX + TNFi
MTX + SSZ + HCQ (→ CsA); n=130
Early RA
MTX monotherapy
(~20 mg/wk)
A
Symptoms <1 yr 3–4 m
No other DMARD
DAS28 >3.2
MTX + IFX (→ ETN); n=128
n=487
B
Screening 3m 12 m 24 m
Randomization 1º endpoint: % pts
if DAS28 >3.2 with EULAR Good
(n=258/487) response
Patient Disposition
• 30% pts responded to the initial 3–4-month
trial of MTX monotherapy (DAS28 <3.2: 16%
remission/14% low)
• At 12 m, 75% maintained low disease activity
• Predictors of response: lower DAS, RF-
CsA, cyclosporine; DAS28, disease activity score (28 joints); HCQ, hydroxychloroquine; INF, infliximab; MTX,
methotrexate; RF, rheumatoid factor; SSZ, sulfasalazine.
van Vollenhoven R et al ACR 2008 Abstracts #717, 1003.
36. Swefot Trial Results
Response MTX + SSZ + HCQ MTX + Infliximab RR (95% CI)
EULAR Good 32 (25%) 50 (39%) 1.59 (1.10, 2.30)
EULAR Good
64 (49%) 77 (60%) 1.22 (0.98, 1.53)
or Moderate
ACR 20 37 (28%) 54 (42%) 1.48 (1.06, 2.08)
ACR 50 19 (15%) 32 (25%) 1.71 (1.02, 2.86)
ACR 70 9 (%) 15 (12%) 1.69 (0.77, 3.73)
• Frequency of adverse events similar between groups
ACR, American College of Rheumatology; EULAR, European League Against Rheumatism; HCQ,
hydroxychloroquine; MTX, methotrexate; RR, relative risk; SSZ, sulfasalazine.
van Vollenhoven RF, et al. Lancet 2009;374:459-466.
37. Treatment of Early Aggressive RA (TEAR)
Study of Traditional vs Newer Biologics
• 755 patients with early RA (≤ 3 years)
– MTX naïve; ≥ 4 TJC/SJC; RF+ or CCP+ or ≥ 2 erosions
• Baseline characteristics
– DAS 5.8; 90% RF+; pred 42%; prior DMARD 24%
• Treatment arms
– Initial combination therapy with triple DMARDs or MTX/ETN
(n=376) or MTX monotherapy (n=379) for 24 weeks
– If DAS >3.2 with MTX alone, step up to triple therapy or MTX/ETN
• 28% achieved LDA on MTX alone
• Study endpoints
– Primary: DAS28 from weeks 48-102
– Secondary: ACR20/50/70, Xray, QOL, DAS remission
• Completers analysis: 63% @ 2 yrs
DMARD, disease-modifying antirheumatic drug; ETN, etanercept; MTX, methotrexate; RF, rheumatoid factor.
Moreland L, et al. ACR 2009; Abstract 1895.
38. TEAR Study Results
DAS28 at ACR20 ACR50 ACR70
Treatment week 102 (6 months) (6 months) (6 months)
Initial MTX/ ETN (IE) 3.0 +/- 1.4 63.6% 35.5% 13.1%
Initial Triple DMARD (IT) 2.9 +/- 1.4 64.0% 38.6% 11.4%
Step-up MTX/ETN (SE) 3.1 +/- 1.4 45.2% 22.1% 3.2%
Step-up triple DMARD (ST) 2.8 +/- 1.3 47.7% 21.5% 4.7%
6
IE IT
5
SE ST
4
DAS28
3
Step-up to multiple
2 DMARD at Week
24 if DAS28 ≥ 3.2
1
0
Week 0 Week 12 Week 24 Week 36 Week 48 Week 60 Week 72 Week 84 Week 96 Week 102
Conclusion: Early benefits to aggressive therapy, but similar outcomes
at 2 years regardless of treatment regimen
Moreland L, et al. ACR 2009; Abstract 1895.
39. Initiation of a Biologic DMARD
• Choice of agent is based on the shared decision of
the patient and rheumatologist
• TNF inhibitors are the biologic DMARDs of choice for
patients with an inadequate response to traditional
DMARDs
• Response rates generally similar across anti-TNF
agents
• Safety considerations
– Cases of tuberculosis reactivation reported for TNF-blocking
agents
– Tuberculosis reactivation risk lower with etanercept (soluble
TNF receptor) than with anti-TNF monoclonal antibodies
DMARD, disease-modifying antirheumatic drug; TNF, tumor necrosis factor.
Nam JL, et al. Ann Rheum Dis. 2010;69:976-986. Saillot C, et al. Ann Rheum Dis. 2011:70:266-271.
40. Numbers Needed to Treat with Biologic
DMARDs to Achieve ACR Responses
Response @ 6 months NNT (95% CI)
ACR 20 3.2 (2.4, 4.0)
ACR 50 4.2 (3.6, 4.8)
ACR 70 7.7 (6.7, 10.0)
Response @ 12 months NNT (95% CI)
ACR 20 3.0 (2.6, 3.6)
ACR 50 3.7 (3.2, 4.2)
ACR 70 5.9 (5.0, 6.7)
ACR, American College of Rheumatology; DMARD, disease-modifying antirheumatic drug; NNT, number needed
to treat.
Nam JL, et al. Ann Rheum Dis. 2010;69:976-986.
41. Efficacy of Biologic DMARDs in Patients with
Inadequate Responses to Methotrexate
Conclusion:
consistent
trend toward
improved
response with
addition of
biologic
DMARD
Salliot C, et al. Ann Rheum Dis.
42. Cost-Effectiveness of TNF
Inhibitors in RA
Cost-effective* • In patients with an inadequate
response to MTX
Not cost-effective • As initial therapy
• In MTX- or traditional DMARD-
naïve patients
*Defined as incremental cost-effectiveness ratio (ICER) < $100,000 per quality-adjusted life year.
DMARD, disease-modifying antirheumatic drug; MTX, methotrexate; TNF, tumor necrosis factor.
van der Velde G, et al. Arthritis Care Res. 2011;63:65-78.
43. Options for Inadequate
Responders to TNF Inhibitors
• Switch to another TNF inhibitor
• Switch to another biologic DMARD with a
different mechanism of action
– Abatacept
– Rituximab
– Tocilizumab
• Response rates generally similar between
biologic DMARDs
DMARD, disease-modifying antirheumatic drug; TNF, tumor necrosis factor.
Bergman GJD, et al. Semin Arthritis Rheum. 2010:39:425-441. Saillot C, et al. Ann Rheum Dis.
44. Numbers Needed to Treat for
ACR 50 Response
Biologic DMARD NNT (95% CI)
Abatacept 4 (3-5)
Certolizumab pegol 4 (3-5)
Golimumab 6 (4-13)
Rituximab 5 (4-10)
Tocilizumab 5 (3-8)
ACR, American College of Rheumatology; DMARD, disease-modifying antirheumatic drug; NNT, number needed
to treat.
Kristensen LE, et al. Scand J Rheumatol. 2010;iFirst:1-7.
45. Role of Glucocorticoids in RA
Management
• Low-dose glucocorticoids effective for:
– Alleviating signs and symptoms
– Reducing functional limitation
– Slowing radiographic progression
• EULAR recommends that dose should be
tapered as rapidly as possible
– No good data, however, on the optimal schedule
for tapering to prevent disease flare
Gorter SL, et al. Ann Rheum Dis. 2010;69:1010-1014.
46. RA and Menopausal Status
• Contraception, fertility issues, and hormone therapy
managed by GYN and/or primary care providers
Premenopause • Recommend contraception during DMARD therapy
• No evidence of interaction between oral contraceptives
and RA
Preconception • Discontinue DMARDs at least 2 menstrual cycles before
trying to conceive
Pregnancy • Expect improvement in RA symptoms during pregnancy
followed by postpartum flare
• Avoid antirheumatic drugs with contraindications in
pregnancy (next slide)
Postmenopause • Refer for hormone therapy at the discretion of the primary
care provider or gynecologist
McNaughton S, et al. J Nurse Pract. 2008;4:370-376.
47. Antirheumatic Drug Risks During Pregnancy
FDA Pregnancy
Drug class Clinical Recommendations
Category
• First-trimester use associated with increased risk of oral cleft
Corticosteroids C
• Increased risk of adrenal insufficiency
Nonbiologic DMARDs
• No increased risk of congenital malformations
Sulfasalazine B
• Combine with folate supplements
Azathioprine D • Can be continued to maintain remission during pregnancy
• Contraindicated in pregnancy
Methotrexate X
• Discontinue 3–6 months before conception
• Contraindicated during pregnancy
Leflunomide X
• Discontinue use 2 years before pregnancy
• HCQ is compatible with pregnancy
Antimalarials C
• Risk for retinal toxicity and ototoxicity higher for chloroquine than for HCQ
Biologic DMARDs
• Anti-TNF antibodies not transferred to embryo/fetus in first trimester of
TNF inhibitors B
pregnancy
• No human pregnancy data available
Abatacept C
• Discontinue 10 weeks before planned pregnancy
• Reversible B-cell depletion or lymphopenia in the neonate
Rituximab C
• Long half-life; discontinue 1 year before planned pregnancy
• No human pregnancy data available
Tocilizumab C
• Discontinue 10 weeks before planned pregnancy
DMARD, disease-modifying antirheumatic drug; HCQ, hydroxychloroquine; TNF, tumor necrosis factor.
Hazes JMW, et al. Rheumatology. 2011;50:1955-1968.
48. Management of RA:
Summary (I)
• Early referral to rheumatology and diagnosis
are of paramount importance
• Traditional DMARDs should be initiated
promptly after diagnosis of RA
• MTX is considered the DMARD of choice
(anchor drug)
• Triple therapy can be considered as an
alternative approach
DMARD, disease-modifying antirheumatic drug; MTX, methotrexate.
49. Management of RA:
Summary (II)
• Patients with an inadequate response to MTX
should be treated with a TNF inhibitor
– Step up therapy using other traditional DMARDs
can be considered
• Patients with an inadequate response to one
TNF inhibitor may be
– Switched to another TNF inhibitor, or
– Treated with a biologic DMARD with a different
mechanism of action
DMARD, disease-modifying antirheumatic drug; MTX, methotrexate; TNF, tumor necrosis factor.
Note: If possible, please add a title to this slide: “Biologics Sites of Action”
Two head-to-head treatment arms A Traditional: MTX + SSZ 1000 mg BID + HCQ 400 mg qd; minor adjustments allowed with intolerance B Biologic: infliximab 3 mg/kg (frequency, not dose increase, allowed) given at 0, 2, 6, and then q 8 wks. Could be replaced with etanercept 50 mg/wk Two arms well-matched at baseline Primary = EULAR good response Secondaries = EULAR moderate response, ACR20, 50, 70 responses, etc Imaging data to come
KEY POINTS ABSTRACT Purpose: No direct data compares triple DMARD (methotrexate [MTX], sulfasalazine [SSZ], hydroxychloroquine [HCQ]) to MTX + anti-TNF therapy (etanercept) in patients with early RA. The relative benefit of a strategy of either combination vs MTX monotherapy with step-up after 6 months is also uncertain. The TEAR trial evaluates both issues. Methods: The investigator-initiated, multi-center, randomized TEAR trial began in 2004 and enrolled 755 participants to compare immediate (I) vs step-up (S) strategy with MTX, etanercept (E) and triple DMARD (T) in 4 arms: immediate MTX + E (IE) or triple therapy (IT); step-up from MTX to MTX+E (SE) or to T (ST). In SE/ST, if DAS28 ≥ 3.2 at 6 months of MTX, patients were blindly stepped-up to IE/IT. Inclusion criteria: disease duration ≤ 3yrs, diagnosis by ACR criteria; RF+, CCP+ or ≥ 2 radiographic erosions; ≥ 4 tender and 4 swollen joints; MTX naïve. The primary endpoint was mean DAS28 from weeks 48-102. Other endpoints: ACR 20, 50, 70; discontinuation for lack of efficacy, DAS28 remission, QOL and Radiographic progression. Results: Subjects were 72% female; 80% Caucasian, 11% African American; with a mean age at entry of 49±13 yrs, with 3.6±6.5 months since diagnosis, 90% RF+. The mean DAS28 at entry 5.8±1.1; 28 joint count: 14.3±6.8 painful and 12.8±6.0 swollen joints. As shown in the Table, during the second year of treatment, patients randomized to S arms had clinical responses that were not statistically different than those who received I combination therapy, regardless of treatment arm (p-values: I vs S: 0.95, E vs T: 0.23). There were significant differences in the outcome of ACR response at 6 months between treatment arms: patients initially receiving IE or IT were significantly more likely to achieve an ACR 20/50/70 response at 6 months than those randomized to step-up arms (all p < 0.0001), regardless of treatment (E vs T). Conclusions: A 2-year double-blinded trial of early RA patients found no differences in the mean levels of DAS28 during weeks 48-102 among patients randomized to etanercept or triple DMARD, regardless of whether they received immediate combination treatment or MTX monotherapy with a step-up. At 6 months immediate combination treatment with either strategy was more effective than MTX monotherapy; however, there were no significant differences in groups at 2 years. Initial use of MTX monotherapy with the addition of SSZ/HCQ or etanercept, if necessary after 6 months, is a reasonable therapeutic strategy for early RA.
KEY POINTS ABSTRACT Purpose: No direct data compares triple DMARD (methotrexate [MTX], sulfasalazine [SSZ], hydroxychloroquine [HCQ]) to MTX + anti-TNF therapy (etanercept) in patients with early RA. The relative benefit of a strategy of either combination vs MTX monotherapy with step-up after 6 months is also uncertain. The TEAR trial evaluates both issues. Methods: The investigator-initiated, multi-center, randomized TEAR trial began in 2004 and enrolled 755 participants to compare immediate (I) vs step-up (S) strategy with MTX, etanercept (E) and triple DMARD (T) in 4 arms: immediate MTX + E (IE) or triple therapy (IT); step-up from MTX to MTX+E (SE) or to T (ST). In SE/ST, if DAS28 ≥ 3.2 at 6 months of MTX, patients were blindly stepped-up to IE/IT. Inclusion criteria: disease duration ≤ 3yrs, diagnosis by ACR criteria; RF+, CCP+ or ≥ 2 radiographic erosions; ≥ 4 tender and 4 swollen joints; MTX naïve. The primary endpoint was mean DAS28 from weeks 48-102. Other endpoints: ACR 20, 50, 70; discontinuation for lack of efficacy, DAS28 remission, QOL and Radiographic progression. Results: Subjects were 72% female; 80% Caucasian, 11% African American; with a mean age at entry of 49±13 yrs, with 3.6±6.5 months since diagnosis, 90% RF+. The mean DAS28 at entry 5.8±1.1; 28 joint count: 14.3±6.8 painful and 12.8±6.0 swollen joints. As shown in the Table, during the second year of treatment, patients randomized to S arms had clinical responses that were not statistically different than those who received I combination therapy, regardless of treatment arm (p-values: I vs S: 0.95, E vs T: 0.23). There were significant differences in the outcome of ACR response at 6 months between treatment arms: patients initially receiving IE or IT were significantly more likely to achieve an ACR 20/50/70 response at 6 months than those randomized to step-up arms (all p < 0.0001), regardless of treatment (E vs T). Conclusions: A 2-year double-blinded trial of early RA patients found no differences in the mean levels of DAS28 during weeks 48-102 among patients randomized to etanercept or triple DMARD, regardless of whether they received immediate combination treatment or MTX monotherapy with a step-up. At 6 months immediate combination treatment with either strategy was more effective than MTX monotherapy; however, there were no significant differences in groups at 2 years. Initial use of MTX monotherapy with the addition of SSZ/HCQ or etanercept, if necessary after 6 months, is a reasonable therapeutic strategy for early RA.
Forest plots showing the ORs for American College of Rheumatology 50% improvement (ACR50) response rates at week 24 in patients with active rheumatoid arthritis (RA) despite methotrexate receiving abatacept7 19 20 or rituximab 16–18 or anti-tumour necrosis factor agents (TNFs) (infliximab, etanercept, adalimumab, certolizumab and golimumab)7–15 versus placebo, using the Mantel–Haenszel method (random effect model).